Relatório Científico Final 2011-13 – UMIB
Transcrição
Relatório Científico Final 2011-13 – UMIB
Relatório Científico Final 2011-13 – UMIB Research Group Title: (RG-Norte-215-2560) - Pharmacology and Neurosciences Principal Investigator: Paulo Jorge Silva Correia Sa Research Area: Health Sciences Home Institution: Instituto de Ciências Biomédicas Abel Salazar Relatório Científico Final 2011-13 – UMIB Research Group Title: (RG-Norte-215-2560) - Pharmacology and Neurosciences Principal Investigator: Paulo Jorge Silva Correia Sa Research Area: Health Sciences Home Institution: Instituto de Ciências Biomédicas Abel Salazar Section – Objectives and Achievements 1. Objectives: The main objective of the Pharmacology and Neurosciences group is to investigate the pathophysiological role of purines (ATP and its metabolites) in human cells signaling and in animal models of human diseases, searching for new targets for therapeutic intervention. Considering the group previous findings on basic physiological mechanisms, ongoing collaborative work with clinical departments of the HGSA-CHPorto, CHVNGaia and the Forensics Institute (INML Porto) and abroad, has opened new avenues towards translational research projects covering the following topics: - The origin and fate of extracellular purines regulating bone formation and neuron-fibroblast interaction using human cells in culture (Collab. Depart. Orthopedics and Maxillofacial Surgery – HGSA-CHPorto and CHVNGaia) Integrative activities with GCR/UMIB) + 3 PhD students (JBNM, ARP, MC) + 2 FCT Projects (PTDC/SAUOSM/73576/2006, 85,324 € and PTDC/SAU-FCF/108263/2008, 121,764 €). - The pharmacological aspects of purinergic signaling of overactive human bladders in situ, in vitro and in the rat in vivo (Collab. Depart. Urology - HGSA-CHPorto) - Integrative activities with GCR/UMIB) + 1 PhD student (MSR) + 1 FCT Project (PTDC/SAU-OSM/104369/2008, 113,424 €). - The purinergic modulation of cavernosal vessel tonus in men with vasculogenic erectile dysfunction (Collab. Depart. Urology – HGSA-CHPorto; Inst. Andrologia (Madrid, Spain); Hosp. Ramon y Cajal (Madrid, Spain) Integrative activities with GCR/UMIB) + 2 PhD students (MF, NL) + 2 Projects (supported by UP / Santander Totta (3,800 €) and Soc. Port. Andrologia / Lilly (10,000 €). - - The functional status of the purinergic system and the neuron-glial interaction in patients with pharmacoresistant Mesial Temporal Lobe Epilepsy (Depart. Neurosciences - HGSA, INML and INSA Dr Ricardo Jorge; Fac. Pharmacy UP) - Integrative activities with IGIA/UMIB + 2 PhD students (ABB, BGL) + 2 FCT Projects (PIC/IC/83297/2007, 100,000 € and PTDC/SAU-TOX/115597/2009, 109,823€); FCT also funded the Eur. Sci. Foundation’s EuroEPINOMICS consortium (200,000 €) + 2 projects (supported by Liga Port. Epilepsia (7,500 €) and by UP / Santander Totta (3,500 €). - Pathophysiological role of subtype-specific ecto-NTPDases in human diseases (Collab. Centre de Recherche en Rhumatologie et Immunologie (Jean Sévigny, Laval, Quebec, Canada) + Tasks in 3 FCT Projects (PTDC/SAUOSM/73576/2006, 85,324 €; PTDC/SAU-FCF/108263/2008, 121,764 €; and PTDC/SAU-OSM/104369/2008, 113,424 €). - Animal-based research studies on the role of purines as potential targets for therapeutic intervention: - Myasthenic syndromes (Collab. Depart. Neurosciences – HGSA; Univ. Estadual de Maringá (Paraná, Brasil); UT Southwestern Med. Center (Steven Vernino, Dallas, USA); Weatheral Inst. Mol. Med., John Radcliffe Hosp. (M. Isabel Leite, Oxford, UK). - Integrative activities with GCR/UMIB) + 2 FCT Projects (PTDC/SAU-FCF/108462/2008, 103,995 €, and PTDC/NEU-NMC/0237/2012, 143,983€ in collaboration with ICETA-Porto/UP, UCL-London and REQUIMTE) + 1 Project (supported by UP / Santander Totta (3,500 €). - Inflammatory instestinal diseases (Collab. Depart. of General Surgery – HGSA); Nestlé Research Centre (Lausanne, Switzerland). 2 PhD students (MDA, CV) + 1 FCT Project (PTDC/CVT/74462/2006, 85,894 €) + 1 Project (supported by Univ. Porto / Santander Totta (3,500 €). - Involvement of purines in heart failure and pulmonary hypertension (Depart. of Physiology – FMUP (Porto, Portugal) + 1 FCT Project (PTDC/DTP-FTO/0802/2012, 121,792 €). The group provides an attractive environment, grounded in cutting-edge pieces of equipment, for molecular biology (e.g. real-time PCR, laser-microdissection system, flow cytometry), life-cell and tissue imaging (e.g. spectral laserscanning confocal microscope), and functional studies (e.g. liquid scintillation counter, electrophysiology equipment, in vivo experimental setups). Metabolite identification potential was recently upgraded from HPLC to UPLC in tandem with mass spectrometry. Research capability of the group attracted scientists (e.g. medicinal chemistry and toxicology from FFUP, biosensors development from FCUP, biomaterials from IST) seeking for collaborative projects. Such an example is the ongoing collaboration with Professor Augusto Matos (Veterinary Clinics, ICBAS) regarding the immunocytochemical analysis of putative prognostic factors (e.g. MMP-2, TIMP-2, VEGF, urokinase plasminogen activation factor) in canine mammary tumors. Two post-docs and one MSc students coming from Brasil (funded by CAPES and CNPQ) worked at the Pharmacology and Neurosciences group during 2012 and 2013. 2. Main Achievements during 2011-13: Data using neurochemistry, electrophysiology and real-time videomicroscopy techniques, indicate that retrograde adenosine release from myasthenic skeletal muscle causes profound changes in the control of neuromuscular transmission (see e.g. Noronha-Matos et al., 2011). We also gathered information indicating that A2A receptors play a significant role in train-of-four fade and tetanic failure produced by antinicotinic muscular relaxants (Bornia et al., 2011; Pereira et al., 2011; 2012; Paula-Ramos et al., 2013). In 2013, we demonstrated for the first time in collaboration with Brazilian colleagues from UNESP (Botucatu, S. Paulo) that the venom from the snake Bothrops jararacussu (Bothropstoxin-I) produce neuromuscular blockade due to the reduction of evoked acetylcholine release from stimulated motor nerve terminals prior to the establishment of the characteristic myonecrosis. This finding may have significant impact on the therapeutic procedure and fatality of snakebite accidents. ATP regulates gastrointestinal transit. The relative contribution of ecto-ATPase (forming ADP) and of ecto-NTPDase (bypassing ADP formation) pathways was tested to probe their role in controlling [3H]ACh release from the myenteric plexus of the rat ileum (Duarte-Araújo, 2011, PhD Thesis). A model of inflammatory disease in the rat ileum was successfully implemented in the lab. Using confocal microscopy we demonstrated that inhibitory A1 and excitatory A2A adenosine receptors are located in different sub-regions of myenteric neurons (Vieira et al., 2011). This must be taken into consideration for data interpretation regarding the pathophysiological implications of the nucleoside on intestinal motility/inflammatory disorders. We provided information showing that cholinergic nerve hyperactivity in patients with outflow bladder obstruction is associated with decreased hydrolysis of ATP released from urothelium, channeling to the activation of excitatory P2X3 receptors (Silva et al., 2011; Correia, 2011, MSc Thesis). In addition, we demonstrated that urinary ATP may be a sensitive dynamic biomarker for the diagnosis and follow-up of detrusor overactivity in women with hyperactive bladder (Silva-Ramos et al., 2013; Silva-Ramos & Correia-de-Sá, 2013). Data from in vivo studies in the anaesthetized rat showed for the first time that uracil nucleotides (UTP and UDP) cause bladder hyperactivity by indirectly releasing ATP from the urothelium, via pannexin-1 hemichannels (Timóteo et al., 2013), and subsequent activation of P2X3 receptors on suburothelial nerve afferents. Using in vivo studies, in vitro myographic recordings, neurochemical and histoenzymatic experiments, and immunofluorescnece confocal microscopy, we demonstrated that bladder overactivity may be partially counteracted by ATP hydrolysis into ADP by ecto-NTPDases, thereby restraining acetylcholine release from cholinergic nerve efferents expressing P2Y1 receptors (Timóteo et al., 2014, in press). ATP is a potent relaxant agent in the human corpus cavernosum (HCC) acting either directly, through P2Y12 receptors located on endothelium and smooth muscle fibres, or indirectly, via adenosine generated by ecto-nucleotidases. Relaxation of the HCC by P2 purinoceptor agonists is severely attenuated in erectile dysfunction (ED) patients (Faria, 2011, PhD Thesis). Involvement of the NO/cyclic GMP pathway has also been investigated (e.g. Angulo et al., 2012) Using single-cell Ca2+ imaging, immunofluorescence confocal microscopy and enzymatic assays, together with methods to evaluate proliferation and osteogenic differentiation, we demonstrated that uracil nucleotides are important regulators of osteogenic differentiation of primary bone marrow stromal cells from postmenopausal women (NoronhaMatos et al., 2012). Endogenous actions of uracil nucleotides, via UDP-sensitive P2Y6 receptors, are balanced through specific ecto-NTPDases determining whether osteoblast progenitors are driven into proliferation or differentiation (Noronha-Matos et al., 2012). Our findings also indicate that adenosine derived from ATP hydrolysis is an important regulator of osteogenic cell differentiation predominantly through the activation of A2B receptors (Costa et al., 2011). Recently, we showed that human and rodent fibroblasts act as inflammatory sensors (e.g. to bradikinin and histamine) and mechano-sensory intermediates between epithelia and primary afferent neurons by releasing purines in a Ca2+dependent manner (Certal, 2011, MSc Thesis). We, therefore, hypothesized that fibroblasts may amplify purinergic signaling between neighboring cells (e.g. sensory neurons) under painful situations (Pinheiro et al, 2013a and 2013b). Adenosine is considered an endogenous anti-convulsing agent, because of its neuromodulation effect regulating brain excitability via widespread inhibitory A1 receptor. At restricted synapses (e.g. hippocampus) adenosine may act on colocalized facilitatory A2A receptors. Data from our group demonstrate that increased adenosine A2A and decreased A1 receptors expression in the hippocampus and adjacent neocortex from patients with mesial temporal lobe epilepsy (MTLE) shifts adenosine modulation towards excitability. The mechanism by which adenosine promotes neuronal excitability may involve Ca2+ influx via VOCC and/or changes in the control of high-affinity GABA and glutamate transport assignment dedicated to terminate neurotransmission and control synaptic excitability (Barros-Barbosa, 2011, MSc Thesis). Concomitantly, a series of high-significant clinical research papers have been produced by members of the research team in collaboration with other groups, working namely in Urology and Neuropathology fields. Section – Activities 1. Integrative/multidisciplinary activities in 2011-13. Special activities that aim to carry out research across disciplines. Ongoing collaborative work with clinical departments of the HGSA-CHPorto, CHVNGaia and the Forensics Institute (INML Porto) and abroad, has opened new avenues towards translational research projects. In addition, efforts have been made to integrate multidisciplinary activities from various groups of UMIB (e.g. Clinical Research Group - CRG, ImmunoGenetics, Inflammation and Auto-immunity Group - IGIA) within the translational framework created by the Pharmacology and Neurosciences Group. Examples of these interactions are as follows (see also Objectives): - The origin and fate of extracellular purines regulating bone formation and neuron-fibroblast interaction using human cells in culture - Integrative activities with CRG/UMIB). - The pharmacological aspects of purinergic signaling of overactive human bladders in situ, in vitro and in the rat in vivo - Integrative activities with CRG/UMIB). - The purinergic modulation of cavernosal vessel tonus in men with vasculogenic erectile dysfunction - Integrative activities with CRG/UMIB). - The functional status of the purinergic system and the neuron-glial interaction in patients with pharmaco-resistant Mesial Temporal Lobe Epilepsy - Integrative activities with IGIA/UMIB. - Animal-based research studies on the role of purines as potential targets for therapeutic intervention: a) Myasthenic syndromes - Integrative activities with CRG/UMIB. 2. Outreach activities during 2011-13. Science and Society/general public/schools, etc. Undergraduates and students from high schools around Porto city visit the Group of Pharmacology and Neurosciences at UMIB/ICBAS/UP on a regular basis. During these visits, students and their tutors are offered simple explanations about the scientific projects undergoing in the lab and how can these be clinically relevant. Concerning the students’ interests, they can follow complete experiments upon appointment. The PI often participates in radio and TV broadcasting debates on the topic of his research. In addition, the University of Porto and affiliated research centres dedicates an open week to public at large; the PI of this group took on his own the responsibility of organizing last year´s show on Biomedical Research and the activities of the International Brain Awareness Week (Portuguese Society for Neuroscience, on behalf of the Dana Farber Foundation) taking place at UMIB/ICBAS/UP. Section – Funding 3. In this section include funding details during the reporting period. Units FCT: Apresentar o total do financiamento recebido pela FCT (ex: projetos de ICDT, Redes Temáticas, etc.), excluindo o financiamento apresentado no ponto anterior. - Eur. Sci. Foundation – EuroEPINOMICS, aiming at identifying novel epilepsy genes and genetic variants predisposing to epilepsy and drug response (FCT, 200,000 €) Projects FCT: Apresentar o total do financiamento recebido directamente pelos projectos financiados pela FCT, a funcionar no âmbito do Laboratório/Unidade - P. Correia-de-Sá et al. (2007-10) Enteric purines as potential therapeutic targets for inflammatory bowel diseases. FCT, PTDC/CVT/74462/2006 (85,894 €). - P. Correia-de-Sá et al. (2007-10) Origin and fate of extacellular purines regulating human bone formation. FCT, PTDC/SAU-OSM/73576/2006 (85,324 €). - C. Pereira & P. Correia-de-Sá (2007-10) Biosensors for endogenous catecholamines. FCT, PTDC/QUI/69685/2006 (93,300 €). - M. Berta Silva & M.G.B. Lobo (2008-11) The relevance of HHV-6B in patients with Mesial Temporal Lobe Epilepsy...... FCT, PIC/IC/83297/2007 (100,000 €). - P. Correia-de-Sá et al. (2010-12) Pathophysiological role of purines (ATP and adenosine) in the human bladder hyperactivity. FCT, PTDC/SAU-OSM/104369/2008 (113,424 €). - P. Correia-de-Sá et al. (2010-12) Fibroblasts as mechano-sensory signalling intermediates between epithelia and primary afferent neurons…FCT, PTDC/SAU-FCF/108263/2008 (121,764 €). - Laura Oliveira & P. Correia-de-Sá (2010-12) Is there a place for adenosine mediating impairment of both neuromuscular and immunological synapses in myasthenics? FCT, PTDC/SAU-FCF/108462/2008 (103,995 €). - Glória Queiroz & P. Correia-de-Sá (2010-12) Astrocyte-microglia crosstalk in astrogliosis: modulation by P2 receptors. FCT, PTDC/SAU-TOX/115597/2009 (109,823€). - Ana Patrícia Fontes Sousa & P. Correia-de-Sá (2013-15) On the role of adenosine signalling in the progression of pulmonary hypertension to heart failure. FCT, PTDC/DTP-FTO/0802/2012 (121,792€). - Jorge Oliveira & P. Correia-de-Sá (2013-15) KDAC inhibition and intracellular dynamics: impact on neuronal development, survival and transmission. FCT, PTDC/NEU-NMC/0237/2012 (143,983€). Other (National): Apresentar o total dos financiamentos recebidos de fontes nacionais que não provenham da FCT - R. Rangel, M. Berta Silva, P. Correia-de-Sá & M.G.B. Lobo (2009-10) Actividade da ADK, ADA e NTPDases sobre os níveis de adenosina endógena no hipocampo e córtex temporal de doentes com MTLE. Supported by Liga Port. Epilepsia (7,500 €). - P. Correia-de-Sá et al. (2009-10) Papel dos receptors da adenosina no crescimento e remodelação dos vasos cavernosos humanos: Repercussão na fisiopatologia da disfunção eréctil vasculogénica. Supported by Univ. Porto / Santander Totta (3,800 €). - P. Correia-de-Sá et al. (2010-11) Toxin-induced myasthenia gravis and in vitro assays to characterize neuromuscular impairment…. Supported by Univ. Porto / Santander Totta (3,500 €). - Fátima Ferreirinha et al. (2010-11) Sinalização purinérgica numa nova sinapse mioentérica tripartida: relevância funcional. Supported by Univ. Porto / Santander Totta (3,500 €). - João Miguel Cordeiro et al. (2010-11) A adenosina na modulação do transporte de GABA e de glutamato em doentes com MTLE. Supported by Univ. Porto / Santander Totta (3,500 €). Other (International): Apresentar o total dos financiamentos recebidos de outras fontes internacionais N/a National Industry: Apresentar o total dos financiamentos diretamente provenientes da industria nacional - N Louro & P. Correia-de-Sá et al. (2008-10) Purinergic signaling in the human corpus cavernosum as a therapeutic target for vasculogenic erectile dysfunction. Supported by Soc. Port. Andrologia / Lilly (10,000 €). International Industry: Apresentar a soma dos financiamentos diretamente provenientes da industria internacional N/a Section – General Indicators This section is designed to provide information regarding the researchers and the technical personnel hired, and the total number of completed PhDs thesis during the reported period. Composition and Training In this section indicate the number of researchers hired through the Ciência Programme, during the reporting period. Include also the total number of integrated Researchers with PhD and the PhD thesis completed in the period. No. of Researchers Hired (Ciência Programme): (Apresentar o número total de doutorados contratados no âmbito do Programa Ciência durante o ano a que respeita o Relatório): 0 No. of Researchers integrated with PhD(Apresentar o número total de membros da equipa doutorados integrados): 17 Training PhDs (PhD thesis completed) (Apresentar o número total de teses de doutoramento concluídas, com a orientação de membros integrados na equipa do respectivo Laboratório/Unidade): 3 Researchers Hired In this section indicate the individual researchers hired in the period by introducing the association key (previously named as public key), their starting date and if applicable their finishing date. In case the researchers also hold a part-time position at another institution (teaching at University or Polytechnic) also indicate this in Other Institution. Chave de Associação* Data de início do contrato (dd-mm-aaaa) Data de fim do contrato (dd-mm-aaaa) Outra Instituição** * Introduzir a chave de associação do investigador contratado pelo Programa Plurianual, pelo Projeto Estratégico ou ainda pelo Programa Ciência. Após inserção da mesma aparece o seu nome para confirmação. Os contratos de bolsas não devem ser considerados neste ponto. ** Caso o contrato seja celebrado com outra instituição que não seja a FCT, apresentar a sua designação Technical Personnel Hired In this section indicate individual technical personal hired. To do so all personal must be registered at the FCT and have an association key. Chave de Associação* Data de início do contrato (dd-mm-aaaa) Data de fim do contrato (dd-mm-aaaa) Outra Instituição** * Introduzir a chave de associação do investigador contratado pelo Programa Plurianual, pelo Projeto Estratégico ou ainda pelo Programa Ciência. Após inserção da mesma aparece o seu nome para confirmação. Os contratos de bolsas não devem ser considerados neste ponto. ** Caso o contrato seja celebrado com outra instituição que não seja a FCT, apresentar a sua designação Additional Comments: In this space you can provide any additional information regarding the Section General Indicators. Section – Group Productivity PRODUCTIVITY (Adicionar items) 1. Publications in peer review Journals 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. Costa MA, Barbosa A, Neto E, Sá-e-Sousa A, Freitas R, Neves JM, Magalhães-Cardoso T, Ferreirinha F, Correia-de-Sá P. On the role of subtype selective adenosine receptor agonists during proliferation and osteogenic differentiation of human primary bone marrow stromal cells. J. Cell. Physiol. (2011) 226, 13531366. Noronha-Matos JB, Morais T, Trigo D, Timóteo MA, Magalhães-Cardoso MT, Oliveira L, Correiade-Sá P. Tetanic failure due to decreased endogenous adenosine A2A tonus operating neuronal Cav1 (L-type) influx in Myasthenia gravis. J. Neurochem. (2011) 117, 797-811. Bornia EC, Correia-de-Sá P, Alves-Do-Prado W. Presynaptic facilitatory A2A receptors mediate fade induced by neuromuscular relaxants that exhibit anticholinesterase activity.Clin. Exp. Pharmacol. Physiol. (2011) 38, 164-169. Pereira MW, Bornia ECS, Correia-de-Sá P, Alves-Do-Prado, W. Presynaptic muscarinic and adenosine receptors involved in 2 Hz-induced train-of-four fade caused by antinicotinic neuromuscular relaxants in the rat. Clin. Exp. Pharmacol. Physiol. (2011) 38, 764-770. Cordeiro JM, Gonçalves PP, Dunant Y. Synaptic vesicles control the time course of neurotransmitter secretion via a Ca²+/H+ antiport. J. Physiol. (London) (2011) 589, 149-167. Vieira C, Ferreirinha F, Silva I, Duarte-Araújo M, Correia-de-Sá P. Localization and function of adenosine receptor subtypes at the longitudinal muscle – myenteric plexus of the rat ileum. Neurochem. Int. (2011) 59, 1043-1055. Falcao-Pires I, Fontes-Sousa AP, Lopes-Conceiçao L, Brás-Silva C, Leite-Moreira AF. Modulation of myocardial stiffness by beta-adrenergic stimulation - its role in normal and failing heart. Physiol Res. (2011) 60, 599-609. Lopes-Conceição L, Dias-Neto M, Fontes-Sousa AP, Mendes-Ferreira P, Maia-Rocha C, HenriquesCoelho T, de Keulenaer G, Leite Moreira AF, Brás-Silva C. Neuregulin1/ErbB system: importance in the control of cardiovascular function. Acta Med Port (2011) 24 Suppl 4:1009-20. Munz MR, Faria MA, Monteiro JR, Aguas AP, Amorim MJ. Surgical porcine myocardial infarction model through permanent coronary occlusion. Comp Med. (2011) 61, 445-452. Taipa R, Martins da Silva A, Santos E, Pinto PS, Melo-Pires M. Gliomatosis cerebri diagnostic challenge: two case reports. Neurologist (2011) 17, 269-272. Pinto PS, Taipa R, Moreira B, Correia C, Melo-Pires M. Acute hemorrhagic leukoencephalitis with severe brainstem and spinal cord involvement: MRI features with neuropathological confirmation. J Magn Reson Imaging. (2011) 33, 957-961. Cavadas V, Branco F, Carvalho FL, Osório L, Gomes MJ, Silva-Ramos M. The quality of reporting of randomized controlled trials in pelvic organ prolapse. Int Urogynecol J. (2011) 22, 1117-1125. Osório L, Carvalho FL, Branco F, Cavadas V, Autorino R, Soares J. Endoscopic removal of an intravesical calcified sling using pneumatic lithotripsy and cystoscopic resection. Urol Int. (2011) 87, 489-491. Branco F, Cavadas V, Osório L, Carvalho F, Martins L, Dias L, Castro-Henriques A, Lima E. The incidence of cancer and potential role of sirolimus immunosuppression conversion on mortality among a single-center renal transplantation cohort of 1,816 patients. Transplant Proc. (2011) 43, 137-141. Branco F, Pini G, Osório L, Cavadas V, Versos R, Gomes M, Autorino R, Correia-Pinto J, Lima E. Transvesical peritoneoscopy with rigid scope: feasibility study in human male cadaver. Surg Endosc. (2011) 25, 2015-2019. Perdonà S, Cavadas V, Di Lorenzo G, Damiano R, Chiappetta G, Del Prete P, Franco R, Azzarito G, Scala S, Arra C, De Sio M, Autorino R. Prostate cancer detection in the "grey area" of prostate-specific antigen below 10 ng/ml: head-to-head comparison of the updated PCPT calculator and Chun's nomogram, two risk estimators incorporating prostate cancer antigen 3. Eur Urol. (2011) 59, 81-87. de Oliveira JT, de Matos AJ, Santos AL, Pinto R, Gomes J, Hespanhol V, Chammas R, Manninen A, Bernardes ES, Albuquerque Reis C, Rutteman G, Gärtner F. Sialylation regulates galectin-3/ligand interplay during mammary tumour progression--a case of targeted uncloaking. Int J Dev Biol. (2011) 55, 823-834. Ferreira RR, Gopegui RR, Matos AJ. Frequency of dog erythrocyte antigen 1.1 expression in dogs from Portugal. Vet Clin Pathol.(2011) 40, 198-201. Santos A, Lopes C, Marques RM, Amorim I, Ribeiro J, Frias C, Vicente C, Gärtner F, de Matos A. Immunohistochemical analysis of urokinase plasminogen activator and its prognostic value in canine mammary tumours. Vet J. (2011) 189, 43-48. Santos A, Lopes C, Frias C, Amorim I, Vicente C, Gärtner F, Matos A. Immunohistochemical evaluation of MMP-2 and TIMP-2 in canine mammary tumours: a survival study. Vet J. (2011) 190, 396-402. 21. Noronha-Matos JB, Costa MA, Magalhães-Cardoso MT, Ferreirinha F, Freitas R, Neves JM, Sévigny J, Correiade-Sá P. Role of ecto-NTPDases on UDP-sensitive P2Y6 receptor activation during osteogenic differentiation of primary bone marrow stromal cells from postmenopausal women. J. Cell. Physiol. (2012) 227:2694-2709. 22. Fernandes C§, Oliveira L§, Tiritan ME, Leitao L, Pozzi A, Noronha-Matos JB, Correia-de-Sá P, Pinto M. Synthesis of new chiral xanthone derivatives acting as nerve conduction blockers in the rat sciatic nerve. Eur. J. Med. Chem. (2012) 55:1-11. 23. Pereira MW, Correia-de-Sá P, Alves-Do-Prado W. Adenosine A2A receptor antagonists are broad facilitators of antinicotinic neuromuscular blockade monitored either with 2-Hz train-of-four or 50-Hz tetanic stimuli. Clin. Exp. Pharmacol. Physiol. (2012) 39:869-877. 24. Correia-de-Sá P, Noronha-Matos JB, Timóteo MA, Ferreirinha F, Marques P, Soares AM, Carvalho C, Cavalcante WLG, Gallacci M. Bothropstoxin-I reduces evoked acetylcholine release from rat motor nerve terminals: radiochemical and real-time video-microscopy studies. Toxicon (2013) 61:16-25, http://dx.doi.org/10.1016/j.toxicon.2012.10.014. 25. Silva R, Carmo H, Vilas-Boas V, Guedes de Pinho P, Dinis-Oliveira R, Carvalho F, Silva I, Correia-de-Sá P, Bastos ML, Remião F. Doxorubicin decreases paraquat accumulation and toxicity in Caco-2 cells. Toxicol. Lett. (2013) 217:34-41, http://dx.doi.org/10.1016/j.toxlet2012.11.028. 26. Matos AJ, Baptista CS, Gärtner MF, Rutteman GR. 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Coelho T, Maia LF, Martins da Silva A, Waddington Cruz M, Planté-Bordeneuve V, Lozeron P, Suhr OB, Campistol JM, Conceição IM, Schmidt HH, Trigo P, Kelly JW, Labaudinière R, Chan J, Packman J, Wilson A, Grogan DR. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology. (2012) 79:785-92. doi: 10.1212/WNL.0b013e3182661eb1. 31. Gomes MJ, Martins da Silva A, Salinas J, Silva MC, Figueiredo A, Cavadas V, Coelho T. Female sexual and pelvic floor muscles dysfunctions in familial amyloidotic polyneuropathy (FAP-Portuguese type). Arch Esp Urol. (2012) 65:476-88. 32. Cavaco S, Martins da Silva A, Santos E, Coutinho E, Marinho A, Moreira I, Gonçalves A, Pinto C, Teixeira-Pinto A, Vasconcelos C. Are cognitive and olfactory dysfunctions in neuropsychiatric lupus erythematosus dependent on anxiety or depression? J Rheumatol. (2012) 39:770-6. doi: 10.3899/jrheum.110574. 33. Da Silva AM, Willmore LJ. Posttraumatic epilepsy. Handb Clin Neurol. 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Cruto C, Taipa R, Monteiro C, Moreira I, Melo-Pires M, Correia M. Multiple cerebral infarcts and intravascular central nervous system lymphoma: A rare but potentially treatable association. J Neurol Sci. (2013) 325:183-5. doi: 10.1016/j.jns.2012.10.012. 38. Taipa R, Pinho J, Melo-Pires M. Clinico-pathological correlations of the most common neurodegenerative dementias. Front Neurol. (2012) 3:68. doi: 10.3389/fneur.2012.00068. 39. Taipa R, Tuna A, Damásio J, Pinto PS, Cavaco S, Pereira S, Milterberger-Miltenyi G, Galimberti D, Melo-Pires M. Clinical, neuropathological, and genetic characteristics of the novel IVS9+1delG GRN mutation in a patient with frontotemporal dementia. J Alzheimers Dis. (2012) 30:83-90. doi: 10.3233/JAD-2012-112084. 40. Silva-Ramos M, Louro N, Versos R, Cavadas V, Marcelo F. Does 3D Ultrasound Enhance the Diagnosis of Bladder Tumours in Patients with Haematuria? ISRN Urol. (2012) 2012:158437. doi: 10.5402/2012/158437. 41. Oliveira A, Neto A, Almeida C, Silva-Ramos M, Versos R, Barros A, Sousa M, Carvalho F. Comparative study of gene expression in patients with varicocele by microarray technology. Andrologia (2012) 44 Suppl 1:260-5. doi: 10.1111/j.1439-0272.2011.01173.x. 42. Figueira AC, Teodósio AS, Carvalheira J, Lacerda M, de Matos A, Gärtner F. P-cadherin expression in feline mammary tissues. Vet Med Int. (2012) 2012:687424. doi: 10.1155/2012/687424. 43. Santos AA, Lopes CC, Marques RM, Amorim IF, Gärtner MF, de Matos AJ. Matrix metalloproteinase-9 expression in mammary gland tumors in dogs and its relationship with prognostic factors and patient outcome. Am J Vet Res. (2012) 73:689-97. doi: 10.2460/ajvr.73.5.689. 44. Silva-Ramos M, SilvaI, Oliveira O, Ferreira S, Reis MJ, Oliveira JC, Correia-de-Sá P. Urinary ATP may be a dynamic biomarker of detrusor overactivity in women with overactive bladder syndrome. PLoS ONE (2013) 8, e64696. doi:10.1371/journal.pone.0064696. 45. Pinheiro AR, Paramos-de-Carvalho D, Certal M, Costa MA, Costa AC, Magalhães-Cardoso MT, Ferreirinha F, Sévigny J, Correia-de-Sá P. Histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to Ca2+ mobilization and cell proliferation. J. Biol. Chem. (2013) 288, 27571–27583. doi: 10.1074/jbc.M113.460865. 46. Pinheiro AR, Paramos-de-Carvalho D, Certal M, Costa AC, Magalhães-Cardoso MT, Costa MA, Correia-de-Sá P. Bradykinin Ca2+ signaling in human subcutaneous fibroblasts involves ATP release via hemichannels and P2Y12 receptors activation. Cell Commun. Signal. (2013) 11, 70. doi:10.1186/1478-811X-11-70. 47. Paula-Ramos E, Antônio MB, Ambiel CR, Correia-de-Sá P, Alves-do-Prado W. Paradoxical neostigmine-induced TOFfade: on the role of presynaptic cholinergic and adenosine receptors. Eur. J. Pharmacol. (2013, in press). doi:pii: S0014-2999(13)00845-5. 10.1016/j.ejphar.2013.11.001. 48. Silva-Ramos M, Correia-de-Sá P. For women with overactive bladder syndrome, urinary ATP may be a dynamic biomarker of detrusor overactivity. UroToday "Beyond the Abstract" (2013) Commentary published on 08 November 2013 in UroToday.com. 49. Timóteo MA, Carneiro I, Silva I, Noronha-Matos JB, Ferreirinha F, Silva-Ramos M, Correia-de-Sá P. ATP released via pannexin-1 hemichannels mediates bladder overactivity triggered by urothelial P2Y6 receptors. Biochem. Pharmacol. (2013, in press). doi:pii: S0006-2952(13)00738-7. 10.1016/j.bcp.2013.11.007. 50. Carneiro I, Timóteo MA, Silva I, Vieira C, Baldaia C, Ferreirinha F, Silva-Ramos M, Correia-de-Sá P. Activation of P2Y6 receptors causes bladder overactivity in the anaesthetized rat by releasing ATP from the urothelium. Br. J. Pharmacol. (2013, submitted 2013-BJP-0849-RP) 51. Oliveira-Monteiro N, Bragança B, Ferreirinha F, Faria M, Fontes-Sousa AP, Correia-de-Sá P. Rationale for understanding chronoselectivity of adenosine A1 receptor in the rat spontaneously beating atria: enrolment of KCa2 (SK) and Cav1 (L-type) ion channels. Am. J. Physiol. (Heart Circ. Physiol.) (2012, submitted H-00711-2012) 2. Other publications 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. M.J. Valente, R. Amorim, R. Viais, M. Faria, J.-M. LaFuente-de-Carvalho & P. Correia-de-Sá. Comparação dos efeitos da adenosine e de outros agents relaxantes dependentes do endotélio no tecido cavernoso humano e de rato. Acta Urológica (2011) 28 (Suppl 1), C179, 26. S. Ferreira, I. Silva, O. Oliveira, M. Duarte-Araújo, J.C. Oliveira, F. Bravo, M. Silva-Ramos & P. Correia-de-Sá. Poderá o ATP urinário desempenhar um papel como biomarcador da bexiga hiperactiva? Acta Urológica (2011) 28 (Suppl 1), C194, 33. L. Oliveira, D. Trigo, T. Morais, A. Sá-e-Sousa, C. Costa, M.T. Magalhães-Cardoso, M.A. Timóteo & P. Correia-de-Sá. Retrograde signalling by adenosine is impaired in toxin-induced Myasthenia gravis: cross-talk with excitatory nicotinic α3β2 and muscarinic M1 autoreceptors. J. Neurochemistry (2011). P. Marques, I. Silva, C. Vieira, F. Ferreirinha, T. Magalhães-Cardoso, M. Duarte-Araújo & P. Correia-deSá. Interstitial Cells of Cajal control cholinergic neurotransmission in the tripartite myenteric synapse by releasing adenosine. J. Neurochemistry (2011). A. Alves, F. Nascimento, P. Correia-de-Sá & J.M. Cordeiro. Presynaptic nicotinic autoreceptors outlying release sites facilitate cholinergic neurotransmission in the Torpedo electric organ. J. Neurochemistry (2011). I. Silva, J. Correia, F. Ferreirrinha, M.T. Magalhães-Cardoso, M. Silva-Ramos, J. Sévigny & P. Correiade-Sá. Bladder overactivity due to global impairment of ecto-NTPDases in humans with lower urifnary tract disorders exhibiting unbalanced ATP / adenosine formation. Autonomic Neuroscience: Basic & Clinical (2011) 163:1-2, P.023, 49-50 & Clinical Autonomic Research (2011) 21:4, P.023, 227. I. Silva, P. Marques, C. Vieira, F. Ferreirrinha, M.T. Magalhães-Cardoso, M. Duarte-Araújo & P. Correia-de-Sá. Amplification of cholinergic neurotransmission by adenosine released from interstitial Cells of Cajal at a tripartite myenteric synapse of the rat ileum Autonomic Neuroscience: Basic & Clinical (2011) 163:1-2, P.063, 64-65 & Clinical Autonomic Research (2011) 21:4, P.063, 242. A.R. Pinheiro, C. Costa, C. Soares, M.T. Magalhães-Cardoso, M.A. Costa & P. Correia-de-Sá. Kinetics of the extracellular catabolism of adenine nucleotides by fibroblasts of the human subcutaneous connective tissue. Purinergic Signalling (2012) 8, PS4.2, p. 160. C. Costa, D. Meireles, M. Viegas, D. Paramos, M.A. Timóteo, M.T. Magalhães-Cardoso, L. Oliveira & P. Correia-de-Sá. Inhibition of adenosine deaminase (ADA) overactivity failed to restore neuromuscular transmission failure in rats with toxin-induced Myasthenia gravis. Purinergic Signalling (2012) 8, PS4.11, p. 165. N. Oliveira-Monteiro, A.P. Fontes-Sousa, B. Bragança, S. Marques, M. Faria & P. Correia-de-Sá. Cav1 (L) channel blockade uncovers adenosine negative inotropism leading to a loss of A1 “chronoselectivity” in the spontaneously beating rat atria. Purinergic Signalling (2012) 8, PS6.3, p. 171. P. Marques, I. Silva, C. Vieira, M. Duarte-Araújo, F. Ferreirinha, T. Magalhães-Cardoso & P. Correia-deSá. M3- and NK1-receptor facilitation of [3H]-acetylcholine release from myenteric motoneurons depends on extracellular adenosine accumulation acting on prejunctional A2A receptors. Neurogastroenterol. Motil. (2012) 24 (Suppl. 2) P006, 44. C. Vieira, J. Oliveira, P. Marques, T. Magalhães-Cardoso, M. Duarte-Araújo & P. Correia-de-Sá. Impairement of the adenosine fine-tuning control of acetylcholine release from myenteric motoneurons in the inflamed rat ileum. Neurogastroenterol. Motil. (2012) 24 (Suppl. 2) P087, 67. M. Duarte-Araújo, P. Marques, C. Vieira, I. Silva, T. Magalhães-Cardoso & P. Correia-de-Sá. Adenosine modulates its own release throught activation of A2A receptors on myenteric cholinergic nerve terminals of the rat ileum. Neurogastroenterol. Motil. (2012) 24 (Suppl. 2): P375, 152. C Rocha-Pereira, JB Sousa, P Fresco, J Gonçalves, SM Arribas, MC González, F Ferreirinha, P Correiade-Sá & C Diniz. Less efficient prejunctional adenosine receptor-mediated inhibitory effects in mesenteric vessels of spontaneously hypertensive rats (SHR). Proceedings of the British Pharmacological Society (2012) 10 (Issue 3): P092, 282 (http://www.pA2online.org/abstracts/Vol10Issue3abst282P.pdf). D Paramos, AR Pinheiro, F Ferreirinha, MA Costa & P Correia-de-Sá. Interplay between P2X7 and P2Y1 receptors controls intracellular [Ca2+] signals in fibroblasts of the human subcutaneous connective tissue. Proceedings of the British Pharmacological Society (2012) 10 (Issue 3): P426, 327 (http://www.pA2online.org/abstracts/Vol10Issue3abst327P.pdf). JB Noronha-Matos, A Sá-e-Sousa, J Coimbra, S Gomes, R Rocha, J Marinhas, R Freitas, J MoraisNeves, MA Costa & P Correia-de-Sá. The P2X7 receptor may be a novel therapeutic target to promote osteogenic differentiation and mineralization of postmenopausal bone marrow stromal cells. Proceedings of the British Pharmacological Society (2012) 10 (Issue 3): P418, 242 (http://www.pA2online.org/abstracts/Vol10Issue3abst242P.pdf). M. Faria, J.-M. LaFuente-de-Carvalho & P. Correia-de-Sá. Thromboxane A2 release from the endothelium mediates transient P2 purinoceptor-induced contractions of the human corpus cavernosum. Proceedings of the British Pharmacological Society (2012) 10 (Issue 3): P511, 563 (http://www.pA2online.org/abstracts/Vol10Issue3abst563P.pdf). 18. AR Pinheiro, M Certal, D Paramos, MA Costa & P Correia-de-Sá. Bradykinin activation of fibroblasts of the rat subcutaneous tissue triggers the release of ATP and P2 purinoceptors activation. Journal of Bodywork and Movement Therapies (Fascia Science and Clinical Applications) (2012) 16 (Issue 2): 155-156 [DOI:10.1016/j.jbmt.2012.01.069]. 19. M.G. Lobo, C. Teixeira, M. Mendes, S. Guerra-Gomes, F. Ferreirinha, A. Santos, R. Rangel, J.M. Cordeiro & P. Correia-de-Sá. A alteração do tonus entre receptors inibitórios A1 e excitatórios A2A da adenosina explica a acumulação de Ca2+ pelos terminais nervosos isolados de deontes com epilepsia do lobo mesial temporal (MTLE). Sinapse (2013) 13 in press. 20. A. Barros-barbosa, S. Guerra-Gomes, F. Ferreirinha, M.T. Magalhães-Cardoso, M.G. Lobo, A. Santos, R. Rangel & P. Correia-de-Sá. Papel dos purinoceptores na modulação do transporte de GABA e de glutamato em doentes com epilepsia do lobo mesial temporal (MTLE) resistente a fármacos. Sinapse (2013) 13 in press. 21. P. Correia-de-Sá, A. Barros-Barbosa, S. Guerra-Gomes, M. Mendes, F. Ferreirinha, M.T. Magalhães-Cardoso, M.G. Lobo & J.M. Cordeiro. Fine-tuning modulation of GABA and glutamate uptake by purinoceptors in the human epileptic neocortex. J. Neurochem. (2013), 125 (Suppl. 1), 259. 22. I. Silva, J. Correia, F. Ferreirinha, M. Silva-Ramos, J. Sévigny & P. Correia-de-Sá. P2Y6-induced release of ATP from the urothelium exerts a dual role in the human urinary bladder. FEBS Journal (2013) 280 (Suppl. 1), 1742-464. 23. M. Silva-Ramos*, I. Silva1*, O. Oliveira, S. Ferreira, M.J. Reis, J.C. Oliveira & P. Correia-de-Sá. Overactive bladder syndrome: Evidence that urinary ATP is a dynamic biomarker of detrusor overactivity. Autonomic Neuroscience: Basic & Clinical (2013) 177 (Issue 1), 21-22. 24. I. Silva, M.A. Timóteo, J. Correia, F. Ferreirinha, M. Silva-Ramos, J. Sévigny & P. Correia-de-Sá. Dual role of P2Y6 receptors in the human urinary bladder: on the role of ATP released from the urothelium. Autonomic Neuroscience: Basic & Clinical (2013) 177 (Issue 1), 21-22. 25. C. Vieira, F. Ferreirinha, M.T. Magalhães-Cardoso, J. Oliveira, P. Marques, M. Duarte-Araújo & P. Correiade-Sá. Changes in the fine-tuning adenosine control of acetylcholine release from myenteric motoneurons in TNBS-inflamed rat ileum. Autonomic Neuroscience: Basic & Clinical (2013) 177 (Issue 1), 21-22. 3. Other national publications 1. J.M. Cordeiro & P. Correia-de-Sá. Acetilcolina. In Neurociências (2011). Eds. C. Rego, C. Duarte & C. Oliveira, LIDEL - Edições Técnicas, Lda – Lisboa. 2. J-M LaFuente de Carvalho & N. Louro. Disfunção eréctil na Diabetes mellitus 2 (2012). LIDEL Edições Técnicas, Lda – Lisboa. 3. P. Correia-de-Sá. Sistema colinérgico. In Terapêutica Medicamentosa e suas Bases Farmacológicas (2013). Eds. S. Guimarães, D. Moura & P. Soares da Silva, 6ª Edição, Porto Editora – Porto (in press). 4. Master and Ph.D. thesis completed PhD Thesis completed: 1. 2. 3. Margarida Duarte Cerqueira Martins de Araújo (2011). Endogenous purines as potential pharmacological targets to control myenteric neurotransmission. PhD in Biomedical Sciences (supervised by P. Correia-de-Sá). Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. Supported by FCT (SFRH/BD/29044/2006). Miguel Augusto Soucasaux Marques Faria (2011). Purinergic regulation of human corpus cavernosum tonus in patients with vasculogenic erectile dysfunction. PhD in Biomedical Sciences (supervised by P. Correia-de-Sá). Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. Supported by FCT (SFRH/BD/25470/2005). Ana Rita Vieira Pinheiro (2013). The purinome in fibroblasts of the human subcutaneous tissue – a contribution to elucidate the pathogenesis of myofascial pain. PhD in Biomedical Sciences (supervised by P. Correia-de-Sá). Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. Supported by FCT (SFRH/BD/47373/2008). Master Thesis completed: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. Sónia Andreia Mimoso Lopes de Oliveira Ferreira (2010-11). O ATP como biomarcador da bexiga hiperactiva e o benefício clínico da toxina botulínica. Master Thesis in Medicine (supervised by M. Silva-Ramos & P. Correia-deSá) (20/20). Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. Cátia Andreia Rodrigues Vieira (2010-11). Distribuição dos receptores da adenosina no plexo mioentérico – músculo longitudinal do íleo de rato: Implicações funcionais. Master Thesis in Chemical Sciences and Biomolecules (supervised by P. Correia-de-Sá) (19/20). Escola Superior de Tecnologia da Saúde do Porto (ESTSP), Instituto Politecnico do Porto. Mariana de Sousa Certal (2010-11). Fibroblastos como intermediáris na sinalização mecano-sensitiva entre o epitélio e os neurónios aferentes primários: o papel do ATP extracelular e das ondas de [Ca2+]i. Master Thesis in Biochemistry (supervised by M.A. Costa, A.R. Pinheiro & P. Correia-de-Sá) (19/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. Aurora Raquel Barros Barbosa (2010-11). Modulação purinérgica do transporte de GABA e glutamato na epilepsia. Master Thesis in Biochemistry (supervised by J.M. Cordeiro, M.G.B. Lobo & P. Correia-de-Sá) (19/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. Patrícia Alexandra Rocha Marques (2010-11). Contribution of interstitial cells of Cajal to the regulation of cholinergic neurotransmission at the rat ileum tripartite myenteric synapse: does endogenous adenosine play a role. Master Thesis in Health Sciences (supervised by P. Correia-de-Sá) (19/20). Escola de Ciências da Saúde – Universidade do Minho. Carla Alexandra Araújo Leite (2010-11). Isolamento e cultura de células do tecido cavernoso humano: Caracterização fenotípica e identificação de purinoceptores por imunofluorescência. Master Thesis in Chemical Sciences and Biomolecules (supervised by P. Correia-de-Sá) (18/20). Escola Superior de Tecnologia da Saúde do Porto (ESTSP), Instituto Politecnico do Porto. Carla Patrícia da Silva e Sousa Reis (2010-11). P2 purinoceptors signaling in fibroblasts of the rat subcutaneous tissue. Master Thesis in Molecular Biology (supervised by M.A. Costa, A.R. Pinheiro & P. Correia-de-Sá) (17/20). Universidade de Aveiro. Catarina Raquel Marques Baldaia Moreira (2010-12). Ectonucleotidases – Relevância fisiopatológica e terapêutica num modelo de bexiga hiperactiva na ratazana. Master Thesis in Molecular Therapy (supervised by T. Magalhães Cardoso & P. Correia-de-Sá) (18/20). Instituto Superior de Ciências da Saúde – Norte (ISCS-N / CESPU). Célia Cristina Moreira Soares (2010-12). Papel da adenosina na proliferação e diferenciação dos fibroblastos do tecido conjuntivo subcutâneo. Master Thesis in Medicine (supervised by A.R. Pinheiro & P. Correia-de-Sá) (20/20). Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. Bruno Miguel Martins Bragança (2011-12). Papel da adenosina na insuficiência cardíaca num modelo animal de hipertensão pulmonar. Master Thesis in Biochemistry (supervised by A.P. Fontes de Sousa & P. Correia-de-Sá) (20/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. Marina Raquel Henriques Mendes (2011-12). Alterações da expressão dos receptores A1 e A2A da adenosina no hipocampo e no neocórtex de doentres com epilepsia mesial temporal (MTLE). Master Thesis in Biochemistry (supervised by F. Ferreirinha & P. Correia-de-Sá). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. Cristina Eusébio Mendes (2012-13). Papel dos receptores P2X7 na transmissão sináptica mioentérica após isquémia e reperfusão do íleo de rato. Master Thesis in Morphofunctional Sciences (supervised by P. Castelucci & P. Correia-de-Sá). Departamento de Anatomia, ICB – Universidade de São Paulo (USP, Brasil). Marisa Rosalina Gonçalves da Cunha (2011-13). Disfunção imunológica na Miastenia Gravis: Papel da via CD39/CD73/A2AR. Master Thesis in Medicine (supervised by L. Oliveira, E. Santos & P. Correia-de-Sá) (19.4/20.0). Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. 14. Elsa Marina Cerqueira Meireles (2011-13). Papel dos recetores P2X7 na diferenciação osteogénica das células mesenquimatosas do estroma da medula óssea - Análise comparativa entre mulheres em idade fértil e pós‐menopáusicas com osteoporose. Master Thesis in Medicine (supervised by J.B. Noronha-Matos & P. Correiade-Sá) (19/20). Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. 15. Mónica Isa Moreira Rodrigues (2012-13). Role of adrenaline on the maturation of adrenoceptors. Master Thesis in Medicine (supervised by D. Moura & P. Correia-de-Sá) (20/20). Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. 16. Sílvia Manuela Nogueira Marques (2012-13). Regulação diferencial do cronotropismo e inotropismo em aurículas isoladas de ratazana a contrair espontaneamente por purinorecetores P1 e P2. Master Thesis in Biochemistry (supervised by A.P. Fontes de Sousa & P. Correia-de-Sá) (19/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. 17. Sónia Isabel Nunes Guerra Gomes (2012-13). The role of adenosine A2A receptors in the regulation of neuronal and immunological responses in rats with Experimental Autoimmune Myasthenia gravis (EAMG). Master Thesis in Biochemistry (supervised by F. Ferreirinha, L. Oliveira & P. Correia-de-Sá) (19/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. 18. Ricardo Silva dos Santos Viais (2012-13, ERASMUS Program, Universitat Autònoma de Barcelona). Dynamics of purinergic and nitrergic neuromuscular transmission in the mouse colon. Master Thesis in Biochemistry (supervised by Marcel Jiménez & P. Correia-de-Sá) (20/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. 19. Carla Daniela da Silva Pereira (2012-13). Papel dos receptores purinérgicos no crescimento e remodelação do tecido cavernoso. Master Thesis Biochemical Technology in Health (supervised by M.A. Costa, M. Faria & P. Correia-de-Sá) (18/20). Escola Superior de Tecnologia da Saúde do Porto (ESTSP), Instituto Politecnico do Porto. Degree Thesis completed: 1. Diana Manuela Ferreira de Meireles (2010-11). Predomínio da actividade dos receptores inibitórios A1 da adenosina no controlo da transmissão neuromuscular num modelo animal de Miastenia Gravis. Degree in Biochemistry (supervised by L. Oliveira & P. Correia-de-Sá) (17/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. 2. Joana Sofia Silva Correia (2009-11). Alterações da expressão da ecto-5’-nucleotidase (CD73) e dos receptores P1 da adenosina na bexiga de doentes com obstrução infravesical: avaliação imunohistoquímica por microscopia confocal. Degree in Biochemistry (supervised by F. Ferreirinha & P. Correia-de-Sá) (17/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. 3. Matilde de Freitas Ribeiro Viegas (2010-11). Immunohistochemical localization of adenosine A1 and A2A receptors at the rat motor endplate: pathophysiological implications in Myasthenia gravis. Degree in Biochemistry (supervised by L. Oliveira & P. Correia-de-Sá) (15/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. 4. Sara Gomes Moreira (2010-11). Ionotropic P2X7 receptor favours osteogenic differentiation and membrane cell dynamics of human bone stromal cells. Degree in Biochemistry (supervised by M.A. Costa, J.B. Noronha-Matos & P. Correia-de-Sá) (17/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar Universidade do Porto. 5. Ricardo Silva Santos Viais (2010-11). Comparação dos efeitos da adenosina e de outros agentes relaxantes dependentes do endotélio no tecido cavernoso de rato e de humano. Degree in Biochemistry (supervised by M. Faria, J.M. LaFuente-de-Carvalho & P. Correia-de-Sá) (19/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. 6. Sílvia Manuela Nogueira Marques (2010-11). Contribuição dos receptores A2A e β1 para o efeito “cronoselectivo” da adenosina na contracção espontânea das aurículas isoladas de ratazana. Degree in Biochemistry (supervised by A.P. Fontes-de-Sousa & P. Correia-de-Sá) (19/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. 7. Filipe Jorge do Nascimento Fernandes (2010-11). Modulação da transmissão colinérgica no órgão eléctrico de Torpedo marmorata. Degree in Biochemistry (supervised by J.M. Cordeiro & P. Correia-de-Sá) (18/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. 8. Diana Isabel Pinto de Almeida (2011-12). On the role of adenosine A2A receptors expressed on motor nerve terminals of rats with Experimental Autoimmune Myasthenia Gravis (EAMG). Degree in Biology (supervised by L. Oliveira & P. Correia-de-Sá) (18/20). Faculdade de Ciências da Universidade do Porto. 9. Pedro Miguel Coelho Paiva (2011-12). Caracterização morfológica e funcional das células endoteliais e musculares lisas do tecido cavernoso de ratazana em cultura por microsccopia confocal. Degrre in Biochemistry (supervised by P. Correia-de-Sá, A. Leite, M. Faria - Dept. Clínicas Veterinárias, and J.-M. LaFuente de Carvalho - Serviço de Urologia, CHP/HGSA) (19/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. 10. Bruna Isabel Nunes Oliveira (2011-12). Caracterização dos receptores nicotínicos pré-sinápticos facilitatórios no órgão eléctrico de Torpedo marmorata. Degree in Biochemistry (supervised by J.M. Cordeiro & P. Correia-de-Sá) (16/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. 11. José Miguel Sousa de Matos (2011-12). Comparative hydrolysis of adenine and uracil nucleotides by NTPDases in rat and human derived mesenchymal cells. Degree in Biochemistry (supervised by M.A. Costa, M.T. MagalhãesCardoso, J.B. Noronha-Matos, A.R. Pinheiro & P. Correia-de-Sá) (16/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto. 12. Ana Catarina Costa Pereira (2011-12). Modulação diferencial do cronotropismo e do inotropismo pelos nucleótidos de adenina e uracilo em aurículas isoladas de Rattus norvegicus. Degree in Biology (supervised by A.P. Fontes de Sousa & P. Correia-de-Sá; co-supervised by A. Silva - UTAD) (19/20). Universidade de Trás-osMontes e Alto Douro (UTAD). 13. Carla Anita Gomes Tavares (2011-12). Atividade histoenzimática das ecto-NTPDases no plexo mioentérico do íleo de ratazanas. Degree in Biotechnology (supervised by M. Duarte-Araújo, F. Ferreirinha and P. Correia-de-Sá; co-supervision by A. Queiroz) (19/20). Escola Superior Agrária de Ponte de Lima, Instituto Politécnico de Viana do Castelo. 14. Carla Adriana Araújo Vinhas (2012-13). Papel dos nucleótidos de adenina e uracilo na proliferação e diferenciação de fibroblastos cardíacos de ratazana. Degree in Biotechnology (supervised by M. Certal, A.R. Pinheiro and P. Correia-de-Sá; co-supervision by A. Queiroz) (18/20). Escola Superior Agrária de Ponte de Lima, Instituto Politécnico de Viana do Castelo. 15. Ana Salomé Monteiro (2012-13). Expressão, localização e actividade das ecto-nucleotidases no intestino de ratazana. Degree in Biotechnology (supervised by M. Duarte-Araújo, M.T. Magalhães-Cardoso, F. Ferreirinha and P. Correia-de-Sá; co-supervision by A. Queiroz) (20/20). Escola Superior Agrária de Ponte de Lima, Instituto Politécnico de Viana do Castelo. 5. Patents/propotypes None. 6. Organization of conferences and scientific meetings PHARMACOLOGICAL STRATEGIES TO ENHANCE PDE5 EFFICACY IN THE TREATMENT OF ERECTILE DYSFUNCTION: PRECLINICAL STUDIES Porto, 15 December 2011 Javier Angulo Servicio de Histologia, Departamento de Investigacion, Hospital Ramon y Cajal, Madrid, Espanha Organizer: P. Correia-de-Sá. PURINERGIC NEUROTRANSMISSION IN THE GI TRACT Porto, 6 December 2011 Marcel Jimenez Dept. of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain Organizer: P. Correia-de-Sá. EPHAR 2012 MEETING Granada (Espanha), 17-20 de Julho de 2012 Federation of European Pharmacological Societies (EPHAR) e Sociedade Espanhola de Farmacologia (SEF) Antonio Zarzuelo (President, University of Granada); Julio Gálvez (Deputy President, Department of Pharmacology, School of Pharmacy, University of Granada), Teresa Tejerina (President of the Spanish Society of Pharmacology Spanish representative in EPHAR, University Complutense of Madrid), Fermín Sánchez-Medina (Treasurer, University of Granada), Rosario Jiménez (Secretary, University of Granada), Juan Tamargo (Spanish representative in EPHAR, University Complutense of Madrid), Ulrich Förstemann (Mainz University, Germany), Daniel McQuenn (University of Edinburgh, UK) and Michael Mulvany (University of Aarhus, Denmark) (Comité Executivo) Marija Carman-Krzan (University of Ljubljana, Slovenia), Paulo Correia-de-Sá (University of Porto, Portugal), Jukka Hakkola (University of Oulu, Finland), Robin Hiley (University of Cambridge, England), Janet Mifsud (University of Malta, Malta) (Comité de Aconselhamento Científico). XLIII REUNIÃO ANUAL DA SOCIEDADE PORTUGUESA DE FARMACOLOGIA, XXXI REUNIÃO DE FARMACOLOGIA CLÍNICA E XII REUNIÃO DE TOXICOLOGIA Porto, 6-8 de Fevereiro de 2013 Sociedade Portuguesa de Farmacologia Organizer: P. Correia de Sá (President Scientific and Organizing Committees) 7. Industry contract research None. 8. Internationalization (Collaborative publication, Research, Graduate Training Networks or other forms of participation of the Research Group at the international level) - European Research Network for investigating adenosine (ADEURO) In collaboration with: Dept. Chem. (Camerino), Rega Instituut (Leuven), Dept. Med. Chem. (Leiden), Dept. Org. Pharmac. Chem. (Uppsala), Lab. Mol. Biol. (München), Inst. Pharmacol. (Vienna), Dept. Pharmacol. (Heidelberg), Dept. Pharmacol. (Milan), Dept. Pharmacol. (Florence), Dept. Pharmacol. (Leiden), Inst. Histol. Neurobiol. (Stockholm), Dept. Pharmacol. (Stockholm), Dept. Pharmacol. (IGC-Oeiras/ICBASPorto). Supported by EC, ADEURO Project. - Harvard Medical School – Portugal Collaboration in Biomedicine and Health Sciences An international collaboration to advance biomedical graduate education and research. Member of the steering group for creating the National Consortium for Biomedicine and Health Sciences. - Collaborative research at the International level Lab. Farmacologia, Univ. Maringá - Paraná (Brazil) - Prof. Alves-do-Prado (modulation of neuromuscular transmission) Inst. Biociências, UNESP, Botucatu, São Paulo (Brazil) - Prof. Márcia Gallacci (mechanisms underlying neuromuscular blockade of BthTX-I – the major myotoxin from Bothrops jararacussu snake venom) Lab. Disfunções Neurogastrointestinais, Instituto de Ciências Biomédicas (ICB), USP (Brazil) - Prof. Patrícia Castelucci (on the role of purinoceptors on synaptic transmission after ischemia/reperfusion of the rat ileum) Inst. Andrology, Hospital Ramon y Cajal, Madrid (Spain) - Prof. J. Angulo (vasculogenic erectile dysfunction) Dept. of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona (Spain) – Prof. Marcel Jimenez (purinergic signaling in the gut) Brain Res. Institute - Amsterdam (The Netherlands) - Prof. F. Lopes-da-Silva (scientific advisor on mesotemporal lobe epilepsy) Nestlé Res. Centre - Lausanne (Switzerland) - Dr. Christine Cherbut, Dr. Gabriela Bergonzelli and Prof. Luisa Lopes (maturation of the intestinal neuromuscular function) UT Southwestern Medical Center, Depart. Neurology - Dallas (USA) – Prof. Steven Vernino (autonomic dysautonomia and myasthenia) Weatheral Inst. Mol. Med., John Radcliffe Hospital - Oxford (UK) – Prof. M. Isabel Leite (translational research on myasthenic syndromes). Centre de Recherche en Rhumatologie et Immunologie, Depart. Anatomy & Physiol., Fac. Medicine, Univ. Laval – Quebec (Canada) – Prof. Jean Sevigny (role of the ectonucleotidase pathway in cell signalling) -Protocol for research collaboration with OLYMPUS Confocal Microscopy International Division UMIB signed with OLYMPUS Portugal a protocol considering the Laboratory of Electrophysiology and Cell Signalling (Pharmacology and Neurobiology Group, UMIB) a centre of reference for developing and testing hardware and software applications for Life-Cell Confocal Microscopy Indicadores de Realização Física Neste quadro deve indicar os valores referentes ao período a que corresponde o Relatório de Progresso. Neste quadro deve apenas indicar concretizações efectivas. Não indique publicações submetidas para publicação, nem teses que ainda não tenham sido discutidas. Indicadores Quantidade realizada A - Publicações Livros 3 Artigos em revistas internacionais 76 Artigos em revistas nacionais 0 B - Comunicações Comunicações em encontros científicos internacionais 54 Comunicações em encontros científicos nacionais 67 C - Relatórios 0 D - Organização de seminários e conferências 4 E - Formação avançada Teses de Doutoramento 3 Teses de Mestrado 19 Outras (e.g. Licenciatura) 15 F - Modelos 0 G - Aplicações computacionais 0 H - Instalações piloto 0 I - Protótipos laboratoriais 0 J - Patentes 0 L - Outros (Prémios) 4 Relatório Científico Final 2011-13 – UMIB Research Group Title: Anatomy: Experimental Medicine Principal Investigator: Artur Perez Águas Research Area: Health Sciences Home Institution: Instituto de Ciências Biomédicas Abel Salazar Relatório de Progresso Informação: Qualquer dúvida relacionada com o preenchimento do Formulário de Relatório de Progresso, por favor contacte-nos. Atenção: - O formato da data a utilizar é dd-mm-yyyy Formulário Relatório de Progresso - Componente Científica Relatório Final Período a que o relatório diz respeito: Data de início: 01-01-2011 Data de fim: 31-12-2013 1. Identificação do Projecto Referência do Projecto: PEst-OE/SAU/UI0215/2011 Investigador Responsável: Paulo Jorge Silva Correia Sa Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP) Data de Início: 01-01-2011 Data de Fim: 31-12-2012 1. Identificação do grupo Nome: Anatomy: Experimental Medicine Investigador Responsável: Professor Ártur Águas Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP) Data de Início: 01-01-2011 Data de Fim: 31-12-2013 2. Resumo dos Trabalhos Desenvolvidos e Desvios à Proposta aprovada EXPERIMENTAL CALICIVIRUS INFECTION Our study on the pathogenesis of rabbit haemorrhagic disease (RHD) has been focused on two major pathogenic mechanisms that could be responsible for the resistance/susceptibility of young and adult rabbits to RHD, namely: the expression of the viral receptor on the membrane of hepatocytes (cell-target of RHDV) and the interaction between RHDV and the immune response of the host. Our findings revealed that the viral hepatic cellular receptor is a macroglycolipid. Additionally, the ELISA assays showed that there seems to be no differences in the expression of the receptor between young and adult rabbits. Alternatively, the flow cytometry analysis indicated that, in RHDV-infected adult rabbits, the infection induces a local and systemic acute lymphocytic depletion as a result of cellular apoptosis that precedes and attends liver damage. RHDV-infected young rabbits, however, developed a rapid and effective inflammatory response by the liver, with few damage hepatocytes, and with a sustained elevation of local and systemic B and T cells. The results also showed that the RHDV infection of adult rabbits is capable of inducing an exacerbated inflammatory response, characterized by a substantial increase of cytokines, especially, TNF-α. The following work + + showed that regulatory T cells (CD4 Foxp3 ), which have an important role in the regulation of inflammation, were significantly decreased in the spleen of infected adult rabbits. In the next study was evaluated the effect of immunosuppression in the response of young rabbits to RHDV infection. The results showed that immunosuppressed and infected young rabbits die within 3 days with a fulminant hepatitis, presenting a large number of damaged hepatocytes that were also RHDV-positive, similarly to infected adult rabbits. This result weakens the hypothesis that the resistance of young rabbits to RHD derives from a different expression of the viral receptor in the liver and also reaffirms the importance of the immune response in the resistance/susceptibility to infection. CLINICAL AND EXPERIMENTAL ENDOCRINOLOGY The research efforts of the Clinical and Experimental Endocrinology field have been dedicated to (i) Study the role of the vagus nerve in the mechanism of action of gastro-intestinal hormones, in particular of GLP-1, in energy and glucose homeostasis, which has been characterized. (ii) Development of innovative medical and surgical treatments for obesity and type 2 diabetes, through the optimization of the surgical techniques used in the clinical setting towards improved outcomes, use of surgical animal models of bariatric surgery and implementation of novel pharmacological approaches for obesity with an anti-ghrelin vaccine. Clinical prospective studies of obese type 2 diabetic patients and patients with metabolic syndrome submitted to long limb metabolic gastric bypass were performed and the surgical modification has shown to improve the diabetes remission rate and metabolic syndrome parameters. Rodent models of experimental bariatric surgery have been successfully established and the alterations induced in the energy regulatory pathways have been described. Since the suppression of ghrelin rise, a gastro-intestinal hormone that increases appetite and decreases energy expenditure, after food deprivation, has been one of the most promising findings after bariatric surgery, an antighrelin therapeutic vaccine has been developed being a promising target for obesity treatment. (iii) Study the role of obesity and metabolic syndrome in prostate cancer progression and the pathways leading to adrenal cancer, since obesity and metabolic syndrome have also been recently linked to the increased risk of endocrine related cancer. Obesity has been shown to modulate cell proliferation and angiogenesis in prostate cancer and p27 has been demonstrated to be a potential novel molecular marker for the diagnosis of adrenal cancer. Desvios à Proposta Aprovada Se tiver havido desvios à proposta aprovada, quer do ponto de vista científico como financeiro, aponte os desvios e justifique-os. Se teve dificuldades na execução do plano de trabalhos aprovado, identifique-os e indique de que modo pretende ultrapassá-los. Se no período em apreço tiver informado a FCT sobre alteração orçamental inter-rubricas (necessitem ou não de autorização por parte da FCT), indique aqui o motivo. (4000 caracteres sem espaços) The research in the Endocrinology field has expanded in to related fields in order to optimize the availability of human and technical resources and the collaborations with other national and international institutions has been enlarged. The research in gastrointestinal hormones been performed in collaboration with the Department of Metabolic Medicine at Imperial College, UK; the clinical research was performed in patients recruited from the Obesity Surgery Outpatient Clinic of Hospital de São Sebastião, CHEDV, under medical follow-up by Mariana P. Monteiro; the rodent models and experimental bariatric surgery, has been performed at Centro de Cirurgia Experimental Avançada (CCEA) by the same group of surgeons that operate human patients; the development of an anti-ghrelin vaccine has been developed with the collaboration of Professor Polly Roy, Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, UK and Professor Felipe Casanueva from Molecular Endocrinology Department of University Santiago de Compostela, Spain; and the research in endocrine related cancer is being developed in collaboration with Professor Pignatelli from IPATIMUP. Equipa de Investigação d a t a data Nome Cargo Tarefas %Te de mpo entra da d e s a Desistiu (marcar com Gru uma X po se for o caso) í d a 1.Study the role of the vagus nerve in the mechanism of action of gastro-intestinal hormones, in particular of GLP-1, in energy and glucose homeostasis. Ana Raquel Dias Pinto Investig ador AN 2.Study the role of obesity and metabolic syndrome in prostate cancer progression and the pathways leading to adrenal cancer, 50 AT 1. What is the molecule responsible for the binding of the virus to the surface of rabbit hepatocytes? 2. Does CV infection interfere with the innate immune response in adult rabbits, António Duarte Costa e Silva Investig António Manuel de Sousa Pereira Investig AN namely with the early production of cytokines? 50 ador ador AT AN A exercer cargo público de direção. 20 AT 1. What is the molecule responsible for the binding of the virus to the surface of rabbit hepatocytes? 2. Does CV infection interfere with the innate immune response in adult rabbits, Artur Manuel Perez Neves Aguas Investig AN namely with the early production of cytokines? ador 50 AT 2. Does CV infection interfere with the innate immune response in adult rabbits, Carlos Manuel Zagalo Fernandes Ribeiro Investig Cristiana Jorge Silva Praça Vasconcelos Investig ador AN namely with the early production of cytokines? ador 20 hormones, in particular of GLP-1, in energy and glucose homeostasis AT AN Study the role of the vagus nerve in the mechanism of action of gastro-intestinal 20 AT 1.Study the role of the vagus nerve in the mechanism of action of gastro-intestinal hormones, in particular of GLP-1, in energy and glucose homeostasis. Joaquim Duarte Monteiro Investig ador Joaquim Luís Ramos Torres Couto Reis Investig ador AN 2.Study the role of obesity and metabolic syndrome in prostate cancer progression and the pathways leading to adrenal cancer. 50 Study the role of the vagus nerve in the mechanism of action of gastro-intestinal hormones, in particular of GLP-1, in energy and glucose homeostasis AT AN 20 AT 2. Does CV infection interfere with the innate immune response in adult rabbits, Jorge Celso Dias Correia da Fonseca Investig AN namely with the early production of cytokines? 20 ador AT 2. Does CV infection interfere with the innate immune response in adult rabbits, José António Mesquita Martins dos Santos Investig AN namely with the early production of cytokines? ador 20 AT 1-Study the role of the vagus nerve in the mechanism of action of gastro-intestinal hormones, in particular of GLP-1, in energy and glucose homeostasis. 2-Development of innovative medical and surgical treatments for obesity and type 2 diabetes. 3-Study the role of obesity and metabolic syndrome in prostate cancer Lídia Mariana Rodrigues Pereira Monteiro Investig AN progression and the pathways leading to adrenal cancer. ador 50 AT 1. What is the molecule responsible for the binding of the virus to the surface of rabbit hepatocytes? 2. Does CV infection interfere with the innate immune response in adult rabbits, Luzia Manuela Lima Teixeira Madalena Cristina Marques da Costa Santos Investig AN namely with the early production of cytokines? ador 100 AT Investig 50 AN Development of innovative medical and surgical treatments for obesity and type 2 ador AT diabetes, Study the role of obesity and metabolic syndrome in prostate cancer progression and the pathways leading to adrenal cancer, Maria Ermelinda Antunes Soares Rodrigues Munz Investig ador Maria Helena Cardoso Pereira da Silva Investig ador Maria João Feytor Pinto Rodrigues de Oliveira de Meireles Moreira AN Deixou de pertencer à Unidade por mudança de instituição de trabalho. 50 AT AN Development of innovative medical and surgical treatments for obesity and type 2 diabetes. X 20 AT 1. What is the molecule responsible for the binding of the virus to the surface of Investig AN rabbit hepatocytes? ador 50 AT 1. What is the molecule responsible for the binding of the virus to the surface of rabbit hepatocytes? 2. Does CV infection interfere with the innate immune response in adult rabbits, Maria Manuela Morais da Silva Investig AN namely with the early production of cytokines? ador 50 AT 1. What is the molecule responsible for the binding of the virus to the surface of rabbit hepatocytes? 2. Does CV infection interfere with the innate immune response in adult rabbits, Paula Cristina Gomes Ferreira Proença Investig AN namely with the early production of cytokines? ador 50 AT 1. What is the molecule responsible for the binding of the virus to the surface of rabbit hepatocytes? 2. Does CV infection interfere with the innate immune response in adult rabbits, Raquel Alexandra Machado Marques AN namely with the early production of cytokines? Bolseiro 100 AT 1. Publicações • Publicações em revistas internacionais com peer review (n=14) Ano Publicações URL Nora M, Guimarães M, Almeida R, Martins P, Gonçalves G, Santos M, Morais T,Freitas C, Monteiro MP. Excess body mass index loss http://www.ncbi.nlm.nih.gov/pmc/articl predicts metabolic syndrome remission after gastric bypass. 2014 es/PMC3881494/ Diabetol Metab Syndr. 2014 Jan 2;6(1):1. (epub em 2013) Moreira A, Pereira SS, Machado CL, Morais T, Costa M, Monteiro MP. Obesity inhibits lymphangiogenesis in prostate tumors. Int J Clin 2013 2013 Exp Pathol. 2013;7(1):348-52. http://www.ncbi.nlm.nih.gov/pmc/articl es/PMC3885490/ Monteiro MP. Obesity vaccines. Hum Vaccin Immunother. 2013 Dec https://www.landesbioscience.com/art 23;10(4). icle/27537/full_text/#load/info/all Guimarães M, Rodrigues P, Gonçalves G, Nora M, Monteiro MP. Heterotopic pancreas in excluded stomach diagnosed after gastric bypass surgery. BMC Surg. 2013 Nov 23;13:56 http://www.biomedcentral.com/14712482/13/56 2013 Pereira SS, Morais T, Costa MM, Monteiro MP, Pignatelli D. The emerging role of the molecular marker p27 in the differential 2013 diagnosis of adrenocortical tumors. Endocr Connect. 2013 Aug http://www.endocrineconnections.co m/content/early/2013/08/07/EC-130025.full.pdf+html 28;2(3):137-45. Andrade S, Pinho F, Ribeiro AM, Carreira M, Casanueva FF, Roy P, 2013 Monteiro MP. Immunization against active ghrelin using virus-like http://www.ncbi.nlm.nih.gov/pmc/articl particles for obesity treatment. Curr Pharm Des. 2013;19(36):6551- es/PMC3850261/ 8. Guimarães M, Nora M, Ferreira T, Andrade S, Ribeiro AM, Oliveira V, 2013 Carreira MC, Casanueva FF, Monteiro MP. Sleeve gastrectomy and http://link.springer.com/article/10.100 gastric plication in the rat result in weight loss with different 7%2Fs11695-013-0886-2/fulltext.html endocrine profiles. Obes Surg. 2013 ;23(5):710-7. Marques, RM, Costa-e-Silva, A, Águas, AP, Teixeira, L, Ferreira, PG. 2012 “Early Inflammatory Response of Young Rabbits Attending Natural http://www.sciencedirect.com/science Resistance to Calicivirus (RHDV) Infection”. Veterinary Immunology /article/pii/S0165242712003686 and Immunopathology. 2012; 150 (3-4):181-8. Marques RM, Costa-E-Silva A, Águas AP, Teixeira L, Ferreira PG. Early inflammatory response of young rabbits attending natural resistance 2012 to calicivirus (RHDV) infection. Vet Immunol Immunopathol. 2012;150(3-4):181-8. http://www.sciencedirect.com/science /article/pii/S0165242712003686 Teixeira, L, Marques, RM, Águas, AP, Ferreira, PG. “Regulatory T cells 2012 are decreased in acute RHDV lethal infection of adult rabbits” http://www.sciencedirect.com/science Veterinary Immunology and Immunopathology. 2012; 148(3-4):343- /article/pii/S0165242712001419 7. Ribeiro AM, Pereira S, Andrade S, Costa M, Lopes C, Aguas AP, Monteiro MP. Insulin prevents leptin inhibition of RM1 prostate 2012 cancer cell growth. Pathol Oncol Res. 2012;18(2):499-507. Monteiro MP. Anti-ghrelin vaccine for obesity: a feasible alternative to dieting? Expert Rev Vaccines. 2011 Oct;10(10):1363-5. 2011 http://link.springer.com/article/10.100 7%2Fs12253-011-9473-9/fulltext.html http://informahealthcare.com/doi/abs/ 10.1586/erv.11.115 Nora M, Guimarães M, Almeida R, Martins P, Gonçalves G, Freire MJ, 2011 Ferreira T, Freitas C, Monteiro MP. Metabolic laparoscopic gastric http://link.springer.com/article/10.100 bypass for obese patients with type 2 diabetes. Obes Surg. 2011 7%2Fs11695-011-0418-x/fulltext.html Nov;21(11):1643-9. Teixeira L, Marques RM, Águas AP, Ferreira PG. A simple and rapid method for isolation of caliciviruses from liver of infected rabbits. Res Vet Sci. 2011 Aug;91(1):164-6. http://www.sciencedirect.com/science /article/pii/S0034528810002699 2011 • Capítulos de livros com distribuição international (n=2) Ano Publicações URL Andrade, S., Carreira M, Casanueva FF, Roy P, Monteiro MP. Anti-ghrelin Therapeutic Vaccine: A Novel Approach for 2014 Obesity Treatment, in Molecular Vaccines, M. Giese, Editor. 2014, Springer International Publishing. p. 463-476. (epub em http://link.springer.com/chapter/10.1007 %2F978-3-319-00978-0_2 2013) Carreira MC, Crujeiras AB, Andrade S, Monteiro MP, Casanueva FF. Ghrelin as a GH-releasing factor. Endocr Dev. 2013 2013;25:49-58. (Karger) http://www.karger.com/Article/FullText/3 46052 • Comunicações orais (n=6) 1- NORA, M.; GUIMARAES, M.; SANTOS, M.; ALMEIDA, R.;MARTINS, P.; MONTEIRO, M. LAPAROCOPIC GASTRIC BYPASS AND METABOLIC SYNDROME REMISSION -STUDY WITH 153 PATIENTS. V Congress of the International Federation for the Surgery of Obesity and Metabolic Disorders, European Chapter (IFSO-EC). Barcelona, April 26 – 28, 2012 2- Morais. T., Pereira. S.S., Andrade. S., Costa. M., Monteiro. D., Monteiro. M.P. The effects of truncal vagotomy in energy homeostasis and acute response to glp-1. World Diabetes Congress, Melbourne – 2013. 3- Pereira. S.S., Morais,T., Costa, M., Monteiro, M.P., Pignatelli, D., The use of a morphometric computerized analysis tool in the differential diagnosis of adrenocortical tumors. European Joint Congress of Clinical Anatomy, Lisbon – 2013. 4- Morais. T., Pereira. S.S., Andrade. S., Monteiro. D., Costa. M., Monteiro. M.P., Phenotypical characterization of vagotomized rat and their feeding response to acute glp-1 administration. European Joint Congress of Clinical Anatomy, Lisbon – 2013. 5- Moreira. A., Pereira. S.S., Morais. T., Machado. C., Costa. M., Monteiro. M.P. Evaluation lymphangiogenesis in prostate tumours induced in different obese mice models. European Joint Congress of Clinical Anatomy, Lisbon – 2013. 6- Costa. M., Guedes. T., Martins. S., Pereira. S.S., Morais. T., Santos. A., Monteiro. M.P., Tissue microarray technology and immunohistochemistry for characterization of the relative distribution of neuroendocrine cells in the human small intestine. European Joint Congress of Clinical Anatomy, Lisbon – 2013. • Comunicações em poster (n=11) 1- Marques, RM, Águas, AP, Teixeira, L, Ferreira, PG., 2012. Is the expression of calicivirus (RHDV) receptor in the membrane of hepatocytes different in young and adult rabbits that are, respectively, resistant and susceptible to the infection? XXXVIII Annual Meeting of the Portuguese Society for Immunology (SPI). Porto, 25-27 November, 2012 2- Raquel M. Marques, Luzia Teixeira, António Costa e Silva, Artur P. Águas, Paula G. Ferreira. “Rabbit haemorrhagic disease fulminant hepatitis: citology of liver damage”. 12th European Joint Congress of Clinical Anatomy. Lisboa, 26-29 de Junho, 2013. 3- Pereira. S., Morais, T., Costa, M., Monteiro, M.P., Pignatelli, D. “Adrenocortical tumors: Evaluation of the role of immunohistochemistry markers in the differential diagnosis of adrenocortical tumors”, One Day Symposium sponsored by European Association for Cancer Research, Porto – 2012 4- Ribeiro, A. M., Pereira, S., Andrade, S., Costa, M., Lopes, C., Aguas, A. P., Monteiro, M. P. “Insulin prevents leptin inhibition of RM1 prostate cancer cell growth” no 2º Congresso da Associação Luso Galaica da Endocrinologia, Diabetes e Metabolismo – 2012 Vencedor do Prémio de Melhor Comunicação. 5- Marta Guimarães, Mário Nora, Tiago Ferreira, Sara Andrade, Andreia M Ribeiro, Vera Oliveira, Marcos C Carreira, Felipe F. Casanueva, Mariana P Monteiro. Sleeve gastrectomy and gastric plication in the rat result in similar weight loss but in different endocrine profiles. 19th European Congress of Obesity. Lyon, 9 a 12 de Maio, 2012. 6- Andrade. S., Casanueva. F., Monteiro. M., Carreira. M., Desarrollo de una vacuna anti-ghrelina para el tratamiento de la obesidade, Sociedad Gallega de Endocrinologia, Nutrición y Metabolismo - 2012 7- Nora. M., Guimarães. M., Almeida. R., Martins. P., Gonçalves. G., Santos. M., Morais. T., Freitas. C., Monteiro. M.P., The excess body mass index loss is the best predictor of metabolic syndrome criteria remission after laparoscopic metabolic gastric bypass, World Diabetes Congress, Melbourne – 2013 8- Moreira. A., Pereira. S.S., Santos. M., Morais. T., Monteiro.M.P., Adipocyte secretome enhances metabolic activity and migration of prostate carcinoma, 17º Congresso Português de Obesidade, Porto 2013 9- Andrade. S., Carreira. M., Fernandéz. B., Diz. D., Crujeiras. M., Monteiro. M.P., Casanueva. F., Effect of alcohol consumption on pre-adipocyte proliferation and adipogenic capacity,17º Congresso Português de Obesidade, Porto - 2013 10- Pereira. S.S., Morais,T., Costa, M., Monteiro, M.P., Pignatelli, D. Possible Use of Immunohistochemistry Markers in the Differential Diagnosis of Adrenocortical Tumors, The Endocrine Society's 95th Annual Meeting & Expo, San Francisco - 2013 11- Pereira. S.S., Morais,T., Costa, M., Monteiro, M.P., Pignatelli, D. “Immunohistochemistry markers in the differential diagnosis of adrenocortical tumors”, XIX Curso Pós Graduado de Endocrinologia, Diabetes e Metabolismo, Porto – 2013 • Teses de Mestrado (n=3) 1- Sofia Daniela da Silva Pereira, Mestrado em Oncologia, com a tese “Tumores do córtex da supra- renal: Avaliação do papel dos marcadores imunocitoquímicos em tumores do córtex da supra-renal”, Outubro de 2012. Orientador: Prof. Mariana P. Monteiro ICBAS/UP e co-orientador Prof. Duarte Pignatelli, IPATIMUP. 2- Tiago André Pereira Guedes, Mestrado Integrado em Medicina do ICBAS/UP, com a tese “Caraterização da distribuição relativa de células neuroendócrinas no jejuno-íleo”, Julho de 2013. Orientador: Prof. Doutora Mariana P. Monteiro ICBAS/UP. 3- Ângela Marisa Almeida Moreira, Mestrado Tecnologia Bioquímica em Saúde, com a tese “Obesidade e cancro da Próstata: Avaliação do efeito dos adipócitos nas células RM1 de carcinoma da próstata, Outubro de 2013. Orientador: Prof. Mariana P. Monteiro ICBAS/UP e co-orientada pelo Prof. Ruben Fernandes, ESTESP/IPP. • Organização de atividades de disseminação científica (n=5) 1- 1st Joint Meeting on Adrenal Cancer, 28th of May 2013, ICBAS-UP, Porto, Portugal. With the special participation of Prof. Gavin Vinson, from Queen Mary, University of London, UK 2- 1ª Reuniao Luso - Galaica de Endocrinologia Experimental, 26 de Outubro 2012, ICBAS-UP, Porto, Portugal. An Exchange meeting between researchers of UMIB and University of Santiago de Compostela, Spain. 3- 17º CONGRESSO PORTUGUÊS DE OBESIDADE, 22 a 24 de Novembro de 2013, Hotel Porto Palácio, Porto, Portugal. Monteiro MP has organized the congress as Vice-President of the Portuguese Obesity Society. 4- 16º CONGRESSO PORTUGUÊS DE OBESIDADE, 9 a 11 de Novembro de 2012, Hotel Olissippo Oriente, Lisboa, Portugal. Monteiro MP has organized the congress as Vice-President of the Portuguese Obesity Society. 5- 15º CONGRESSO PORTUGUÊS DE OBESIDADE, 11 a 13 de Novembro 2011, Hotel Vila Galé, Coimbra, Portugal. Monteiro MP has organized the congress as Vice-President of the Portuguese Obesity Society 4. Indicadores de Realização Física Neste quadro deve indicar os valores referentes ao período a que corresponde o Relatório de Progresso. Neste quadro deve apenas indicar concretizações efectivas. Não indique publicações submetidas para publicação, nem teses que ainda não tenham sido discutidas. Indicadores Quantidade realizada A - Publicações Livros 2 Artigos em revistas internacionais 14 Artigos em revistas nacionais 0 B - Comunicações Comunicações em encontros científicos internacionais 12 Comunicações em encontros científicos nacionais 5 C - Relatórios 1 D - Organização de seminários e conferências 5 E - Formação avançada Teses de Doutoramento 0 Teses de Mestrado 3 Outras 0 F - Modelos 0 G - Aplicações computacionais 0 H - Instalações piloto 0 I - Protótipos laboratoriais 0 J - Patentes 0 L - Outros 5. Ficheiros Anexos (opcional) Poderá enviar, apenas se entender como estritamente necessário, ficheiros com formato PDF, que tenham sido referidos no relatório, por exemplo, gráficos, esquemas, fotografias. O conjunto dos ficheiros (em número máximo de cinco) ou o arquivo comprimido a enviar não poderão ultrapassar 10MB. Nome do ficheiro Agradecemos a sua colaboração. Ponto do Relatório de Progresso Descrição Relatório Científico Final 2011-13 – UMIB Research Group Title: Biology and Genetics of Reproduction Principal Investigator: Mario Leite de Sousa Research Area: Health Sciences Home Institution: Instituto de Ciências Biomédicas Abel Salazar Relatório de Progresso Informação: Qualquer dúvida relacionada com o preenchimento do Formulário de Relatório de Progresso, por favor contacte-nos. Atenção: - O formato da data a utilizar é dd-mm-yyyy Formulário Relatório de Progresso - Componente Científica Relatório Final Período a que o relatório diz respeito: Data de início: 01-01-2011 Data de fim: 31-12-2013 1. Identificação do Projecto Referência do Projecto: PEst-OE/SAU/UI0215/2011 Investigador Responsável: Paulo Jorge Silva Correia Sa Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP) Data de Início: 01-01-2011 Data de Fim: 31-12-2012 1. Identificação do grupo Nome: Biology and Genetics of Reproduction Investigador Responsável: Professor Mário Sousa Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP) Data de Início: 01-01-2011 Data de Fim: 31-12-2013 3. Resumo dos Trabalhos Desenvolvidos e Desvios à Proposta aprovada Resumo dos trabalhos Descreva de forma breve as actividades desenvolvidas no período em apreço e os resultados alcançados. Refira-se em concreto às tarefas que tiveram execução no período a que o relatório respeita. (6000 caracteres sem espaços) 1-Divulgação: Divulgou-se a nossa área de investigação básica e aplicada à clínica através de Palestras (Liceus; Universidades), e na formação com orientação de Projectos de Licenciatura, Mestrados e Doutoramentos. 2-Parte científica: Obteve-se um excelente número de publicações internacionais, com várias colaborações (Univ. Beira Interior-UBI; Univ. Trás os Montes e Alto Douro-UTAD; Fac. Medicina da Univ Porto-FMUP; IPATIMUP; Univ. Lisboa-FFUL; Instituto de genética Médica –IGM; Centro Hospitalar do Porto-CHP; Univ. Aveiro-UA; Germany), tendo-se contribuído para um melhor conhecimento da regulação da espermatogénese humana, normal e patológica, bem como para uma melhor tomada de decisões em termos clínicos na área da infertilidade: 2.1-RAT AND HUMAN SPERMATOGENESIS -Rat and Human Sertoli Cell Metabolism -The effect of sex steroid hormones on human Sertoli cell metabolism provided the first assessment of androgens and estrogens as metabolic modulators of human Sertoli cells. (UBI) Int J Androl (2011) 34: e612–e620. Curr Med Chem (2013) 2: 4037-4049. -We first report the effect of insulin-deprivation on human Sertoli cell metabolism. (UBI) Biochim Biophys Acta (2012) 1820: 84–89; Mol Hum Reprod (2012) 18: 161–170; Biochim Biophys Acta (2012) 1823: 1389–1394. -Rat and Human Androgen and Estrogen Actions -Deregulation of the expression of Aven (apoptosis inhibitor) was shown to be related with male infertility. Expression of Regucalcin (calcium binding protein: regulates intracellular calcium homeostasis and is a sex steroid-regulated gene) was shown to be age dependent and upregulated by the non-aromatizable androgen DHT. (UBI) Reproduction (2011) 142: 447-456; Fertil Steril (2011) 96: 745-750. Mol Hum Reprod (2012) 18: 161–170. -This is the first report revealing the existence of Androgen Receptor variants in the testis of evolutionarily distant vertebrate species and in non-pathological tissues. (UBI) Andrologia (2013) 45: 187-194; -Apoptosis in Human Azoospermia -Results suggest that apotosis is induced by nuclear lesions in tubular obstruction and by mitochondrial lesions in hypospermatogenesis. (FMUP) Int J Androl (2011) 34: e407-4014. J Assist Reprod Genet (2013) 30:487–495. -Effects of Hormones in Human Spermatogenesis -Using organ culture, a gradual loss of germ cells, no decrease in Sertoli cell numbers, and maintenance of the general architecture were observed. Both FSH and testosterone increased germ cell survival, spermatogonia proliferation, and germ cell differentiation. Reprod Sci (2012) 19: 1063-1074. -Expression of Stem Cell Markers in the Male Germinal Epithelium -We determined the specific markers of testicular stem cells. Syst Biol Reprod Med (2013) 59: 233–243. 2.2-BOVINE OOCYTES -We could demonstrate the presence of three distinct follicular cell populations in cumulus cells. (UTAD) Anim Reprod Sci (2011) 123: 23–31. 2.3-ANIMAL TOXICOLOGY -We determined the effects of sublethal and lethal copper concentrations on the gill epithelium. (UTAD) Zool Studies (2012) 51: 977-987. 2.4-HUMAN CORD BLOOD -We established the best culture medium to induce de differentiation and proliferation of natural killer cells. (FMUP-Germany). Cell Comm Adhes (2011) 18: 45-55. J Recep Signal Transd (2012) 32: 238-249. 2.5-HUMAN ENDOMETRIUM -We characterized the epithelium cell types during the implantation window. Reprod Sci (2011) 18: 525-539. 2.6-HUMAN OOCYTE DIMORPHISMS -The clinical use of human oocytes with large tubular smooth endoplasmic reticulum aggregates should not be implemented as they are associated with newborn malformations. Fertil Steril (2011) 96: 143–149. 2.7-HUMAN SPERM -Protein phosphorilation -We report for the first time the identification of three new serine/threonine-protein PPs, and two tyrosine-PPs in human sperm. (UA) OMICS: J Integ Biol (2013) 17: 1-13. 2.8-HUMAN GENETICS -Prenatal Diagnosis -Microsatellite markers can accurately assess zygosity with the same STRs applied in aneuploidy screening with a high power of discrimination and a matching probability of over 99.999999%. (IGM) Twin Res Hum Genet (2011) 14: 221-227. -Imprinting in Human Spermatogenesis -Methylation imprints are established in spermatogonia A and are maintained in subsequent stages and DNA methyltransferases are expressed throughout human spermatogenesis. (FMUP) Epigenetics (2011) 6: 1354-1361. -Pyruvate Dehydrogenase Complex We determined which type of germ cells express the PDHA2 gene. The switch from the X-linked to autosomic gene expression (PDHA1) occurred in spermatocytes. (FFUL) Gene (2012) 506: 173–178. -Y Chromosome Microdeletions -Three new deletion patterns were identified in oligozoospermic patients presenting AZFb and AZFc microdeletions. (FMUP) Fertil Steril (2012) 97: 858–863. -DNA Mismatch Repair -MLH3 mutation analysis in patients with maturation arrest showed two missence and one intronic mutation. One missence mutation predicted to affect MLH3 function. Two patients overexpressed MLH3 and one also overexpressed MLH1. (FMUP) Reprod Sci (2012) 19: 587-596. -Varicocele -Microarrays analysis in patients with varicocele showed decreased expression levels of genes involved in stress situations and increased expression levels of genes involved in normal function of spermatogenesis after surgery. (CHP) Andrologia (2012) 44: 260–265. -Cystic Fibrosis Transmembrane Receptor -We demonstrated the localization of CFTR in normal and disrupted human spermatogenesis. (FMUP) Syst Biol Reprod Med (2013) 59:53-59. -Rare Deleterious Mutations -DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure and that other recurrent CNVs are potential causes of idiopathic azoospermia. (FMUP-IPATIMUP) PLOS Genetics (2013) 9: 1-16. 2.9-ASSISTED REPRODUCTION TECHNOLOGIES: -Embryo Culture and Cryopreservation -Extended culture to the blastocyst stage and the efficient freeze–thaw procedure for blastocysts are associated with high clinical success rates. Arch Gynecol Obstet (2012) 285: 1473-1478. -Preservation of Fertility in Males -An efficient method for cryopreservation of enriched fractions in diploid germ cells isolated from human testicular biopsies was developed. The open pulled straw vitrification was found to be the protocol that best preserved cell viability. Andrologia (2012) 44: 366–372. Desvios à Proposta Aprovada Se tiver havido desvios à proposta aprovada, quer do ponto de vista científico como financeiro, aponte os desvios e justifique-os. Se teve dificuldades na execução do plano de trabalhos aprovado, identifique-os e indique de que modo pretende ultrapassá-los. Se no período em apreço tiver informado a FCT sobre alteração orçamental inter-rubricas (necessitem ou não de autorização por parte da FCT), indique aqui o motivo. (4000 caracteres sem espaços) Nenhum. Equipa de Investigação desistiu Nome Cargo (marcar com Tarefas % Tempo Ângela Raquel Pinto Rocha Alves data de data de entrada saída uma X se for o caso) Gr Técnica Investigador Elsa Maria de Deus Gonçalves de Oliveira 40 BGR 50 BGR 50 BGR 50 BGR Técnica Investigador Mário Manuel Silva Leite Sousa IR Investigador Rosália Maria Pereira de Oliveira e Sá Investigador Investigador 4. Publicações • Peer reviewed paper published in international journals: 34 1. Calado AM, Oliveira E, Colaço A, Sousa M (2011) Ultrastructural and Cytochemical Characterization of Follicular Cell Types in Bovine (Bos taurus) Cumulus-Oocyte Complexes Aspirated from Small and Medium Antral Follicles during the Estrus Cycle. Animal Reproduction and Science, 123 (1) 23-31. 2. Bartosch C, Lopes JM, Beires J, Sousa M (2011) Human endometrium during the implantation window: a new perspective of the epithelium cell types. Reproductive Sciences, 18 (6): 525539. 3. S. Pires, A.J.A. Nogueira, O. Pinho, T. Delgado, M. Sousa, R. Santos, P. Jorge (2011) Statistical approach to prenatal zygosity assessment following a decade of molecular aneuploidy screening. Twin Research and Human Genetics, 14 (3): 221-227. 4. Sá R, Cunha M, Silva J, Luís A, Oliveira C, Teixeira da Silva J, Barros A, Sousa M (2011) Ultrastructure of tubular smooth endoplasmic reticulum aggregates in human MII oocytes and clinical implications. Fertil Steril 96 (1): 143-149, 149.e1-149.e7. 5. Almeida C, Cunha M, Ferraz L, Barros, Sousa M (2011) Caspase-3 detection in human testicular spermatozoa from azoospermic and non-azoospermic patients. International Journal of Andrology, 34: E407-e414. 6. Sandra Laurentino, Sara Correia, José Eduardo Cavaco, Pedro Fontes Oliveira, Luís Rato, Mário Sousa, Alberto Barros, Sílvia Socorro (2011). Regucalcin is broadly expressed in reproductive tissues and a new androgen target gene in mammalian testis. Reproduction, 142 (3) 447-456. 7. Pinho MJ, Barros A, Sousa M (2011) Ex vivo differentiation of natural killer cells from human umbilical cord blood CD34+ progenitor cells. Cell Communication and Adhesion, 18(3) 45-55. 8. Laurentino S, Gonçalves J, Cavaco JEB, Oliveira PF, Alves M, Sousa M, Barros A, Socorro S (2011) Apoptosis-inhibitor Aven is down regulated in defective spermatogenesis and a novel estrogen target gene in mammalian testis. Fertil Steril., 96 (3): 745-750 9. Marques CJ, Pinho MJ, Marques P, Carvalho F, Bieche I, Barros A, Sousa M (2011) DNA methylation imprinting marks and DNA methyltransferases expression in human spermatogenic cell stages. Epigenetics. 6 (11): 1354-1361. 10. Oliveira PF, Alves MG, Rato L, Sá R, Barros A, Sousa M, Carvalho RA, Cavaco JE, Socorro S (2011) Influence of 5a-Dihydrotestosterone and 17b-Estradiol on Human Sertoli Cells Metabolism. Int J Androl., 34: e612-e620. 11. Oliveira PF, Alves MG, Rato L, Laurentino S, Silva J, Sá R, Barros A, Sousa M, Carvalho RA, Cavaco JE, Socorro S (2012) Effect of insulin deprivation on metabolism and metabolismassociated gene transcript levels on in vitro cultured human Sertoli cells. Biochimica et Biophysica Acta (BBA)- General Subjetcs, 1820 (2): 84-89. DOI: 10.1016/j.bbagen.2011.11.006 12. Sandra Laurentino, Sara Correia, José Eduardo Cavaco, Pedro Fontes Oliveira, Luís Rato, Mário Sousa, Alberto Barros, Sílvia Socorro (2011). Regucalcin, a calcium-binding protein with a role in male reproduction?. Molecular Human Reproduction. 18 (4) 161-170. DOI: 10.1093/MOLEHR/GAR075 13. Ana Soares, Paula Costa, Joaquina Silva, Mário Sousa, Alberto Barros, Susana Fernandes (2012) AZFb microdeletions and oligozoospemia-Which mechanisms? Fertil Steril, 97 (4) 858863. DOI: 10.1016/j.fertnstert.2012.099 14. Oliveira A, Neto A, Almeida C, Silva-Ramos M, Versos R, Barros A, Sousa M, Carvalho F (2012) Comparative study of gene expression in patients with varicocelo by microarrays technology. Andrologia, 44 (5) (suppl s1): 260-265. DOI: 10.1111/j.1439-0272.2011.01173.x 15. Sousa M, Cunha M, Viana P, Silva J, Teixeira da Silva J, Oliveira C, Barros A (2012) Outcomes of human blastocyst transfer after slow-freezing using sequential culture: a clinical report. Arch Gynecol Obstet, 285 (5): 1473-1478. DOI 10.1007/s00404-011-2174-5 16. Ferrás C, Fernades S, Silva J, Barros A, Sousa M. (2012) Expression analysis of MLH3, MLH1 and MSH4 in maturation arrest. Reprod Sc 19 (6): 587-596. DOI: 10.1177/1933719111428521 17. Alves MG, Socorro S, Silva J, Barros A, Sousa M, Cavaco JE, Oliveira PF (2012) In vitro cultured human Sertoli cells secrete high amounts of acetate that is stimulated by 17<beta> estradiol and suppressed by insulin deprivation. Biochimica et Biophysica Acta (BBA) - Mol Cell Res 1823 (8): 1389-1394. DOI: 10.1016/j.bbamcr.2012.06.002 18. Pinheiro A, Silva MJ, Graça I, Silva J, Sá R, Sousa M, Barros A, Almeida IT, Rivera I. (2012) Pyruvate dehydrogenase complex: transcriptional and translational patterns of PDHalfa subunit genes in human spermatogenesis. Gene 506 (1): 173-178. DOI: 10.1016/j.gene.2012.06.068 19. Sá R, Inês Graça, Joaquina Silva, Isabel Malheiro, Filipa Carvalho, Alberto Barros, Mário Sousa (2012) Quantitative analysis of cellular proliferation and differentiation of the human seminiferous epithelium in vitro. Reprod Sciences, 19 (10) 1063-1074. DOI: 10.1177/1933719112440746 20. MJ Pinho, CJ Marques, F Carvalho, M Punzel, M Sousa and A Barros (2012) Genetic regulation on ex-vivo differentiated natural killer cells from human umbilical cord blood CD34+ cells. J Receptor and Signal Transduction, 32 (5): 238-249. DOI: 10.3109/10799893.2012.700716 21. Sá R, Miranda C, Leite C, Malheiro I, Carvalho F, Silva J, Barros A, Sousa M. (2012). Biomarkers Expression in Human Seminiferous Epithelium. Microsc Microanal, 18 (Suppl 5): 15-16. DOI: 10.1017/S1431927612012731 22. Sá R, Nieves Cremades, Isabel Malheiro, Mário Sousa (2012) Cryopreservation of human testicular diploid germ cell suspensions. Andrologia, 44 (6): 366-372. DOI: 10.1111/j.14390272.2012.01290.x 23. Lima M; Sousa M, Oliveira C, Teixeira da Silva J, Cunha M, Viana, P, Barros A (2013) Ovarian Hyperstimulation Syndrome. Experience of a Reproductive Medicine Center from 2005-2011. Proceedings of the 17th World Congress on Controversies in Obstetrics, Gynaecology & Infertility (COGI). Ben-Rafael Z (Ed.). Nonduzzi Editoriale / Proceedings : 97-100. 24. Lima P, Monteiro M, Machado J, Sousa M (2013) A histological study of the oogenesis of the freshwater mussel Anodonta cygnea (Linnaeus, 1771) in Mira lagoon, Portugal. Malacologia 55(2): 251-261 25. Sílvia Teixeira, Rosália Sá, Ana Grangeia, Joaquina Silva, Cristiano Oliveira, Luís Ferráz, Ângela Alves, Sandra Paiva, Alberto Barros, Mário Sousa (2013) Immunohystochemical analysis of CFTR in normal and disrupted spermatogenesis. Syst Biol Reprod Med. 59 (1): 53-59. DOI: 10.3109/19396368.2012718851 26. Almeida C, Correia S, Rocha E, Alves A, Ferraz L, Silva J, Sousa M, Barros A (2013) Caspase signalling pathways in human testicular disorders. J Ass Reprod Genet. 30 (4): 487-493. DOI: DOI 10.1007/s10815-013-9938-8 27. Lopes AM, Aston KI, Carvalho F, Gonçalves J, Matthiesen R, Huang N, Ramu A, Downie JM, Fernandes S, Amorim A, Barros A, Hurles M, Moskovtsev S, Ober C, Schiffman JD, Schelegel PN, Sousa M, Carrell DT, Conrad DF (2013) Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1. PLOS Genetics 9 (3): 1-16. DOI: 10.1371/journal.pgen.1003349 28. Monteiro SM, Oliveira E, Fontaínhas-Fernandes A, Sousa M (2013) Effects of sublethal and lethal copper concentrations on the ultrastructural organization on the gill epithelium ultrastructure in tilapia Oreochromis niloticus. Zoological Studies. 51 (7): 977-987. 29. Cabral M, Pires I, Figueiredo H, Oliveira E, Sousa M, Ferraz L (2013) Ultraestrutura de um caso de astenozoospermia. Rev Int Androl 10 (4): 156-159. DOI: 1698-031X/$ 30. Sandra Laurentino, Patrícia Pinto, Joana Tomas, José Eduardo Cavaco, Mário Sousa, Alberto Barros, Deborah Power, Adelino Canário, Sílvia Socorro (2013). Identification of androgen receptor variants in testis from humans and other vertebrates. Andrologia 45 (3) 187-194. DOI: 10.1111/j.1439-0272.2012.01333.x 31. Bernardino RL, Jesus TT, Martins AD, Sousa M, Barros A, Cavaco EJ, Socorro S, Alves MG, Oliveira PF (2013) Molecular Basis of bicarbonate membrane transport in th emale reproductive tract. Current Medicinal Chemistry, 20 (32): 4037-4049. DOI: 0929-8673/13$58.00+.00 32. Fardilha M, Ferreira M, Pelech S, Vieira S, Rebelo S, Korrodi-Gregorio L, Sousa M, Barros A, Silva V, da Cruz e Silva OAB, da Cruz e Silva EF (2013) “OMICS” of human sperm: Profiling Protein Phosphatases. OMICS: A Journal of Integrative Biology 17 (9): 460-472. DOI: 10.1089/omi.2012.0119 33. Sá R, C Miranda, F Carvalho, A Barros, M Sousa (2013) Expression of stem cell markers, OCT4, KIT, ITGA6 and ITGB1 in the male germinal epithelium. Syst Biol Repro Med. 59 (5): 233243. DOI: 10.3109/19396368.2013.804964 34. Mário Sousa, José Teixeira da Silva, Joaquina Silva, Mariana Cunha, Paulo Viana, Elsa Oliveira, Rosália Sá, Célia Soares, Cristiano Oliveira, Alberto Barros (2013) Embryological, clinical and ultrastructural study of human oocytes presenting indented zona pellucida. Zygote, 2 (): 1-13. DOI: 10.1017/SO967199413000403 • Other International Publications (6000 ca.): 11 Book Chapters: 4 1. Marques CJ, Barros A, Sousa M (2011) Sperm Epigenetic Profile. In: Sperm Chromatin: Biological and Clinical Application in Male Infertility and Assisted Reproduction. Armand Zini and Ashok Agarwal, Editors. Human Press, Springer. Part 2, Chapter 17, 243-257. 2. Merkan M, Sousa M (2011) Ultrastructural studies of vitellogenesis in Asellus aquaticus (Crustacea, Isopoda). In: Perspectives in Animal Ecology and Reproduction. Volume VII. ViJay K Gupta, Editor. Anil Mittal, Daya Publishing House, New Delhi, India. Chapter 20, 294-315. 3. Marques CJ, Sousa M (2013) Inprinted Gene Anomalies in Sperm In: Paternal Influences in Human Reproductive Success. Carrell DT (ed). Cambridge University Press, USA. Chapter 4, pp.: 27-37. 4. Sá R, Sousa M (2013) Androgens and the ovary. In: Protein Biochemistry, Synthesis, Structure and Cellular Functions. Androgen Receptors. Structural Biology, Genetics and Molecular Defects, Chapter VII. Socorro S (ed.). Nova Biomedical, Nova Science Publishers Inc., NY, USA. pp: 165-190. Indexed Abstracts: 7 5. Almeida C, Correia S, Rocha E, Alves A, Cunha M, Ferraz L, Silva S, Sousa M, Barros A (2011) Caspase signalling pathways in human testicular disorders. Hum Reprod 26 (suppl 1): i144. 6. Carvalho B, Silva J, Cunha M, Viana P, Leite R, Stevenson D, Carvalho A, Oliveira C, Teixeira da Silva J, Póvoa AM, Soares S, Calejo L, Sousa S, Xavier P, Sousa M, Barros A, Carvalho F (2012). Preimplantation genetic diagnosis for portuguese familial amyloidotic polyneuropathy- 12 year’s experience. RBMOnline, 24 (suppl 2): S59. DOI: 7. A Cunha, M.; Viana, P.; Gonçalves, A.; Silva, J.; Oliveira, C.; Teixeira da Silva, J.; Ferráz, L.; Madureia, C., Dória, S., Sousa, M.; and Barros, A. (2012) Evaluation of 140 patients with Klinefelter syndrome – clinical outcomes after intracytoplasmic sperm injection. Hum Reprod, 27 (suppl 2): 30-31. DOI: 10.1093/humrep/27.s2.74. 8. Alves M, Socorro S, Silva J, Barros A, Sousa M, Cavaco J, Oliveira PF (2012) Human Sertoli cells Produce High Amounts of Acetate that is Under Strict Hormonal Control. J. Reproduktionsmed. Endokrinol. 9 (5): 370. DOI: 9. Teixeira da Silva J, Cunha M, Silva J, Viana P, Gonçalves A, Barros N, Oliveira C, Sousa M, Barros A (2013) Low-dose human Chorionic Gonadotropin at oocyte retrieval after Gonadotropin-releasing hormone agonist triggering: retrospective study. 29th ESHRE Annual Meeting, London, UK, 7-10 July. Hum Reprod 28 (suppl 1): i 319 (P-486) 10. Gomes M, Gonçalves A, Rocha E, Silva J, Barros A, Sousa M (2013) In vitro effect of lead chloride on sperm parameters and sperm DNA damage. ASEBIR 18 (2): 220. 11. Mário Sousa, José Teixeira da Silva, Joaquina Silva, Mariana Cunha, Paulo Viana, Elsa Oliveira, Rosália Sá, Célia Soares, Cristiano Oliveira, Alberto Barros (2013) Embryological, clinical and ultrastructural study of human oocytes presenting indented zona pellucida. ASEBIR. 18 (2): 242-243. • National Publications: 5 Book chapters: 2 1- Azevedo C, Sousa M (2012) Especializações da Membrana. In: Biologia Celular e Molecular. Azevedo C, Sunkel C (eds), Edições Técnicas Lidel, Porto, Cap. 4, pp 58-77. 2- Sousa M (2012) Fertilização Animal. In: Biologia Celular e Molecular. Azevedo C, Sunkel C (eds), Edições Técnicas Lidel, Porto, Cap. 26, pp 436-454. Artigos científicos: 3 3- Mariana Lima, Mário Sousa, Cristiano Oliveira, Joaquina Silva, José Teixeira da Silva, Mariana Cunha, Paulo Viana, Alberto Barros (2013) Síndrome de Hiperestimulação ovárica. Experiência de um Centro de Medicina da Reprodução: 2005-2011. Acta Médica Portuguesa 26 (1): 24-32. 4- Cunha M, Sousa M, Silva J, Xavier P, Viana P, Teixeira da Silva J, Oliveira C, Gonçalves A, Osório C, Barros N, Barros A (2013) Impacto da acupunctura na Medicina da Reprodução: revisão do estado da arte e considerações a propósito de um caso clínico. Arquivos de Medicina. 26 (1): 17-25. 5- Oliveira A, Sousa M, Granja B (2013) A Percepção de Si Enquanto Mulher Infértil. Saúde Reprodutiva, Sexualidade e Sociedade 3 (): 5-19. PhD Thesis Completed: 5 • 1- Carolina Neves de Sousa e Almeida (2011). Regulação da Apoptose no Epitélio Germinal Masculino. Doutoramento em Biomedicina. Departamento de Genética, Faculdade de Medicina, Universidade do Porto (FMUP). Co-orientador. Prof. Doutor Mário Sousa 2- Sandra Filipa Tomás Sequeira Laurentino (2011). Sexual steroid regulation of spermatogenesis: new actors enter the stage. Doutoramento em Biomedicina. Faculdade de Ciências da Saúde, Universidade da Beira Interior (UBI). Co-orientador. Prof. Doutor Mário Sousa 3- Ana Sofia Costa Pinheiro (2011). Somatic expression of the testis-specific PDHA2 gene: mechanisms of activation/silencing. Doutoramento em Biomedicina. Reitoria da Universidade de Lisboa. Acompanhamento: Prof. Doutor Mário Sousa 4- Maria João Nascimento de Pinho (2012) In vitro determination and functional maturation of natural killer cells from umbilical cord blood progenitor cells. Doutoramento em Biomedicina. Faculdade de Medicina do Porto, Universidade do Porto. Co-orientador. Prof. Doutor Mário Sousa 5- Rosália Maria Pereira de Oliveira e Sá (2012) Molecular Cell Biology Characterization Of Human Male Testicular Adult Stem Cells. Doutoramento em Ciências Biomédicas. Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto. Acompanhamento: Prof. Doutor Mário Sousa MSc Thesis Completed: 3 • 1- Liliana Alexandra Marques de Castro (2012) Mestrado em Biologia Clínica Laboratorial Universidade de Trás-os-Montes e Alto Douro, Vila Real. Correcção da Tese: Prof. Dr. Mário Sousa 2- Eurico Costa (2012) Caracterização molecular de crianças com Síndrome de Cornélia Lange (CdLS). Mestrado em Biologia, Instituto de Genética Médica Jacinto Magalhães, Porto. Orientador: Prof. Dr. Mário Sousa 3- Diana Raquel Veloso Cardona (2013) Epidemiologia da infertilidade. Mestrado em Medicina Legal. Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto. Orientador: Prof. Dr. Mário Sousa Indicadores de Realização Física Neste quadro deve indicar os valores referentes ao período a que corresponde o Relatório de Progresso. Neste quadro deve apenas indicar concretizações efectivas. Não indique publicações submetidas para publicação, nem teses que ainda não tenham sido discutidas. Indicadores A - Publicações Livros : Book chapters Internacionais Capítulos de Livro Nacionais Artigos em revistas internacionais Abstracts Internacionais indexados Artigos em revistas nacionais B - Comunicações Quantidade realizada 45 / 5 4/2 34 / 7 3 17 /31 Comunicações em encontros científicos internacionais 17 Comunicações em encontros científicos nacionais 31 C - Relatórios 7 D - Organização de seminários e conferências 0 E - Formação avançada Teses de Doutoramento 5 Teses de Mestrado 3 Outras Teses de Licenciatura 3 F - Modelos 0 G - Aplicações computacionais 0 H - Instalações piloto 0 I - Protótipos laboratoriais 0 J - Patentes 0 L - Outros 6. Ficheiros Anexos (opcional) Poderá enviar, apenas se entender como estritamente necessário, ficheiros com formato PDF, que tenham sido referidos no relatório, por exemplo, gráficos, esquemas, fotografias. O conjunto dos ficheiros (em número máximo de cinco) ou o arquivo comprimido a enviar não poderão ultrapassar 10MB. Nome do ficheiro Agradecemos a sua colaboração. Ponto do Relatório de Progresso Descrição Relatório Científico Final 2011-13 – UMIB Research Group Title: ImmunoGenetics, Inflammation and Autoimmunity (IGIA) Principal Investigator: Berta Silva Research Area: Health Sciences Home Institution: Instituto de Ciências Biomédicas Abel Salazar Relatório de Progresso Informação: Qualquer dúvida relacionada com o preenchimento do Formulário de Relatório de Progresso, por favor contacte-nos. Atenção: - O formato da data a utilizar é dd-mm-yyyy Formulário Relatório de Progresso - Componente Científica Relatório Final Período a que o relatório diz respeito: Data de início: 01-01-2011 Data de fim: 31-12-2013 1. Identificação do Projecto Referência do Projecto: PEst-OE/SAU/UI0215/2011 Investigador Responsável: Paulo Jorge Silva Correia Sa Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP) Data de Início: 01-01-2011 Data de Fim: 31-12-2013 1. Identificação do grupo Nome: ImmunoGenetics, Inflammation and Autoimmunity (IGIA) Investigador Responsável: Professora Berta Silva Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP) Data de Início: 01-01-2011 Data de Fim: 31-12-2013 5. Resumo dos Trabalhos Desenvolvidos e Desvios à Proposta aprovada Resumo dos trabalhos Descreva de forma breve as actividades desenvolvidas no período em apreço e os resultados alcançados. Refira-se em concreto às tarefas que tiveram execução no período a que o relatório respeita. (6000 caracteres sem espaços) 1. Epilepsy 1.1. MTLE-HS We were able to show that the IL-1B -511T allele is associated with MTLE-HS susceptibility, as previously reported for other populations. Separately, the role of Human HerpesVirus-6B (HHV-6B) in epileptogenic lesion in MTLE patients was assessed. We concluded that this viral infection is not an important etiopathogenic factor for MTLE-HS in the Portuguese population. Regarding the role of the glutamatergic pathways in this disease, we observed that Glutamate transporter EAAT1 was over-expressed in the adjoining cortex indicates that this area may also be involved in disease evolution. Evidences from animal models have implicated the serotonergic system in epileptogenesis. HTR2A expression levels may be modulated by a 102 T>C polymorphism. We did not find differences in allelic or genotype frequencies between MTLE-patients and healthy controls. HTR2A function may be influenced by the rs6314 polymorphism that but no association with disease development was found in our population. Serotonin receptors HTR1A could have an anti-convulsant effect. HTR1A expression may be modulated by the polymorphism rs6295. The frequency of rs6295CC genotype was higher in MTLE-HS patients when compared to controls. Serotonin transporter (5-HTT) plays a key role in the regulation of serotonin levels. The expression of the 5-HTT gene could be modulated by a 17bp variable number of tandem repeats in the second intron (5-HTTVNTR). In our population the genotype 12/9 was overrepresented in MTLE patients compared to controls. Variations in the 5-HTT gene expression may lead to changes in serotonergic neurotransmission and consequently in brain homeostasis, lowering the threshold for seizure development. During 2011 we established a collaboration with the group of Prof. Sanjay Sisodiya from University College London (UCL). In February 2012 our PhD student Bárbara Leal spent two weeks in UCL participating in a Genome Wide Association Study. The results of this study suggest SCN1A involvement in a common epilepsy syndrome and give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures opening new avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures (Brain. 2013 Oct;136(Pt 10):3140-50). 1.2. Progressive Mioclonic Epilepsy We described a patient with Unverricht-Lundborg disease with a new splicing alteration in the cystatin B gene (CSTB). Mutation Gln22Gln leads to abnormal splicing and partial inclusion of the intronic sequence. This is a rare case of homozygosity for a non-classic mutation and adds to mutational heterogeneity of CSTB. Separately, two siblings with PME and a rare new lysossomopathy due to 2-LIMP-2 (SCARB2) mutation were identified. Substrate-reduction therapy, to correct the storage of glucocerebroside in the cells was instituted in one of the siblings, and a significant improvement was observed (Seizure 2011, 20(9)). 2. Systemic Lupus Erythematosus In the context of the European BioLupus project, further refinement of the ongoing association studies took place. New publications explore the IL2/IL21, PP2CA, TRAF6, and complement factor-H genes. More recently, a role for the microRNA gene miRNA-146a and for the AID susceptibility gene BLK was uncovered. Genetic factors relevant in gender and ethnic differences were also explored (Ann Rheum Dis 2012; Genes Immun 2012). Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry and may influence auto-antibody production ( PLoS One. 2013;8(8):e69404). It has been previously described an association between rs3853839G allele (gene of Toll-like receptor 7 (TLR7)) and SLE development. This polymorphism is a binding site for the epigenetic factor miR-3148. The rs3853839G allele has lower affinity to miR-3148 than rs3853839C. So, these data establish rs3853839 of TLR7 as a shared risk variant of SLE (PLoS Genet. 2013;9(2):e1003336). It has been showed that SLE and Systemic sclerosis (SSc) share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, it was performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. In this study, we add KIAA0319L, PXK, JAZF1 and KIAA0319L new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity (Hum Mol Genet. 2013 Oct 1;22(19):40219). 3. Multiple Sclerosis 3.1. Iron and Vitamin D We found that the HFE C282Y polymorphism may be implicated in MS aggressiveness, being a marker of worse prognosis. A high prevalence of vitamin D insufficiency was found in MS patients. Patients with higher disability seemed especially prone to vitamin D deficiency (lower levels of sun exposure?). These results suggest that vitamin D may be a disease modifier in genetically susceptible individuals. Tailoring vitamin D supplementation to genetic profile (i.e. selecting for the presence of HLA-DRB1*15) may be an efficient method for providing benefits. Vitamin D acts via its receptor (VDR), a nuclear receptor that is expressed in multiple immune cell types. Various singlenucleotide polymorphisms in the VDR gene have been described, but only for FokI polymorphism a functional impact on the immune response has been demonstrated. In our population the ff genotype frequency was significantly higher in the patient’s group compared to controls. 3.2. KIR We have observed that the presence of activating KIR2DS1 gene decreased the risk of MS independently from the presence of HLA-DRB1*15. No significant associations were found for age at onset or disease course (results accepted for publication in Journal of Neuroimmunology ). 3.3. ApoE We have not found a negative impact of the APOE-epsilon4 allele on the physical and cognitive manifestations of MS disease, in agreement with recent reports. 3.4. NF-kB pathway A collaborative study with Miguel Soares from the IGC in Oeiras began recently, that aims to translate to the human disease the results from animal studies establishing the importance of the transcription factor Nfr2 in neuroinflammation. 4. Behçet’s Disease Association studies were extended to a larger cohort of patients, with negative results. We confirmed that APoE polymorphism does not contribute to pathogenesis in BD. We have pursued nevertheless, as this cohort is one of the largest studied in European populations (accepted for publication in Journal of Rheumatology). 5. Systemic Sclerosis (SSc) We sought to determine whether the innate immunity-related KIR genotypes are associated with SSc. We confirmed the protective role of the KIR2DS2 phenotype, in the presence of KIR2DL2, as previously described. The role of the HLA system was also explored. We found that autoantibody production in SSc is associated with the presence of certain HLADRB1 alleles. Overall these results confirm previous reports in larger cohorts. 6. Psoriasis A study to evaluate cardiovascular disease risk in psoriatic patients and associated genetic determinants is underway. Both classical immunogenetic markers and a panel of 30 SNP(s) already described as associated with CVD risk or other known comorbidities were already assayed in 200 patients. Statistical evaluation is underway (J Dermatol. 2013; accepted for publication in American Journal of Clinical Dermatology) 7. Amyloidosis In Familial Amyloidotic Polyneuropathy, type I, a genetic disease relatively common in the north of Portugal, activation of signaling cascades, such as ERK, mediated by engagement of RAGE receptors by pre-amyloid protein aggregates, leads to up regulation of the NF-kB parthway, oxidative stress and apoptosis. We have underway a project to elucidate the role of these functional disturbances in the dysregulation of the erythropoietin (EPO) gene, that is known to be under expressed both in patients and pre-symptomatic carriers, resulting in a high incidence of severe anemia, but also possibly implicated in neurodegeneration, since EPO has been recently reported as a potent neuroprotective hormone. 8. HLA-NET The HLA-NET Action (COST BM0803) involves 21 European countries, and aims at networking researchers working in bone marrow transplantation, epidemiology and population genetics to improve the molecular characterization of the HLA genetic diversity of human populations. Culminating several rounds of workgroup meetings and biocomputational developmental work, new guidelines and methodological recommendations were published (Int J Immunogenet 2012, 39(6)). Desvios à Proposta Aprovada Se tiver havido desvios à proposta aprovada, quer do ponto de vista científico como financeiro, aponte os desvios e justifique-os. Se teve dificuldades na execução do plano de trabalhos aprovado, identifique-os e indique de que modo pretende ultrapassá-los. Se no período em apreço tiver informado a FCT sobre alteração orçamental inter-rubricas (necessitem ou não de autorização por parte da FCT), indique aqui o motivo. (4000 caracteres sem espaços) Não se verificaram desvios assinaláveis à proposta aprovada. Equipa de Investigação desistiu Nome Cargo Tarefas %Tempo data de data de (marcar com entrada saída uma X se for o Gr caso) Ana Alexandra Duarte Martins da Silva Investigador 25 IGIA Andreia Alexandra Ferreira dos Santos Investigador 100 IGIA Andreia Manuela Teixeira Bettencourt Investigador 100 IGIA Augusto Manuel Rodrigues Faustino Investigador 50 IGIA Bárbara Alexandra Padrão Guerra Leal Investigador 100 IGIA Carlos Alberto da Silva e Vasconcelos Investigador 20 IGIA Cláudia Alexandra Moreira de Carvalho Investigador 80 IGIA Helena Maria Sousa Barreiros Martins Investigador 15 IGIA Henrique Luis Lopes Ferreira Reguengo da Luz Investigador 15 IGIA Isabel Maria Pereira Alves de Almeida Investigador 20 IGIA João Manuel Monteiro Chaves Investigador 15 IGIA José Carlos Azevedo Oliveira Investigador 15 IGIA Maria Berta de Jesus Duarte Silva Investigador 50 IGIA Maria Fátima Graça Farinha Investigador 20 IGIA Maria Fernanda Ramos Bravo Investigador 15 IGIA Maria Júlia da Silva Reis Investigador 15 IGIA Paulo Jorge Barbosa Carvalho Investigador 20 IGIA Paulo Manuel de Castro Pinho e Costa Investigador 20 IGIA 6. Publicações 1. T, Torres, R Sales, C Vasconcelos, B Martins da Silva, M Selores. “Framingham Risk Score underestimates cardiovascular disease risk in severe psoriatic patients: Implications in cardiovascular risk factors management and primary prevention of cardiovascular disease.” J Dermatol. 2013 Oct 16. doi: 10.1111/1346-8138.12267 http://www.ncbi.nlm.nih.gov/pubmed/24128349 2. C. Carvalho, S. L. Calvisi, B. Leal, A. Bettencourt, A. Marinho, I. Almeida, F. Farinha, P. P.Costa, B. M.Silva, C. Vasconcelos. ”CCR5Delta32: implications in SLE development” Int J Immunogenet. 2013 Oct 29. doi: 10.1111/iji.12094 http://www.ncbi.nlm.nih.gov/pubmed/24164722 3. D. Kasperavičiūtė, C. B. Catarino, M. Matarin, C. Leu, J. Novy, A. Tostevin, B. Leal,et al. “Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A” Brain. 2013 Oct;136(Pt 10):3140-50. doi: 10.1093/brain/awt233 http://www.ncbi.nlm.nih.gov/pubmed/24014518 4. Amato N, Riva N, Cursi M, Martins-Silva A, Martinelli V, Comola M, Fazio R, Comi G, Leocani L. “Different Frontal Involvement in ALS and PLS Revealed by Stroop Event-Related Potentials and Reaction Times.” Front Aging Neurosci. 2013 Dec 12;5:82. doi: 10.3389/fnagi.2013.00082. http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+24376417 5. da Silva AM, Santos ME; On behalf of the Portuguese JEMS Study Investigators.” JCV epidemiology in MS (JEMS)-Epidemiology of anti-JCV antibody prevalence in multiple sclerosis patients-Portuguese data.” Neurol Sci. 2013 Dec 1. pii: S0022-510X(13)03060-8. doi: 10.1016/j.jns.2013.11.031 http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+24369270 6. Teixeira F, Moreira I, Silva AM, Vasconcelos C, Farinha F, Santos E “Neurological involvement in Primary Sjögren Syndrome.” Acta Reumatol Port. 2013 Jan-Mar;38(1):29-36. http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+24131909 7. Coelho T, Maia LF, da Silva AM, Cruz MW, Planté-Bordeneuve V, Suhr OB, Conceiçao I, Schmidt HH, Trigo P, Kelly JW, Labaudinière R, Chan J, Packman J, Grogan DR. “Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy.” J Neurol. 2013 Nov;260(11):2802-14. doi: 10.1007/s00415-013-7051-7. http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+23974642 8. Martin JE, Assassi S, Diaz-Gallo LM, Broen JC, Simeon CP, Castellvi I, Vicente-Rabaneda E, Fonollosa V, Ortego-Centeno N, González-Gay MA, Espinosa G, Carreira P; Spanish Scleroderma Group; SLEGEN consortium; U.S. Scleroderma GWAS group; BIOLUPUS, Camps M, Sabio JM, D'alfonso S, Vonk MC, Voskuyl AE, Schuerwegh AJ, Kreuter A, Witte T, Riemekasten G, Hunzelmann N, Airo P, Beretta L, Scorza R, Lunardi C, Van Laar J, Chee MM, Worthington J, Herrick A, Denton C, Fonseca C, Tan FK, Arnett F, Zhou X, Reveille JD, Gorlova O, Koeleman BP, Radstake TR, Vyse T, Mayes MD, Alarcón-Riquelme ME, Martin J. “A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci”. Hum Mol Genet. 2013 Oct 1;22(19):4021-9. doi: 10.1093/hmg/ddt248. http://www.ncbi.nlm.nih.gov/pubmed/23740937 9. Deng Y, Zhao J, Sakurai D, Kaufman KM, Edberg JC, Kimberly RP, Kamen DL, Gilkeson GS, Jacob CO, Scofield RH, Langefeld CD, Kelly JA, Ramsey-Goldman R, Petri MA, Reveille JD, Vilá LM, Alarcón GS, Vyse TJ, Pons-Estel BA; Argentine Collaborative Group, Freedman BI, Gaffney PM, Sivils KM, James JA, Gregersen PK, Anaya JM, Niewold TB, Merrill JT, Criswell LA, Stevens AM, Boackle SA, Cantor RM, Chen W, Grossman JM, Hahn BH, Harley JB, Alarcόn-Riquelme ME; BIOLUPUS and GENLES networks, Brown EE, Tsao BP. “MicroRNA-3148 modulates allelic expression of toll-like receptor 7 variant associated with systemic lupus erythematosus.” PLoS Genet. 2013;9(2):e1003336. doi: 10.1371/journal.pgen.1003336. Epub 2013 Feb 28. http://www.ncbi.nlm.nih.gov/pubmed/23468661 10. N. Costa, A. E. Pires, A. M. Gabriel, L. F. Goulart, C. Pereira, B. Leal, A. C. Queiros, W. Chaara, M. F. Moraes-Fontes, C. Vasconcelos, C. Ferreira, J. Martins, M. Bastos, M. J. Santos, M. A. Pereira, B. Martins, M. Lima, C. João, A. Six, J. Demengeot, C. Fesel. “Broadened T-cell repertoire diversity in ivIg-treated SLE patients is also related to the individual status of regulatory T-cells.” J. Clin Immunol. 2013 Feb;33(2):349-60. doi: 10.1007/s10875-012-9816-7. http://www.ncbi.nlm.nih.gov/pubmed?term=23064977 11. Löfgren SE, Frostegård J, Truedsson L, Pons-Estel BA, D'Alfonso S, Witte T, Lauwerys BR, Endreffy E, Kovács L, Vasconcelos C, Martins da Silva B, Kozyrev SV, Alarcón-Riquelme ME. “Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene”. Genes Immun. 2012 Apr;13(3): PMID:22218224 http://www.ncbi.nlm.nih.gov/pubmed?term=Genetic%20association%20of%20miRNA146a%20with%20systemic%20lupus%20erythematosus%20in%20Europeans%20through%20decreased%20expression%20of%20the %20gene 12. Fesel C, Barreto M, Ferreira RC, Costa N, Venda LL, Pereira C, Carvalho C, Morães-Fontes MF, Ferreira CM, Vasconcelos C, Viana JF, Santos E, Martins B, Demengeot J, Vicente AM. “Compensatory T-cell regulation in unaffected relatives of SLE patients, and opposite IL-2/CD25-mediated effects suggested by coreferentiality modeling.”. PLoS One. 2012;7(3). PubMed PMID: 22479496 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2022479496 13. Costa M, Cruz E, Barton JC, Thorstensen K, Morais S, da Silva BM, Pinto JP, Vieira CP, Vieira J, Acton RT, Porto G. “Effects of highly conserved major histocompatibility complex (MHC) extended haplotypes on iron and low CD8+ T lymphocyte phenotypes in HFE C282Y homozygous hemochromatosis patients from three geographically distant areas.” PLoS One. 2013 Nov 25;8(11):e79990. doi: 10.1371/journal.pone.0079990 http://www.ncbi.nlm.nih.gov/pubmed/24282517 14. Namjou B, Kim-Howard X, Sun C, Adler A, Chung SA, Kaufman KM, Kelly JA, Glenn SB, Guthridge JM, Scofield RH, Kimberly RP, Brown EE, Alarcón GS, Edberg JC, Kim JH, Choi J, Ramsey-Goldman R, Petri MA, Reveille JD, Vilá LM, Boackle SA, Freedman BI, Tsao BP, Langefeld CD, Vyse TJ, Jacob CO, Pons-Estel B; Argentine Collaborative Group, Niewold TB, Moser Sivils KL, Merrill JT, Anaya JM, Gilkeson GS, Gaffney PM, Bae SC, Alarcón-Riquelme ME; BIOLUPUS and GENLES Networks, Harley JB, Criswell LA, James JA, Nath SK. “PTPN22 association in systemic lupus erythematosus (SLE) with respect to individual ancestry and clinical subphenotypes.” PLoS One. 2013 Aug 7;8(8):e69404. doi: 10.1371/journal.pone.0069404 http://www.ncbi.nlm.nih.gov/pubmed/23950893 15. Ferrao C, Faria RM, Farrajota P, Vasconcelos C. “Lucky to meet RS3PE”. BMJ Case Rep. 2013 Oct 7;2013(oct07_1). doi:pii: bcr2013010363. 10.1136/bcr-2013-010363. http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+24099760 16. Ribeiro S, Ferreira B, Duarte R, Almeida I, Vasconcelos C. Primary nasal tuberculosis during anti-tumour necrosis factor alpha treatment of a patient with rheumatoid arthritis. Scand J Infect Dis. 2013 Aug 19. http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+23957541 17. Freitas AI, Vasconcelos C, Vilanova M, Cerca N. Optimization of an automatic counting system for the quantification of Staphylococcus epidermidis cells in biofilms. J Basic Microbiol. 2013 May 20. doi: 10.1002/jobm.201200603. http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+23686681. 18. Delgado-Vega AM, Dozmorov MG, Quirós MB, Wu YY, Martínez-García B, Kozyrev SV, Frostegård J, Truedsson L, de Ramón E, González-Escribano MF, Ortego-Centeno N, Pons-Estel BA, D'Alfonso S, Sebastiani GD, Witte T, Lauwerys BR, Endreffy E, Kovács L, Vasconcelos C, da Silva BM, Wren JD, Martin J, Castillejo-López C, Alarcón-Riquelme ME. 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Elsa Bronze-da-Rocha & Ana Nóvoa & Natércia Teixeira & Carlos Vasconcelos & Conceição Cerveira & João Castro e Melo & Manuel Cirne Carvalho. Evaluation of the Reactivity of Sera from Patients with Systemic Lupus Erythematosus Against the Human MCP1 J Clin Immunol (2012) 32:721–728. PMID: 22371290 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2022371290 35. George Bertsias , Maria Tektonidou, Zahir Amoura, Martin Aringer, Ingeborg Bajema, Jo Berden, John Boletis, Ricard Cervera, Thomas Dörner, Andrea Doria, Franco Ferrario, Jurgen Floege, Frederic Houssiau, John P. A. Ioannidis, David Isenberg, Cees G. Kallenberg, Liz Lightstone, Stephen D. Marks, Alberto Martini, Gabriela Moroni, Irmgard Neumann, Manuel Praga, Martin Schneider, Vladimir Tesar, Carlos Vasconcelos, Ronald van Vollenhoven, Elena Zakharova, Marion Haubitz, Caroline Gordon, David Jayne, Dimitrios T. BoumpasJoint European League Against Rheumatism & European Renal Association - European Dialysis and Transplant Association (EULAR/ERA-EDTA) Recommendations for the Management of Adult and Paediatric Lupus Nephritis. Ann Rheum Dis. 2012 Nov;71(11):1771-82. PMID: 22851469 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2022851469 36. Stoenoiu MS, Aydin S, Tektonidou M, Ravelingien I, le Guern V, Fiehn C, Remy P, Delahousse M, Petera P, Quémeneur T, Vasconcelos C, D'Cruz D, Gilboe IM, Jadoul M, Karras A, Depresseux G, Guillevin L, Cervera R, Cosyns JP, Houssiau FA; MAINTAIN Nephritis Trial Group. Repeat kidney biopsies fail to detect differences between azathioprine and mycophenolate mofetil maintenance therapy for lupus nephritis: data from the MAINTAIN Nephritis Trial. Nephrol Dial Transplant. 2012 May;27(5):1924-30. PMID: 22110048 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2022110048 37. Salvador F, Ribeiro S, Macedo C, Neves J, Teixeira S, Farinha F, Almeida I, Vasconcelos C. Vacinação para gripe A (H1N1) em doentes com Lupus Eritematoso Sistémico Influenza A (H1N1) vaccination in Systemic Lupus Erythematosus patients. Medicina INterna 2012, 19, 140-44 38. Andreia Bettencourt, Ana Martins da Silva, Paulo Pinho e Costa, Berta Martins Silva. “Molecular genetic studies of multiple sclerosis in the Portuguese population.” Acta Med Port 2012 Jul-Aug;25(4):224-230. 39. Beirão M, Matos E, Beirâo I, Costa PP, Torres P. Anticipation of presbyopia in Portuguese familial amyloidosis ATTR V30M. Amyloid. 2011 Sep;18(3):92-7. doi: 10.3109/13506129.2011.576719. Epub 2011 May 19. PubMed PMID: 21591979. http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2021591979 40. Beirão NM, Matos E, Beirão I, Costa PP, Torres P. Recurrence of vitreous amyloidosis and need of surgical reintervention in Portuguese patients with familial amyloidosis ATTR V30M. Retina. 2011 Jul-Aug;31(7):1373-7. PubMed PMID: 21358362. http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2021358362 41. Nery F, Franca M, Almeida I, Vasconcelos C. From Clinical Presentation to the Outcome: the Natural History of PML in a Portuguese Population of HIV Infected Patients. J Clin Med Res. 2011 Feb 12;3(1):17-22. PMID: 22043267 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2022043267 42. Zhao J, Wu H, Khosravi M, Cui H, Qian X, Kelly JA, Kaufman KM, Langefeld CD, Williams AH, Comeau ME, Ziegler JT, Marion MC, Adler A, Glenn SB, Alarcón-Riquelme ME; BIOLUPUS Network; GENLES Network, Pons-Estel BA, Harley JB, Bae SC, Bang SY, Cho SK, Jacob CO, Vyse TJ, Niewold TB, Gaffney PM, Moser KL, Kimberly RP, Edberg JC, Brown EE, Alarcon GS, Petri MA, RamseyGoldman R, Vilá LM, Reveille JD, James JA, Gilkeson GS, Kamen DL, Freedman BI, Anaya JM, Merrill JT, Criswell LA, Scofield RH, Stevens AM, Guthridge JM, Chang DM, Song YW, Park JA, Lee EY, Boackle SA, Grossman JM, Hahn BH, Goodship TH, Cantor RM, Yu CY, Shen N, Tsao BP. Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility. PLoS Genet. 2011 . PMID: 21637784 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2021637784 43. Vasconcelos C, Kallenberg C, Shoenfeld Y. Refractory disease in autoimmune diseases. Autoimmun Rev. 2011 Sep;10(11):653-4. 2 PMID: 21601657 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2021601657 44. Campar A, Farinha F, Vasconcelos C. Refractory disease in systemic lupus erythematosus. Autoimmun Rev. 2011 Sep;10(11):685-92. PMID: 21600313 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2021600313 45. Almeida I, Faria R, Vita P, Vasconcelos C. Systemic sclerosis refractory disease: from the skin to the heart. Almeida I, Faria R, Vita P, Vasconcelos C. Autoimmun Rev. 2011 PMID: 21575745 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2021575745 46. Tan W, Sunahori K, Zhao J, Deng Y, Kaufman KM, Kelly JA, Langefeld CD, Williams AH, Comeau ME, Ziegler JT, Marion MC, Bae SC, Lee JH, Lee JS, Chang DM, Song YW, Yu CY, Kimberly RP, Edberg JC, Brown EE, Petri MA, Ramsey-Goldman R, Vilá LM, Reveille JD, Alarcón-Riquelme ME, Harley JB, Boackle SA, Stevens AM, Scofield RH, Merrill JT, Freedman BI, Anaya JM, Criswell LA, Jacob CO, Vyse TJ, Niewold TB, Gaffney PM, Moser KL, Gilkeson GS, Kamen DL, James JA, Grossman JM, Hahn BH, Tsokos GC, Tsao BP, Alarcón GS; BIOLUPUS Network; GENLES Network. Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups. Arthritis Rheum. 2011 Sep;63(9):2755-63. PMID: 21590681 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2021590681 47. Hughes T, Kim-Howard X, Kelly JA, Kaufman KM, Langefeld CD, Ziegler J, Sanchez E, Kimberly RP, Edberg JC, Ramsey-Goldman R, Petri M, Reveille JD, Martín J, Brown EE, Vilá LM, Alarcón GS, James JA, Gilkeson GS, Moser KL, Gaffney PM, Merrill JT, Vyse TJ, Alarcón-Riquelme ME; BIOLUPUS Network, Nath SK, Harley JB, Sawalha AH. Fine-mapping and transethnic genotyping establish IL2/IL21 genetic association with lupus and localize this genetic effect to IL21. Arthritis Rheum. 2011: PMID: 21425124 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2021425124 48. Abecasis AB, Martins A, Costa I, Carvalho AP, Diogo I, Gomes P, Camacho RJ. Portuguese Hiv-1 Resistance Study Group Molecular epidemiological analysis of paired pol/env sequences from Portuguese HIV type 1 patients. AIDS Res Hum Retroviruses. 2011 Jul;27(7):803-5. 49. Sarmento-Castro R, Vasconcelos C, Aguas MJ, Marques R, Oliveira J. Virologic suppression in treatment-experienced patients after virologic rebound or failure of therapy. Curr Opin HIV AIDS. 2011 Dec;6 Suppl 1:S12-20 . PMID: 21198411 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2021198411 50. Valadares D, Neves J, Almeida A, Lopes C, Vasconcelos C. Iron Lady: A Case of Eosinophilic Fasciitis. J Med Cases 2011;2(1):34-36 Duarte R, Carvalho C, Pereira C, Bettencourt A, Carvalho A, Villar M, Domingos A, Barros H, Marques J, Pinho Costa P, Mendonça D, Martins B. HLA class II alleles as markers of tuberculosis susceptibility and resistance Rev Port Pneumol. 2011 Jan-Feb;17(1):15-9. PMID: 21251479 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2021251479 51. Bettencourt A, Silva AM, Santos E, Gomes S, Mendonça D, Costa PP, Faustino P, Silva BM. HFE gene polymorphisms and severity in Portuguese patients with multiple sclerosis. Eur J Neurol. 2011 Apr;18(4):663-6. PubMed PMID: 20586792. http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2020586792 52. Tavares I, Lobato L, Moreira L, Santos J, Lacerda P, Pinheiro J, Costa P. Long-term follow-up of patients with hereditary fibrinogen A alpha-chain amyloidosis. Amyloid. 2011 Jun;18 Suppl 1:216-7. PubMed PMID: 1838495. http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%201838495 53. Duarte R, Carvalho C, Pereira C, Bettencourt A, Carvalho A, Villar M, Domingos A,Barros H, Marques J, Pinho Costa P, Mendonça D, Martins B. HLA class II alleles as markers of tuberculosis susceptibility and resistance. Rev Port Pneumol. 2011 Jan-Feb;17(1):15-9. English, Portuguese. PubMed PMID: 21251479. http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2021251479 54. Chaves J, Beirão I, Balreira A, Gaspar P, Caiola D, Sá-Miranda MC, Lima JL. Progressive myoclonus epilepsy with nephropathy C1q due to SCARB2/LIMP-2 deficiency: clinical report of two siblings. Seizure. 2011 Nov;20(9):738-40. PMID: 21782476 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2021782476 Participação /agradecimento Christopher J. Lessard,1,2 Indra Adrianto,1 John A. Ice,1 Graham B. Wiley,1 Jennifer A. Kelly,1 Stuart B. Glenn,1 Adam J. Adler,1 He Li,1,2 Astrid Rasmussen,1 Adrienne H. Williams,3 Julie Ziegler,3 Mary E. Comeau,3 Miranda Marion,3 Benjamin E. Wakeland,4 Chaoying Liang,4 Paula S. Ramos,5 Kiely M. Grundahl,1 Caroline J. Gallant,6 Marta E. Alarcón-Riquelme for the BIOLUPUS and GENLES Networks. Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as Susceptibility Loci for Systemic Lupus Erythematosus in a Large-Scale Multiracial Replication Studys. Am J Hum Genet. 2012 April 6; 90(4): 648–660. PMID: 22464253 http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2022464253 Indicadores de Realização Física Neste quadro deve indicar os valores referentes ao período a que corresponde o Relatório de Progresso. Neste quadro deve apenas indicar concretizações efectivas. Não indique publicações submetidas para publicação, nem teses que ainda não tenham sido discutidas. Indicadores Quantidade realizada A - Publicações Livros 0 Artigos em revistas internacionais 50 Artigos em revistas nacionais 4 B - Comunicações Comunicações em encontros científicos internacionais 51 Comunicações em encontros científicos nacionais 28 C - Relatórios 0 D - Organização de seminários e conferências 0 E - Formação avançada Teses de Doutoramento 0 Teses de Mestrado 6 Outras 0 F - Modelos 0 G - Aplicações computacionais 0 H - Instalações piloto 0 I - Protótipos laboratoriais 0 J - Patentes 0 L - Outros 7. Ficheiros Anexos (opcional) Poderá enviar, apenas se entender como estritamente necessário, ficheiros com formato PDF, que tenham sido referidos no relatório, por exemplo, gráficos, esquemas, fotografias. O conjunto dos ficheiros (em número máximo de cinco) ou o arquivo comprimido a enviar não poderão ultrapassar 10MB. Nome do ficheiro Agradecemos a sua colaboração. Ponto do Relatório de Progresso Descrição Relatório Científico Final 2011-13 – UMIB Research Group Title: Parkinson Disease Study Group Principal Investigator: António Bastos Lima / Sara Cavaco Research Area: Health Sciences Home Institution: Instituto de Ciências Biomédicas Abel Salazar Relatório de Progresso Informação: Qualquer dúvida relacionada com o preenchimento do Formulário de Relatório de Progresso, por favor contacte-nos. Atenção: - O formato da data a utilizar é dd-mm-yyyy Formulário Relatório de Progresso - Componente Científica Relatório Final Período a que o relatório diz respeito: Data de início: 01-01-2011 Data de fim: 31-12-2013 1. Identificação do Projecto Referência do Projecto: PEst-OE/SAU/UI0215/2011 Investigador Responsável: Paulo Jorge Silva Correia Sa Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP) Data de Início: 01-01-2011 Data de Fim: 31-12-2013 1. Identificação do grupo Nome: Parkinson Disease Study Group Investigador Responsável: Professor António Bastos Lima/Professora Sara Cavaco Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP) Data de Início: 01-01-2011 Data de Fim: 31-12-2013 7. Resumo dos Trabalhos Desenvolvidos e Desvios à Proposta aprovada Resumo dos trabalhos Descreva de forma breve as actividades desenvolvidas no período em apreço e os resultados alcançados. Refira-se em concreto às tarefas que tiveram execução no período a que o relatório respeita. (6000 caracteres sem espaços) De acordo com o planeado, em 2011, 2012 e 2013, o grupo de estudos da doença de Parkinson focalizou-se: 1) na caracterização dos sintomas não motores da doença de Parkinson; No âmbito das teses de doutoramento da Dra. Alexandra Gonçalves (FMP), do Dr. Alexandre Mendes (ICBAS) e do Dr. Nuno Vila-Chã (FMP), estão a ser estudados transversalmente todos os doentes de Parkinson da consulta de doenças do movimento do Centro Hospitalar do Porto para os sintomas motores e não motores (cognitivos, olfactivos, da dor, do sono, neuropsiquiátricos e disautonómicos) e para a qualidade de vida. Foram estudados 200 doentes de Parkinson até ao final de 2013. Dados preliminares dos estudos foram apresentados em comunicações (orais ou pósteres). Estão também a ser estudados sujeitos saudáveis da comunidade como amostra de controlo. Encontra-se em fase avançada de preparação um artigo científico que ilustra pela primeira vez o efeito da reserva cerebral nas manifestações motoras da doença de Parkinson. Em colaboração com o Grupo de Imunogenética, Inflamação e Autoimunidade está a ser recolhido e estudado material genético de todos os doentes que integram o estudo transversal, de forma a melhor compreender os sintomas não motores da doença de Parkinson. Em colaboração com o grupo IGIA e com o laboratório Lysosome & Peroxisome Biology do IBMC, uma aluna de mestrado de Ciências Forenses do ICBAS sob a orientação da Prof. Dra. Sara Cavaco e Prof. Dra. Berta Martins (grupo IGIA) explorou a mutação de Gaucher (mutação do gene da glucocerebrosidase - N370S) numa amostra de 100 doentes de Parkinson. Esta mutação foi encontrada em dois doentes (esta frequência não é superior à da população portuguesa). Nesta amostra de doentes foram também exploradas associações entre polimorfismos do sistema dopaminérgico, do sistema glutamatérgico e do sistema serotoninérgico e a Perturbação no Controlo de Impulsos na doença de Parkinson. Foi encontrada uma associação significativa entre o polimorfismo do sistema glutamatérgico e a ocorrência da Perturbação no Controlo de Impulsos. Está prevista a divulgação destes resultados em reuniões científicas nacionais e internacionais. 2) na avaliação custo-eficiência da opção pela estimulação cerebral profunda sub-talámica (STN-DBS) vs. a melhor terapêutica médica no tratamento da doença de Parkinson em fases avançadas ou com complicações motoras incapacitantes; O estudo custo-eficiência da STN-DBS foi explorado por uma aluna de medicina do ICBAS sob a orientação do Dr. Alexandre Mendes. A STNDBS apresentou claro beneficio motor e relativa segurança cognitiva (dados apresentados em comunicações orais ou pósteres). Nos primeiros dois anos após a cirurgia, a STN-DBS apresentou-se relativamente mais dispendiosa do que a melhor terapêutica médica. No entanto, verificouse uma marcada redução dos custos da opção STN-DBS com o tempo. A componente económica do estudo foi divulgada em reuniões científicas nacionais. 3) na aferição e validação de instrumentos de avaliação cognitiva e psicopatológica para a população Portuguesa Foram aferidos para a população portuguesa, usando técnicas de co-normalização, a Dementia Rating Scale – 2 (Cavaco & Teixeira-Pinto, 2011), o Trail Making Test (Cavaco et al., 2013), a fluência verbal categorial (Cavaco et al., 2013), a fluência verbal literal (Cavaco et al., 2013), e o Brief smell identification test (Martins da Silva et al 2012; Cavaco et al 2012; comunicações orais e pósteres). Foi desenvolvida em colaboração com o grupo CINTESIS uma aplicação online (neuropsi.up.pt) para uso mais fácil das fórmulas de aferição baseadas na regressão do Trail Making Test, da fluência verbal categorial e da fluência verbal literal, por parte de clínicos e investigadores portugueses. Os dados normativos recolhidos na aferição do Trail Making Test, da fluência verbal categorial, da fluência verbal literal e do Auditory Verbal Learning Test integraram o estudo multicêntrico liderado pela Johns Hopkins University School of Medicine, chamado International Neuropsychological Normative Database Initiative (http://inndi.org/), que procura desenvolver a aferição mundial de um conjunto de testes neuropsicológicos, através de técnicas de regressão que tenham em conta não só as variáveis demográficas como também as característics culturais e linguísticas dos sujeitos. Foram desenvolvidos trabalhos de validação clínica destes instrumentos para a doença de Parkinson sem demência, para a doença de Huntington, para a doença de Alzheimer, para a demência frontotemporal e para doenças auto-imunes (Cavaco & Teixeira-Pinto, 2011; Martins da Silva et al, 2011a, 2011b, 2012; Cavaco et al 2012; Taipa et al., 2012; comunicações orais e pósteres). Desvios à Proposta Aprovada Se tiver havido desvios à proposta aprovada, quer do ponto de vista científico como financeiro, aponte os desvios e justifique-os. Se teve dificuldades na execução do plano de trabalhos aprovado, identifique-os e indique de que modo pretende ultrapassá-los. Se no período em apreço tiver informado a FCT sobre alteração orçamental inter-rubricas (necessitem ou não de autorização por parte da FCT), indique aqui o motivo. (4000 caracteres sem espaços) O reconhecimento de emoções em expressões faciais continuou a ser explorado em doentes de Parkinson. Começou também a ser explorado noutras populações neurológicas (esclerose múltipla, esclerose mesial e doença de Huntington). Os resultados preliminares para doentes de Parkinson e para doentes com esclerose mesial foram apresentados em comunicações (orais ou pósteres). O estudo do reconhecimento de emoções em expressões faciais foi completado em doentes com esclerose múltipla (Pinto et al., 2012) e doença de Huntington (Van Asselen et al., 2012). O Professor Dr. Bastos Lima integrou o estudo epidemiológico de avaliação da prevalência da Doença de Parkinson em Portugal, chamado Estudo PrevPark. A Prof. Dra. Sara Cavaco integrou o grupo multicêntrico de estudo da doença de Huntington, chamado Euro-Huntington’s Disease Network (http://www.euro-hd.net) (Orth et al., 2011; Quarrell et al., 2012) e o grupo multicêntrico de aferição de testes neuropsicológicos, chamado International Neuropsychological Normative Database Initiative (http://inndi.org/) O Grupo de Estudos da Doença de Parkinson organizou em colaboração com a Reitoria da Universidade do Porto e com o Centro Hospitalar do Porto “O Curso em Neurociências Clínicas: da patologia a avaliação diagnóstica”, que se realizou a 18 e 19 de Novembro de 2011. Este curso de educação contínua destinou-se a profissionais das áreas de medicina, neurociências e psicologia. Continuou a colaboração com o Grupo de Imunogenética, Inflamação e Autoimunidade e o com o Laboratório de Neurobiologia do Comportamento Humano para os estudos “Funcionamento cognitivo em doenças autoimunes multi-sistémicas” e “Funcionamento cognitivo numa população de doentes portugueses com Esclerose Múltipla”. Continuou a colaboração com a University of Iowa Carver College of Medicine Division of Behavioral Neurology and Cognitive Neuroscience e com o Laboratório de Neurobiologia do Comportamento Humano para o estudo “Envolvimento do cortex parietal posterior na aprendizagem de skills”. Equipa de Investigação desistiu (marcar com Nome Cargo Tarefas %Tempo data uma X data de de se for o entrada saída caso) Gr X PDSG Ana Paula Andrade Correia de Mesquita Guimarães Investigador 20 - Investigador principal em diversos estudos António Fernando Bastos Lima Investigador de investigação; 20 PDSG 20 PDSG 20 PDSG 25 PDSG 25 PDSG - Colaborou em estudos de investigação relacionados com a cirurgia STN-DBS em António José Verdelho Vieira Investigador doentes de Parkinson; - Colaborou em diversos estudos de investigação: aferição e validação de provas neuropsicológicas; estudos relacionados com a cirurgia STN-DBS em doentes de Cláudia Sofia Teles de Meneses Malheiro Pinto Parkinson; estudos em doenças autoimunes Investigador (esclerose múltipla, lúpus) - Colaborou em diversos estudos de investigação relacionados com a doença de Parkinson; - Orientação do “Estudo económico da estimulação bilateral dos núcleos subtalâmicos na doença de Parkinson” realizado pela aluna do ICBAS Sofia Daniela Martins Carvalho - Iniciou o Programa Doutoral em Ciências Médicas, do ICBAS – Universidade do Porto; Tema da tese: Evolução da doença de Parkinson – operacionalização da decisão cirúrgica; Orientadores: Professor Doutor Fernando Alexandre Pereira Mendes Bastos Lima, Professora Dra. Sara Cavaco e Investigador Professor Doutor Paul Krack - Colaborou em diversos estudos de investigação: aferição e validação de provas neuropsicológicas; estudos relacionados com a cirurgia STN-DBS em doentes de Parkinson; estudos em doenças autoimunes (esclerose múltipla, lúpus); Filomena Maria Correia Gomes Investigador - Iniciou o Programa Doutoral em Neurociências, da Faculdade de Medicina – Universidade do Porto; Tema da tese: Test of Memory Malingering: Utility of Neuropsychophysiological measures for detecting malingering; Orientadores: Professora Dra. Sara Cavaco e Professora Dra. Carolina Garrett - Colaborou em estudos de investigação Luis Filipe Botelho Casal dos Santos relacionados com a cirurgia STN-DBS em Investigador doentes de Parkinson; 15 PDSG 50 PDSG - Colaborou em diversos estudos de investigação: aferição e validação de provas neuropsicológicas; estudos em doenças autoimunes (esclerose múltipla, lúpus); - Iniciou o Programa Doutoral em Neurociências, da Faculdade de Medicina – Universidade do Porto; Tema da tese: Nonmotor symptoms in Parkinson's disease: a comprehensive and integrated approach; Orientadores: Maria Alexandra Ribeiro Gonçalves Prof. Doutora Sara Cavaco e Prof. Doutor Investigador Marques-Teixeira - Colaborou em diversos estudos de investigação: aferição e validação de provas neuropsicológicas; estudos relacionados com a cirurgia STN-DBS em doentes de Parkinson; estudos em doenças autoimunes (esclerose múltipla, lúpus); - Em 2012, registou-se uma mudança de Maria Inês Dias Moreira Investigador estatuto, passou de investigadora a bolseira 50 x PDSG Investigador 25 X PDSG Marina Justino Matias de Magalhaes Castelo Branco - Colaborou em diversos estudos de investigação relacionados com a doença de Parkinson; - Iniciou o Programa Doutoral em Investigação Clínica e em Serviços de Saúde, da Faculdade de Medicina – Universidade do Porto Tema da tese: Dor na doença de Parkinson; Orientador: Professor Doutor José Manuel Castro Lopes, Professor Catedrático da Faculdade de Medicina – Universidade do Nuno Miguel dos Santos Vila-Chã Investigador Porto 15 PDSG - Investigadora principal e colaboradora em Sara Marta Pereira dos Santos Cavaco diversos estudos de investigação; Investigador - Orientação de teses de doutoramento 50 PDSG 3. Publicações Apenas para o período a que respeita o Relatório de Progresso, indique trabalhos apresentadas ou aceites para publicação ou apresentação, e trabalhos submetidos no período a que o relatório respeita. A informação pretendida neste campo é inserida em formato livre. Para cada publicação deve ser indicada a seguinte informação: 1. Descrição, contendo os seguintes elementos: • Em livros ou monografias: autor(es), título, número e/ou identificação da edição, número do volume, lugar da publicação, número de páginas; • Em revistas científicas: autor(es), título, título da revista, lugar da publicação, número do volume, número da primeira e última página; • Em artigos ou abstracts de comunicações científicas ou outras participações de índole científica em congressos internacionais ou nacionais: autor(es), título do artigo • ou comunicação, nome da publicação, volume, número de páginas; 2. Estado, indicando a situação: • Publicado/Apresentado; • Aceite para publicação/apresentação; • Submetido. Nos trabalhos aceites para apresentação ou publicação, a data de aceitação deve ser indicada no campo descrição. Nota em 22-11-2011: Para os trabalhos que tenham sido publicados ou apresentados deve ser indicado o URL onde o mesmo possa ser consultado, devendo este URL ser mantido pelo mesmo período do dossier de projecto. Exemplos: • Aceite - I. Santos, J. Rodrigues, "Non linear control design of a team of autonomous vehicles", aceite (Dezembro de 2008) para apresentação na IEEE Conference on Control Systems, Madrid, Espanha, Maio de 2009. URL: http://www.xpto.xpto.pt • Publicado - A. Silva, P. Oliveira, "Social behaviour of a dog colony in extreme conditions", Journal of Animal Behaviour, Elsevier, Vol. 2, Nº3, pp.373-395, September 2009. URL: http://www.xpto.xpto.pt • Apresentado - V. Santos, J. Rodrigues, "Medical image segmentation for endoscopy applications", Proc. of the International Conference on Medical Imaging, Pittsburgh, USA, March 2009, pp. 304-312. URL: http://www.xpto.xpto.pt • Submetido - M. Santos, P. Oliveira, "Comparative Analysis of Elephant Populations", submetido (Fevereiro de 2009) para apresentação na International Conference on Veterinary Studies, S. Paulo, Brasil, Novembro de 2009. Nota em 22-11-2011: Chama-se a atenção para a necessidade absoluta do cumprimento das Normas de Informação e Publicidade disponíveis para consulta em http://www.fct.pt/apoios/projectos/regulamentos Nessas normas são indicadas frases tipo de publicitação para o caso de artigos científicos e teses. (até 6000 caracteres sem espaços) Ferramenta online: http://neuropsi.up.pt/ Livro: Publicado - Cavaco S. & Teixeira-Pinto A. (2011). Dementia Rating Scale-2: Manual Técnico (Versão Portuguesa). Lisboa: Cegoc-Tea. http://www.cegoc.pt/teste/escala-de-avaliacao-da-demencia-2/ ISBN: 978-972-8817-62-6 Artigos originais: Publicado - Cavaco S, Anderson, SW, Correia M, Magalhães M, Pereira C, Tuna A, Taipa R, Pinto P, Pinto C, Cruz R, Bastos Lima A, Castro-Caldas A, Martins da Silva A, Damásio H. Task specific contribution of the human striatum to perceptual-motor skill learning. Journal of Clinical and Experimental Neuropsychology. 2011; 33(1): 51-62. http://www.ncbi.nlm.nih.gov/pubmed/20603739 Publicado - Martins da Silva Ana, Cavaco S, Taipa R, Pinto P, Melo Pires M. Medulloblastoma and gliomatosis cerebri: rare brain tumors in Multiple Sclerosis patients. Neurological Sciences. 2011. 32(5):893-7. http://www.ncbi.nlm.nih.gov/pubmed/21234776 Publicado - Martins da Silva Ana, Vilhena E, Lopes A, Santos E, Gonçalves MA, Pinto C, Moreira I, Mendonça D, Cavaco S. Depression and anxiety in a Portuguese MS population: associations with physical disability and severity of disease. Journal of the Neurological Sciences. 2011; 306: 66–70. http://www.ncbi.nlm.nih.gov/pubmed/21497358 Publicado - Martins Silva A, Santos E, Moreira I, Coutinho E, Bettencourt A, Gonçalves A, Pinto C, Montalban X, Cavaco S. Olfactory dysfunction in multiple sclerosis: association with secondary progression. Multiple Sclerosis. 2012; 18(5):616-21. http://www.ncbi.nlm.nih.gov/pubmed/22020420 Publicado - Cavaco S, Martins da Silva Ana, Santos E, Coutinho E, Marinho A, Moreira I, Gonçalves A, Pinto C, Teixeira-Pinto A, Vasconcelos C. Are Cognitive And Olfactory Dysfunctions In Neuropsychiatric Lupus Erythematosus Dependent on Anxiety or Depression? J Rheumatol. 2012; 39(4):770-6. http://www.ncbi.nlm.nih.gov/pubmed/22382338 Publicado - Pinto C, Gomes F, Moreira I, Rosa B, Santos E, Martins Silva A, Cavaco S. Emotion recognition in Multiple Sclerosis. Journal of Eyetracking, Visual Cognition and Emotion. 2012, 2(1): 76-81. Publicado - Taipa R, Tuna A, Damásio J, Pinto PS, Cavaco S, Pereira S, Milterberger-Miltenyi G, Galimberti D, Melo Pires M. Clinical, neuropathological and genetic characteristics of the novel IVS9+1delG GRN mutation in a patient with frontotemporal dementia. J Alzheimers Dis. 2012, 30(1):83-90. http://www.ncbi.nlm.nih.gov/pubmed/22366770 Publicado - Van Asselen M, Júlio F, Januário C, Bobrowicz Campos E, Almeida I, Cavaco S, Castelo Branco M. Scanning patterns of faces do not explain impaired emotion recognition in Huntington Disease: Evidence for a high level mechanism. Frontiers in Psychology 2012, 3, 31. http://www.ncbi.nlm.nih.gov/pubmed/22355293 Publicado - Cavaco S, Feinstein JS, van Twillert H, Tranel D. Musical memory in a patient with severe anterograde amnesia. Journal of Clinical and Experimental Neuropsychology. 2012, 34 (10), 1089-1100. http://www.ncbi.nlm.nih.gov/pubmed/23036073 Publicado - Barros J, Mendes A, Matos I, Pereira-Monteiro J. Psychotic aura symptoms in familial hemiplegic migraine type 2 (ATP1A2). The Journal of Headache and Pain 2012, 13 (7): 581-585. http://www.ncbi.nlm.nih.gov/pubmed/22661290 Publicado - Cavaco S; Gonçalves A, Pinto C, Almeida E, Gomes F, Moreira I, Fernandes J, Teixeira-Pinto A. Trail Making Test: regression-based norms for the Portuguese population. Archives of Clinical Neuropsychology. 2013, 28(2):189-98. http://www.ncbi.nlm.nih.gov/pubmed/23299183 Publicado - Cavaco S; Gonçalves A, Pinto C, Almeida E, Gomes F, Moreira I, Fernandes J, Teixeira-Pinto A. Semantic Fluency and Phonemic Fluency: regression-based norms for the Portuguese population. Archives of Clinical Neuropsychology. 2013, 28(3):262-271. http://www.ncbi.nlm.nih.gov/pubmed/23341434 Artigos listados como colaborador: Publicado - Orth M; European Huntington's Disease Network, Handley OJ, Schwenke C, Dunnett S, Wild EJ, Tabrizi SJ, Landwehrmeyer GB. Observing Huntington's disease: the European Huntington's Disease Network's REGISTRY. Journal Of Neurology Neurosurgery And Psychiatry 2011; 82(12):1409-12. http://www.ncbi.nlm.nih.gov/pubmed/21097549 Publicado - Quarrell OW, Handley O, O'Donovan K, Dumoulin C, Ramos-Arroyo M, Biunno I, Bauer P, Kline M, Landwehrmeyer GB; European Huntington’s Disease Network. Discrepancies in reporting the CAG repeat lengths for Huntington's disease. European Journal of Human Genetics. 2012; 20(1):20-6. http://www.ncbi.nlm.nih.gov/pubmed/21811303 Publicado - Hubers AA, van Duijn E, Roos RA, Craufurd D, Rickards H, Bernhard Landwehrmeyer G, van der Mast RC, Giltay EJ; REGISTRY investigators of the European Huntington's Disease Network. Suicidal ideation in a European Huntington's disease population. J Affect Disord. 2013 Oct;151(1):248-58. http://www.ncbi.nlm.nih.gov/pubmed/23876196 Resumos Publicados em reuniões nacionais e internacionais com arbitragem: Publicado - Cavaco S, Martins Silva Ana, Santos E, Coutinho E, Moreira I, Gonçalves A, Pinto C, Teixeira-Pinto A, Marinho A, Vasconcelos C. Olfactory dysfunction in systemic lupus erythemathosus with neuropsychiatric manifestations. Lupus 2011; 20(4): 381. Publicado - Cruto C, Freitas J, Carvalheiras G, Mendes A, Bastos Lima A. HIV infection and Parkinson’s Disease: is there a causal relationship? Journal of Neurology 2011; 258 (supplement 1): S86. Publicado - Cruto C, Martins da Silva A, Lopes J, Vila-Chã J. Movimentos periódicos das pernas como manifestação paraneoplásica. Sinapse 2011; 11(2): 89. Publicado - Rua A, Cruto C, Monteiro C, Damásio J, Vila-Chã, N. Duas etiologias tratáveis para uma síndrome demencial e tremor. Sinapse 2011; 11(2): 66. Publicado - Martins da Silva Ana, Cavaco S, Santos E, Coutinho E, Moreira I, Gonçalves A, Pinto C, Vasconcelos C. Quality Of Life In Systemic Lupus Erythematosus With Neuropsychiatric Manifestations. Lupus 2011; 20(4): 400. Publicado - Cavaco S, Martins da Silva Ana, Santos E, Coutinho E, Moreira I, Gonçalves A, Pinto C, Vasconcelos C. Are neuropsychological impairments in systemic lupus erythematosus independent of psychopathology? Lupus 2011; 20(4): 349. Publicado - Bettencourt A, Martins da Silva Ana, Tavares A, Carvalho C, Leal B, Santos E, Gonçalves A, Moreira I, Vasconcelos C, Costa PP, Cavaco S, Silva BM. No association between apoE polymorphisms and neurolupus in Portuguese patients. Lupus 2011; 20(4): 362. Publicado - Leal B, Bettencourt A, Martins da Silva Ana, Carvalho C, Maia S, Santos E, Pinto C, Moreira I, Costa PP, Vasconcelos C, Cavaco S, Silva BM. The serotonin HTR2A receptor 102 T>C gene polymorphism is associated with depression in Portuguese patients with systemic lupus erythematosus. Lupus 2011; 20(4): 362 Publicado - Martins Silva Ana, Bettencourt A, Ribeiro A, Gonçalves A, Pinto C, Moreira I, Santos E, Coutinho E, Tavares A, Costa P, Martins Silva B, Cavaco S. Dementia in Multiple Sclerosis: demographic, clinical and genetic features. Journal of Neurology 2011; 258 (supplement 1): S91. Publicado - Martins Silva Ana, Bettencourt A, Gonçalves A, Pinto C, Santos E, Moreira I, Tavares A, Coutinho E, Gomes F, Costa P, Martins Silva B, Cavaco S. Does APOE-epsilon4 have a detrimental effect in Multiple Sclerosis? Journal of Neurology 2011; 258 (supplement 1): S148. Publicado - Cavaco S, Vila-Chã N, Moreira I, Mendes A, Bastos Lima A. Validação do Brief-Smell Identification Test para a doença de Parkinson. Sinapse 2011; 11(2): 85. Publicado - Correia FD, Domingos J, Ferreira J, Roque R, Taipa R, Cavaco S, Correia J, Martins da Silva Ana. Meningoencefalite recorrente como apresentação sistémica de artrite reumatoide. Sinapse 2011; 11(2): 80. Publicado - Domingos J, Santos E, Coutinho E, Pinho C, Gonçalves A, Cavaco S, Martins da Silva Ana. Afasias agudas em doentes com Esclerose Múltipla. Sinapse 2011; 11(2): 42. Publicado - Taipa R, Tuna A, Damásio J, Pinto PS, Cavaco S, Miltenberger G, Galimberti D, Manuel Melo-Pires. Características clínicas, genéticas e neuropatológicas de uma nova mutação da progranulina na DFT. Sinapse 2011; 11(2): 44-45. Publicado - Martins da Silva Ana, Vilhena E, Cavaco S, Santos E, Pinto C, Gonçalves A, Moreira I, Mendonça D, Pais-Ribeiro J. Predictor factors of quality of life in MS Portuguese patients. European Journal Of Neurology, 18 (Supplement 2): 585. Publicado - Vila-Chã N, Mendes A, Cavaco S, Bastos Lima A. Avaliação da qualidade dos registos clínicos na Doença de Parkinson. Sinapse 2011; 11(2): 49-50. Publicado - Costa A, Rocha S, Mendes A, Ramalheira J. A importância dos distúrbios do sono na abordagem da Sindrome da Deficiência de Desidrogenase Semialdeído Succínica. Sinapse 2011; 12(2): 116. Publicado - Verdelho A, Silva C, Mendes A, Vila Chã N, Felgueiras R, Temudo T, Botelho L, Bastos Lima A. Report of GPi-DBS in two patients with Pantothenate Kinase-Associated Neurodegeneratation: long term follow-up and video illustration. Stereotact Funct Neurosurg, 2012, 90(S1): 55. Publicado - Almeida E, Gomes F, Gonçalves A, Pinto C, Moreira I, Lopes Lima J, Chaves J, Cavaco S. Qualidade de vida na Epilepsia: Relação com características clínicas, demográficas e psicopatológicas. Sinapse 2012; 12(1): 141. Publicado - Moreira I, Cavaco S, Pinto C, Gonçalves A, Almeida E, Marinho A, Santos E, Martins da Silva Ana, Vasconcelos C. Psicopatologia no Lúpus Eritematoso Sistémico e na doença de Behçet. Sinapse 2012; 12(1): 150. Publicado - Gomes F, Pinto C, Moreira I, Verdelho A, Silva C, Botelho L, Vila-Chã N, Mendes A, Bastos Lima A, Cavaco S. Identificação de Emoções na doença de Parkinson antes e após STN-DBS. Sinapse 2012; 12(1): 170. Publicado - Gonçalves A, Moreira I, Pinto C, Cavaco S, Mendes A, Vila-Chã N, Bastos Lima A. Dementia Rating Scale-2 e Doença de Parkinson. Sinapse 2012; 12(1): 130. Publicado - Fernandes J, Moreira I, Cavaco S, Damásio J, Loureiro R, Magalhães M, Quality of life in Huntington disease and its association with psychopathology. European Journal of Neurology 2012, 19 (Supplement 1): 330. Publicado - Taipa R, Pinto PS, Monteiro C, Santos E, Cavaco S, Correia AP. Presenting symptoms and structural MRI analysis of early onset Alzheimer’s disease and frontotemporal lobar degeneration. Dementia and Geriatric Cognitive Disorders 2012, 33 (Supplement 1): 244-245. Publicado - Taipa, R, Santos, E, Pinto, PS, Cavaco, S, Galimberti, D, Correia, AP. Demencia frontotemporal e doença de neurónio motor: descrição de 3 casos com expansão do gene C9orf72. Sinapse 2013; 13(1): 68. Publicado - Moreira I, Cavaco S, Gomes F, Moreira I, Chaves J. Efeitos da lateralidade da esclerose mesial na identificação de emoções. Sinapse 2013; 13(1): 185. Publicado - Domingos J, Rodrigues T, Pinto P, Taipa R, Melo Pires M, Cavaco S, Mendes A, Magalhães M, Damásio J. Síndrome cortico-basal: caracterização clínica e imagiológica de uma série de doentes. Sinapse 2013; 13(1): 206. Publicado - Gomes F, Gonçalves A, Pinto C, Almeida E, Moreira I, Verdelho A, Silva C, Botelho L, Vila-Chã N, Mendes A, Bastos Lima A, Cavaco S. STN-DBS na Doença de Parkinson: Importância da Fluência Verbal na Selecção dos Candidatos. Sinapse 2013; 13(1): 208. Publicado - Gonçalves A, Mendes A, Moreira I, Vila-Chã N, Bastos Lima A, Cavaco S. Apatia na Doença de Parkinson. Sinapse 2013; 13(1): 210. . Publicado - Fernandes J, Moreira I, Gonçalves A, Pinto C, Almeida E, Gomes F, Damásio J, Loureiro R, Magalhães M, Cavaco S Fluência verbal na doença de Huntington. Sinapse 2013; 13(1): 212. Publicado - Pinto C, Pinto P, Cavaco S, Taipa R. Variante direita da Demência Semântica: descrição de dois casos. Sinapse 2013; 13(2): 173. Publicado - Gomes F, Pinto C, Pinto, Correia AP, Santos E, Taipa R, Cavaco S. Funcionamento cognitivo, características clínicas e imagiológicas na Demência de Alzheimer e Degenerescência Lobar Frontotemporal. Sinapse 2013; 13(2): 172. Publicado - Varanda S, Rangel R, Chaves J, Moreira B, Cavaco S, Martins da Silva A, Lopes J, Ramalheira J. Cirurgia da epilepsia com monitorização invasiva. Sinapse 2013; 13(2): 99. . Publicado - Moreira I, Vila-Chã N, Gonçalves A, Moreira Inês, Cavaco S, Bastos Lima A, Alexandre Mendes Flutuações motoras nos primeiros 5 anos da doença de Parkinson. Sinapse 2013; 13(2): 77. Publicado - Domingos J, Alves JE, Correia F, Cavaco S, Damásio J, Pessegueiro Miranda H, Magalhães M. Degenerescência hepato-cerebral adquirida: caracterização de um coorte de 26 doentes. Sinapse 2013; 13(2): 77. Publicado - Martins Silva Ana, Moreira I, Pinto C, Santos E, Samões R, Gonçalves A, Bettencourt A, Montalban X, Cavaco S. The influence of education on cognition in Multiple Sclerosis. Multiple Sclerosis 2013, 19(11 suppl): 203. Publicado - Samões R, Lopes D, Moreira I, Santos E, Fernandes J, Bettencourt A, Cavaco S, Martins Silva Ana. Smoking and age of onset in Multiple Sclerosis patients. Multiple Sclerosis 2013, 19(11 suppl): 106. Publicado - Mendes A, Gonçalves A, Vila-Chã N, Moreira I, Cavaco S, Bastos Lima. Association between gait and cognitive functioning in Parkinson’s Disease. Journal of Neurology 2013, 260 (1 supplement): S140-141. Publicado - Gonçalves A, Mendes A, Vila-Chã N, Moreira I, Moreira I, Bastos Lima A, Cavaco S. Axial symptoms and cognitive functioning in Parkinson's disease. Journal of the Neurological Sciences 2013, 333: e76. Publicado - Domingos J, Correia F, Cavaco S, Almeida A, Damasio J, Miranda HP, Magalhães M. Acquired hepatocerebral degeneration: characterization of a cohort of 17 patients. Journal of Neurology 2013, 260 (1 supplement): S62 Publicado - Domingos JP, Alves JE, Cavaco S, Ferreira S, Lopes V, Pereira JP, Moreira B, Miranda HP, Magalhães M. The role of liver transplant in the treatment of acquired hepatocerebral degeneration and hepatic encephalopathy. Journal of the Neurological Sciences 2013, 333: e78. Outras comunicações (orais ou pósteres) em reuniões internacionais: Apresentado - Domingos, R Loureiro, J Damásio, M Magalhães, P Krack, A Mendes. Symptoms Progression in a DYT1 Positive Patient with Gpi-DBS – failure of a second lead implant. 5th International Dystonia Symposium, Barcelona, October 2011. http://www.internationaldystoniasymposium.org/programa.pdf Apresentado - Sá J, Mendes A, Quelhas D, Salomons GS, Jakobs C, Soares G. Succinic Semialdehyde Dehydrogenase Deficiency: a rare disease affecting two sisters. VIII International Symposium SPDM, Porto, November 2011. Indicadores de Realização Física Neste quadro deve indicar os valores referentes ao período a que corresponde o Relatório de Progresso. Neste quadro deve apenas indicar concretizações efectivas. Não indique publicações submetidas para publicação, nem teses que ainda não tenham sido discutidas. Indicadores Quantidade realizada A - Publicações Livros 1 12 artigos originais Artigos em revistas internacionais 3 artigos listados como colaboradores Artigos em revistas nacionais 0 artigos B - Comunicações 18 resumos publicados Comunicações em encontros científicos internacionais +2 comunicações sem resumo Comunicações em encontros científicos nacionais 23 resumos publicados C - Relatórios D - Organização de seminários e conferências 1 E - Formação avançada Teses de Doutoramento 4 doutorandos Teses de Mestrado 0 Outras 0 F - Modelos 0 G - Aplicações computacionais 1 H - Instalações piloto 0 I - Protótipos laboratoriais 0 J - Patentes 0 L - Outros 8. Ficheiros Anexos (opcional) Poderá enviar, apenas se entender como estritamente necessário, ficheiros com formato PDF, que tenham sido referidos no relatório, por exemplo, gráficos, esquemas, fotografias. O conjunto dos ficheiros (em número máximo de cinco) ou o arquivo comprimido a enviar não poderão ultrapassar 10MB. Nome do ficheiro Agradecemos a sua colaboração. Ponto do Relatório de Progresso Descrição Relatório Científico Final 2011-13 – UMIB Research Group Title: Blood, lymphopoietic and haematopoietic disorders Principal Investigator: Margarida Lima Research Area: Health Sciences Home Institution: Instituto de Ciências Biomédicas Abel Salazar UMIB - FORMULÁRIO RELATÓRIO FINAL - COMPONENTE CIENTÍFICA 2011 – 2012 - 2013 Nota Informativa: Relatório de Execução Científica O Relatório de Execução Científica (pontos 2 a 9) tem de ser obrigatoriamente lacrado pelo IR no prazo de 1 mês após o envio da comunicação da FCT a solicitar o seu preenchimento, a fim de ser disponibilizado ao painel de avaliação final. O ponto 8 deve conter uma descrição pormenorizada (incluindo tabelas, quadros ou mapas) da execução dos trabalhos do projecto ao longo do período considerado, de acordo com a programação e calendarização constante na proposta aprovada, bem como análise dos desvios verificados face ao programado, a fim de permitir a avaliação dos trabalhos de investigação desenvolvidos. Deve ser feito upload de um ficheiro PDF contendo esta informação. Ficheiros anexos podem ser incluídos no ponto 9. Relatório de Execução Financeira Após conclusão da análise da execução financeira por parte da FCT, o Investigador Responsável será contactado para, no prazo de 10 dias úteis: Lacrar a Componente Financeira do Relatório Final (RF) Imprimir o Termo de Responsabilidade que, devidamente assinado e autenticado pelos subscritores e rubricado pelo Investigador Responsável em todas as páginas, deverá ser enviado por correio para a FCT, I.P. ao cuidado de: Departamento de Suporte à Rede de Instituições Científicas e Tecnológicas. Atenção - A sessão expira ao fim de 20 minutos de inactividade; - O formato da data a utilizar é dd-mm-yyyy; - No Ponto 8, o tamanho máximo do ficheiro em PDF é de 5MB; - No Ponto 9, a soma do tamanho dos ficheiros PDF não pode exceder 10MB! Caso não consiga fazer o Upload dos ficheiros é favor contactar [email protected] Componente Financeira do Relatório Final (RF) Nota: Os dados que surgem nos quadros da Componente Financeira do Relatório Final são provisórios, até à conclusão da análise da execução por parte da FCT. 1. Identificação do Projecto Referência do Projecto: PEst-OE/SAU/UI0215/2011 Investigador Responsável: Paulo Jorge Silva Correia Sa Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP) Data de Início: 01-01-2011 Data de Fim: 31-12-2013 2. Caracterização Sumária do Projecto Objectivos do Projecto (indicar endereço electrónico do(s) site(s) criado(s), quando aplicável) Breve descrição das actividades desenvolvidas bem como dos desvios ocorridos durante a execução do projecto Objectivos atingidos Realização Financeira (justificação sumária dos desvios ocorridos durante a execução do projecto) 3. Instituições que Participam no Projecto Designação Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP) Centro Hospitalar do Porto, EPE (CHP/MS) Nº Pessoas Mês 14289 0 14290 0 Lista de membros da equipa (preenchido automaticamente) PhD = 4 1. Ana Paula Guimarães da Mota, graduated in Clinical Analysis, PhD in Biomedical Sciences 2. Magdalena Ann Leander, graduated in Pharmaceutical Sciences, PhD in Biomedical Sciences 3. Margarida Maria de Carvalho Lima, MD, PhD in Medical Sciences 4. Maria Beatriz Beça Gonçalves Porto e Vasconcelos, graduated in Biology, PhD in Human Genetics MhD = 9 + 1 = 10 Desistiu 1. Ana Helena Ribeiro Santos, graduated in Clinical Analysis, graduated in History of Art, MsD in Health Organization Management. 2. Cláudia Angelina Borges Torres, graduated in Biochemistry, MsD in Biochemistry, PhD student (ICBAS/UP) 3. Ivette Conceição Filipe Fernandes de Lima, graduated in Pharmaceutical Sciences, MsD in Pharmaceutical Sciences 4. João Bernardo Coelho Pinho Sousa Rodrigues, graduated in Microbiology, MsD in Microbiology 5. Maria Esmeralda de Azevedo Rodrigues Neves, MD (Clinical Pathology), MsD in Clinical Pathology and Chemistry, PhD student (ICBAS/UP) 6. Maria Luís Araújo Queirós, graduated in Pharmaceutical Sciences, MsD in Pharmaceutical Sciences, PhD student (FF/UP) 7. Marlene Araújo dos Santos, graduated in Clinical Analysis, MsD in Clinical Analysis 8. Marta Marina Melo Gomes, graduated in Clinical Analysis, MsD in Clinical Analysis 9. Mónica Cristina Teixeira Pereira, graduated in Biochemistry, MsD in Molecular Genetics, PhD student (ICBAS/UP) 10. Paula Cristina dos Santos Lino Carneiro, graduated in Pharmaceutical Sciences, MsD in Clinical Analysis GRADUATED = 15 + 5 = 20 1. Fernanda José Teixeira Leite, MD (Immunohemotherapy), PhD student (FM/UP) 2. José Alberto Barcelos de Morais Barbot MD (Clinical Hematology) (*) 3. Júlia Maria Andrade Mendes de Vasconcelos, MD (Clinical Pathology) 4. Laura Elvira Gonçalves Novo da Hora Marques, MD (Pediatrics) 5. Manuel César Santos Araújo de Campos, MD (Clinical Hematology) 6. Margarida Maria dos Santos Guedes Carolino, MD (Pediatrics) 7. Margarida Sara Mendes Moreira MD (Psichiatry) (*) 8. Maria Catarina Panelas Nunes Lau, MD (Immunohemotherapy) 9. Maria da Conceição Ramos de Morais Cerveira, MD (Clinical Pathology) (*) 10. Maria de Lurdes Baptista de Oliveira Marques Fino, graduated in Clinical Analysis, graduated in Pharmacia 11. Maria del Rosário Alves dos Santos, MD (Dermatology, Dermatopathology) 12. Maria dos Anjos Coutinho Teixeira, MD (Immunohemotherapy) 13. Maria Fernanda Soares Teixeira, MD (Pediatrics) 14. Maria Inês Oliveira Azevedo Freitas, MD (Clinical Pathology) (*) 15. Maria Judite Varela de Almeida Guimarães, graduated in Pharmaceutical Sciences 16. Maria Luciana Gomes de Pinho, MD (Clinical Pathology) (*) 17. Marika Mónica Bini Antunes, MD (Immunohemotherapy) 18. Marta Sofia da Cunha Gonçalves, graduated in Biochemistry 19. Sara Maria Teixeira Simões Morais, MD (Immunohemotherapy) 20. Sónia Cristina Pinho da Fonseca, graduated in Clinical Analysis (*) Estiveram integrados no período 2011-2013, mas deixaram de estar em 2014 5. Indicadores de Realização Física Indicadores A - Publicações 2011 2012 2013 Quantidade realizada 25 38 18 81 Livros 1 1 0 2 Artigos em revistas internacionais 22 33 13 68 Artigos em revistas nacionais 2 4 5 11 B - Comunicações 78 70 13 161 Comunicações em encontros científicos 26 24 6 52 46 7 1 1 1 11 10 8 internacionais Comunicações em encontros científicos nacionais C - Relatórios D - Organização de seminários e conferências 56 105 3 29 E - Formação avançada 1 1 1 3 Teses de Doutoramento 1 0 0 1 Teses de Mestrado 0 1 1 2 Outras 0 0 0 0 F - Modelos 0 0 0 0 G - Aplicações computacionais 0 0 0 0 H - Instalações piloto 0 0 0 0 I - Protótipos laboratoriais 0 0 0 0 J - Patentes 0 0 0 0 L - Outros 0 0 0 0 6. Publicações Ano Publicações 2013 A CASE OF HEPATOPULMONARY SYNDROME SOLVED BY MYCOPHENOLATE MOFETIL (AN INHIBITOR OF ANGIOGENESIS AND NITRIC OXIDE PRODUCTION). Moreira Silva H, Reis G, Guedes M, Cleto E, Vizcaíno JR, Kelly D, Gennery AR, Santos Silva E. J Hepatol. 2013 Mar;58(3):630-3. doi: 10.1016/j.jhep.2012.10.021. Epub 2012 Oct 24. No abstract available. URL http://www.ncbi.nlm.nih.gov/pubmed/?term=23104163 PMID: 23104163 2013 A DRAMATIC CASE OF BEHÇET http://www.ncbi.nlm.nih.gov/pubmed/?term=24021377 DISEASE SUCCESSFULLY TREATED WITH INFLIXIMAB. PintoAlmeida T, Amorim I, Alves R, Selores M. Dermatol Online J. 2013 Apr 15;19(4):18187. PMID: 24021377. 2013 A NOVEL SYNDROME OF http://www.ncbi.nlm.nih.gov/pubmed/?term=23553769 CONGENITAL SIDEROBLASTIC ANEMIA, B-CELL IMMUNODEFICIENCY, PERIODIC FEVERS, AND DEVELOPMENTAL DELAY (SIFD). Wiseman DH, May A, Jolles S, Connor P, Powell C, Heeney MM, Giardina PJ, Klaassen RJ, Chakraborty P, Geraghty MT, MajorCook N, Kannengiesser C, Thuret I, Thompson AA, Marques L, Hughes S, Bonney DK, Bottomley SS, Fleming MD, Wynn RF. Blood. 2013 Jul 4;122(1):112-23. doi: 10.1182/blood-2012-08-439083. Epub 2013 Apr 3. PMID: 23553769 2013 AGGRESSIVE MATURE NATURAL http://www.ncbi.nlm.nih.gov/pubmed/?term=23816348 KILLER CELL NEOPLASMS: FROM EPIDEMIOLOGY TO DIAGNOSIS. Lima M. Orphanet J Rare Dis. 2013 Jul 1;8:95. doi: 10.1186/1750-1172-895. PMID: 23816348 2013 BONE MARROW CELL TRANSCRIPTS FROM FANCONI ANAEMIA PATIENTS REVEAL IN VIVO ALTERATIONS IN MITOCHONDRIAL, REDOX AND DNA REPAIR PATHWAYS.Pagano G, Talamanca AA, Castello G, http://www.ncbi.nlm.nih.gov/pubmed/?term=23646927 d'Ischia M, Pallardó FV, Petrović S, Porto B, Tiano L, Zatterale A. Eur J Haematol. 2013 Aug;91(2):141-51. doi: 10.1111/ejh.12131. Epub 2013 Jun 15. PMID: 23646927 2013 BROADENED T-CELL REPERTOIRE http://www.ncbi.nlm.nih.gov/pubmed/?term=23064977 DIVERSITY IN IVIG-TREATED SLE PATIENTS IS ALSO RELATED TO THE INDIVIDUAL STATUS OF REGULATORY T-CELLS. Costa N, Pires AE, Gabriel AM, Goulart LF, Pereira C, Leal B, Queiros AC, Chaara W, Moraes-Fontes MF, Vasconcelos C, Ferreira C, Martins J, Bastos M, Santos MJ, Pereira MA, Martins B, Lima M, João C, Six A, Demengeot J, Fesel C. J Clin Immunol. 2013 Feb;33(2):349-60. doi: 10.1007/s10875-012-9816-7. Epub 2012 Oct 14. PMID: 23064977 2013 CYTOGENETIC AND http://www.ncbi.nlm.nih.gov/pubmed/?term=23514064 IMMUNOLOGICAL EFFECTS ASSOCIATED WITH OCCUPATIONAL FORMALDEHYDE EXPOSURE. Costa S, García-Lestón J, Coelho M, Coelho P, Costa C, Silva S, Porto B, Laffon B, Teixeira JP. J Toxicol Environ Health A. 2013;76(4-5):217-29. doi: 10.1080/15287394.2013.757212. PMID: 23514064 2013 FOSFOMYCIN INCREASES http://www.ncbi.nlm.nih.gov/pubmed/?term=23624100 CHROMOSOME INSTABILITY IN LYMPHOCYTES FROM FANCONI ANEMIA PATIENTS. Sousa R, Ponte F, Teixeira S, Andrade L, Gonçalves C, Barbot J, Coutinho J, Carvalho F, Porto B. Mutat Res. 2013 Jun 14;754(1-2):58-62. doi: 10.1016/j.mrgentox.2013.04.005. Epub 2013 Apr 25. PMID: 23624100 2013 FROM CLINICAL DESCRIPTION, TO http://www.ncbi.nlm.nih.gov/pubmed/?term=23376230 IN VITRO AND ANIMAL STUDIES, AND BACKWARD TO PATIENTS: OXIDATIVE STRESS AND MITOCHONDRIAL DYSFUNCTION IN FANCONI ANEMIA. Pagano G, Talamanca AA, Castello G, d'Ischia M, Pallardó FV, Petrović S, Porto B, Tiano L, Zatterale A. Free Radic Biol Med. 2013 May;58:118-25. doi: 10.1016/j.freeradbiomed.2013.01.015. Epub 2013 Jan 29. PMID: 23376230 2013 GROUP B STREPTOCOCCUS http://www.ncbi.nlm.nih.gov/pubmed/?term=23658816 HIJACKS THE HOST PLASMINOGEN SYSTEM TO PROMOTE BRAIN ENDOTHELIAL CELL INVASION. Magalhães V, Andrade EB, Alves J, Ribeiro A, Kim KS, Lima M, Trieu-Cuot P, Ferreira P. PLoS One. 2013 May 2;8(5):e63244. doi: 10.1371/journal.pone.0063244. PMID: 23658816 2013 IMMUNOGLOBULIN DEFICIENCIES: http://www.ncbi.nlm.nih.gov/pubmed/?term=22809661 THE B-LYMPHOCYTE SIDE OF DiGEORGE SYNDROME. Patel K, Akhter J, Kobrynski L, Benjamin Gathmann MA, Davis O, Sullivan KE; International DiGeorge Syndrome Immunodeficiency Consortium. (Marques L). J Pediatr. 2012 Nov;161(5):950-3. doi: 10.1016/j.jpeds.2012.06.018. Epub 2012 Jul 17. Erratum in: J Pediatr. 2013 Mar;162(3):658. Gathman, Benjamin [corrected to Benjamin Gathmann, M A]. PMID: 22809661 2013 IRON DEFICIENCY ANEMIA DUE TO LYMPHOCYTIC GASTRITIS WITH HELICOBACTER PYLORI INFECTION IN CHILDHOOD: CASE REPORT. Santalha MF Jr, Costa E, Miguel N, Vizcaíno R, Barbot J, Pereira F. J Pediatr Hematol Oncol. http://www.ncbi.nlm.nih.gov/pubmed/?term=23528908 2013 May;35(4):321-2. doi: 10.1097/MPH.0b013e318286d129. PMID: 23528908 2013 CARACTERIZAÇÃO DAS INFEÇÕES http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_arttext&pid=S0872-07542013000100002&lng=en&nrm=iso EM DOENTES COM SÍNDROME DE DELECÇÃO 22q11. Oliveira M, Teixeira C, Vasconcelos J, Neves E, Álvares S, Guedes M, Marques L. Nascer e Crescer 2013; 22(1): 8-11. ISSN 0872-0754. 2013 MASTOIDITE AGUDA: AUMENTO http://revistas.rcaap.pt/app/article/view/498/2388 DA INCIDÊNCIA E DAS COMPLICAÇÕES? Silva HM, Zilhão C, Soares T, Coutinho M, Senra V, Guedes M. Acta Pediatr Port 2013; 44: 25-9. 2013 NEUTROPENIA IN A PATIENT WITH http://www.journalmc.org/index.php/JMC/article/view/1176/726 RHEUMATOID ARTHRITIS ASSOCIATED WITH ab/gd T-CELL LARGE GRANULAR LYMPHOCYTE LYMPHOPROLIFERATIVE DISORDER MANIFESTING AS FELTY’S SYNDROME: FROM DIAGNOSIS TO THERAPY. Cabral R, Lau C, Rodrigues J, Lima M. J Med Cases • 2013;4(6):450-457. doi: http://dx.doi.org/10.4021/jmc1176w 2013 O IMPACTO DO RISCO SOCIAL http://revistas.rcaap.pt/app/article/view/2941/2386 NUM INTERNAMENTO PEDIÁTRICO. Nascimento J, Ferreira I, Zilhão C, Pinto S, Ferreira C, Caldas L, Guedes M, Senra V. Acta Pediatr Port 2013; 44(1):15-9. 2013 REMÉDIO SEM RECEITA. Guedes M. Nascer e Crescer 2013; 22(2):130130. ISSN 0872-0754. http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_arttext&pid=S0872-07542013000200016&lng=en&nrm=iso 2012 [ANTICOAGULATION CLINICS, http://www.ncbi.nlm.nih.gov/pubmed/?term=22541036 PRESENT SITUATION AND FUTURE PERSPECTIVES]. Cruz E, Campos M. Rev Port Cardiol. 2012 Apr;31 Suppl 1:51-7. Portuguese. PMID: 22541036 2012 A CASE OF BLASTIC http://www.ncbi.nlm.nih.gov/pubmed/?term=22577284 PLASMACYTOID DENDRITIC CELL NEOPLASM. Pinto-Almeida T, Fernandes I, Sanches M, Lau C, Lima M, Alves R, Selores M. Ann Dermatol. 2012 May;24(2):235-7. doi: 10.5021/ad.2012.24.2.235. Epub 2012 Apr 26. No abstract available. PMID: 22577284 2012 ADAMS-OLIVER SYNDROME AND http://www.ncbi.nlm.nih.gov/pubmed/?term=22307742 PORTAL HYPERTENSION: FORTUITOUS ASSOCIATION OR COMMON MECHANISM? Silva G, Braga A, Leitão B, Mesquita A, Reis A, Duarte C, Barbot J, Silva ES. Am J Med Genet A. 2012 Mar;158A(3):648-51. doi: 10.1002/ajmg.a.34435. Epub 2012 Feb 3. PMID: 22307742 2012 APREPITANT: EVIDENCE OF ITS http://www.ncbi.nlm.nih.gov/pubmed/?term=22177649 EFFECTIVENESS IN PATIENTS WITH REFRACTORY PRURITUS CONTINUES. Torres T, Fernandes I, Selores M, Alves R, Lima M. J Am Acad Dermatol. 2012 Jan;66(1):e145. doi: 10.1016/j.jaad.2011.01.016. No abstract available. PMID: 22177649 2012 CAN THE LEVEL OF CD52 EXPRESSION ON SÉZARY CELLS BE USED TO PREDICT THE RESPONSE OF SÉZARY SYNDROME TO ALEMTUZUMAB? Fernandes IC, Gonçalves M, dos Anjos Teixeira M, Gonçalves C, Coutinho J, Selores M, Alves R, Lima M. J Am Acad Dermatol. 2012 http://www.ncbi.nlm.nih.gov/pubmed/?term=23062898 Nov;67(5):1083-5. doi: 10.1016/j.jaad.2012.05.010. No abstract available. PMID: 23062898 2012 CASE FOR DIAGNOSIS. Fernandes http://www.ncbi.nlm.nih.gov/pubmed/?term=23197221 IC, Sanches M, Alves R, Selores M. An Bras Dermatol. 2012 NovDec;87(6):933-5. PMID: 23197221 2012 CD8-POSITIVE PRIMARY http://www.ncbi.nlm.nih.gov/pubmed/?term=22062773 CUTANEOUS PERIPHERAL T-CELL LYMPHOMA, UNSPECIFIED. Rosmaninho A, Sanches M, Alves R, Lima M, Selores M. Eur J Dermatol. 2012 Jan-Feb;22(1):131-2. doi: 10.1684/ejd.2011.1564. No abstract available. PMID: 22062773 2012 COMPLETE RESOLUTION OF http://www.ncbi.nlm.nih.gov/pubmed/?term=22693017 ZOON BALANITIS WITH PHOTODYNAMIC THERAPY--A NEW THERAPEUTIC OPTION? Pinto-Almeida T, Vilaça S, Amorim I, Costa V, Alves R, Selores M. Eur J Dermatol. 2012 Jul-Aug;22(4):540-1. doi: 10.1684/ejd.2012.1779. No abstract available. PMID: 22693017 2012 DEMOGRAPHIC AND CLINICAL http://www.ncbi.nlm.nih.gov/pubmed/?term=22321904 DATA IN ACQUIRED HEMOPHILIA A: RESULTS FROM THE EUROPEAN ACQUIRED HAEMOPHILIA REGISTRY (EACH2). Knoebl P, Marco P, Baudo F, Collins P, Huth-Kühne A, Nemes L, Pellegrini F, Tengborn L, Lévesque H; EACH2 Registry Contributors (Campos M). J Thromb Haemost. 2012 Apr;10(4):622-31. doi: 10.1111/j.15387836.2012.04654.x. PMID: 22321904 2012 ERYTHROPHAGOCYTOSIS BY NEUTROPHILS IN PAROXYSMAL COLD HAEMOGLOBINURIA. Santos F, Costa E, Pinto RM, Barbot J, Freitas I. Eur J Haematol. 2012 Oct;89(4):371. doi: 10.1111/j.1600- http://www.ncbi.nlm.nih.gov/pubmed/?term=22823511 0609.2012.01829.x. Epub 2012 Aug 2. No abstract available. PMID: 2282,3511 2012 EUROFLOW ANTIBODY PANELS http://www.ncbi.nlm.nih.gov/pubmed/?term=22552007 FOR STANDARDIZED NDIMENSIONAL FLOW CYTOMETRIC IMMUNOPHENOTYPING OF NORMAL, REACTIVE AND MALIGNANT LEUKOCYTES. van Dongen JJ, Lhermitte L, Böttcher S, Almeida J, van der Velden VH, Flores-Montero J, Rawstron A, Asnafi V, Lécrevisse Q, Lucio P, Mejstrikova E, Szczepański T, Kalina T, de Tute R, Brüggemann M, Sedek L, Cullen M, Langerak AW, Mendonça A, Macintyre E, Martin-Ayuso M, Hrusak O, Vidriales MB, Orfao A; EuroFlow Consortium (EU-FP6, LSHB-CT2006-018708) (Lima M, Santos AH). Leukemia. 2012 Sep;26(9):1908-75. doi: 10.1038/leu.2012.120. Epub 2012 May 3. PMID: 22552007 2012 EXUBERANT CUTANEOUS http://www.ncbi.nlm.nih.gov/pubmed/?term=22948065 ULCERS ON THE BUTTOCKS CAUSED BY MULTI-RESISTANT KLEBSIELLA PNEUMONIAE. PintoAlmeida T, Rosmaninho A, Lobo I, Alves R, Selores M. Dermatol Online J. 2012 Aug 15;18(8):15. PMID: 22948065 2012 HB IBERIA [Α104(G11)CYS → ARG,TGC>CGC (Α2) (HBA2:C.313T>C)], A NEW ΑTHALASSEMIC HEMOGLOBIN VARIANT FOUND IN THE IBERIAN PENINSULA: REPORT OF SIX CASES. Bento C, Oliveira AC, Neves J, Gameiro M, Cunha E, Coucelo M, Costa RM, Barbot J, Costa E, Fernández-Lago C, Ribeiro ML. http://www.ncbi.nlm.nih.gov/pubmed/?term=23181747 Hemoglobin. 2012;36(6):517-25. doi: 10.3109/03630269.2012.742911. PMID: 23181747 2012 HAEMOPHILIA CARE IN EUROPE: http://www.ncbi.nlm.nih.gov/pubmed/?term=22639833 THE ESCHQoL STUDY. Schramm W, Gringeri A, Ljung R, Berger K, Crispin A, Bullinger M, Giangrande PL, Von Mackensen S, Mantovani LG, Nemes L, Serban M; ESCHQOL Study Group.(Campos M) Haemophilia. 2012 Sep;18(5):729-37. doi: 10.1111/j.1365-2516.2012.02847.x. Epub 2012 May 29. PMID: 22639833 2012 IgM+IgD+CD27+ B CELLS ARE http://www.ncbi.nlm.nih.gov/pubmed/?term=23002119 MARKEDLY REDUCED IN IRAK-4-, MYD88-, AND TIRAP- BUT NOT UNC-93B-DEFICIENT PATIENTS. Weller S, Bonnet M, Delagreverie H, Israel L, Chrabieh M, Maródi L, Rodriguez-Gallego C, Garty BZ, Roifman C, Issekutz AC, Zitnik SE, Hoarau C, Camcioglu Y, Vasconcelos J, Rodrigo C, Arkwright PD, Cerutti A, Meffre E, Zhang SY, Alcais A, Puel A, Casanova JL, Picard C, Weill JC, Reynaud CA. Blood. 2012 Dec 13;120(25):4992-5001. doi: 10.1182/blood-2012-07-440776. Epub 2012 Sep 21. PMID: 23002119 2012 IMMUNOSUPPRESSION FOR ACQUIRED HEMOPHILIA A: RESULTS FROM THE EUROPEAN ACQUIRED HAEMOPHILIA REGISTRY (EACH2). Collins P, Baudo F, Knoebl P, Lévesque H, Nemes L, Pellegrini F, Marco P, Tengborn L, Huth-Kühne A; EACH2 registry collaborators (Campos M). Blood. 2012 Jul 5;120(1):47-55. doi: http://www.ncbi.nlm.nih.gov/pubmed/?term=22517903 10.1182/blood-2012-02-409185. Epub 2012 Apr 18. PMID: 22517903 2012 IMPROVEMENT OF GENETIC http://www.ncbi.nlm.nih.gov/pubmed/?term=22591656 STABILITY IN LYMPHOCYTES FROM FANCONI ANEMIA PATIENTS THROUGH THE COMBINED EFFECT OF Α-LIPOIC ACID AND N-ACETYLCYSTEINE. Ponte F, Sousa R, Fernandes AP, Gonçalves C, Barbot J, Carvalho F, Porto B. Orphanet J Rare Dis. 2012 May 16;7:28. doi: 10.1186/1750-11727-28. PMID: 22591656 2012 INFANTILE PYKNOCYTOSIS: AN http://www.ncbi.nlm.nih.gov/pubmed/?term=23253864 UNDER-RECOGNIZED FORM OF NEONATAL HEMOLYTIC ANEMIA? Coutinho M, Costa E, Monteiro T, Silva G, Costa H, Guedes A, Freitas I, Barbot J. Lab Hematol. 2012 Dec;18(4):27-9. doi: 10.1532/LH96.12005. PMID: 23253864 2012 JUVENILE GANGRENOUS http://www.ncbi.nlm.nih.gov/pubmed/?term=22796721 VASCULITIS OF THE SCROTUM: AN EXCEPTIONAL CAUSE OF SCROTAL ULCERS. Pinto-Almeida T, Rosmaninho A, Lobo I, Alves R, Selores M. Eur J Dermatol. 2012 SepOct;22(5):689-90. doi: 10.1684/ejd.2012.1804. No abstract available. PMID: 22796721 2012 KAWASAKI DISEASE AND SENSORINEURAL HEARING LOSS: AN (UN)EXPECTED COMPLICATION. Novo A, Pinto S, Prior AC, Alvares S, Soares T, Guedes M. Eur J Pediatr. 2012 May;171(5):851-4. doi: http://www.ncbi.nlm.nih.gov/pubmed/?term=22227968 10.1007/s00431-011-1667-3. Epub 2012 Jan 7. PMID: 22227968 2012 LETTER: PRIMARY CUTANEOUS http://www.ncbi.nlm.nih.gov/pubmed/?term=22398233 MARGINAL ZONE B CELL LYMPHOMA OF THE FACE: A CHALLENGING DIAGNOSIS. Oliveira A, Caetano M, Alves R, Lima M, Selores M. Dermatol Online J. 2012 Feb 15;18(2):12. PMID: 22398233 2012 LICHEN PLANUS PEMPHIGOIDES http://www.ncbi.nlm.nih.gov/pubmed/?term=22645288 IN A CHILD. Conde Fernandes I, Pinto Almeida T, Mendes I, Cunha Velho G, Alves R, Selores M. Eur J Dermatol. 2012 Jul-Aug;22(4):570-1. doi: 10.1684/ejd.2012.1764. No abstract available. PMID: 22645288 2012 MANAGEMENT OF BLEEDING IN http://www.ncbi.nlm.nih.gov/pubmed/?term=22618709 ACQUIRED HEMOPHILIA A: RESULTS FROM THE EUROPEAN ACQUIRED HAEMOPHILIA (EACH2) REGISTRY. Baudo F, Collins P, HuthKühne A, Lévesque H, Marco P, Nemes L, Pellegrini F, Tengborn L, Knoebl P; EACH2 registry contributors (Campos M). Blood. 2012 Jul 5;120(1):39-46. doi: 10.1182/blood-2012-02-408930. Epub 2012 May 22. PMID: 22618709 2012 MULTIPLE GENOTOXIC ACTIVITIES http://www.ncbi.nlm.nih.gov/pubmed/?term=22565221 OF PTAQUILOSIDE IN HUMAN LYMPHOCYTES: ANEUGENESIS, CLASTOGENESIS AND INDUCTION OF SISTER CHROMATID EXCHANGE. Gil da Costa RM, Coelho P, Sousa R, Bastos MM, Porto B, Teixeira JP, Malheiro I, Lopes C. Mutat Res. 2012 Aug 30;747(1):77-81. doi: 10.1016/j.mrgentox.2012.04.010. Epub 2012 Apr 28. PMID: 22565221 2012 NEONATAL ALLOIMMUNE http://www.ncbi.nlm.nih.gov/pubmed/?term=22995923 NEUTROPENIA: STILL A DIAGNOSTIC AND THERAPEUTICAL CHALLENGE. Águeda S, Rocha G, Ferreira F, Vítor B, Lima M, Guimarães H. J Pediatr Hematol Oncol. 2012 Oct;34(7):497-9. PMID: 22995923 2012 PREGNANCY-ASSOCIATED http://www.ncbi.nlm.nih.gov/pubmed/?term=22901076 ACQUIRED HAEMOPHILIA A: RESULTS FROM THE EUROPEAN ACQUIRED HAEMOPHILIA (EACH2) REGISTRY. Tengborn L, Baudo F, Huth-Kühne A, Knoebl P, Lévesque H, Marco P, Pellegrini F, Nemes L, Collins P; EACH2 registry contributors (Campos M). BJOG. 2012 Nov;119(12):1529-37. doi: 10.1111/j.1471-0528.2012.03469.x. Epub 2012 Aug 20. PMID: 22901076 2012 PROLIFERATING TRICHILEMMAL http://www.ncbi.nlm.nih.gov/pubmed/?term=23197215 TUMOR OF THE NOSE. Rosmaninho A, Caetano M, Oliveira A, Pinto de Almeida T, Selores M, Alves R. An Bras Dermatol. 2012 NovDec;87(6):914-6. PMID: 23197215 2012 SYSTEMIC LUPUS http://www.ncbi.nlm.nih.gov/pubmed/?term=22674017 ERYTHEMATOSUS, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, AND TCD4+ LYMPHOPENIA. Brandão M, Damásio J, Marinho A, da Silva AM, Vasconcelos J, Neves E, Almeida I, Farinha F, Vasconcelos C. Clin Rev Allergy Immunol. 2012 Dec;43(3):3027. doi: 10.1007/s12016-012-8327-x. PMID: 22674017 2012 THE CIRCULATING PLATELET COUNT IS NOT DICTATED BY THE LIVER, BUT MAY BE DETERMINED IN PART BY THE BONE MARROW – ANALYSES FROM HUMAN LIVER http://www.ncbi.nlm.nih.gov/pubmed/?term=22642442 AND STEM CELL TRANSPLANTATIONS. Lisman T, Pittau G, Leite FJT, de Bóer MT, Kluin-Nelemans H, Huls G, te Boone LCJ, Kuball J, Nowak G, Fan ST, Azoulay D, Porte RJ. J Thromb Haemost 2012;10(8):1624-30. PMID 22642442 2012 TWO NOVEL MUTATIONS IN THE http://www.ncbi.nlm.nih.gov/pubmed/?term=22765023 TMPRSS6 GENE ASSOCIATED WITH IRON-REFRACTORY IRONDEFICIENCY ANAEMIA (IRIDA) AND PARTIAL EXPRESSION IN THE HETEROZYGOUS FORM. Pellegrino RM, Coutinho M, D'Ascola D, Lopes AM, Palmieri A, Carnuccio F, Costa M, Zecchina G, Saglio G, Costa E, Barbot J, Porto G, Pinto JP, Roetto A. Br J Haematol. 2012 Sep;158(5):668-72. doi: 10.1111/j.1365-2141.2012.09198.x. Epub 2012 Jul 5. No abstract available. PMID: 22765023 2012 USE OF HYBRID CHITOSAN MEMBRANES AND HUMAN MESENCHYMAL STEM CELLS FROM THE WHARTON JELLY OF UMBILICAL CORD FOR PROMOTING NERVE REGENERATION IN AN AXONOTMESIS RAT MODEL. Gärtner A, Pereira T, Simões, Armada-da-Silva PA, França ML, Sousa R, Bompasso S, Raimondo S, Shirosaki Y, Kakamura Y, Hayakawa S, Osakah A, Porto B, Luís AL, Varejão AS, Maurício AC. Neural Regeneration Research, 7(29), 22472258. doi:10.3969/j.issn.16735374.2012.29.002 http://www.crter.org/nrr-2012-qkquanwen.html 2012 USE OF POLY(DL-LACTIDE-Ε- http://www.ncbi.nlm.nih.gov/pubmed/?term=23142731 CAPROLACTONE) MEMBRANES AND MESENCHYMAL STEM CELLS FROM THE WHARTON'S JELLY OF THE UMBILICAL CORD FOR PROMOTING NERVE REGENERATION IN AXONOTMESIS: IN VITRO AND IN VIVO ANALYSIS. Gärtner A, Pereira T, Alves MG, Armada-da-Silva PA, Amorim I, Gomes R, Ribeiro J, França ML, Lopes C, Carvalho RA, Socorro S, Oliveira PF, Porto B, Sousa R, Bombaci A, Ronchi G, Fregnan F, Varejão AS, Luís AL, Geuna S, Maurício AC. Differentiation. 2012 Dec;84(5):355-65. doi: 10.1016/j.diff.2012.10.001. PMID: 23142731 2012 VESICO-BULLOUS SUBACUTE http://www.ncbi.nlm.nih.gov/pubmed/?term=22948063 CUTANEOUS LUPUS ERYTHEMATOSUS--AN UNCOMMON ENTITY SUCCESSFULLY TREATED WITH DAPSONE AND HYDROXYCHLOROQUINE. PintoAlmeida T, Sanches M, Alves R, Selores M. Dermatol Online J. 2012 Aug 15;18(8):13. PMID: 22948063 2012 CONTRACEÇÃO PARA ADOLESCENTES COM LÚPUS http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_arttext&pid=S087207542012000200004&lng=en&nrm=iso ERITEMATOSO SISTÉMICO. Couto C, Sousa H, Guedes M. Nascer e Crescer 2012; 21(2): 86-91. ISSN 0872-0754. 2012 FEBRE DE ETIOLOGIA INDETERMINADA – ENCRUZILHADA DE DIAGNÓSTICOS. Oliveira M, Meireles C, Costa P, Guedes M, Lobo A. Nascer e Crescer 2012; 21: 54-57. ISSN 0872-0754 http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_arttext&pid=S087207542012000100011&lng=en&nrm=iso 2012 INFECÇÃO POR H1N1 NUM SERVIÇO DE PEDIATRIA. http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_arttext&pid=S087207542012000100002&lng=en&nrm=iso Magalhães J, Pinho L, Mendes C, Dias, Zilhão A, Garrido C, Pinto S, Reis G, Guedes M. Nascer e Crescer 2012; 21: 8-12. ISSN 0872-0754 2012 UM CERTO SENTIDO DE HUMOR… http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_arttext&pid=S0872Guedes M. Nascer e Crescer 2012; 07542012000400016&lng=en&nrm=iso 21(4): 268-268. ISSN 0872-0754. 2011 ACINETOBACTER COMMUNITY- http://www.ncbi.nlm.nih.gov/pubmed/?term=21963110 ACQUIRED PNEUMONIA IN A HEALTHY CHILD. Moreira Silva G, Morais L, Marques L, Senra V. Rev Port Pneumol. 2011 Sep 28. [Epub ahead of print] English, Portuguese. PMID: 21963110 2011 AUTOIMMUNE http://www.ncbi.nlm.nih.gov/pubmed/?term=22525637 LYMPHOPROLIFERATIVE SYNDROME. Rodrigues V, Conde M, Figueiredo A, Vasconcelos J, Dias A. Acta Med Port. 2011 SepOct;24(5):833-6. Epub 2011 Dec 29. Portuguese. PMID: 22525637 2011 CHRONIC LIVER DISEASE AND http://www.ncbi.nlm.nih.gov/pubmed/?term=21108341 CIRRHOSIS AMONG PATIENTS WITH HEPATITIS B VIRUS INFECTION IN NORTHERN PORTUGAL WITH REFERENCE TO THE VIRAL GENOTYPES. Mota A, Areias J, Cardoso MF. J Med Virol. 2011 Jan;83(1):71-7. doi: 10.1002/jmv.21939. PMID: 21108341 2011 ERYTHROPOIESIS VERSUS INFLAMMATION IN HEREDITARY SPHEROCYTOSIS CLINICAL OUTCOME. Rocha S, Costa E, Rocha-Pereira P, Ferreira F, Cleto E, Barbot J, Quintanilha A, Belo L, Santos-Silva A. Clin Biochem. 2011 Sep;44(13):1137-43. doi: 10.1016/j.clinbiochem.2011.06.006. Epub 2011 Jun 17. PMID: 21704613 http://www.ncbi.nlm.nih.gov/pubmed/?term=21704613 2011 FANCONI ANEMIA: CYTOGENETIC http://www.ncbi.nlm.nih.gov/pubmed/?term=22015027 DIAGNOSIS OF 40 CASES. Porto B, Sousa R, Ponte F, Torgal A, Campilho F, Campos A, Gonçalves C, Barbot J. Acta Med Port. 2011 MayJun;24(3):405-12. Epub 2011 Aug 12. Portuguese. PMID: 22015027 2011 GIANT CUTANEOUS HORN ON THE http://www.ncbi.nlm.nih.gov/pubmed/?term=22233746 LOWER LIP. Pinto-Almeida T, Oliveira A, da Cunha Velho G, Alves R, Caetano M, Selores M. Dermatol Online J. 2011 Dec 15;17(12):10. PMID: 22233746 2011 GIANT MERKEL CELL CARCINOMA. http://www.ncbi.nlm.nih.gov/pubmed/?term=21622090 Pinto-Almeida T, Oliveira A, Sanches M, Alves R, Caetano M, Selores M. Eur J Dermatol. 2011 JulAug;21(4):603-4. doi: 10.1684/ejd.2011.1,367. No abstract available. PMID: 21622090 2011 GRANULOMA ANNULARE OF THE http://www.ncbi.nlm.nih.gov/pubmed/?term=21543288 PENIS - SUBCUTANEOUS PRESENTATION. Pinto-Almeida T, Torres T, Sanches M, Alves R, Selores M. Eur J Dermatol. 2011 May-Jun;21(3):448-9. doi: 10.1684/ejd.2011.1353. No abstract available. PMID: 21543288 2011 HEPATITIS B GENOTYPE http://www.ncbi.nlm.nih.gov/pubmed/?term=22521016 DISTRIBUTION IN PORTUGAL AND WORLDWIDE. Mota A, Areias J, Cardoso MF. Acta Med Port. 2011 Jul-Aug;24(4):587-94. Epub 2011 Dec 12. Review. Portuguese. PMID: 22521016 2011 IMUNODEFICIÊNCIA COMBINADA http://www.spp.pt/Userfiles/File/App/Artigos/27/20110729093843_CasoClinico_Teixeira_C_42(2).pdf GRAVE: A IMPORTÂNCIA DO DIAGNÓSTICO PRECOCE. Teixeira C, Sizenando Cunha J, Carvalho C, Martinho I, Vasconcelos J, Marques L. Acta Ped Port, 2011;. 42(2): 67-70. 2011 LETTER: PENILE KAPOSI http://www.ncbi.nlm.nih.gov/pubmed/?term=21696692 SARCOMA: A CASE OF COMPLETE RESOLUTION WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ALONE. Pinto-Almeida T, Torres T, Rosmaninho A, Sanches M, Alves R, Caetano M, Selores M. Dermatol Online J. 2011 Jun 15;17(6):12. PMID: 21696692 2011 LICHEN PLANUS PEMPHIGOIDES http://www.ncbi.nlm.nih.gov/pubmed/?term=21428725 INDUCED BY A WEIGHT REDUCTION DRUG. Rosmaninho A, Sanches M, Oliveira A, Alves R, Selores M. Cutan Ocul Toxicol. 2011 Dec;30(4):306-8. doi: 10.3109/15569527.2011.566234. Epub 2011 Mar 23. PMID: 21428725 2011 MANIFESTAÇÃO ATÍPICA DE http://www.spp.pt/Userfiles/File/App/Artigos/31/20120305174519_Caso%20Clinico_Diasl_42.pdf INFECÇÃO POR BARTONELLA HENSELAE? Dias A, Pinto D, Borges T, Guedes M. Acta Pediatr Port 2011; 42: 277-9. 2011 MIXED NEUROTHEKEOMA OF THE http://www.ncbi.nlm.nih.gov/pubmed/?term=21727057 UPPER LIMB. Rosmaninho A, Selores M, Alves R. Eur J Dermatol. 2011 Sep-Oct;21(5):815-6. doi: 10.1684/ejd.2011.1472. No abstract available. PMID: 21727057 2011 NODULAR SECONDARY SYPHILIS. http://www.ncbi.nlm.nih.gov/pubmed/?term=21233073. Rosmaninho A, Sanches M, Lobo I, Alves R, Selores M. Eur J Dermatol. 2011 Jan-Feb;21(1):136-7. doi: 10.1684/ejd.2010.1200. No abstract available. PMID: 21233073. 2011 OCCUPATIONAL EXPOSURE TO FORMALDEHYDE: GENOTOXIC RISK EVALUATION BY COMET ASSAY AND MICRONUCLEUS TEST USING HUMAN PERIPHERAL LYMPHOCYTES. Costa S, Pina C, Coelho P, Costa C, Silva S, Porto B, Laffon B, Teixeira JP. J Toxicol Environ Health A. 2011;74(15- http://www.ncbi.nlm.nih.gov/pubmed/?term=21707428 16):1040-51. doi: 10.1080/15287394.2011.582293. PMID: 21707428 2011 ORIGIN, FUNCTIONAL ROLE, AND http://www.ncbi.nlm.nih.gov/pubmed/?term=21273304 CLINICAL IMPACT OF FANCONI ANEMIA FANCA MUTATIONS. Castella M, Pujol R, Callén E, Trujillo JP, Casado JA, Gille H, Lach FP, Auerbach AD, Schindler D, Benítez J, Porto B, Ferro T, Muñoz A, Sevilla J, Madero L, Cela E, Beléndez C, de Heredia CD, Olivé T, de Toledo JS, Badell I, Torrent M, Estella J, Dasí A, Rodríguez-Villa A, Gómez P, Barbot J, Tapia M, Molinés A, Figuera A, Bueren JA, Surrallés J. Blood. 2011 Apr 7;117(14):3759-69. doi: 10.1182/blood-2010-08-299917. Epub 2011 Jan 27. PMID: 21273304 2011 PRIMARY CUTANEOUS CD30 http://www.ncbi.nlm.nih.gov/pubmed/?term=21764128 POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA--REPORT OF A CASE TREATED WITH BEXAROTENE. Oliveira A, Fernandes I, Alves R, Lima M, Selores M. Leuk Res. 2011 Nov;35(11):e190-2. doi: 10.1016/j.leukres.2011.06.029. Epub 2011 Jul 20. No abstract available. PMID: 21764128 2011 PROTECTIVE EFFECT OF ACETYL- http://www.ncbi.nlm.nih.gov/pubmed/?term=21807063 L-CARNITINE AND Α-LIPOIC ACID AGAINST THE ACUTE TOXICITY OF DIEPOXYBUTANE TO HUMAN LYMPHOCYTES. Ponte F, Carvalho F, Porto B. Toxicology. 2011 Oct 28;289(1):52-8. doi: 10.1016/j.tox.2011.07.009. Epub 2011 Jul 22. PMID: 21807063 2011 SCLEROMYXEDEMA VS SCLEREDEMA: A DIAGNOSTIC CHALLENGE. Conde Fernandes I, http://www.ncbi.nlm.nih.gov/pubmed/?term=21771713 Sanches M, Velho G, Lobo I, Alves R, Selores M. Eur J Dermatol. 2011 Sep-Oct;21(5):822-3. doi: 10.1684/ejd.2011.1493. No abstract available. PMID: 21771713 2011 SEZARY SYNDROME PRESENTING http://www.ncbi.nlm.nih.gov/pubmed/?term=22136862 WITH LEONINE FACIES AND TREATED WITH LOW-DOSE SUBCUTANEOUS ALEMTUZUMAB. Oliveira A, Lobo I, Alves R, Lima M, Selores M. Dermatol Online J. 2011 Nov 15;17(11):6. PMID: 22136862 2011 TREATMENT OF RECALCITRANT http://www.ncbi.nlm.nih.gov/pubmed/?term=22134573 GENERALIZED GRANULOMA ANNULARE WITH ADALIMUMAB. Torres T, Pinto Almeida T, Alves R, Sanches M, Selores M. J Drugs Dermatol. 2011 Dec;10(12):1466-8. PMID: 22134573 2011 UNS... E OS OUTROS. Guedes M. http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_arttext&pid=S0872-07542011000100016&lng=en&nrm=iso Nascer e Crescer, Mar 2011, vol.20, no.1, p.57-57. ISSN 0872-0754. 2011 HYPER-IGE SYNDROME: REPORT http://www.journalmc.org/index.php/JMC/article/view/213/165 OF THREE CASES ADN REVIEW OF THE LITERATURE. Brandão M, Marinho A, Vita P, Farinha F, Vasconcelos J, Vasconcelos C, Journal of Medical Cases 2011; 2 (4): 151-155. doi: 10.4021/jmc213w 7. Equipamento Equipamento Nº Recibo Data Observações NÃO HÁ EQUIPAMENTO ADQUIRIDO PARA O GRUPO BLDH 8. Descrição detalhada das actividades desenvolvidas BLOOD, LYMPHOPOIETIC AND HEMATOPOIETIC DISORDERS (BLHD) RG-HESC-Norte-Porto-215-2923 DESCRIÇÃO DO GRUPO DE INVESTIGAÇÃO The BLHD group is dedicated to clinical research in blood, lymphopoietic and hematopoietic disorders and integrates health professionals from clinical and laboratory sectors. For the last years the group developed research activities mainly in five areas: lymphoid malignancies, hemostase, red blood cell (RBC) disorders, bone marrow (BM) failure syndromes, and immunopathology. Lymphoid malignancies The CHP has a large number of patients with leukemia and lymphoma, whose diagnosis is supported by differentiated labs. The Laboratory of Cytometry is a reference lab for the diagnosis of T- and NK-cell lymphoproliferative disorders (LPD) and there is a multidisciplinary consulting for cutaneous lymphomas. In this area we focused on the immunophenotypic (IF) characterization of the normal mature T- and NK- cells, as well as on the IF criteria for the diagnosis and classification of the T-cell and NK-cell LPD, such as large granular lymphocyte (LGL) leukemia (LGLL) and cutaneous T cell lymphoma (CTCL). With this purpose, we integrated the EuroFlow consortium, whose objective is the development and standardization of flow cytometry (FC) tests for diagnosis and classification of hematological malignancies. In order to better understand the mechanisms by which leukemia and lymphoma cells infiltrate different organs and tissues, we have studied the expression of chemokine receptors (CKR) on the neoplastic cells from different types of T-cell LPD, and addressed the role of single nucleotide polymorphisms (SNP) of genes coding for the immunoregulatory molecules in LGLL. In addition, we have tested the value of FC studies for the diagnosis and classification of lymphoma, when compared to histopathology studies on lymph node biopsies. Especial attention was dedicated to the diagnosis of central nervous system lymphoma, by studying systematically, by FC, the cerebral biopsies. Data are now being analyzed. Partners: Centro Invest. Cancer, Salamanca, ES; Erasmus MC, Univ. Med. Center, Rotterdam, NL; Hosp. Univ. Virgen de las Nieves, Granada, ES. Consortia: Euroflow. Bone marrow failure síndromes The Hospital has a significant number of patients with congenital and acquired BM failure syndromes, including Paroxystic Nocturnal Hemoglobinuria (PNH), Fanconi Anemia (FA) and Myelodysplastic Syndromes (MDS). The hospital laboratories have a large experience in diagnosing and monitoring of patients with PNH, as well as in characterizing the abnormal maturation patterns observed in the BM of patients with MDS. In addition, the Laboratory of Cytogenetic of ICBAS/UP is a reference Lab for the diagnosis of FA. In this area we have been dedicated to the study of PNH and FA, and participated in the International Fanconi Anemia Register (IFAR). Fanconi Anemia is a genetically heterogeneous disease characterized by congenital abnormalities, progressive BM failure and predisposition to cancer. Chromosome instability is a major defect, and FA cells are hypersensitive to inter-strand cross-linking agents, such as diepoxybutane (DEB). PNH is a rare disease caused by acquired mutations in the gene encoding for glycosylphosphatidylinositol (GPI) that lead to deficiency of the GPI-anchored proteins in the RBC membrane. Clinically, PNH is characterized by intravascular hemolytic anemia and increased risk for thrombosis. It may develop on its own or in association with other BM disorders such as aplastic anemia and MDS. Today, the gold standard for the diagnosis of PNH is FC. Partners: Dpt. Genetics, Univ. Aut. Barcelona, ES; Dept. Physiology, Fac. Medicina y Odontología, Univ. Valencia, ES; Inst. Nazionale Tumori, Fondazione G. Pascale, Napoles, IT; Lab. Toxicologia, Fac. Farmácia, Univ. Porto, PT. Red blood cell disorders The Hospital has a large number of patients with anemia and the hospital´ laboratories have a large experience on the study of such conditions. Our research activity has addressed the maturation of the RBC in the BM and in the peripheral blood, as well as the study of congenital RBC membrane defects such as Hereditary Spherocytosis (HS). The key questions were: Is FC useful to study the BM erythropoiesis and the terminal maturation of reticulocytes into mature RBC? What about RBC changes due to ageing? What are the factors determining disease severity in HS? Can FC be used for the diagnosis of HS? Partners: Laboratory of Hematology, Fac. Farmácia, Univ. Porto, PT. Hemostase The Hematology Department of CHP is a reference center for the diagnosis and treatment of hemorrhagic diseases derived either from plasmatic (e.g. Hemophilia and von Willebrand disease, vWD) and platelet glycoprotein and granule (i.e., storage pool diseases, SPD) defects. Our research activity consisted on the participation in clinical trials and observational studies for Hemophilia and on the evaluation of risks factors for thrombosis and hemorrhage. New studies of platelets and endothelial cells (EC) are being developed. The key questions were: What are the mechanisms involved in thrombosis and hemorrhage? Can EC be used as biomarkers for thrombosis? What is the best treatment for acquired hemophilia? Partners: EAAC Facility, Fac. Life Sciences, Univ. Manchester, UK; Serv. Hematologia y Hemoterapia, Comp. Hosp. Juan Canalejo, Coruña, ES; Angelo Bianchi Bonomi, Univ. Milan, IT. Immunopathology The Laboratory of Immunology of the Hospital is a reference for the diagnosis of immunodeficiencies and immune-mediated diseases. The hospital has a large number of patients with immunodeficiency, either primary or secondary, as well as with autoimmune diseases (AID) and allergy. In the last years we have participated in multiple research projects in this area, most of which are presently undergoing: role of T cells in allergy; role of T cells and EC in Systemic Sclerosis (SS); immunological abnormalities in patients with Systemic Lupus Erythematous (SLE); in vitro differentiation of blood monocytes into dendritic cells and cytokine production of stimulated monocytes; expression of different types of killer receptors on blood CD56+ NK-cells and T-cells from patients with Multiple Sclerosis (MS); vitamin D and immune deregulation in SLE, T-cell abnormalities in high risk pregnancies; role of the pro-inflammatory CD14+CD16+ monocytes in chronic inflammatory intestinal disease (CIID) and obesity; characterization of the intestinal lymphocytic infiltrates from patients with CIID and correlation with the levels of TCR glycosylation; T- and B-cell abnormalities in patients with Common Variable Immunodeficiency (CID) and their correlations with clinical manifestations; clinical and immunological phenotype in a pediatric population with 22q11 deletion; AID and auto-antibodies in children with chronic granulomatous disease (CGD) and their families (multicenter study conducted in collaboration with the Karolinska University). Concerning infectious diseases, our studies have addressed the epidemiology of the hepatitis B infection (HBV) infection in the Northern of Portugal, as well as of the human immunodeficiency virus (HIV) and invasive pneumococcal disease (IPD) in Portugal. We have also been participating in the Portuguese Group for Primary Immunodeficiencies (GPIP), as well as in the ESID and the Portuguese Registers for Primary Immunodeficiencies (REPORID). Partners: The Rockefeller Univ., St. Giles Lab. Human Genetics of Infectious Diseases, New York, USA; Univ. Paris René Descartes, Fac. Médecine, Hôp. Necker-Enfants Malades, INSERM U550, U768 and U783, Paris, FR; Central Lab. Netherlands Blood Transfusion Service and Lab. Experimental and Clinical Immunology, Acad. Medical Center, Amsterdam, NL; Hospital Vall d'Hebron, Pediatric Infectious Diseases and Immunodeficiencies Unit, Barcelona, ES; Karolinska University; Lab. of Immunology and Immunogenetics, ICBAS/UP; Research Group Glycobiology of Cancer, IPATIMUP, and Dpt. Biochemistry, FMUP, Porto, PT. Portuguese Working Groups: Working Group on Invasive Pneumococcal Disease in Children (GTDPIC); Working Group on HIV infection in Children (GTIVIHC); Portuguese Group for Primary Immunodeficiencies (GPIP). PRINCIPAIS RESULTADOS ALCANÇADOS During the 3 years (2011-2013), 79 papers were published in peer-reviewed journals, from which 68 papers (86%) were indexed in the MedLine (PMID indicated in brackets), with a median IF of 2.053 in 2011, 2.711 in 2012 and 3.035 in 2013. About 20% of papers resulted from the collaboration with foreign groups and another 20% involved other national teams. In addition, the results were presented in scientific meetings and several MsD and PhD thesis are presently ongoing. We also organized scientific meetings and courses, supervised academic projects, trained health professionals and students and participated in academic juries. Lymphoid malignancies The results from the Euroflow consortium are being published (22552007) and a new flow cytometry (FC) software (Infinicyt) is already commercialized. Our effort was oriented to the definition of the best IF protocols to diagnose and classify the T- and NK-cell LPD, such as the LGLL, and other T- and NK-cell leukemia and lymphoma. Continuing our previous studies on the LGLL (16437145; 12875995; 12111871; 11696446), we evaluated, in collaboration with other groups, the SNP of genes coding for the immunoregulatory molecules in patients with CD4+ vs. CD8+ T-LGLL. (18361934); our results suggested that the SNP studied are not associated with the development of T-LGLL. Concerning the role of CKR expression in determining the clinical manifestations (tissue tropism and organ involvement) of T-LGLL, in comparison to peripheral T-cell lymphoma (PTCL) (18842429); we observed that T-LGLL cells express mainly late inflammatory CKR whereas PTCL cells usually have one or more organ homing CKR. Concerning CTCL, we implemented a protocol for the treatment of the Sezary Syndrome (SS), with low-doses subcutaneous alemtuzumab (anti-CD52 mAb). This study revealed that alemtuzumab induces responses in the majority of SS´ patients and suggested that FC analysis of CD52 expression on Sezary cells can be used to predict response to treatment (23062898; 22136862). We also tested the effectiveness of Aprepitant in alleviating the intractable pruritus observed in CTCL (22177649). In addition, we participated in a clinical trial in CTCL (EudraCT: 2011-001076-18). We also published case reports of patients with cutaneous B- (22398233; 19945162), T- (22136862; 22062773) or anaplastic large cell (21764128) lymphomas and dendritic cell neoplasms (22577284) with unique characteristics. Bone marrow failure syndromes Concerning FA, we presented the results from the DEB induced chromosome instability and breakage studies, allowing for the diagnosis of 34 cases of FA (22015027) and characterized the audiologic abnormalities observed in these patients (19086307). Using propidium iodide, bromodeoxyuridin and 7amino-actinomycin D based FC-based protocols we have been analyzing the cell cycle of blood lymphocytes from patients with FA, cultured in different conditions, with or without DEB. In collaboration with other research groups we described the protective effect of the RBC (21039995) and anti-oxidant molecules against the genotoxicity of DEB to human lymphocytes (21807063; 22591656), as well as the genotoxic activity of various substances (22565221; 21707428; 9146986). In addition, we participated in collaborative studies, to describe the origin, functional role, and clinical impact of the FANCA mutations in FA patients (21273304). Red blood cell disorders Concerning the investigation of patients with anemia, we collaborated in studies on HS in order to better characterize the biomarkers for disease severity (21138793), the effects of the RBC membrane protein destabilization (20346007; 18387321) and chronic inflammation (21704613) in determining the disease outcome, as well as the role of the (TA)nTAA polymorphism of UGT1A1 gene promoter region in determining the bilirubin levels in HS (19931474). We also contributed for the identification of new mutations in patients with talassemia (23181747), syderoblastic anemia (19693999) and iron-refractory iron-deficiency anemia (IRIDA) (22765023), as well as for the study of rare forms of hemolytic anemia (23253864). In addition, we investigated the immune and inflammatory mechanisms underlying anemia severity and response to treatment in patients with kidney disease (20649681; 18375155; 18205031). Hemostase In that concerning the hemorrhagic disorders, we participated in several clinical trials (EudraCT: 2009-011186-88; 2010-020558-33; 2005-005697-71) and observational collaborative studies (ESCHQoL, OBSITI, SIPPET, EACH2) in patients with Hemophilia. Some of the results obtained have already been published including those from the EACH2 (22517903; 22321904; 22618709; 22901076) and the ESCHQoL (22639833). Our research effort on thrombosis focused on the study of the EC. Using FC, we quantified and characterized the circulating EC (CEC) and EC progenitors in patients with venous thrombo-embolism (VTE) as well as in patients with Myeloproliferative Neoplasms (MPN); the results suggest that CEC counts reveal EC injury in patients with VTE and MPN and that CEC may express different activation-related phenotypes (10.1371/journal.pone.0081574). Immunopathology Our collaboration with other groups in the area of Primary Immunodeficiencies (PID) allowed for the publication of papers in scientific journals with high Impact Factor. These papers report on the characterization of the clinical features and outcome (21057262), infections (18669862; 19633526) and B cell defects (23002119) and other immunological disturbances (18591412) observed in different types of PID. In the area of AID, we dedicated our attention to the study of autoimmune lymphoproliferative syndrome (22525637), then contributing for the identification of disease biomarkers (19176318). We have also characterized some of the immune abnormalities observed in AID (19474774) and described several unique clinical cases (1859141; 22227968; 22674017; 18031500; 22995923). Concerning the epidemiology of HBV infection, genotypes A and D were found to be the most prevalent in the North of Portugal. Patients infected with genotype D had higher levels of HBV DNA and HBeAg was associated with genotype D, viral load, ALT and AST (19475628; 19475628). 21107506. Several important data were also obtained with the epidemiological studies on HIV and IPD in children. PHD THESES COMPLETED UNDER THE SUPERVISION OF INTEGRATED MEMBERS PHD THESIS CONCLUDED WITH THE SUPERVISION OF INTEGRATED UMIB MEMBERS (N=4) 1. PhD student: Ana Filipa Brinco de Oliveira Ponte. PhD program: Biomedical Sciences (ICBAS/UP). PhD thesis: CHROMOSOME INSTABILITY IN FANCONI ANEMIA: SEARCHING DRUGS TO PREVENT THE PROGRESSION OF THE DISEASE. Faculty/University: ICBAS/UP. Supervisors: Beatriz Porto (ICBAS/UP; UMIB/ICBAS/UP). Dates: 2007/2008-2012 (concluded 19-07-2012). 2. PhD student: Patrícia Clara dos Santos Coelho. PhD program: Biomedical Sciences (ICBAS/UP). PhD thesis: BIOMONITORING OF ENVIRONMENTAL CONTAMINATION RESULTING FROM MINING ACTIVITIES ON EXPOSED POPULATIONS. Faculty/University: ICBAS/UP. Supervisors: João Paulo Teixeira (INRJ); Beatriz Porto (ICBAS/UP; UMIB/ICBAS/UP). Dates: 2006/2007-2013 (concluded 23-112013). 3. PhD student: Sofia Castanheira Pais. PhD program: Educational Sciences (FPCE/UP). PhD thesis: VIVÊNCIA E QUALIDADE DE VIDA ESCOLAR, EMPODERAMENTO E PARTICIPAÇÃO: O CASO DAS CRIANÇAS E JOVENS COM DOENÇA CRÓNICA E SUAS FAMÍLIAS. Faculty/University: FPCE/UP. Supervisors: Isabel Menezes (FPCE/UP); Margarida Guedes (HSA/CHP; ICBAS/UP; UMIB/ICBAS/UP). Dates: 2007/2007-2012 (concluded 23/04/2012). PHD THESIS CONCLUDED OF UMIB MEMBERS (N=1) 1. PhD student / UMIB member: Ana Paula Mota (HSA/CHP; UMIB/ICBAS/UP). PhD program: Biomedical Sciences, ICBAS/UP. PhD thesis: GENÓTIPOS DO VÍRUS DA HEPATITE B, VARIÁVEIS ASSOCIADAS, CARACTERÍSTICAS E DISTRIBUIÇÃO NUMA AMOSTRA DA POPULAÇÃO PORTUGUESA. Supervisors: Jorge Areias (HSA/CHP; ICBAS/UP; UMIB/ICBAS/UP); Margarida Cardoso (ICBAS/UP). Faculty/University: ICBAS/UP. Dates: 2006-2011 (concluded 08-07-2011). BOOKS AND CHAPTERS IN BOOKS 2012 1. LABORATÓRIO DE CITOMETRIA DO SERVIÇO DE HEMATOLOGIA CLÍNICA DO HOSPITAL DE SANTO ANTÓNIO: 20 ANOS DE HISTÓRIA. Authors: Lima M. Editor: Fórum Hematológico do Norte. 1st Edition. Year: 2012. Depósito legal: PT 339815/12. 2. RECOMENDAÇÕES PORTUGUESAS PARA O TRATAMENTO DA INFECÇÃO POR VIH1 E VIH2 2012. Marques L. Brochure. Programa Nacional para a infecção VIH/SIDA. Electronic edition. Available in: http://www.aidsportugal.com/Modules/WebC_Docs/GetDocument.aspx?DocumentId=2828 . 2011 3. A INFEÇÃO VIH NA CRIANÇA E NO ADOLESCENTE. Authors: Grupo de Trabalho sobre Infeção VIH na Criança (GTVIHC). Coordinators: Rocha G; Gonçalo Marques J; Marques L, Prata F, Tavares M. Editor: Asic – Associação de Saúde Infantil de Coimbra. 1st Edition. Year: 2011. ISBN: 978-989-20-2656-5. Depósito Legal: PT 333862/11. Available in: http://www.spp.pt/UserFiles/file/Protocolos/Infecao_VIH_Crianca_Adolescente_Marco_2011.pdf 4. HEMOGLOBINÚRIA PAROXÍSTICA NOCTURNA: VÁRIAS FACES DA MESMA DOENÇA, DO DIAGNÓSTICO AO TRATAMENTO. Authors: Queirós ML, Lima M. Editor: Fórum Hematológico do Norte. 1st Edition. Year: 2011. ISBN: 978-989-20243-7-0. Depósito legal: PT 328231/11. ORGANISATION OF SCIENTIFIC ACTIVITIES (TRAINING COURSES, SYMPOSIUMS, CONFERENCES, SEMINARS, ETC., ORGANISED BY THE RESEARCH GROUP) 1. SIMPÓSIOS INTERNACIONAIS DE TROMBOSE E HEMOSTASE / REUNIÕES DO FÓRUM HEMATOLÓGICO DO NORTE. (Porto, Portugal: 31/03- 01/04/2011). 2. REUNIÕES ANUAIS DA SOCIEDADE PORTUGUESA DE HEMATOLOGIA (Porto, Portugal. 08/11/2012 - 10/11/2012). 3. REUNIÕES ANUAIS DA SOCIEDADE PORTUGUESA DE IMUNOLOGIA (Porto, Portugal. 25-27/11/2012). 4. EUROFLOW MEETINGS. (Porto, Portugal. 12-15/03/2013). 5. CONGRESSOS NACIONAIS DE DOENÇAS INFECCIOSAS E MICROBIOLOGIA CLÍNICA / CONGRESSOS NACIONAIS SOBRE SIDA (Porto, Portugal. 12-15/12/2012). 6. CONGRESSOS NACIONAIS DE PEDIATRIA (Albufeira, Portugal. 6-8/10/2011). 7. REUNIÕES DE GRUPOS DE TRABALHO: DOENÇA PNEUMOCÓCICA INVASIVA (Braga, Portugal. 18/05/2011). 8. CURSOS: REUMATOLOGIA PEDIÁTRICA (Porto, Portugal. 18/11/2011); INFECÇÃO POR VIH NA CRIANÇA. (Braga, Portugal. 21/05/2011); FORMAÇÃO CONTÍNUA EM PEDIATRIA “ENCONTROS À 6ª FEIRA (Porto, Portugal. 28/10/2011-25/05/2012). 9. JORNADAS NACIONAIS DE INFECCIOLOGIA PEDIATRICA (XII) - IMUNIDADE & INFECÇÃO (Braga, Portugal. 19-21/05/2011). RESEARCH CONTRACTS WITH NATIONAL OR INTERNATIONAL ENTITIES CONSORTIA (n=1) 1. Euroflow consortium (UMIB members: Margarida Lima, Ana Helena Santos). Dates: 2009-. State in November 2013: Ongoing. CLINICAL TRIALS (n=8) 2. Clinical trial: INHIBITOR DEVELOPMENT IN PREVIOUSLY UNTREATED PATIENTS (PUPS) OR MINIMALLY BLOOD COMPONENT-TREATED PATIENTS (MBCTPS) WHEN EXPOSED TO PLASMA-DERIVED VON WILLEBRAND FACTOR-CONTAINING FACTOR VIII (VWF/FVIII) CONCENTRATES AND TO RECOMBINANT FACTOR VIII (RFVIII) CONCENTRATES: AN INDEPENDENT, INTERNATIONAL, MULTICENTRE, PROSPECTIVE, CONTROLLED, RANDOMISED, OPEN LABEL, CLINICAL TRIAL. Medical condition: Severe Hemophilia A. EudraCT number: 2009-011186-88. Protocol number: ABB-09-001. Sponsor: Fondazione Centro Emofilia e Trombosi Angelo Bianchi Bonomi. UMIB investigators: Manuel Campos; Sara Morais. Dates: 2009-. State in November 2013: Ongoing. 3. Clinical trial: A-LONG: AN OPEN-LABEL, MULTICENTER EVALUATION OF THE SAFETY, PHARMACOKINETICS, AND EFFICACY OF RECOMBINANT FACTOR VIII FC FUSION PROTEIN (RFVIIIFC) IN THE PREVENTION AND TREATMENT OF BLEEDING IN PREVIOUSLY TREATED SUBJECTS WITH HEMOPHILIA A. Medical condition: Severe Hemophilia A. EudraCT number: 2010-020558-33. Protocol number: 997HA301. Sponsor: Biogen Idec Hemophilia, Inc. UMIB investigators: Manuel Campos; Sara Morais. Dates: 2011-. State in November 2013: Concluded. 4. Clinical trial: RAHF-PFM: ANTIHEMOPHILIC FACTOR (RECOMBINANT), PLASMA/ALBUMIN FREE METHOD: A PHASE 3/4, PROSPECTIVE, CONTROLLED, RANDOMIZED, MULTI-CENTER STUDY TO COMPARE THE EFFICACY AND SAFETY OF CONTINUOUS INFUSION (CI) VERSUS INTERMITTENT BOLUS INFUSION (BI) IN SUBJECTS WITH SEVERE OR MODERATELY SEVERE HAEMOPHILIA AN UNDERGOING UNILATERAL PRIMARY KNEE REPLACEMENT. Medical condition: Severe or moderately severe Hemophilia A. EudraCT number: 2005-005697-71. Protocol number: 060402. Sponsor: Baxter Innovations GmbH. Baxter Healthcare Corporation, Áustria: UMIB investigators: Manuel Campos; Sara Morais. Dates: 2009-. State in November 2013: Ongoing. 5. Clinical trial: A PHASE 2, SINGLE-ARM, OPEN-LABEL, MULTICENTER STUDY OF THE HISTONE DEACETYLASE INHIBITOR (HDACI) JNJ26481585 IN SUBJECTS WITH PREVIOUSLY TREATED STAGE IB-IVA CUTANEOUS T-CELL LYMPHOMA. Medical condition: Stage Ib-IVa Cutaneous T-cell Lymphoma. EudraCT Number: 2011-001076-18. Protocol number: 26481585LYM2001. Promotor: Janssen-Cilag International. Sponsor: Janssen-Cilag International. UMIB Investigators: Rosário Alves; Margarida Lima. Dates: 2011-2012. State in November 2013: Concluded. 6. Clinical trial: JUVENIL IDIOPATHIC ARTHRITIS (JIA) REGISTRY (STRIVE). A LONG-TERM, MULTI-CENTER, LONGITUDINAL POSTMARKETING, OBSERVATIONAL REGISTRY TO ASSESS LONG TERM SAFETY AND EFFECTIVENESS OF HUMIRA® (ADALIMUMAB) IN CHILDREN WITH MODERATELY TO SEVERELY ACTIVE POLYARTICULAR OR POLYARTICULAR-COURSE JUVENILE IDIOPATHIC ARTHRITIS (JIA) – STRIVE. Medical condition: Juvenil Idiopathic Arthritis. Promotor: AbbVie (prior sponsor, Abbott). Sponsor: AbbVie (prior sponsor, Abbott). UMIB investigators: Margarida Guedes. State in November 2013: Ongoing. 7. Clinical trial: A PHASE II, OPEN-LABEL TRIAL, TO EVALUATE THE SAFETY, TOLERABILITY AND ANTIVIRAL ACTIVITY OF TMC125 IN ANTIRETROVIRAL EXPERIENCED HIV-1 INFECTED CHILDREN AND ADOLESCENTS / ESTUDO CLÍNICO DE FASE II, ABERTO PARA AVALIAR A SEGURANÇA, TOLERABILIDADE E ACTIVIDADE ANTIVRAL DO TMC125 EM CRIANÇAS E ADOLESCENTES INFECTADOS PELO VIH-1 E COM EXPERIÊNCIA TERAPÊUTICA. Medical condition: HIV-1 infected children and adolescents. EudraCT number: 2009-01312616. Protocol number: TMC125-TiDP35-C239. Promotor: Tibotec Pharmaceuticals c/o Tibotec BVBA / Janssen Cilag. UMIB investigators: Laura Marques. Dates: 2009-. State in November 2013: Ongoing. 8. Clinical trial: KONCERT: A KALETRA ONCE DAILY RANDOMISED TRIAL OF THE PHARMACOKINETICS, SAFETY AND EFFICACY OF TWICE-DAILY VERSUS ONCE-DAILY LOPINAVIR/RITONAVIR TABLETS DOSED BY WEIGHT AS PART OF COMBINATION ANTIR. EudraCT number: 2009-013648-35. Protocol number: PENTA 18. Promotor: PENTA foundation. Sponsor: PENTA foundation. UMIB investigators: Laura Marques. Dates: 2010-. State in November 2013: Completed. OBSERVATIONAL AND REGISTRY STUDIES (n=3) 9. Observational / Registry study: EUROPEAN STUDY OF CLINICAL, HEALTH ECONOMIC AND QUALITY OF LIFE OUTCOMES IN HEMOPHILIA TREATMENT (ESCHQoL). Sponsor: ISTH. UMIB investigators: Manuel Campos; Sara Morais. Dates: 2005-2006. State in November 2013: Completed. 10. Observational / Registry study: OBSERVATIONAL IMMUNE TOLERANCE INDUCTION RESEARCH PROGRAM (OBSITI). Promotor: Paediatric Centre of the Johann Wolfgang-Goethe University Frankfurt, Germany; Haemophilia Centre Rhine-Main (HZRM), Frankfurt-Mörfelden, Germany. Sponsor: Octapharma AG. Study coordinator: Wolfhart Kreuz and Carmen Escuriola-Ettingshausen Johann Wolfgang Goethe-University, Frankfurt, Germany. UMIB investigators: Manuel Campos; Sara Morais. Dates: 2005-. State in November 2013: Ongoing. 11. Observational / Registry study: SURVEY OF INHIBITORS IN PLASMA PRODUCT EXPOSED TODDLERS (SIPPET). Promotor: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center. Sponsor: Fondazione Angelo Bianchi Bonomi. Study coordinator: Pierr Mannucio Mannucci, University of Milan, Italy. UMIB investigators: Manuel Campos; Sara Morais. Dates: 2009-2014. State in November 2013: Ongoing. RESEARCH FELLOWS 1. Magdalena Anna Leander (PhD). From 1 April 2011 to 31 April 2012 (12 months). Fórum Hematológico do Norte. 2. Ana Raquel Martins Figueiredo Fonseca (MsD). 2012: 6 months (1 July 2012 to 31 December 2012) (6 months); 2013: 2 months (1 January 2013 to 28 February 2013). FCT PARTNERS / COLLABORATIONS HEMATOLOGY Hemato-oncology International collaborations o Centro de Investigación del Cancer (CIC) (Salamanca, Spain) (Alberto Orfao; Julia Almeida). o Erasmus MC, University Medical Center, Department of Immunology, Unit of Molecular Immunology (Rotterdam, The Netherlands) (Jacques van Dongen) o Hospital Universitario de Salamanca (USAL) (Salamanca, Spain) (Alberto Orfao; Julia Almeida). o Hospital Universitario Virgen de las Nieves (Granada, Spain) (Francisco Ruiz Cabello; Pillar Garrido). o Centro de Estudios de Mastocitosis de Castilla la Mancha (CLMast) (Toledo, Spain) (Luís Escribano) o European Competence Network on Mastocytosis (ECNM) (Viena de Áustria, Áustria) (Peter Valent) National collaborations o Instituto Português de Oncologia Francisco Gentil de Lisboa, Consulta Multidisciplinar de Linfomas Cutâneos (Lisboa, Portugal) (Fernanda Sasche, Mariana Cravo and Rute Alvarez) o Instituto Português de Oncologia Francisco Gentil de Lisboa (Lisboa, Portugal), Serviço de Hematologia, Lisboa, Portugal. (Maria Gomes da Silva, Paulo Lúcio) o Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Cancer Glycobiology Research Group, Porto, Portugal. (Salomé Pinho) Hemostasis International collaborations o Complejo Hospitalario Juan Canalejo, Servicio de Hematologia e Hemoterapia (La Coruña, Spain) (Francisco Javier Battle) o Hôpital Cardiologique, Laboratory Pathologie Cellulaire de l'Hémostase (Pessac, France) (Allan Nurden) o University of Manchester, Faculty of Life Sciences, European Action on Anticoagulation Central Facility (EAAC) (Manchester, UK) (Leon Poller) o University of Milan, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center (Milan, Italy) (Pier Mannucio Mannucci) National collaborations o No collaborations in this area. Bone marrow failure syndromes International collaborations o Instituto Nazionale Tumori (IRCCS), Fondazione G. Pascale, (Napoles, Italy) (Giovanni Pagano) o Universidad Autónoma de Barcelona, Department of Genetics (Barcelona, Spain) (Jordi Surralés Calonge) o University of Valencia, Facultad de Medicina y Odontología, Department of Phisiology (Valencia, Spain) (Federico Pallardo) National collaborations o Universidade do Porto, Faculdade de Farmácia (FF/UP), Department of Biological Sciences, Laboratory of Toxicology (Porto, Portugal) (Félix Carvalho) o Universidade do Porto, Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP), Department of Microscopy, Laboratory of Cytogenetics (Porto, Portugal) (Beatriz Porto) IMMUNOPATHOLOGY International collaborations o Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center (Amsterdam, The Netherlands) (Dirk Roos). o Hospital Vall d'Hebron, Pediatric Infectious Diseases and Immunodeficiencies Unit (Barcelona, Spain). o The Rockefeller University, St. Giles Laboratory of Human Genetics of Infectious Diseases (New York, USA) (Jean Laurent Casanova) o Université Paris René Descartes, Faculté de Médecine, Hôpital Necker-Enfants Malades, INSERM U550 (Human Genetics of Infectious Diseases) (Paris, France) (Jean Laurent Casanova) o Université Paris René Descartes, Faculté de Médecine, Hôpital Necker-Enfants Malades, INSERM U768 (Normal and Pathological Development of the Immune System) (Paris, France) (Alain Fischer) o Université Paris René Descartes, Faculté de Médecine, Hôpital Necker-Enfants Malades, INSERM U783 (Development of the Immune System) (Paris, France) (Claude-Agnès Reynaud). National collaborations o Centro Hospitalar do Porto (CHP), Hospital de Santo António (HSA), Unidade de Imunologia Clínica (UIC) e Grupo de Investigação em Imunologia Clínica. o Instituto Gulbenkian da Ciência (Oeiras, Portugal) (Constantin Fezel). o Instituto Português de Oncologia Francisco Gentil de Lisboa (Lisboa, Portugal), Serviço de Hematologia, Lisboa, Portugal. (Maria Gomes da Silva, Paulo Lúcio). o Universidade do Porto, Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP), Department of Immunophisiology and Pharmacology, Laboratory of Immunology (Porto, Portugal) (Manuel Vilanova; Paula Ferreira) o Universidade do Porto, Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP), Department of Pathology and Molecular Immunology, Laboratory of Immunogenetics (Porto, Portugal) (Berta Martins). o Universidade do Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Grupo de Investigação Glicobiologia do Cancro, Porto, Portugal. (Salomé Pinho). 9. Ficheiros Anexos (opcional) Nome Ponto do RF Descrição Validar e Lacrar Relatório Final - Componente Científica A fim de dar cumprimento ao estipulado no Artº. 20º do mesmo regulamento vimos informar que o relatório final relativo às atividades realizadas no âmbito do projeto estratégico no período 2011/2013 (1 de janeiro de 2011 a 31 de dezembro de 2013) está já disponibilizado para preenchimento e deverá ser lacrado até às 17 horas do dia 31 de janeiro de 2014. Relatório Científico Final 2011-13 – UMIB Research Group Title: Working Group for Clinical Research (GIC) Principal Investigator: Margarida Lima Research Area: Health Sciences Home Institution: Instituto de Ciências Biomédicas Abel Salazar Brief explanation In 2006, a department (DEFI, Departamento de Ensino, Formação e Investigação) was created in the Hospital de Santo António (HSA, now integrated at the Centro Hospitalar do Porto, CHP) in order to coordinate the teaching, training and research activities. By that time, most of the clinical research activities were not organized, in the sense that they were not conducted by a research team, according to a specific protocol, neither had separately budgeted or specific funding. Also in 2006, the UMIB was a relatively small research Unit with 46 members (13 PhD) in the area of the Human and Veterinary Health Sciences, structurally subdivided into four groups: Pharmacology and Neurosciences (role of the purines in various biological processes), Anatomy (experimental viral hemorrhagic disease, vibroacustic disease and immune toxicity of heavy metals), Cell Biology (reproductive biology, with emphasis to spermatogenesis) and Veterinary Virology (infectious diseases in the field of veterinary medicine). At the beginning of 2007, when the DEFI was just starting its activity, the UMIB began a process of internal reorganization in order to accommodate research areas that were emerging mainly as a consequence of the ligation between the ICBAS and the HSA. For instance, the Pharmacology & Neurosciences group was investigating the role of the purinergic signaling in the control of synaptic transmission (Neurology), overactive bladder and erectile dysfunction (Urology); the Anatomy group was studying the effect of the gastric hormones in bariatric surgery (Endocrinology), as well as the anatomic and inflammatory events in the myelomeningocele (Neurosurgery), and was planning to investigate the myocardial revascularization through cardiac venous system. At the same time, the Laboratory of Immunogenetics of the ICBAS was just starting to investigate epilepsy (Neurology and Neurosurgery) and autoimmune diseases (Immunology and Chemistry). Thus, some hospital investigators from these clinical areas were invited to be registered and the UMIB groups were reformulated. Shortly thereafter, the UMIB manifested the intention to expand the collaborations with the Hospital to other areas, by incorporating more clinical investigators and promoting translation programs. Consequently, in June 2007, all the hospital investigators were formally invited to inscribe at the UMIB, and dozens of them responded positively to the call. By the same time, the rules for the creation of research groups were released at the hospital. By July 2007, four research groups were approved and subsequently affiliated to the UMIB, three of them in specific research areas (“Parkinson Disease Study Group”, PDSG; “Blood, Lymphopoietic and Hematopoietic Disorders”, BLHD; and “Nephrology, Dialysis and Transplantation”, NDT) and one of them as a general clinical research group, this being designated “Working Group for Clinical Research” (Grupo de Investigação Clínica, GIC) (Table 1). Mainly as a consequence of the incorporation of hospital researchers the number of UMIB members increased from 46 (13 PhD) in 2006, to 73 (23 PhD) and then to 152 (31 PhD) in 2007, from which 100 (15 PhD) were from the CHP, reaching the maximum (200; 50 PhD) in 2008, and stabilizing thereafter with a tendency to decrease. Simultaneously, the number of UMIB research groups increased from 4 in 2006 to 10 in 2007, 2 groups being extinguished at the end of 2010. At the end of 2012, the UMIB comprised 8 research groups and included 148 researchers (44 PhD). Table 1: UMIB groups from 2003 to 2013 Group Group designation Principal number Host institution investigator Date of Status in December approval 2013 2003 Extinguished 2003-2006 2007-2010 2011-2013 215-2465 Anatomy Anatomy I: Structural pathology Extinguished (12/2010) Artur Águas ICBAS/UP 215-2642 - Anatomy II: Experimental Medicine Anatomy: Experimental Medicine Artur Águas ICBAS/UP 215-2408 Cell Biology Biology and Genetics of Biology and Genetics of Mário Sousa ICBAS/UP 2003 Active Reproduction Reproduction Pharmacology and Neurosciences Pharmacology and Neurosciences Paulo Correia Sá ICBAS/UP 2003 Active Infectious diseases Extinguished Gertrude ICBAS/UP 2003 (12/ 2010) Thompson ImmunoGenetics, Inflammation and ImmunoGenetics, Inflammation and Berta Martins ICBAS/UP 2007 Active Autoimmunity (IGIA) Autoimmunity (IGIA) Parkinson's disease study group Parkinson's disease study group António Bastos HSA/CHP 2007 Active (PDSG) (PDSG) Lima (2007-2012) Margarida Lima HSA/CHP 2007- Active Luísa Lobato HSA/CHP 2007- Active Margarida Lima HSA/CHP 2007 Extinguished (***) (*) 215-2560 Pharmacology and 2007 Active Neurosciences 215-2448 215-2748 215-2956 Veterinary Virology - - Extinguished (**) Sara Cavaco (2012-) 215-2923 215-2990 215-2945 - - - Blood, lymphopoietic & Blood, lymphopoietic & hematopoietic disorders (BLHD) hematopoietic disorders (BLHD) Nephrology, Dialysis & Nephrology, Dialysis & Transplantation (NDT) Transplantation (NDT) Working Group for Clinical Working Group for Clinical Research (GIC) Research (GIC) Extinguished (12/2012 – 06/2013) Abbreviations: CHP, Centro Hospitalar do Porto; HSA, Hospital de Santo António; ICBAS, Instituto de Ciências Biomédicas Abel Salazar; UMIB, Unidade Multidisciplinar de Investigação Biomédica; UP, Universidade do Porto. (*) The “Anatomy I: Structural Pathology” group was extinguished by the end of 2010, following the comments made by the Evaluation Panel, in 2008, regarding the need for reorganization of the two groups of Anatomy (Anatomy I: Structure Pathology and Anatomy II: Experimental Medicine) in order to focus their research interests and to strengthen the potential impact of the group in the scientific community. Fusion of these two groups was not difficult to achieve, since both groups had the same PI (Prof. Artur Águas) and a very similar composition with respect to PhD researchers. The group adopted the designation “Anatomy: Experimental Medicine”. (**) In December 2010, the PI (Gertrude Thompson) and most of the researchers of the group “Infectious Diseases” asked permission to move to another research unit more focused on biological diversity and animal research. Therefore, this group stopped its activity at UMIB at the end of 2010. (***) The “Working Group of Clinical Analysis” was created in 2007, in order to integrate the clinical investigators that have registered at the UMIB and were not affiliated with specific groups. For logistical reasons, it was subsequently decided that all the investigators from the hospital will be included in this group, independently of being or not integrated into other specific groups. The head of the Department for Teaching, Training and Research (DEFI) of the CHP (Prof. Margarida Lima) assumed the responsibility for the GIC, whose aim was not to perform, but rather to promote and organize the clinical research at the CHP. The group was supposed to be extinguished within a 3-year period, which had prolonged for another 3 years, till July of 2013, when Prof. Margarida Lima left the position of director of the DEFI. The GIC was created in order to integrate the clinical investigators that have registered at the UMIB and that were not affiliated with specific groups. However, for logistical reasons, it was subsequently decided that all the investigators from the hospital will be included in this group, independently of being or not integrated into other specific groups. The head of the DEFI (Margarida Lima) assumed the responsibility for the GIC, whose aim was not to perform, but rather to promote and organize the clinical research at the CHP. The following priorities were defined: to organize research teams; to provide common facilities & support services for clinical research; to promote scientific education and training for researchers; to collect and disseminate information about the academic and scientific activity of the hospital; to encourage inter-institutional partnerships; and to provide funding for clinical research. The group was supposed to be extinguished within a 3-year period, which had prolonged for another 3 years, till July of 2013. A) ORGANIZATION OF RESEARCH TEAMS IN THE HOSPITAL The GIC was initially formed by the amalgamation of already existing research investigators, which were supposed to organize themselves into structured research groups, on a step-wise approach. The teams should have a scientific leader and were obligated to define their research scope & aims, to plan their activity by conceiving research projects in order to answer clinical relevant questions and to report periodically their activity. From 2008 to date, 9 research teams were approved in the Hospital (2008: 6 groups; 2010: 2 groups; 2013: 1 group) (Table 2): Anemia physiopathology, Biopathology of systemic autoimmune diseases, Hemochromatosis, Immunoallergology, Neurobiology of human behaviour, Primary immunodeficiencies, Clinical Immunology, Intensive Care and Neuropediatrics. Table 2: Research teams approved in the Hospital from 2008 to 2013 Research team Date of Principal investigator National Partners State approval Anemia physiopathology Biopathology of systemic autoimmune diseases 2008 2008* in December 2013 Alice Santos Silva, FF/UP; Margarida Lima, FF/UP, IBMC/UP (Biology of Inflammation and Reproduction), CHP FMUC Active Elsa Bronze, FF/UP; Conceição Cerveira, FF/UP, IBMC/UP (Biology of Inflammation and Reproduction) Extinguished in 2012 Active CHP Hemochromatosis 2008 Graça Porto, CHP IBMC/UP (Basic & Clinical Research on Iron Biology) Immunoallergology 2008 Helena Falcão, CHP FMUP Neurobiology of human behavior 2008 Sara Cavaco, CHP UMIB/ICBAS/UP Extinguished in 2012 (ImmunoGenetics, Inflammation and Active UMIB/UP (Blood, Lymphopoietic and Hematopoietic Disorders, Active Autoimmunity, IGIA) Primary immunodeficiencies (PID) 2008 Esmeralda Neves, CHP BLHD) IBMC/UP (Immunobiology) Clinical Immunology 2010 Carlos Vasconcelos, CHP UMIB/ICBAS/UP (ImmunoGenetics, Inflammation and Active Autoimmunity, IGIA) IGC (Lupus And Autoreactive Immune Repertoires) Intensive Care 2010 Irene Aragão, CHP SBIM/FMUP Active Neuropediatrics (NeuroPED) 2013 (*) Teresa Temudo, CHP CDC/CHUC ECS/ICVS/UP, CIFI2D, FEUP, LABIOMEP, FADEUP Active * Proposed in 2012, approved in 2013. Abbreviations: CIFI2D/UP, Centro de Investigação, Formação, Inovação e Intervenção em Desporto do Porto (HESC-Norte-Porto-4068); ECS/ICVS/UM, Escola de Ciências da Saúde do Instituto de Ciências da Vida e da Saúde da Universidade do Minho; FADEUP, Faculdade de Desporto e Educação Física da Universidade do Porto; FEUP, Faculdade de Engenharia da Universidade do Por to; FF/UP, Faculdade de Farmácia da Universidade do Porto; FMUC, Faculdade de Medicina da Universidade de Coimbra; FMUP, Faculdade de Medicina da Universidade do Porto; IBMC/UP, Instituto de Biologia Molecular e Celular da Universidade do Porto; ICBAS/UP, Instituto de Ciências Biomédicas da Universidade do Porto; UMIB/ICBAS/UP, Unidade Multidisciplinar da Universidade do Porto; LABIOMEP, Laboratório de Biomecânica da Universidade do Porto; CDC/CHUC, Centro de Desenvolvimento da Criança do Centro Hospitalar e Universitário de Coimbra; SBIM/FMUP, Serviço de Bioestatística e Informática Médica da Faculdade de Medicina da Universidade do Porto. These teams incorporated investigators from the CHP, as well as from other national academic and research centers, such as ECS/ICVS/UM, FADEUP, FEUP, FFUP, FMUC, FMUP, ICBAS/UP, CIFI2D, IBMC/UP, LABIOMEP and UMIB/ICBAS/UP. Nevertheless, some problems compromised the possibility of organizing more research teams inside the hospital and/or proposing these teams as independent groups inside the UMIB: a) Firstly, in most cases the natural leaders were not PhD and/or the team did not have enough PhD investigators to be considered as independent research group by the FCT; b) Secondly, in some areas (e.g. Neurosciences), the research effort was fragmented thought more or less structured areas (e.g. Epilepsy, Cerebrovascular diseases, Neuroimmunology, Neuroanesthesia, etc.) and no agreement was reached between the natural leaders in order to create research groups; c) Thirdly, some of the clinical investigators chose to integrate other UMIB groups (e.g. IGIA: Clinical Immunology and Neurobiology of Human Behavior; BLDH: Anemia physiopathology, Immunoallergology and Primary Immunodeficiencies; P&N: Urology and Neurology and Orthopedics; PDSG: Neurology and Neurosurgery). d) Finally, other clinical investigators decided to integrate groups from other FCT Units with which they already had long-standing collaboration (e.g. IBMC/UP – Hemochromatosis; Neurosciences/Headaches; Anemia physiopathology; INEB/UP – Orthopedics). B) RESEARCH FACILITIES & SUPPORT SERVICES A Research Coordination Unit (Gabinete Coordenador da Investigação, GCI) was created in 2007 at the CHP, where different areas were subsequently organized in order to provide support to research: coordination of clinical trials, analysis of research proposals, project management, biostatistics, and collection of output indicators, among others. Simultaneously, the Hospital made available common facilities and services, including a training center, an auditorium and a library. B1. RESEARCH COORDINATION UNIT Clinical trials core: The conduct of high quality clinical trials is essential to the overall mission of the Hospital. Thus, for the last years our investment was in creating, inside the GCI, a core facility for coordination and supervision of clinical trials which provides centralized protocol development and implementation services, data management, reporting, and administrative oversight. It also promotes education and training for clinical research coordinators, research nurses, and individual investigators. In order to provide support to clinical trials, a team of study coordinators and research nurses was created in 2012, which is now being expanded. Specific objectives are to: 1) facilitate activation and conduct of clinical trials in the hospital; 2) promote awareness and availability of active studies; 3) facilitate enrolment of eligible patients onto clinical trials; and 4) promote quality assurance, research compliance, and adherence to Good Clinical Practices (GCP). In this area, the CHP became a member of the PtCRIN (Portuguese Clinical Research Infrastructure Network), a national research infrastructure aiming to facilitate and improve quality in clinical research and to increase research collaboration. http://web.fcm.unl.pt/ptcrin/ Research proposals core: This team provides technical and scientific support to clinical investigators and students for the elaboration of research proposals and analyses the research studies that are submitted at the CHP, before being analyzed by the Ethical Committee. Biostatistics core: The biostatistics core provides statistical support to the investigators regarding the preparation of study design and data analysis. With that purpose, the CHP contracted a PhD consultant in Biostatistics. Project management core: This core supports clinical researchers in the preparation of grant applications. It is also in charge to identify funding opportunities, as well as of managing the funded projects, including grant payments, monitoring the expenses and organising the archiving of supporting documents. Open Access core: In order to increase the visibility, accessibility and dissemination of the academic and scientific activity of the Hospital community and to facilitate the management and access to information, in 2010 the CHP became an active member of the RCAAP, a FCCN supported project aimed to collect, aggregate and index Open Access scientific contents from institutional repositories. Since 2007, hundreds of documents were archived at the CHP repository, including manuscripts, congress books, master and doctoral thesis, among others. http://repositorio.chporto.pt/ Dissemination of opportunities: New software was developed in order to disseminate by e-mail the opportunities (e.g. courses, conferences, funding programs, etc.) to the hospital community. Scientific journals: NASCER E CRESCER is a quaternary journal focused to all health professionals with an interest in the area of Maternal and Child Health that publishes scientific articles related to Pediatrics, Perinatology, Mental Health of Children and Adolescents, and Bioethics. It is published regularly since 1991, being indexed by EMBASE/ Excerpta Medica since 1996, SCOPUS, LATINDEX Catalog since 2004, and Scielo since 2011. http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_serial&pid=0872-0754&lng=en&nrm=iso. In October 2008, the Journal becomes under the technical coordination of the DEFI. From 2008 to 2012, the editorial and the scientific boards were reformulated as did the scope and the policy and the instructions for the authors. B2. COMMON FACILITIES AND SERVICES Auditorium and Training Center: The auditorium and training center facilities were reformulated and reequipped. At the Auditorium, the conference room accommodates seat capacity for 150 participants; n addition, the upper floor, with optional dividing walls, accommodates three separate sessions. At the Training Center, 4 additional rooms are available, one of them being equipped with 14 laptop computers. All these facilities are equipped with computers with Internet connection, slide and overhead projectors, data-shows and projection screens and multi-media, being available for congresses, seminars, courses and other events. Library: New library facilities, which are open to the hospital staff as well as to students, were inaugurated in July 2008 and totally reequipped. Printed resources include about 800 periodicals and over 5,000 monographs, books and manuals, beyond historical documents. On-line resources include: B-On/FCCN (http://www.b-on.pt/) (signed by the CHP from 2007 to 2010; shared with the UP since then); UptoDate/WKH (http://www.uptodate.com/) (evidence-based, physician-authored clinical decision support resource developed by the Wolters Kluwer Health, WKH) (since September 2009); OvidSP/LWW (http://www.ovid.com/) (online access to over 250 medical and nursing journals published by Lippincott Williams & Wilkins, LWW) (since 2010) and Clinical Key/Elsevier (https://www.clinicalkey.com/) (online access to over 1,000 books, 500 journals, thousands of videos, and millions of images from medical specialties) (since December 2012) platforms. The CHP Library Web Page and the Virtual CHP Library were made available in 2010. Using AtoZ/EBSCO, a Web-based tool for organizing and providing links to library’s e-resources, they facilitate the access to all the on-line resources subscribed by the CHP (e.g. UpToDate/WKH, OvidSP/LWW, ClinicalKey/Elsevier, etc.), beyond other free on-line resources (e.g. PubMed and MeSH), allowing to search by subject / term and linking to the full text of numerous online publications in the field of Health, Medical and Biomedical Sciences. E) SCIENTIFIC EDUCATION AND RESEARCH TRAINING The GCI provided education and training for the clinical researchers by organizing advanced courses on organization and coordination of clinical trials, elaboration of research proposals, biostatistics, etc. (Tables 3 and 4) In addition, the Auditorium and the Learning Center gave the logistic support to hundreds of scientific and academic events promoted by the Hospital community. In 2007, a discipline for the initiation on clinical research (Disciplina de Iniciação à Investigação Clínica, DIIC) was created an optional discipline for the medical students of the ICBAS/UP. From 2007 to 2012, 31 medical students conceived and realized their research projects; at the end of 2013, 10 additional projects are being conceived and 9 projects are going-on. Since 2009, a congress is organized every year, where the students present their research proposals or the results obtained (Journeys of Initiation to Clinical Research, JIIC). https://sites.google.com/site/jiicmargaridalima/ Our proactive attitude to encourage the attainment of academic degrees by health professionals resulted in a high number of clinicians, nurses and technicians engaging in post-graduation courses, master and doctoral programs (please see below). Table 3: Courses and congresses promoted by the GCI from 2007 to 2012* Year Courses (number) Congresses and seminars (number) 2007 Clinical trials (1) - 2008 Clinical trials (1); Research projects (1) - 2009 Research projects (1) Initiation to Clinical Research (for students) (1) 2010 Clinical Trials (2) Initiation to Clinical Research (for students) (1) 2011 Clinical Trials (3), EndNote Web (2); Initiation to Clinical Research (for students) (1) 2012 Biostatistics (2); Authorship (1); EndNote Web (1); PubMed (1); SPSS (2); Web of Science (1); Zotero (1) Initiation to Clinical Research (for students) (1) Regenerative Medicine (3) Table 4: ORGANISATION OF SCIENTIFIC DISSEMINATION ACTIVITIES (TRAINING COURSES, SYMPOSIUMS, CONFERENCES, SEMINARS, etc.) 2013 1. JORNADAS DE INICIAÇÃO À INVESTIGAÇÃO CLÍNICA (5ªs). Promoter: DIIC/MIM/ICBAS/UP e GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: 28/06/2013. 2. CURSO DE ENSAIOS CLÍNICOS PARA INVESTIGADORES. Promoter: GCI/DEFI/CHP e BIAL. CHP, Porto, Portugal. Place: Auditório Prof. Doutor Alexandre Moreira e Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 01/02/2013. 3. CURSO DE ENSAIOS CLÍNICOS PARA COORDENADORES DE ENSAIOS. Promoter: GCI/DEFI/CHP e BIAL. DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira e Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 31/01/2013 e 01/02/2013. 4. SPSS: ANÁLISE ESTATÍSTICA DE DADOS COM A UTILIZAÇÃO DO SPSS E DO MS EXCEL (3ª edition). Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. 2012 5. CONCEPÇÃO, REDACÇÃO E PUBLICAÇÃO DE ARTIGOS CIENTÍFICOS. Promoter: XXIV Reunião Anual de Pediatria do CHP e GCI/DEFI/CHP. Place: Ipanema Park Hotel Porto, Portugal. Date: 21/11/2012. 6. ZOTERO: APLICAÇÃO INFORMÁTICA PARA RECUPERAÇÃO E GESTÃO DE REFERÊNCIAS BIBLIOGRÁFICAS. Promoter: GCI/DEFI/CHP. Date: 20/10/2012. 7. DIREITOS DE AUTOR: PUBLICAÇÕES CIENTÍFICAS, AUTORIA E DIREITOS DE AUTOR. Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 22/09/2012. 8. JORNADAS DE INICIAÇÃO À INVESTIGAÇÃO CLÍNICA (4ªs). Promoter: DIIC/MIM/ICBAS/UP e GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: 29/06/2012. 9. ENDNOTE WEB (3ª EDIÇÃO): FUNCIONALIDADES E CARACTERÍSTICAS DA APLICAÇÃO INFORMÁTICA PARA RECUPERAÇÃO E GESTÃO DE REFERÊNCIAS BIBLIOGRÁFICAS. Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 11, 13 e 15/06/2012. 10. SEMINÁRIOS INEB/ICBAS/CHP 2012: CONTROVÉRSIAS AO ALMOÇO – FACTOS E MITOS EM … MEDICINA REGENERATIVA – QUAIS OS LIMITES BIOLÓGICOS DA REGENERAÇÃO? Promoter: INEB/UP, ICBAS/UP e GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: 06/06/2012. 11. SEMINÁRIOS INEB/ICBAS/CHP 2012: CONTROVÉRSIAS AO ALMOÇO – FACTOS E MITOS EM … MEDICINA REGENERATIVA – TERAPIA CELULAR. Promoter: INEB/UP, ICBAS/UP e GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: 09/05/2012. 12. SPSS: ANÁLISE ESTATÍSTICA DE DADOS COM A UTILIZAÇÃO DO SPSS E DO MS EXCEL, Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 7, 9, 14, 16, 21, 23 e 28/05/2012. 13. SEMINÁRIOS INEB/ICBAS/CHP 2012: CONTROVÉRSIAS AO ALMOÇO – FACTOS E MITOS EM … MEDICINA REGENERATIVA – COMO REGENERAR TECIDOS E ÓRGÃOS HUMANOS? Promoter: INEB/UP, ICBAS/UP e GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: 04/04/2012. 14. CURSO AVANÇADO DE BIOESTATÍSTICA E SUAS APLICAÇÕES EM CIÊNCIAS DA SAÚDE. Promoter: GCI/DEFI/CHP e ICBAS/UP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 05/03/2012-17/03/2012 (27h). 15. PUBMED. Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 02-04/03/2012. 16. WEB OF SCIENCE: FUNCIONALIDADES E CARACTERÍSTICAS DA BASE DE DADOS E DA PESQUISA DE E POR CITAÇÕES. Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 28/02/2012-01/03/2012. 17. CURSO DE INTRODUÇÃO À BIOESTATÍSTICA E SUAS APLICAÇÕES EM CIÊNCIAS DA SAÚDE. Promoter: GCI/DEFI/CHP e ICBAS/UP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 30/01/2012-11/02/2012. 2011 18. CURSO DE ENSAIOS CLÍNICOS (4a. Edição): Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 10/10/2011. 19. JORNADAS DE INICIAÇÃO À INVESTIGAÇÃO CLÍNICA (3ªs). Promoter: GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: 01/07/2011. 20. ENDNOTE WEB (2ª edição). FUNCIONALIDADES E CARACTERÍSTICAS DA APLICAÇÃO INFORMÁTICA PARA RECUPERAÇÃO E GESTÃO DE REFERÊNCIAS BIBLIOGRÁFICAS. Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 27 e 29/06/2012. 21. ENDNOTE WEB (1ª edição). FUNCIONALIDADES E CARACTERÍSTICAS DA APLICAÇÃO INFORMÁTICA PARA RECUPERAÇÃO E GESTÃO DE REFERÊNCIAS BIBLIOGRÁFICAS. Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 20 e 22/06/2012. 2010 22. CURSO DE ENSAIOS CLÍNICOS CHP (3ª edição): Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 26/11/2010. 23. JORNADAS DE INICIAÇÃO À INVESTIGAÇÃO CLÍNICA (2ªs): Promoter: DIIC/MIM/ICBAS/UP e GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: 02/07/2010. 24. ENSAIOS CLÍNICOS: Curso de Ensaios Clínicos CHP (2ª edição): Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 30/06/2010. 2009 25. JORNADAS DE INICIAÇÃO À INVESTIGAÇÃO CLÍNICA (1ªs). Promoter: DIIC/MIM/ICBAS/UP e GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: 26/06/2009. 26. PROJECTOS DE INVESTIGAÇÃO: ELABORAÇÃO DE PROPOSTAS (2ª edição). Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 19-22 e 27/01/2009. 2008 27. PROJECTOS DE INVESTIGAÇÃO II: ELABORAÇÃO DE PROPOSTAS” (1ª edição). Promoter: GCI/DEFI/CHP. Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 24-27/11/2008; 02/12/2008. 28. “ABC DO HOSPITAL”: 20 sessions held throughout the year in 2008, involving 83 Departments, Services, Sectors and Units and were attended by about 1000 participants. Promoter: Direcção clínica do CHP e DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. 2007 29. COLÓQUIOS DO HGSA: INVESTIGAÇÃO EM SAÚDE. Promoter: Clinical Direction HSA and DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: 2006 30. COLÓQUIOS DO HGSA: CUIDADOS DE SAÚDE. Promoter: Clinical Direction HSA and DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: D) SCIENTIFIC OUTPUT For the last years, an effort was made in order to improve records of research activities and scientific production of the Hospital, by registering systematically the research studies performed, the scientific papers published in peer-reviewed scientific journals and the academic graduations. With this purpose, new software (REFI) was developed in 2010 and 2011 to record the teaching, training and research activities conducted at Hospital, being used since 2012 for the elaboration of the annual reports. Software for submission and approval of the research studies at the hospital is now being conceived. Research studies: From 2007 to 2012, the number of research studies/year increased from 111 to 312: clinical trials with drugs and medical devices: 20 to 28, research projects and observational studies: 39 to 124; academic projects: 52 to 160. Total number: 1198 (155 + 411 + 632) (Table 5). Table 5: Number of research studies at the CHP from 2007 to 2012 Year 2007 2008 2009 2010 2011 2012 2007-2012 Clinical trials with drugs 18 22 23 23 30 25 141 Studies with medical devices 2 2 2 2 3 3 14 Research projects and observational studies 39 48 62 64 74 124 411 Academic projects 52 76 87 116 141 160 632 Total 111 148 174 205 248 312 1198 Papers published: From 2007 to 2012, the number of papers published annually in peer reviewed scientific journals with peer-review increased from 170 to 259 (indexed in the Medline: 92 to 187; non-indexed in the Medline: 78 to 72). Total number: 1221 (779 + 442). (Table 6) Table 6: Number of papers in periodicals with peer-review from 2007 to 2012 Year Indexed in the MedLine Non-indexed in the MedLine Total 2007 92 78 170 2008 99 78 177 2009 103 68 171 2010 139 93 232 2011 159 53 212 2012 186 72 258 2007-2012 778 442 1220 1988-1997: 509 (51/year) (365 MedLine + 153 non-MedLine); 1998-2007 (10 years): 1374 (137/year) (822 MedLine + 552 nonMedLine); 2007-2012 (6 years): 1219 (203/year) (777 MedLine + 442 non-MedLine) Books published: A Guide for Good Research Clinical Practices was edited in 2010. In the same year another book was edited, collecting all the papers published from the CHP professionals between 1988 and 2007; since than, a book is edited yearly on the subject. http://repositorio.chporto.pt/bitstream/10400.16/859/1/GUIA%20DE%20BOAS%20PR%C3%81TICAS%20EM%20INVESTIGA%C3%87%C3%83O %20cLINICA%20DO%20CHP.pdf Academic graduations: Between 2007 and 2012, 75 health professionals from the CHP enrolled in PhD programs and 18 PhD theses were concluded (Table 7); at the end of 2012, 78 PhD theses were ongoing. Also from 2007 to 2012, 133 health professionals from the CHP enrolled in MsD programs and 123 MsD graduations were obtained (Table 7); at the end of 2012, 33 MsD dissertations were ongoing. At the end of 2013, the CHP has 41 PhD (38 MD, 1 administrator, 2 technicians) and 151 MsD. Table 7: Number of academic graduations from health professionals of the CHP Year PhD MsD Ongoing Concluded Starting date (total) Ongoing Concluded Starting date (total) Initiated Initiated Finished Initiated Initiated Finished Before 2007 11 71 55 82 12 72 31 84 2007 3 3 5 6 5 22 8 27 2008 11 2 4 13 10 24 10 34 2009 16 2 1 18 9 18 20 27 2010 20 1 2 21 12 22 40 34 2011 13 0 3 13 11 0 19 11 2012 4 0 3 4 NA 0 26 0 2013 NA 0 6 NA NA 0 4 NA 2007-2012 67 8 18 75 47 86 123 133 Till 2012 78 79 73 157 59 158 154 217 Till 2013 NA 79 79 (*) NA 59 (**) 158 158 (***) 217 NA, data not available; (*) 23/12/2013: 40 active health professionals with PhD; (**) 23/12/2013: 33 going on + 26 dropouts (***) 23/12/2013: 151 active professionals with MsD. National survey on scientific and technological activities (IPCTN): From 2007 to 2011 the number of researchers (in full time equivalents, FTE) at the CHP increased from 37.0 to 72.8 FTE and the total expenses with I&D increased from 1.854.442 to 7.801.801 €/year, corresponding to the first position in the national ranking in the majority of the evaluated parameters. Data from the 2012 survey are not yet available. http://www.dgeec.mec.pt/np4/206/ (Table 8) Table 8: Results from the national survey on scientific and technological activities (IPCTN)* IPCTN I&D Units Research (Year) (n, %) projects (n) Researchers (n) Researchers (FTE) NR 2007 PhD researchers (FTE) NR Researchers (mean % Expenses (€) NR 1.854.442 NA 3.556.430 1º 5.449.273 1º 6.189.333 1º 7.801.801 3º NA NA TDR) 25 100 199 37,0 NA NA NA (40%) 2008 32 157 198 34,3 3º NA NA 6,0 (52%) 2009 35 204 274 51,8 1º NA NA 10,8 (56%) 2010 38 290 322 64,3 1º 4,6 6º 15,0 (60%) 2011 28 NA 365 72,8 3º 5,9 6º 15,0 (43%) 2012 NA NA NA NA NA NA NA * Data from GPEARI/MCTES; NA, Not yet available; TDR, Time dedicated to research; FTE, Full Time Equivalents E) INTER-INSTITUCIONAL PARTNERSHIPS The research activity in the Hospital is developed in collaboration with other national and foreign academic, research and health care centers, as well as with professional and scientific societies and working groups. In addition, the Hospital collaborates with a large number of public and private schools, at different levels: teaching of disciplines and courses, collaborating in academic projects, training health professionals (medical doctors, lab technicians, nurses, etc.) and students, etc. In the last two years, the Hospital signed collaboration protocols with nearly 50 polytechnic and university schools. Some of the collaborations established with other FCT Research Units included: Cardiology - IPATIMUP; Gastroenterology - IPATIMUP; Hematology - IBMC/UP and UMIB; Immunology – IGC and UMIB/UP; Neurology – IBMC/UP and UMIB/UP; Orthopedics - INEB/UP and UMIB; F) RESEARCH FUNDING A) Hospital funding (FID) – Grants: 343.300€ (individual grants: 253.300€; grants for research projects: 80.000€; grants for PhD projects: 40.000€) B) Hospital funding (FID) – Awards: 100.000€ (investigators: 75.000€; clinical departments: 25.000€) C) Hospital funding – Library resources: 1.600.000€ (printed: 720.000€; electronic: 880.000€) D) ICBAS/UP funding – Research grants (research projects for medical students, DIIC): 67.500 €. E) FCT funding – Research grants (research projects): 196.069,00€ F) European Union funding – Research grants (research projects): 67.405 € From 2008 to 2012, hospital expenses with library resources totalized ~ 1.400.000€ (Table 9). Table 9: CHP funding for library resources Printed resources On-line resources B-On UpToDate AtoZ OvidSP ClinicalKey Year Periodicals and others(*) (FCCN) (WKH) (EBSCO) (LWW) (Elsevier) Total 2007 120000,00 97122,88 - - - - 217122,88 2008 120000,00 97122,88 - - - - 217122,88 2009 120000,00 121540,80 45500,00 - - - 287040,80 2010 120000,00 216144,00 45500,00 2765,07 23952,50 - 408361,57 2011 120000,00 - 63145,43 2765,07 28982,53 - 214893,03 2012 120000,00 - 63145,43 2765,07 28982,53 48040,00 262933,03 2007-2012 720000,00 531930,56 217290,86 8295,21 81917,56 48040,00 1607474,19 2007-2012 720000,00 2008-2012 600000,00 434807,68 217290,86 81917,56 48040,00 1390351,31 2008-2012 600000,00 887474,19 8295,21 1607474,19 790351,31 1390351,31 By creating a Fund for Research and Development (FID) (financial support from the pharmaceutical industry, mainly from clinical trials), during the same period, the CHP attributed individual grants, mainly for post-graduation programs (213.300€), grants for research projects (80.000€), PhD studies (40.000€) (Table 10) and for research fellows (3 grants in 2012, totalizing 40.750€, which were renewed in 2013), as well as awards for the hospital departments (25.000€) and investigators (75.000€) (Tables 11 and 12). Simultaneously, the remaining funds from research studies (clinical trials and observational studies) promoted and funded by external entities (mainly pharmaceuticals) were made available to the services to be applied in teaching, training and research activities, as well as to contract research fellows. In addition, the hospital received grants for research projects from the FCT (196.069€).and from the European Community (67.405 €) (Tables 13 and 14). Table 10: CHP funding (FID) for individual grants and grants for research projects and doctoral thesis* Year Individual grants & scholarships (€) Research projects (€) PhD projects (€) Total founding (€) 2007 40.000€ - - 40.000€ 2008 40.000€ - - 40.000€ 2009 40.000€ 20.000€ 10.000€ 70.000€ 2010 40.000€ 20.000€ 10.000€ 70.000€ 2011 46.650€ 20.000€ 10.000€ 76.650€ 2012 46.650€ 20.000€ 10.000€ 76.650€ 2007-2012 253.300€ 80.000€ 40.000€ 373.300€ 2008-2012 213.300€ 80.000€ 40.000€ 343.300€ * Training programs; doctoral, master and other post-graduation courses Abbreviations: FID, Fundo para a Investigação e Desenvolvimento (Fund for Research and Development) Table 11: CHP funding (FID) for awards for CHP departments and investigators Year Awards for the clinical department with the best scientific activity Awards for the investigators with the best publication Total founding 2007 - - - 2008 5.000€ 15.000€ 20.000€ 2009 5.000€ 15.000€ 20.000€ 2010 5.000€ 15.000€ 20.000€ 2011 5.000€ 15.000€ 20.000€ 2012 5.000€ 15.000€ 20.000€ 2007-2012 25.000€ 75.000€ 100.000€ 2008-2012 25.000€ 75.000€ 100.000€ Abbreviations: FID, Fundo para a Investigação e Desenvolvimento (Fund for Research and Development) Table 12. Awards for the investigators with the best publications Year CHP investigator (Author) Published manuscript (€) 2007 - - - 2008 Teresa Temudo Stereotypies in Rett syndrome: analysis of 83 patients with and without detected MECP2 mutations 10.000€ 2009 Estevão Lima Endoscopic closure of transmural bladder wall perforations 10.000€ 2010 Ana Mota Epidemiological Study of Genotypes of Hepatitis B Vírus in Norther Portugal 10.000€ Angélica Rodrigues Bilateral Submandibulectomy for the Treatment of Drooling in Children With Neurological Disability - 2011 Idalina Beirão Erythropoietin production by distal nephron in normal and familiar amyloidotic adult human kidneys 7.500€ La Fuente de Carvalho Diabetes exacerbates the functional deficiency of NO/cGMP pathway associated with erectile dysfunction in human corpus cavernosum and penile arteries 2.500€ 2012 Ana Martins da Silva Olfactory dysfunction in multiple sclerosis: association with secondary progression 7.500€ Maria de La Salete Martins One Hundred Eleven Simultaneous Pancreas-Kidney Transplantations: 10-Year Experience From a Single Center in Portugal 2.500€ (*) Approximate values (values in 2013 were similar to those indicated for 2012). Table 13: FCT funding for research projects Reference number Project title PIC/IC/82858/2007 Tendências na incidência e prognóstico dos Acidentes Neurológicos: o segundo estudo de base populacional no norte de Portugal GALENO - Modelação e controlo para administração personalizada de fármacos (Nº registo Variabilidade fenotípica e genes modificadores na Polineuropatia Amiloidótica Familiar Prevenção/intervenção precoces em distúrbios de comportamento: eficácia de programas parentais e escolares Superfícies de nanohidroxiapatite com características antibacterianas para presenção de infecção óssea associada a biofilmes (NaNOBiofilm) Total PTDC/SAUBEB/103667/2008 PTDC/SAUGMG/100240/2008 PTDC/PSIPED/102556/2008 PTDC/SAUBMA/111233/2009 Host institution HSA/CHP Total funding € 178.000 Funding for the CHP € 160.368 FU/UP 185.000 8.640 IBMC/UP 199.275 15.061 FPCE/UC 165.031 6.000 INEB/UP 150.000 6.000 877.360 € 196.069 € Table 14: European Community funding for research projects Reference number Project title WebSite Host institution Starting date Duration Grant Agreement 2008 13 05 DSDP - Day Surgery Data Project http://www.dsdp.eu/ ARSS, Venezia, Italia 01-092009 Grant Agreement 2009 11 04 DSP - Day Safe Project http://www.daysafe.eu/ ARSS, Venezia, Italia 01-102010 TOTAL ARSS, Agenzia Regionale Socio-Sanitaria del Veneto. 36 months Total funding (EC funding)€ ? Funding for the CHP€ 25.308 36 months (EC: 300.000) 1.094.740 42.097 (EC: 650.000) (EC: 950.000) 67.405 Relatório Científico Final 2011-13 – UMIB Research Group Title: Nephrology, Dialysis and Transplantation Principal Investigator: Luisa Lobato Research Area: Health Sciences Home Institution: Instituto de Ciências Biomédicas Abel Salazar