Quality of life of adolescents with type 1 diabetes

INTRODUCTION: Diabetes mellitus is a highly prevalent chronic disease. Type 1 diabetes mellitus usually develops during infancy and adolescence and may affect the quality of life of adolescents. OBJECTIVE: To evaluate the quality of life of adolescents with type 1 diabetes mellitus in a metropolitan region of western central Brazil. METHODS: Adolescents aged 10-19 years who had been diagnosed with type 1 diabetes mellitus at least 1 year previously were included. Patients with verbal communication difficulties, severe disease, and symptomatic hypo- or hyperglycemic crisis as well as those without an adult companion and who were ;7%. In general, the adolescents consistently reported having a good quality of life. The median scores for the domains of the instrument were as follows: “satisfaction”: 35; “impact”: 51; and “worries“: 26. The total score for all domains was 112. Bivariate analysis showed significant associations among a lower family income, public health assistance, and insulin type in the “satisfaction” domain; and a lower family income, public health assistance, public school attendance, and a low parental education level in the “worries“ domain and for the total score. A longer time since diagnosis was associated with a lower total score. Multivariable analysis confirmed the association of a worse quality of life with public health assistance, time since diagnosis, and sedentary lifestyle in the “satisfaction” domain; female gender in the “worries” domain; and public health assistance for the total score. CONCLUSIONS: Overall, the adolescents evaluated in this study viewed their quality of life as good. Specific factors that led to the deterioration of quality of life, including public assistance, time since diagnosis, sedentary lifestyle, and female gender, were identified. No potential conflict of interest was reported

Infecção por virus sincicial respiratório: o papel dos anticorpos séricos específicos

INTRODUCTION: Respiratory syncytial virus (RSV) is a major etiological agent of lower respiratory tract infection in infants. Genotypes of this virus and the role of the infants' serum antibodies have yet to be fully clarified. This knowledge is important for the development of effective therapeutic and prophylactic measures. OBJECTIVES: To evaluate the types and genotypes of RSV causing respiratory tract infection in infants, to analyze the association of subtype-specific serum antibodies with the occurrence of infection and to evaluate the presence of subtype-specific antibodies in the infants' mothers and their association with the profile of the childrens' serum antibodies. METHODS: This was a prospective study on infants hospitalized with respiratory infection. Nasopharyngeal secretions were collected for viral investigation using indirect immunofluorescence and viral culture and blood was collected to test for antibodies using the Luminex Multiplex system. RESULTS: 192 infants were evaluated, with 60.9% having RSV (73.5%- A and 20.5% B). Six genotypes of the virus were identified: A5, A2, B3, B5, A7 and B4. The seroprevalence of the subtype-specific serum antibodies was high. The presence and levels of subtype-specific antibodies were similar, irrespective of the presence of infection or the viral type or genotype. The mothers' antibody profiles were similar to their infants'. CONCLUSIONS: Although the prevalence of subtype-specific antibodies was elevated, these antibodies did not provide protection independently of virus type/genotype. The similarity in the profiles of subtype-specific antibodies presented by the mothers and their children was consistent with transplacental passage.INTRODUÇÃO: O vírus sincicial respiratório é um dos principais agentes etiológicos das infecções do aparelho respiratório inferior em lactentes. Os genótipos deste vírus e o papel dos anticorpos séricos ainda não estão esclarecidos. Este conhecimento é importante para o desenvolvimento de medidas terapêuticas e profiláticas. OBJETIVOS: Avaliar: os tipos e genótipos do vírus sincicial que causam infecção respiratória em lactentes e a associação dos anticorpos séricos subtipo-específicos com a ocorrência de infecção; a presença de anticorpos subtipo-específicos nas mães e sua associação com o perfil de anticorpos da criança. MÉTODOS: Estudo prospectivo incluindo lactentes hospitalizados com infecção respiratória. Foi coletada secreção de nasofaringe para investigação viral usando imunofluorescência indireta e cultivo viral. Foi coletado sangue para pesquisa de anticorpos usando o sistema Luminex Multiplex. RESULTADOS: Avaliados 192 lactentes: 60,9% com vírus sincicial (73,5% - A e 20,5% - B). Seis genótipos de vírus sincicial respiratório foram identificados: A5,A2,B3,B5,A7 e B4. A soroprevalência dos anticorpos subtipos-específicos foi alta. A presença e o nível de anticorpos subtipos-específicos foram semelhantes, independentemente da presença de infecção, tipo e genótipo do vírus. As mães e as crianças apresentaram perfis semelhantes de anticorpos. CONCLUSÕES: A prevalência dos anticorpos subtipos-específicos foi elevada mas estes anticorpos não conferiram proteção, independentemente do tipo/genótipo do vírus. A semelhança dos perfis de anticorpos das mães e das crianças foi compatível com transmissão transplacentária

Fortes militares : uma nova oportunidade : turismo militar no Forte de São João Batista da Foz : cidade do Porto

Mestrado Integrado em ArquitecturaExame público realizado em 6 de Junho de 2017Ambiciona-se com a presente dissertação abordar a vertente específica da Arquitetura Militar, nomeadamente os fortes militares. Elegeu-se o Forte de São João Batista da Foz, localizado na cidade do Porto, para idealizar uma proposta de arquitetura apoiada no conceito do “Turismo Militar”. Pretende-se reabilitar/preservar este forte com valorização histórica e adaptá-lo aos dias de hoje com um toque de modernidade. O projeto pretende preservar o caráter militar do forte,salvaguardando sempre a sua originalidade mas, com uma estratégia contemporânea capaz de cativar um maior número de visitantes. O Forte Militar de São João Batista da Foz surge com uma nova oportunidade. Aliado ao novo conceito do “Turismo Militar”, ganha uma nova vida, contemporânea mas, que desperta as memórias históricas militares que caraterizam a sua origem. Tradição e modernidade fundem-se e assumem um papel associado ao turismo e à transmissão de acontecimentos históricos militares de Portugal. Constitui-se um enorme desafio poder contribuir com uma proposta que, segudo este estudo, se afigura como solução adequada para a promoção da fortaleza como estratégia de valorização do monumento histórico e transmissão de valores culturais, sociais e histórico militares. O Instituto da Defesa Nacional (IDN), sediado neste forte, continua a desempenhar as mesmas atividades mas, passa a ter como complemento uma zona habitacional junto às muralhas e um snack bar/restaurante no interior das mesmas. Assim desperta-se o interesse pela preservação de locais da cidade onde se dinamiza a história, o património e o “Turismo Militar” junto da sociedade.The present work deals with the specific aspects of military architecture, especially the military fortress. It was elected the Fort of São João Batista da Foz, located in Porto city, to idealize an architectural proposal based on the concept of “Military Tourism”. It is intended to rehabilitate/preserve this fort with historical valorization and adapt it to nowadays with a content of modernity. The project intends to maintain the military character of the fort, always preserving its originality but with a contemporary strategy able to attract a greater number of visitors. The Military Fort of São João Batista da Foz comes with a new opportunity. Coupled with the new concept of “Military Tourism”, gets a new life, contemporary, but also awakening military historical memories that caracterize its origin. Tradition and modernity merge and assume a role associated with tourism and the transmission of military historical events of Portugal. It constitutes a major challenge to contribute with a proposal that, according to the study, seems to be a suitable solution for the promotion of the fort as an appreciation strategy of the historical monument and transmission of cultural, social and military history values. The NID (National Institute of Defense), based in this fort, continues to perform the same activities, but shall be supplemented by a housing area next to the walls and a snack bar/restaurant inside the same. Therefore is awaken the interest for the preservation of city places where is invigorated the history, the patrimony and the “Military Tourism” near the society

O tráfego subcelular da Proteína Precursora de Amilóide de Alzheimer (PPA) é dependente de fosforilação

Doutoramento em BiologiaA Doença de Alzheimer (DA) é uma das doenças neurodegenerativas mais comuns, e apresenta uma incidência mundial de 2-7% em indivíduos com mais de 65 anos e de cerca de 15% em indivíduos acima dos 85 anos de idade. Apesar da sua etiologia multifactorial, há uma correlação bem descrita entre esta patologia e um peptídeo neurotóxico denominado Abeta. Este peptídeo deriva fisiológica e proteoliticamente de uma glicoproteína transmembranar com características de receptor: a Proteína Percursora de Amilóide de Alzheimer (PPA). As possíveis funções fisiológicas da proteína PPA, o seu destino e vias de processamento celulares, conjuntamente com possíveis proteínas celulares que com ela interajam, são assim tópicos de interesse e objectos de investigação científica mundial. Neste contexto tem sido amplamente descrito o envolvimento do processo de fosforilação de proteínas, uma importante modificação pós-transducional que regula muitos e variados acontecimentos intracelulares, na regulação do processamento da PPA. Apesar do exposto, muito pouco é conhecido acerca da fosforilação directa da própria PPA. Esta proteína possui na sua estrutura primária sequências consenso para fosforilação, quer no seu ectodomínio quer no seu domínio intracelular, já descritas como sofrendo fosforilação “in vitro” e “in vivo”. O resíduo Serina 655 pertence a um motivo funcional da APP, 653YTSI656, que forma um sinal de internalização e/ou de “sorting” basolateral. Este domínio é também o local de ligação para a APPBP2, uma proteína que interage com os microtubulos da célula. Embora ainda mal elucidados, os mecanismos pelos quais a fosforilação proteica regula o processamento da PPA parecem incluir uma alteração no tráfego desta proteína, sugerindo que o domínio fosforilável 653YTSI656 desempenha um papel importante nesse processo. Esta dissertação visou assim contribuir para elucidar o papel da fosforilação directa da molécula de APP, mais especificamente no seu resíduo Serina 655, na regulação do direcionamento e tráfego subcelular da proteína, e nas suas possíveis clivagens proteolíticas. De forma a respondermos a essas questões desenvolvemos um modelo experimental para seguir o tráfego intracelular, que usa uma combinação de biologia molecular, técnicas de microscopia de epifluorescência e técnicas de cultura celular. Os resultados obtidos implicam este resíduo como um sinal de direcionamento subcelular da proteína APP, e revelam como o redireccionamento desta proteína por fosforilação favorece um tipo de processamento não amiloidogénico desta. Adicionalmente, a fosforilação do resíduo Serina 655 parece possuir um papel regulador da actividade da PPA como molécula de transdução de sinais. As implicações destas observações na DA e em novas aplicações terapêuticas para a doença são subsequentemente discutidas.Alzheimer’s Disease (AD) is a common neurodegenerative disease affecting individuals worldwide with an incidence of 2-7% of post-65 and 15% of post-85 years old. This disease is multifactorial in its etiology but central to its pathology is a neurotoxic peptide termed Abeta. This peptide is physiologically derived by a proteolytic process on the transmembranar Alzheimer’s Amyloid Precursor Protein (APP). Protein phosphorylation-dependent APP processing has been widely described and although the mechanisms involved remain far from clarified, alterations in APP trafficking seem to occur as part of the answer. Furthermore, the occurrence of consensus phosphorylation sites in the APP intracellular domain has been known for long, but little was known regarding the direct phosphorylation of APP. Efforts in unravelling the role of these domains are finally being successful in placing them as key control points in APP targeting and processing. Among these consensus sequences, the less studied 653YTSI656 motif forms a characteristic internalisation and/or basolateral sorting signal sequence, and is known to be the binding site for a microtubuleinteracting protein (APPBP2). Phosphorylation of this motif was thus suggested to be involved in APP targeting regulation, hitherto all attempts failed to confirm it or even to reveal substantial evidences. In this project, the role of the 653YTSI656 idomain, and in particular the phosphorylatable serine 655, in APP trafficking and proteolytic processing was studied. In order to address this question a new experimental methodology was developed, which coupled molecular biology, fluorescence imaging, and cell culture techniques. APP point mutants, mimicking serine 655 phosphorylatedand dephosphorylated-status, and tagged with the green-fluorescent protein, were used to study protein trafficking dynamics and processing. Results obtained place serine 655 phosphorylation as a key signal in APP sorting and targeting to specific subcellular locations. Also of high relevance was the observed implication of serine 655 phosphorylation as a regulatory mechanism that maybe involved in controlling APP function as a signal transducer. The implications of these observations in AD pathogenesis and therapeutic approaches are discussed.FCT - PRAXIS XXI/BD/16218/98FCT - POCTI/BCI/34349/1999Project DIADEM, QLK3-CT- 2001/02362Fundação Calouste GulbenkianFundação Astrazenec

Retrieval of the Alzheimer's amyloid precursor protein from the endosome to the TGN is S655 phosphorylation state-dependent and retromer-mediated

Background: Retrograde transport of several transmembrane proteins from endosomes to the trans-Golgi network (TGN) occurs via Rab 5-containing endosomes, mediated by clathrin and the recently characterized retromer complex. This complex and one of its putative sorting receptor components, SorLA, were reported to be associated to late onset Alzheimer's disease (AD). The pathogenesis of this neurodegenerative disorder is still elusive, although accumulation of amyloidogenic Abeta is a hallmark. This peptide is generated from the sucessive β- and γ- secretase proteolysis of the Alzheimer's amyloid precursor protein (APP), events which are associated with endocytic pathway compartments. Therefore, APP targeting and time of residence in endosomes would be predicted to modulate Abeta levels. However, the formation of an APP- and retromer-containing protein complex with potential functions in retrieval of APP from the endosome to the TGN had, to date, not been demonstrated directly. Further, the motif(s) in APP that regulate its sorting to the TGN have not been characterized. Results: Through the use of APP-GFP constructs, we show that APP containing endocytic vesicles targeted for the TGN, are also immunoreactive for clathrin-, Rab 5- and VPS35. Further, they frequently generate protruding tubules near the TGN, supporting an association with a retromer-mediated pathway. Importantly, we show for the first time, that mimicking APP phosphorylation at S655, within the APP 653YTSI656 basolateral motif, enhances APP retrieval via a retromer-mediated process. The phosphomimetic APP S655E displays decreased APP lysosomal targeting, enhanced mature half-life, and decreased tendency towards Abeta production. VPS35 downregulation impairs the phosphorylation dependent APP retrieval to the TGN, and decreases APP half-life. Conclusions: We reported for the first time the importance of APP phosphorylation on S655 in regulating its retromer-mediated sorting to the TGN or lysosomes. Significantly, the data are consistent with known interactions involving the retromer, SorLA and APP. Further, these findings add to our understanding of APP targeting and potentially contribute to our knowledge of sporadic AD pathogenesis representing putative new targets for AD therapeutic strategies

The importance of viral load in the severity of acute bronchiolitis in hospitalized infants

OBJECTIVE: The relationship between viral load and the clinical evolution of bronchiolitis is controversial. Therefore, we aimed to analyze viral loads in infants hospitalized for bronchiolitis. METHODS: We tested for the presence of human respiratory syncytial virus (HRSV) or human rhinovirus (HRV) using quantitative molecular tests of nasopharyngeal secretions and recorded severity outcomes. RESULTS: We included 70 infants [49 (70%) HRSV, 9 (13%) HRV and 12 (17%) HRSV+HRV]. There were no differences among the groups according to the outcomes analyzed individually. Clinical scores showed greater severity in the isolated HRSV infection group. A higher isolated HRSV viral load was associated with more prolonged ventilatory support, oxygen therapy, and hospitalization days, even after adjustment for the age and period of nasopharyngeal secretion collection. In the co-infection groups, there was a longer duration of oxygen therapy when the HRSV viral load was predominant. Isolated HRV infection and co-infection with a predominance of HRV were not associated with severity. CONCLUSION: Higher HRSV viral load in isolated infections and the predominance of HRSV in co-infections, independent of viral load, were associated with greater severity. These results contribute to the development of therapeutic and prophylactic approaches and a greater understanding of the pathophysiology of bronchiolitis

Natural-origin materials for tissue engineering and regenerative medicine

Recent advances in tissue engineering and regenerative medicine have shown that combining biomaterials, cells, and bioactive molecules are important to promote the regeneration of damaged tissues or as therapeutic systems. Natural origin polymers have been used as matrices in such applications due to their biocompatibility and biodegradability. This article provides an up-to-date review on the most promising natural biopolymers, focused on polysaccharides and proteins, their properties and applications. Membranes, micro/nanoparticles, scaffolds, and hydrogels as biomimetic strategies for tissue engineering and processing are described, along with the use of bioactive molecules and growth factors to improve tissue regeneration potential. Finally, current biomedical applications are also presented.The authors would like to thank to the financial support from the Portuguese Foundation for Science and Technology (FCT) for the fellowship grants of Simone S Silva (SFRH/BPD/112140/2015), Emanuel M Fernandes (SFRH/BPD/96197/2013), Joana-Silva Correira (SFRH/BPD/100590/2014), Sandra Pina (SFRH/BPD/108763/2015), Silvia Vieira (SFRH/BD/102710/2014), “Fundo Social Europeu”- FSE and “ Programa Diferencial de Potencial Humano POPH”, and to the distinction attributed to J.M. Oliveira under the Investigator FCT program (IF/00423/2012). It is also greatly acknowledged the funds provided by FCT through the project EPIDisc (UTAP-EXPL/BBBECT/0050/2014), financed in the Framework of the “International Collaboratory for Emerging Technologies, CoLab”, UT Austin|Portugal Program.info:eu-repo/semantics/publishedVersio

Environmental risk factors associated with biliary atresia in Rio Grande do Sul, Brazil

Biliary atresia (BA) seems to be a multifactorial disorder in which environmental factors interact with the patient’s genetic constitution. This study aimed to analyze information concerning environmental risk factors associated with BA in southern Brazil. A case-control study with mothers of patients with BA and mothers of patients with cystic fibrosis (CF) was conducted. Inquiry included questions related to exposition to environmental risk factors during the periconceptional and gestational (second and third trimesters) periods. Mothers of BA patients had smoked during pregnancy more frequently in comparison with the mothers of CF patients, but no significant difference was found in a multivariate analysis. There was no between group difference in terms of seasonality, but the multivariate analysis showed a significant difference within the BA group between date of conception in winter compared to other seasons. In conclusion, smoking during pregnancy seemed to increase the risk of BA while date of conception in winter decreased it.Keywords: Biliary atresia; environmental risk factor; etiology; seasonality; smokin

Interaction between IRF6 and TGFA Genes Contribute to the Risk of Nonsyndromic Cleft Lip/Palate

Previous evidence from tooth agenesis studies suggested IRF6 and TGFA interact. Since tooth agenesis is commonly found in individuals with cleft lip/palate (CL/P), we used four large cohorts to evaluate if IRF6 and TGFA interaction contributes to CL/P. Markers within and flanking IRF6 and TGFA genes were tested using Taqman or SYBR green chemistries for case-control analyses in 1,000 Brazilian individuals. We looked for evidence of gene-gene interaction between IRF6 and TGFA by testing if markers associated with CL/P were overtransmitted together in the case-control Brazilian dataset and in the additional family datasets. Genotypes for an additional 142 case-parent trios from South America drawn from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), 154 cases from Latvia, and 8,717 individuals from several cohorts were available for replication of tests for interaction. Tgfa and Irf6 expression at critical stages during palatogenesis was analyzed in wild type and Irf6 knockout mice. Markers in and near IRF6 and TGFA were associated with CL/P in the Brazilian cohort (p<10-6). IRF6 was also associated with cleft palate (CP) with impaction of permanent teeth (p<10-6). Statistical evidence of interaction between IRF6 and TGFA was found in all data sets (p = 0.013 for Brazilians; p = 0.046 for ECLAMC; p = 10-6 for Latvians, and p = 0.003 for the 8,717 individuals). Tgfa was not expressed in the palatal tissues of Irf6 knockout mice. IRF6 and TGFA contribute to subsets of CL/P with specific dental anomalies. Moreover, this potential IRF6-TGFA interaction may account for as much as 1% to 10% of CL/P cases. The Irf6-knockout model further supports the evidence of IRF6-TGFA interaction found in humans. © 2012 Letra et al