A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease

We acknowledge iNOVA4Health—UID/Multi/04462/2019, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. Funding from the INTERFACE Programme, through the Innovation, Technology and Circular Economy Fund (FITEC) is gratefully acknowledged. This study was also supported by FCT via PTDC/BIA-MOL31104/2017 and UID/Multi/04462/2019-SubProj iNOVA4Health 44 to RM and PD/BD/135504/2018 to AR. Sociedade Portuguesa de Diabetologia for the Nuno Castelo-Branco Prize−2016, attributed to RM, was also acknowledged. IM acknowledges FCT-MCTES Program Concurso de Estímulo ao Emprego Científico (CEECIND/01670/2017).Diabetes affects hundreds of millions of patients worldwide. Despite the advances in understanding the disease and therapeutic options, it remains a leading cause of death and of comorbidities globally. Islet amyloid polypeptide (IAPP), or amylin, is a hormone produced by pancreatic β-cells. It contributes to the maintenance of glucose physiological levels namely by inhibiting insulin and glucagon secretion as well as controlling adiposity and satiation. IAPP is a highly amyloidogenic polypeptide forming intracellular aggregates and amyloid structures that are associated with β-cell death. Data also suggest the relevance of unprocessed IAPP forms as seeding for amyloid buildup. Besides the known consequences of hyperamylinemia in the pancreas, evidence has also pointed out that IAPP has a pathological role in cognitive function. More specifically, IAPP was shown to impair the blood–brain barrier; it was also seen to interact and co-deposit with amyloid beta peptide (Aß), and possibly with Tau, within the brain of Alzheimer's disease (AD) patients, thereby contributing to diabetes-associated dementia. In fact, it has been suggested that AD results from a metabolic dysfunction in the brain, leading to its proposed designation as type 3 diabetes. Here, we have first provided a brief perspective on the IAPP amyloidogenic process and its role in diabetes and AD. We have then discussed the potential interventions for modulating IAPP proteotoxicity that can be explored for therapeutics. Finally, we have proposed the concept of a “diabetes brain phenotype” hypothesis in AD, which may help design future IAPP-centered drug developmentstrategies against AD.publishersversionpublishe

Primeiro registo do tubarão-anão, Squaliolus laticaudus (Smith & Radcliffe, 1912) nos Açores, estendendo a sua distribuição ocidental no Atlântico Nordeste

A presente nota documenta a primeira observação do tubarão-anão, Squaliolus laticaudus (Smith & Radcliffe, 1912), nos Açores, estendendo a sua distribuição ocidental no Atlântico Nordeste até ao arquipélago. A ocorrência da espécie nos arquipélagos macaronésicos é igualmente discutida.ABSTRACT: This paper reports the first observation of the spined pygmy shark, Squaliolus laticaudus, from the Azores, extending its westernmost distribution in the North-eastern Atlantic as far as this archipelago. The occurrence of this species in the Macaronesian archipelagos is also discussed

Clustering of risk factors for chronic diseases among adolescents from Southern Brazil

AbstractObjectiveTo investigate the clustering of risk behaviors for chronic non-communicable diseases and their associated factors among adolescents from Southern Brazil.MethodsIn 2008, a survey was conducted with 3990 adolescents aged 14–15years (mean: 14.3; SD: 0.6) from the 1993 Pelotas Birth Cohort Study. Clustering was determined by comparing observed (O) and expected (E) prevalence of all possible combinations of the four risk factors investigated (smoking, alcohol intake, low fruit intake, and physical inactivity). We carried out Poisson regression to evaluate the effect of individual characteristics on the presence of at least three risk behaviors.ResultsAll risk factors tended to cluster together (O/E prevalence=3.0), especially smoking and alcohol intake (odds ratio to present on behavior in the presence of other >5.0). Approximately 15% of adolescents displayed three or more risk behaviors. Females (adjusted OR=1.55), people 15years and older (OR=1.47), with black skin color (OR=1.23), and of low socioeconomic level (OR=1.29) were more likely to display three or more risk factors.ConclusionThese findings suggest that lifestyle-related risk factors tend to cluster among adolescents. Identifying subgroups at greater risk of simultaneously engaging in multiple risk behaviors may aid in the planning of preventive strategies

Adiposity, depression and anxiety: interrelationship and possible mediators

OBJECTIVES: To explore the association between adiposity, major depressive disorder and generalized anxiety disorder, and to assess the role of inflammation, diet quality and physical activity in this association. METHODS: We used data from 2,977 individuals from the 1993 Pelotas Cohort (Brazil) who attended the 18- and 22-year follow-ups. We assessed general obesity using body mass index, fat mass index, and abdominal obesity using waist circumference. Major Depressive Disorder and generalized anxiety disorder were assessed using the mini-international neuropsychiatric interview. C-reactive protein and interleukin-6 (IL-6) levels were used as a measure of inflammation; diet quality was estimated using the revised diet quality index, and physical activity was assessed by the International physical activity questionnaire (IPAQ, min/day). The association between adiposity and major depressive disorder and generalized anxiety disorder was assessed using logistic regression, and the natural indirect effect via the mediators was estimated using G-computation. RESULTS: General obesity assessed by body mass index (OR: 2.3; 95% CI:1.13; 4.85), fat mass index (OR: 2.6; 95%CI: 1.37; 4.83), and abdominal obesity (OR: 2.5; 95%CI: 1.18; 5.39) were associated with higher odds of major depressive disorder, whereas major depressive disorder was only associated with obesity assessed by body mass index (OR=1.9; 95% CI: 1.09; 3.46). Obesity and generalized anxiety disorder were not associated. C-reactive protein, diet quality and physical activity did not mediate the effect of obesity on major depressive disorder, and C-reactive protein mediated about 25% of the effect of major depressive disorder on adiposity. CONCLUSIONS: Depression, but not generalized anxiety disorder, is associated with adiposity in both directions, with a stronger evidence for the direction obesity-depression. Inflammation explains part of the effect of major depressive disorder on obesity but not the other way around. Further research should explore other mechanisms that could be involved in the association between obesity and depression

Alginate beads to improve viability of Lactobacillus plantarum to heat stress

Peer Reviewe

Prevalência de atividade física em adolescentes e fatores associados

OBJECTIVE: To estimate the prevalence and identify correlates of physical activity among adolescents. METHODS: Cross-sectional study nested within a cohort of 4,325 subjects from the city of Pelotas, Southern Brazil, aged 14-15 years in 2008. Physical activity was analyzed using three different approaches: (1) prevalence of any leisure-time physical activity; (2) prevalence of any active commuting to school; and (3) prevalence of engaging in at least 300 minutes per week of both (1) and (2) combined. Independent variables included sociodemographic, behavioral, social, and biological characteristics, and number of different leisure-time physical activites practiced. Statistical analyses were carried out using Poisson regression. RESULTS: The proportion of adolescents involved in any type of leisure-time physical activity was 75.6%, while 73.4% displayed some form of active commuting to school. Prevalence of total physical activity score (>; 300 min/week) was 48.2%, being greater among boys (62.6%) than among girls (34.5%). Furthermore, prevalence increased along with the number of physical activity modalities practiced (pOBJETIVO: Estimar la prevalencia de actividad física entre adolescentes y identificar los factores asociados. MÉTODOS: Estudio transversal anidado en una cohorte con 4.325 individuos de 14-15 años en Pelota, Sur de Brasil, en 2008. La actividad física fue analizada por medio de tres diferentes abordajes: 1) prevalencia de alguna actividad física de ocio; 2) prevalencia de algún traslado activo para la escuela; 3) prevalencia de compromiso de por lo menos 300 minutos por semana en la combinación de ambos (1 y 2). Variables independientes incluyeron características demográficas, socioeconómicas, comportamentales, sociales y biológicas y número de actividades físicas practicadas en el tiempo de ocio. Los análisis estadísticos fueron hechos por la regresión de Poisson. RESULTADOS: La proporción de adolescentes envueltos en alguna actividad física de ocio fue 75,6% mientras que 73,4% presentaron alguna forma de traslado activo para la escuela. La prevalencia de actividad física total (escore ³ 300 min/sem) fue 48,2% siendo mayor para los niños (62,6%) que para las niñas (34,5%). Además, la prevalencia aumentó de acuerdo con el número de actividades físicas practicadas (pOBJETIVO: Estimar a prevalência de atividade física entre adolescentes e identificar fatores associados. MÉTODOS: Estudo transversal aninhado em uma coorte com 4.325 indivíduos de 14-15 anos em Pelotas, RS, em 2008. A atividade física foi analisada por meio de três diferentes abordagens: 1) prevalência de alguma atividade física de lazer; 2) prevalência de algum deslocamento ativo para a escola; 3) prevalência de engajamento em pelo menos 300 minutos por semana da combinação de ambos (1 e 2). Variáveis independentes incluíram características demográficas, socioeconômicas, comportamentais, sociais e biológicas e número de atividades físicas praticadas no tempo de lazer. As análises estatísticas foram feitas pela regressão de Poisson. RESULTADOS: A proporção de adolescentes envolvidos em alguma atividade física de lazer foi 75,6%, enquanto 73,4% apresentou alguma forma de deslocamento ativo para a escola. A prevalência de atividade física total (escore >; 300 min/sem) foi 48,2%, sendo maior para os meninos (62,6%) do que para as meninas (34,5%). Além disso, a prevalência aumentou de acordo com o número de atividades físicas praticadas (p < 0,001). Os fatores associados à maior prática de atividade física (lazer + deslocamento) nos níveis recomendados foram: cor de pele não-branca, ter repetido de ano na escola e jogar videogame. As variáveis menor nível socioeconômico, maior tempo de uso de computador e atividade física dos pais estiveram associadas ao desfecho apenas entre as meninas. CONCLUSÕES: Menos da metade dos adolescentes atingiu as recomendações para a prática de atividade física, e essa proporção tende a diminuir entre os sujeitos de maior nível socioeconômico. Os fatores associados diferiram entre lazer e deslocamento. Engajamento em uma ampla variedade de atividades físicas deve ser encorajado desde a infância

Infancy and childhood growth and physical activity in adolescence: prospective birth cohort study from Brazil.

BACKGROUND: The Developmental Origins of Health and Disease hypothesis suggests that intrauterine, infancy and early childhood variables play a key role at programming later health. However, little is known on the programming of behavioral variables, because most studies so far focused on chronic disease-related and human capital outcomes. The aim of the present study was to evaluate the effects of prenatal, infancy and childhood weight and length/height gains on objectively-measured physical activity (PA) in adolescence. METHODS: This is a prospective birth cohort study in Pelotas, Brazil, including 457 adolescents (mean age: 13.3 years) with weight and length/height data at birth, one, three and six months, one and four years of age. PA was measured using a GT1M Actigraph accelerometer, and expressed as (a) minutes per day spent on sedentary, light, moderate, vigorous and very-vigorous activities; (b) total counts per day. RESULTS: 61.3% of the adolescents accumulated 60+ minutes of moderate-to-vigorous PA per day. Weight and length/height trajectories in infancy and childhood were similar between those classified as active or inactive at 13.3 years. However, those classified as inactive were heavier and taller at all ages; differences were statistically significant only in terms of length at three, six and 12 months. CONCLUSIONS: Weight gain in infancy and childhood did not predict variability in adolescent PA, but those active in adolescence showed somewhat smaller average gains in length in infancy. These findings suggest that PA may partially be sensitive to early hormonal programming, or that genetic factors may affect both early growth and later metabolism or predisposition for PA.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Chemerin receptor blockade improves vascular function in diabetic obese mice via redox-sensitive- and Akt-dependent pathways

Chemerin and its G protein-coupled receptor [chemerin receptor 23 (ChemR23)] have been associated with endothelial dysfunction, inflammation, and insulin resistance. However, the role of chemerin on insulin signaling in the vasculature is still unknown. We aimed to determine whether chemerin reduces vascular insulin signaling and whether there is interplay between chemerin/ChemR23, insulin resistance, and vascular complications associated with type 2 diabetes (T2D). Molecular and vascular mechanisms were probed in mesenteric arteries and cultured vascular smooth muscle cells (VSMCs) from C57BL/6J, nondiabetic lean db/m, and diabetic obese db/db mice as well as in human microvascular endothelial cells (HMECs). Chemerin decreased insulin-induced vasodilatation in C57BL/6J mice, an effect prevented by CCX832 (ChemR23 antagonist) treatment. In VSMCs, chemerin, via oxidative stress- and ChemR23-dependent mechanisms, decreased insulin-induced Akt phosphorylation, glucose transporter 4 translocation to the membrane, and glucose uptake. In HMECs, chemerin decreased insulin-activated nitric oxide signaling. AMP-activated protein kinase phosphorylation was reduced by chemerin in both HMECs and VSMCs. CCX832 treatment of db/db mice decreased body weight, insulin, and glucose levels as well as vascular oxidative stress. CCX832 also partially restored vascular insulin responses in db/db and high-fat diet-fed mice. Our novel in vivo findings highlight chemerin/ChemR23 as a promising therapeutic target to limit insulin resistance and vascular complications associated with obesity-related diabetes

Prevalência e fatores de risco para tabagismo em adolescentes

OBJECTIVE: Tobacco smoking is one of the main causes of preventable disease and premature disability. Th estudy was aimed at measuring smoking prevalence and related risk factors among adolescents. METHODS: A population-based cross-sectional study was carried out in a representative sample of 1,187 adolescents aged 10 to 19 years living in the urban area of Pelotas, southern Brazil. All adolescents were interviewed separately using a confidential coded questionnaire. Kaplan-Meier test was performed for survival curve analysis. RESULTS: The overall smoking prevalence rate in the sample was 12.1% (95% CI 10.3%-14%). Boys and girls had similar prevalence rates. The following were the risk factors for smoking found in the multivariate logistic regression analysis: older age (OR=28.7; 95% CI 11.5-71.4), older smoking siblings (OR=2.4; 95% CI 1.5-3.8), three or more smoking friends (OR=17.5; 95% CI 8.8-34.8) and low schooling (OR=3.5; 95% CI 1.5-8.0). CONCLUSIONS: The prevalence of smoking among adolescents in the city of Pelotas was high. Campaigns against tobacco use should be aimed at the community and families, targeting adolescents. The government must adopt legal actions in order to prevent adolescents to have access to to smoking.OBJETIVO: O tabagismo é uma das principais causas de enfermidades evitáveis e incapacidades prematuras. Nesse sentido, realizou-se estudo com o objetivo de medir a prevalência e estudar fatores de risco associados ao tabagismo nos adolescentes. MÉTODOS: A partir de um delineamento transversal de base populacional, estudou-se uma amostra representativa de 1.187 adolescentes de 10 a 19 anos, da zona urbana de Pelotas, sul do Brasil. Todos os adolescentes da amostra, de cada domicílio, foram entrevistados por meio de questionário pré-codificado, individual e confidencial. Utilizou-se o teste de Kaplan-Meier para análise da curva de sobrevida. RESULTADOS: A prevalência de tabagismo na amostra foi de 12,1% (IC95% 10,3%-14%). As prevalências foram similares para os sexos femininos e masculinos. Os fatores de risco para tabagismo na análise multivariada, por regressão logística, foram: maior idade, odds ratio (OR) de 28,7 (11,5-71,4), irmãos mais velhos fumantes, OR de 2,4 (1,5-3,8), três ou mais amigos fumantes, OR de 17,5 (8,8-34,8) e baixa escolaridade OR de 3,5 (1,5-8,0). CONCLUSÕES: A prevalência de tabagismo na adolescência mostrou-se alta, na cidade de Pelotas. Campanhas antitabágicas devem ser direcionadas à comunidade e à família tendo o adolescente como alvo. Medidas legais adotadas pelo governo são importantes para impedir o acesso dos adolescentes ao cigarro

Variability of the bond and mechanical properties of self-compacting concrete

This main objective of this research is to evaluate the variability of the mechanical properties (compressive strength, modulus of elasticity and tensile strength) and bond strength of the self-compacting concrete (SCC), with 50 MPa compressive strength at 28 days, varying the maximum aggregate size and the SCC fluidity. The tests were made in 15 x 30 cm concrete cylinders and in beams standardized by Rilem-Ceb-Fib (1973). In agreement with the obtained results, can be concluded that the variability of the self-compacting concrete is small for the modulus of elasticity and for the compressive strength, but the tensile strength presented a significant variability due to the failure mode. About the bond strength, the variability was small showing that the self-compacting concrete is reliable and possesses great potential for use in the civil construction.Peer ReviewedPostprint (published version