Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex

Mucopolysaccharidosis type I (MPS I) is caused by genetic deficiency of alpha-l-iduronidase and impairment of lysosomal catabolism of heparan sulfate and dermatan sulfate. In the brain, these substrates accumulate in the lysosomes of neurons and glial cells, leading to neuroinflammation and neurodegeneration. Their storage also affects lysosomal homeostasis-inducing activity of several lysosomal proteases including cathepsin B (CATB). In the central nervous system, increased CATB activity has been associated with the deposition of amyloid plaques due to an alternative pro-amyloidogenic processing of the amyloid precursor protein (APP), suggesting a potential role of this enzyme in the neuropathology of MPS I. In this study, we report elevated levels of protein expression and activity of CATB in cortex tissues of 6-month-old MPS I (Idua -/- mice. Besides, increased CATB leakage from lysosomes to the cytoplasm of Idua -/- cortical pyramidal neurons was indicative of damaged lysosomal membranes. The increased CATB activity coincided with an elevated level of the 16-kDa C-terminal APP fragment, which together with unchanged levels of beta-secretase 1 was suggestive for the role of this enzyme in the amyloidogenic APP processing. Neuronal accumulation of Thioflavin-S-positive misfolded protein aggregates and drastically increased levels of neuroinflammatory glial fibrillary acidic protein (GFAP)-positive astrocytes and CD11b-positive activated microglia were observed in Idua -/- cortex by confocal fluorescent microscopy. Together, our results point to the existence of a novel CATB-associated alternative amyloidogenic pathway in MPS I brain induced by lysosomal storage and potentially leading to neurodegeneration

Compromiso organizacional y satisfacción laboral: un estudio exploratorio en unidades de salud familiar portuguesas

Explorou-se a relação entre compromisso organizacional e satisfação laboral nos colaboradores de unidades de saúde familiar. Participaram seis unidades de saúde familiar do norte de Portugal e 105 profissionais (médico, enfermeiros e secretários clínicos). Utilizaram-se as adaptações portuguesas da Escala do Compromisso Organizacional de Meyer & Allen (1997) e do Questionário de Satisfação com o Trabalho (Spector, 1985). Os resultados sugerem associação positiva entre compromisso organizacional e satisfação laboral. Os profissionais estão moderadamente satisfeitos e comprometidos com as unidades de saúde familiar, sendo a natureza do trabalho, a relação com os colegas e a comunicação os aspectos mais satisfatórios, e as recompensas o mais insatisfatório. A componente afetiva do compromisso evidencia-se, salientando o envolvimento e a identificação dos profissionais com o projeto unidades de saúde familiar. O modelo de regressão linear revelou-se significativo, o compromisso organizacional explica 22,7% da variância da satisfação com o trabalho. Para esta amostra, o compromisso organizacional prediz a satisfação com o trabalho.This study explored the relationship between organizational commitment and job satisfaction among workers in family health units. Six family health units in the North of Portugal participated, including 105 health professionals (physicians, nurses, and clinical secretaries). The study used the Portuguese adaptations of the Organizational Commitment Scale by Meyer & Allen (1997) and the Job Satisfaction Survey (Spector, 1985). The results suggest a positive association between organizational commitment and job satisfaction. The professionals are moderately satisfied and committed to the family health units; the most satisfactory aspects are the nature of the work, relationship to coworkers, and communication, while pay is the most unsatisfactory. The affective component of the commitment appears, highlighting the professionals' involvement in (and identification with) the family health units project. The linear regression model proved significant, and organizational commitment explains 22.7% of the variance in job satisfaction. For this sample, organizational commitment predicts job satisfaction.Instituto Nacional de Saúde Dr Ricardo Jorgeinfo:eu-repo/semantics/publishedVersio

Prevalence of Helicobacter pylori infection and associated factors among adults in Southern Brazil: a population-based cross-sectional study

BACKGROUND: Helicobacter pylori (Hp) infection is associated with several upper gastrointestinal disorders. Local data on the epidemiology of the infection are scarce in Brazil. The purpose of this study is to measure the prevalence rate and to explore the associated factors among the adult population living in Pelotas, a southern Brazilin city. METHODS: This was a population-based cross-sectional study. Through a multi-stage sampling method all individuals 20 years and over living at the selected households at the urban area of the city were interviewed regarding past and current socio-economic indicators; demographic characteristics; nutritional and behavioural habits; and history of upper gastrointestinal symptoms.Hp infection was ascertained through the (13)C-UBT. Due to the high prevalence, data were analysed through robust Poisson regression. All analyses took into account the family clustering of the data. RESULTS: Among 563 eligible individuals, 363 agreed to perform the (13)C-UBT (refusal rate of 35.5%). Refusals were associated with female sex, consumption of mate drinking, and presence of upper gastrointestinal symptoms. The prevalence rate of H. pylori infection was 63.4% (95%CI 59.3%–69.3%). In crude analyses, prevalence was associated with increasing age, non-white skin colour, lower current family income, lower education level, higher size of the family, low socio-economic conditions in childhood, higher number of siblings and attendance to day-care centres in childhood, and presence of dyspeptic symptoms. In adjusted analysis the level of education of the father was inversely associated with the infection, whereas number of siblings and attendance to day-care centre in childhood were directly associated with it. Non-white skin colour remained significantly associated with increased prevalence even after allowing for past and current socio-economic characteristics, age and sex. Compared to non-symptomatic individuals, those reporting dyspeptic symptoms presented a higher prevalence of the infection even after allowing for current and past socio-economic conditions, ethnicity, age, and sex. CONCLUSION: Hp infection is as common among adults in southern Brazil as it is in other developing countries. Socio-economic conditions in childhood besides ethnicity and presence of dyspeptic symptoms were the factors significantly associated with the infection