Prognostic value of disability on mortality: 15-year follow-up of the Bambuí Cohort Study of Aging

BACKGROUND: Disability is a concern in the context of population ageing. The extent of an individual’s disability is a major determinant of whether or not they require long-term care or survival time. We investigated the effect of three disability domains as predictors of all-cause mortality over 15-year follow-up in a Brazilian socioeconomically disadvantaged and multiracial older adult population. METHODS: We estimated Cox proportional hazards models using data from 1333 community-dwelling individuals aged 60 and older from the Bambuí Cohort Study of Ageing. Disability was defined as a great difficulty or not being able to perform one and two or more activities in each domain: mobility, instrumental activities of daily living (IADL) and basic activities of daily living (BADL). RESULTS: The overall mortality rate was 46.1 per 1000 person-years at risk (pyrs) and it was higher in men. Among men, the fully adjusted Hazard Ratios (HRs) were 1.92 (95%CI: 1.43-2.58), 2.07 (95%CI: 1.53-2.79) and 1.65 (95%CI: 1.11-2.45), and among women 1.75 (95%CI: 1.38-2.21), 1.43 (95%CI: 1.11-1.84) and 1.43 (95%CI: 1.05-1.95), for two or more disability in mobility tasks, IADLs and BADLs, respectively, compared to those with no difficulty or some difficulty to perform all the tasks. CONCLUSION: A similar risk of death for mobility, IADL and BADL in both genders was found, suggesting that any of these domains can be used to identify risk of all-cause mortality among older adults. The number of activities with limitations in each domain was an important factor

Vulnerability of Brazilian municipalities to hantavirus infections based on multi‑criteria decision analysis

Background: Hantavirus infection is an emerging zoonosis transmitted by wild rodents. In Brazil, high case-fatality rates among humans infected with hantavirus are of serious concern to public health authorities. Appropriate preventive measures partly depend on reliable knowledge about the geographical distribution of this disease. Methods: Incidence of hantavirus infections in Brazil (1993–2013) was analyzed. Epidemiological, socioeconomic, and demographic indicators were also used to classify cities’ vulnerability to disease by means of multi-criteria decision analysis (MCDA). Results: From 1993 to 2013, 1752 cases of hantavirus were registered in 16 Brazilian states. The highest incidence of hantavirus was observed in the states of Mato Grosso (0.57/100,000) and Santa Catarina (0.13/100,000). Based on MCDA analysis, municipalities in the southern, southeastern, and midwestern regions of Brazil can be classified as highly vulnerable. Most municipalities in northern and northeastern Brazil were classified as having low vulnerability to hantavirus cardiopulmonary syndrome. Conclusions: Although most human infections by hantavirus registered in Brazil occurred in the southern region of the country, a greater vulnerability to hantavirus was found in the Brazilian Midwest. This result reflects the need to strengthen surveillance where the disease has thus far gone unreported

Network Physiology reveals relations between network topology and physiological function

The human organism is an integrated network where complex physiologic systems, each with its own regulatory mechanisms, continuously interact, and where failure of one system can trigger a breakdown of the entire network. Identifying and quantifying dynamical networks of diverse systems with different types of interactions is a challenge. Here, we develop a framework to probe interactions among diverse systems, and we identify a physiologic network. We find that each physiologic state is characterized by a specific network structure, demonstrating a robust interplay between network topology and function. Across physiologic states the network undergoes topological transitions associated with fast reorganization of physiologic interactions on time scales of a few minutes, indicating high network flexibility in response to perturbations. The proposed system-wide integrative approach may facilitate the development of a new field, Network Physiology.Comment: 12 pages, 9 figure

Post-translational allosteric activation of the P2X 7 receptor through glycosaminoglycan chains of CD44 proteoglycans

Here, we present evidence for the positive allosteric modulation of the P2X7 receptor through glycosaminoglycans (GAGs) in CHO (cell line derived from the ovary of the Chinese hamster) cells. The marked potentiation of P2X7 activity through GAGs in the presence of non-saturating agonists concentrations was evident with the endogenous expression of the receptor in CHO cells. The presence of GAGs on the surface of CHO cells greatly increased the sensitivity to adenosine 5′-triphosphate and changed the main P2X7 receptor kinetic parameters EC50, Hill coefficient and Emax. GAGs decreased the allosteric inhibition of P2X7 receptor through Mg2+. GAGs activated P2X7 receptor-mediated cytoplasmic Ca2+ influx and pore formation. Consequently, wild-type CHO-K1 cells were 2.5-fold more sensitive to cell death induced through P2X7 agonists than mutant CHO-745 cells defective in GAGs biosynthesis. In the present study, we provide the first evidence that the P2X7 receptor interacts with CD44 on the CHO-K1 cell surface. Thus, these data demonstrated that GAGs positively modulate the P2X7 receptor, and sCD44 is a part of a regulatory positive feedback loop linking P2X7 receptor activation for the intracellular response mediated through P2X7 receptor stimulation

P2X 7 receptor activity regulation: the role of CD44 proteoglycan GAG chains

P2X7 receptors have received special attention in the literature for their involvement in several diseases characterized by inflammatory processes such as cancer, arthritis, neurodegenerative pathologies and chronic pains

Predictive value of multiple cytokines and chemokines for mortality in an admixed population: 15-year follow-up of the Bambui-Epigen (Brazil) cohort study of aging

Inflammation, particularly elevated IL-6 serum levels, has been associated with increased mortality risk, mostly in Caucasians. The influence of genetic ethno-racial background on this association is unknown. We examined associations between baseline serum levels of Interleukin-6 (IL-6) and other cytokines (IL1-2, TNF, IL-10, and IL1β) and chemokines (CCL2, CCL5, CXCL8, CXCL9 and CXCL10) with 15-year mortality in 1,191 admixed Brazilians aged 60 years and over. Elevated IL6 level (but not other biomarkers) was associated with increased risk of deaths with fully adjusted hazard ratios of 1.51 (95% CI = 1.15, 1.97), 1.54 (95% CI = 1.20, 1.96) and 1.79 (95% CI = 1.40, 2.29) for the 2nd, 3rd and the highest quartiles, respectively. Genomic African and Native American proportions did not modify the association (p > 0.05). The discriminatory ability to predict death of a model based on IL-6 alone was similar as that of a comprehensive morbidity score (C statistics = 0.59 and 0.60, respectively). The abilities of IL-6 and the morbidity score models to predict death remained stable for very long term after the baseline measurement. Our results indicate that genome-based African and Native American ancestries have no impact on the prognostic value of IL-6 for mortality

A Lewis Base Catalysis Approach for the Photoredox Activation of Boronic Acids and Esters

We report herein the use of a dual catalytic system comprising of a Lewis base catalyst such as quinuclidin-3-ol or 4- dimethylaminopyridine combined with a photoredox catalyst to generate carbon radicals from either boronic acids or esters. This system enabled a wide range of alkyl boronic esters and aryl or alkyl boronic acids to react via radical addition with electron-deficient olefins to efficiently form C–C coupled products in a redox neutral fashion. The Lewis base catalyst was shown to form a redox-active complex with either boronic esters or the trimeric form of the boronic acids (boroxines) in solution.We are grateful to Novartis Pharma AG (F.L.), the Erasmus Scholarship Scheme (L.G. and S.J.), and the EPSRC (S.V.L., Grants EP/K009494/1, EP/K039520/1, and EP/M004120/1) for financial support. U.K.S. and D.S. are thankful to the University of Leuven for postdoctoral funding and the FWO for a visiting postdoctoral scholarship (U.K.S.) at the University of Cambridge. E.V.V.d.E. would like to thank the Ministry of Education and Science of the Russian Federation for financial support (agreement number 02.a03.0008). We thank Dr. Berthold Schenkel and Dr. Gottfried Sedelmeier for insightful discussions. We thank Merck Rahway USA for the generous gift of the PC(1) photoredox catalyst