Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease

BACKGROUND: The recent growing evidence that the proximal tubule underlies the early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and promising perspectives. This pathophysiological concept links tubulointerstitial oxidative stress, inflammation, hypoxia, and fibrosis with the progression of DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal tubular cells emerge as an innovative opportunity for prevention and management of DKD as well as to improve diabetic dysmetabolism. SUMMARY: The mercapturate pathway (MAP) is a classical metabolic detoxification route for xenobiotics that is emerging as an integrative circuitry detrimental to resolve tubular inflammation caused by endogenous electrophilic species. Herein we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of proximal tubular cell function, and cysteine-S-conjugates might represent targets for early intervention in DKD. Moreover, the biomonitoring of urinary mercapturates from metabolic inflammation products might be relevant for the implementation of preventive/management strategies in DKD.info:eu-repo/semantics/publishedVersio

Inequalities in access to cardiac rehabilitation after an acute coronary syndrome: the EPiHeart cohort

Objectives To estimate cardiac rehabilitation (CR) referral and participation rates among patients with acute coronary syndrome (ACS) and to identify their determinants, in two Portuguese regions. Design Prospective cohort study. Setting Patients consecutively admitted to the cardiology department of two hospitals, one in the district of Porto and one in the north-east region (NER) of Portugal, were enrolled in the EPIHeart cohort and then followed up for 6 months. Participants Between August 2013 and December 2014, 939 patients were included in the cohort, and 853 were re-evaluated at 6-month follow-up. Outcome measures Referral rate was defined as the proportion of eligible patients who were referred to a CR programme, whereas participation rate was defined as the proportion of eligible patients who completed a CR programme, as was recommended by their physicians. Results Patients referred were 32.3% and 10.7% of those eligible in Porto and NER, respectively. In both regions, referral to CR decreased with age and with longer travel times to CR centres and increased with education or social class. At follow-up, 128 patients from Porto (26.2% of those eligible and 81.0% of those referred) and 26 from NER (7.1% of those eligible and 66.7% of those referred) reported actually participating in a CR programme. In Porto, the main barriers to participation were the long time until a programme was available and lack of perceived benefit. Patients in NER identified distance to CR and costs as the main barriers. Conclusions CR remains clearly underused in Portugal, with major inequalities in access between regions. Achieving equitable and greater use of CR requires a multilevel approach addressing barriers related to healthcare system, providers and patients in order to improve provision, referral and participation.This study was supported by FEDER through the Operational Programme Competitiveness and Internationalisation and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) (FCOMP-01-0124-FEDER-028709), under the project ‘Inequalities in coronary heart disease management and outcomes in Portugal’ (FCT PTDC/DTP-EPI/0434/2012) and the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; ref UID/DTP/04750/2013)

Thermalization from gauge/gravity duality: Evolution of singularities in unequal time correlators

We consider a gauge/gravity dual model of thermalization which consists of a collapsing thin matter shell in asymptotically Anti-de Sitter space. A central aspect of our model is to consider a shell moving at finite velocity as determined by its equation of motion, rather than a quasi-static approximation as considered previously in the literature. By applying a divergence matching method, we obtain the evolution of singularities in the retarded unequal time correlator $G^R(t,t')$, which probes different stages of the thermalization. We find that the number of singularities decreases from a finite number to zero as the gauge theory thermalizes. This may be interpreted as a sign of decoherence. Moreover, in a second part of the paper, we show explicitly that the thermal correlator is characterized by the existence of singularities in the complex time plane. By studying a quasi-static state, we show the singularities at real times originate from contributions of normal modes. We also investigate the possibility of obtaining complex singularities from contributions of quasi-normal modes.Comment: 35 pages, 4 figure

Intersetorialidade e potenciais conflitos de interesse entre governos e setor privado comercial no âmbito das ações de alimentação e nutrição para o enfrentamento de doenças crônicas não transmissíveis | Intersectoriality and potential conflicts of interest between governments and private, commercial sector within the context of food and nutrition actions to deal with chronic non-communicable diseases

Neste artigo foram analisados os potenciais conflitos entre interesses governamentais e privados de caráter comercial em torno das ações de alimentação e nutrição (AN) no âmbito de propostas intersetoriais de enfrentamento das DCNT no Brasil. Para tal, foram identificados artigos acadêmicos e documentos institucionais publicados a partir de 2000 que abordassem as ações de AN em políticas de DCNT pautadas pela intersetorialidade. Foram priorizados elementos que contribuíssem para a compreensão dos potenciais conflitos de interesse entre governos e o setor privado comercial no âmbito de estratégias intersetoriais de enfrentamento de DCNT. Concluiu-se que o princípio da intersetorialidade, desassociado de um processo político que problematize os critérios de eleição e as práticas institucionais dos setores que respondem pelo conjunto de ações que compõe as políticas governamentais, pode servir como facilitador do favorecimento de interesses comerciais. A participação no processo decisório de setores de interesse comercial cujas práticas ferem objetivos e princípios das políticas públicas, movidos pela expansão da demanda por seus produtos e pela concentração progressiva de poder, pode retardar, atenuar ou impedir ações efetivas na redução de DCNT. Esta possibilidade é particularmente relevante no âmbito de atribuições que são próprias aos entes Estatais, especialmente as estratégias regulatórias. ------------------------------------------------------------------------------------------- This article analyzed the potential conflicts of interest between government and private commercial sectors in the area of food and nutrition (FN) activities within the context of intersectoral proposals for dealing with chronic non-communicable diseases (CNCD) in Brazil. To this end, academic articles and institutional documents published after 2000 were identified that addressed FN actions in CNCD policies guided by intersectoriality. Elements that contributed to understanding the potential conflicts of interest between governments and the private, commercial sector within the context of intersectoral strategies to deal with CNCD were prioritized. It was concluded that the principle of intersectoriality disassociated from a political process that complicates the eligibility criteria and institutional practices of the sectors responsible for the set of actions that comprise government policies may serve as facilitators for favoring commercial interests. Participation in the decision-making process of the sectors of commercial interest whose practices, driven by increased demand for their products and the progressive concentration of power, contradict the purposes and principles of public policy, may delay, reduce, or prevent effective actions to reduce CNCD. This possibility is particularly relevant in the context of attributions that are specific to government entities, especially regulatory strategies

Intersetorialidade e potenciais conflitos de interesse entre governos e setor privado comercial no âmbito das ações de alimentação e nutrição para o enfrentamento de doenças crônicas não transmissíveis

This article analyzed the potential conflicts of interest between government and private commercial sectors in the area of food and nutrition (FN) activities within the context of intersectoral proposals for dealing with chronic non-communicable diseases (CNCD) in Brazil. To this end, academic articles and institutional documents published after 2000 were identified that addressed FN actions in CNCD policies guided by intersectoriality. Elements that contributed to understanding the potential conflicts of interest between governments and the private, commercial sector within the context of intersectoral strategies to deal with CNCD were prioritized. It was concluded that the principle of intersectoriality disassociated from a political process that complicates the eligibility criteria and institutional practices of the sectors responsible for the set of actions that comprise government policies may serve as facilitators for favoring commercial interests. Participation in the decision-making process of the sectors of commercial interest whose practices, driven by increased demand for their products and the progressive concentration of power, contradict the purposes and principles of public policy, may delay, reduce, or prevent effective actions to reduce CNCD. This possibility is particularly relevant in the context of attributions that are specific to government entities, especially regulatory strategies.Neste artigo foram analisados os potenciais conflitos entre interesses governamentais e privados de caráter comercial em torno das ações de alimentação e nutrição (AN) no âmbito de propostas intersetoriais de enfrentamento das DCNT no Brasil. Para tal, foram identificados artigos acadêmicos e documentos institucionais publicados a partir de 2000 que abordassem as ações de AN em políticas de DCNT pautadas pela intersetorialidade. Foram priorizados elementos que contribuíssem para a compreensão dos potenciais conflitos de interesse entre governos e o setor privado comercial no âmbito de estratégias intersetoriais de enfrentamento de DCNT. Concluiu-se que o princípio da intersetorialidade, desassociado de um processo político que problematize os critérios de eleição e as práticas institucionais dos setores que respondem pelo conjunto de ações que compõe as políticas governamentais, pode servir como facilitador do favorecimento de interesses comerciais. A participação no processo decisório de setores de interesse comercial cujas práticas ferem objetivos e princípios das políticas públicas, movidos pela expansão da demanda por seus produtos e pela concentração progressiva de poder, pode retardar, atenuar ou impedir ações efetivas na redução de DCNT. Esta possibilidade é particularmente relevante no âmbito de atribuições que são próprias aos entes Estatais, especialmente as estratégias regulatórias

Levels of Angiopoietin 2 Are Predictive for Mortality in Patients Infected With Yellow Fever Virus

In 2018 there was a large yellow fever outbreak in São Paulo, Brazil, with a high fatality rate. Yellow fever virus can cause, among other symptoms, hemorrhage and disseminated intravascular coagulation, indicating a role for endothelial cells in disease pathogenesis. Here, we conducted a case-control study and measured markers related to endothelial damage in plasma and its association with mortality. We found that angiopoietin 2 is strongly associated with a fatal outcome and could serve as a predictive marker for mortality. This could be used to monitor severe cases and provide care to improve disease outcome

Using the IUCN Red List to map threats to terrestrial vertebrates at global scale

The Anthropocene is characterized by unparalleled human impact on other species, potentially ushering in the sixth mass extinction. Yet mitigation efforts remain hampered by limited information on the spatial patterns and intensity of the threats driving global biodiversity loss. Here we use expert-derived information from the International Union for Conservation of Nature Red List on threats to 23,271 species, representing all terrestrial amphibians, birds and mammals, to generate global maps of the six major threats to these groups: agriculture, hunting and trapping, logging, pollution, invasive species, and climate change. Our results show that agriculture and logging are pervasive in the tropics and that hunting and trapping is the most geographically widespread threat to mammals and birds. Additionally, current representations of human pressure underestimate the overall pressure on biodiversity, due to the exclusion of threats such as hunting and climate change. Alarmingly, this is particularly the case in areas of the highest biodiversity importance

The major barriers to evidence-informed conservation policy and possible solutions

Conservation policy decisions can suffer from a lack of evidence, hindering effective decision-making. In nature conservation, studies investigating why policy is often not evidence-informed have tended to focus on Western democracies, with relatively small samples. To understand global variation and challenges better, we established a global survey aimed at identifying top barriers and solutions to the use of conservation science in policy. This obtained the views of 758 people in policy, practice, and research positions from 68 countries across six languages. Here we show that, contrary to popular belief, there is agreement between groups about how to incorporate conservation science into policy, and there is thus room for optimism. Barriers related to the low priority of conservation were considered to be important, while mainstreaming conservation was proposed as a key solution. Therefore, priorities should focus on convincing the public of the importance of conservation as an issue, which will then influence policy-makers to adopt pro-environmental long-term policies.NERC (1653183) Grantham Foundation for the Protection of the Environment Kenneth Miller Trust (unknown) NERC (1653183) NERC (NE/L002507/1) European Commission (308454

Using habitat models to identify marine Important Bird and Biodiversity Areas for Chinstrap penguins in the South Orkney Islands

Tracking individual marine predators can provide vital information to aid the identification of important activity (foraging, commuting, rafting, resting, etc.) hotspots and therefore also to delineate priority sites for conservation. However, in certain locations (e.g. Antarctica) many marine mammal or seabird colonies remain untracked due to logistical constraints, and the colonies that are studied may not be the most important in terms of conservation priorities. Using data for one of the most abundant seabirds in the Antarctic as a case study (the Chinstrap penguin Pygoscelis antarcticus), we tested the use of correlative habitat models (used to predict distribution around untracked colonies) to overcome this limitation, and to enable the identification of important areas at-sea for colonies where tracking data are not available. First, Important Bird and Biodiversity Areas (IBA) were identified using a standardised, published approach using empirical data from birds tracked from colonies located in the South Orkney Islands. Subsequently, novel approaches using predicted distributions of Chinstrap penguins derived from habitatcorrelative habitat models were applied to identify important marine areas, and the results compared with the IBAs. Data were collected from 4 colonies over 4 years and during different stages of the breeding season. Results showed a high degree of overlap between the areas identified as important by observed data (IBAs) and by predicted distributions, revealing that habitat preference models can be used with a high degree of confidence to identify marine IBAs for these penguins. We provide a new method for designating a network of marine IBAs for penguins in Antarctic waters, based on outputs from habitatcorrelative habitat models when tracking data are not available. This can contribute to an evidence-based and precautionary approach to aid the management framework for Antarctic fisheries and for the protection of birds