O Projeto Nacional de Saneamento Rural (1985-1989) no Brasil: limites e potencialidades

In this article, the principles of the National Rural Water and Sanitation Project (PNSR), elaborated during the 1980s, are analyzed, discussing the advances and the limits reached in the development of rural water supply and sanitation in Brazil. The methodology used was an analysis of the content of documents and interviews with key actors. The results have demonstrated that the formulation of the PNSR promoted a new contribution of knowledge to the water and sanitation sector in Brazil, bringing innovations concerning the approach to water and basic sanitation in rural areas, especially relating to its integration with health, the processes of education and social participation, the decentralization of services, the use of appropriate technologies and community involvement in the management of services. Although it did not result in a government program, the legacy left by the PNSR has provided a great contribution in the form of studies, which are still relevant today.Neste artigo são analisados os princípios do Projeto Nacional de Saneamento Rural (PNSR), elaborado na década de 1980, discutindo-se os avanços e limites alcançados no desenvolvimento do saneamento rural no Brasil no período. Empregou-se como metodologia a análise de conteúdo de documentos e de entrevistas com atores-chave. Os resultados demonstram que a formulação do PNSR promoveu um novo aporte de conhecimentos ao setor de saneamento no país, com inovações no que se refere à abordagem sobre saneamento básico em áreas rurais, especialmente em sua integração à saúde, aos processos de educação e participação social, à descentralização dos serviços, ao emprego de tecnologias apropriadas e ao envolvimento comunitário na gestão dos serviços. Embora não tenha sido efetivado como um programa de governo, o PNSR deixou como legado uma vasta contribuição sob a forma de estudos, ainda hoje pertinentes

Rurality as a conditioner of basic sanitation solutions

A definição de rural é estratégica para a formulação e a implementação de políticas públicas, contribuindo para o alcance de maior efetividade nas ações direcionadas para as populações rurais. Com o objetivo de compreender a relação existente entre a ruralidade e o acesso às soluções sanitárias existentes em comunidades rurais brasileiras, o presente artigo apresenta análises estatísticas descritivas utilizando o novo conceito de rural adotado pelo Programa Nacional de Saneamento Rural e análises qualitativas provenientes de estudos de caso no semiárido nordestino. Os resultados apontam a inter-relação existente entre diferentes ruralidades e as condições de acesso aos serviços de saneamento, influenciadas por aspectos demográficos (proximidade das áreas urbanas, densidade populacional, distribuição espacial dos domicílios), sociais (organização em associações comunitárias), ambientais (qualidade da água disponível) e culturais (resistência ao cloro e prática da defecação a céu aberto)672201535The definition of rural is strategic for the formulation and implementation of public policies, contributing to the achievement of greater effectiveness in actions directed to rural populations. In order to understand the relationship between rurality and access to sanitary solutions in rural Brazilian communities, this article presents descriptive statistical analysis using the new concept of rural adopted by the National Rural Sanitation Program and qualitative analyzes from case studies in the semi-arid northeastern region. The results point to the interrelationship between different ruralities and the conditions of access to sanitation services, influenced by demographic (proximity to urban areas, population density, spatial distribution of households), social (organization in community associations), environmental (water quality) and cultural aspects (resistance to chlorine and practice of open defecation

The Role of Metformin in Controlling Oxidative Stress in Muscle of Diabetic Rats

Metformin can act in muscle, inhibiting the complex I of the electron transport chain and decreasing mitochondrial reactive oxygen species. Our hypothesis is that the inhibition of complex I can minimize damage oxidative in muscles of hypoinsulinemic rats. The present study investigated the effects of insulin and/or metformin treatment on oxidative stress levels in the gastrocnemius muscle of diabetic rats. Rats were rendered diabetic (D) with an injection of streptozotocin and were submitted to treatment with insulin (D+I), metformin (D+M), or insulin plus metformin (D+I+M) for 7 days. The body weight, glycemic control, and insulin resistance were evaluated. Then, oxidative stress levels, glutathione antioxidant defense system, and antioxidant status were analyzed in the gastrocnemius muscle of hypoinsulinemic rats. The body weight decreased in D+M compared to ND rats. D+I and D+I+M rats decreased the glycemia and D+I+M rats increased the insulin sensitivity compared to D rats. D+I+M reduced the oxidative stress levels and the activity of catalase and superoxide dismutase in skeletal muscle when compared to D+I rats. In conclusion, our results reveal that dual therapy with metformin and insulin promotes more benefits to oxidative stress control in muscle of hypoinsulinemic rats than insulinotherapy alone

Aggressive PDACs show hypomethylation of repetitive elements and the execution of an intrinsic IFN program linked to a ductal cell of origin

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylation(low) tumors are characterized by higher expression of endogenous retroviral (ERV) transcripts and dsRNA sensors which leads to a cell intrinsic activation of an interferon signature (IFNsign). This results in a pro-tumorigenic microenvironment and poor patient outcome. Methylation(low)/IFNsign(high) and Methylation(high)/IFNsign(low) PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived Kras(G12D)/Trp53(−/−) mouse PDACs show higher expression of IFNsign compared to acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylation(low)/IFNsign(high) subtype potentially targetable by agents blocking intrinsic IFN-signaling

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Adaptogenic potential of royal jelly in liver of rats exposed to chronic stress.

Restraint and cold stress increase both corticosterone and glycemia, which lead to oxidative damages in hepatic tissue. This study assessed the effect of royal jelly (RJ) supplementation on the corticosterone level, glycemia, plasma enzymes and hepatic antioxidant system in restraint and cold stressed rats. Wistar rats were allocated into no-stress, stress, no-stress supplemented with RJ and stress supplemented with RJ groups. Initially, RJ (200mg/Kg) was administered for fourteen days and stressed groups were submitted to chronic stress from the seventh day. The results showed that RJ supplementation decreases corticosterone levels and improves glycemia control after stress induction. RJ supplementation also decreased the body weight, AST, ALP and GGT. Moreover, RJ improved total antioxidant capacity, SOD activity and reduced GSH, GR and lipoperoxidation in the liver. Thus, RJ supplementation reestablished the corticosterone levels and the hepatic antioxidant system in stressed rats, indicating an adaptogenic and hepatoprotective potential of RJ

Biomarkers of chronic stress in liver tissue of rats stressed by restraint and cold.

<p>Plasma corticosterone level after seven days of stress-induction (A). No stress (NS), No Stress supplemented with Royal Jelly (NSRJ), Stress (S) and Stress supplemented with Royal Jelly (SRJ). Blood glucose level before and after the last stress induction (B). No stress (NS), No Stress supplemented with Royal Jelly (NSRJ), Stress group before the last stress session (Sb), Stress group after the last stress session (Sa), Stress group supplemented with RJ before the last stress session (SRJb), Stress group supplemented with RJ after the last stress session (SRJa). Pearson correlation of mean values of corticosterone levels and blood glucose after the last stress-induction (C). Values are expressed as means ± SEM. *p < 0.05 vs NS, # p < 0.05 vs S, & p < 0.05 vs Sb, § p < 0.05 vs Sa (One-way ANOVA followed by Tukey test). Outliers were detected by performing Grubb’s test using an online GraphPad outlier calculator (<a href="http://graphpad.com/quickcalcs/Grubbs1.cfm" target="_blank">http://graphpad.com/quickcalcs/Grubbs1.cfm</a>).</p