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

Catálogo Taxonômico da Fauna do Brasil: setting the baseline knowledge on the animal diversity in Brazil

The limited temporal completeness and taxonomic accuracy of species lists, made available in a traditional manner in scientific publications, has always represented a problem. These lists are invariably limited to a few taxonomic groups and do not represent up-to-date knowledge of all species and classifications. In this context, the Brazilian megadiverse fauna is no exception, and the Catálogo Taxonômico da Fauna do Brasil (CTFB) (http://fauna.jbrj.gov.br/), made public in 2015, represents a database on biodiversity anchored on a list of valid and expertly recognized scientific names of animals in Brazil. The CTFB is updated in near real time by a team of more than 800 specialists. By January 1, 2024, the CTFB compiled 133,691 nominal species, with 125,138 that were considered valid. Most of the valid species were arthropods (82.3%, with more than 102,000 species) and chordates (7.69%, with over 11,000 species). These taxa were followed by a cluster composed of Mollusca (3,567 species), Platyhelminthes (2,292 species), Annelida (1,833 species), and Nematoda (1,447 species). All remaining groups had less than 1,000 species reported in Brazil, with Cnidaria (831 species), Porifera (628 species), Rotifera (606 species), and Bryozoa (520 species) representing those with more than 500 species. Analysis of the CTFB database can facilitate and direct efforts towards the discovery of new species in Brazil, but it is also fundamental in providing the best available list of valid nominal species to users, including those in science, health, conservation efforts, and any initiative involving animals. The importance of the CTFB is evidenced by the elevated number of citations in the scientific literature in diverse areas of biology, law, anthropology, education, forensic science, and veterinary science, among others

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Influence of parasite load on renal function in mice acutely infected with Trypanosoma cruzi.

BACKGROUND: Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. Despite the vast number of studies evaluating the pathophysiological mechanisms of the disease, the influence of parasite burden on kidney lesions remains unclear. Thus, the main goal of this work was to evaluate the effect of T. cruzi infection on renal function and determine whether there was a correlation between parasite load and renal injury using an acute experimental model of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Low, medium and high parasite loads were generated by infecting C57BL/6 mice with 300 (low), 3,000 (medium) or 30,000 (high) numbers of "Y" strain trypomastigotes. We found that mice infected with T. cruzi trypomastigotes show increased renal injury. The infection resulted in reduced urinary excretion and creatinine clearance. We also observed a marked elevation in the ratio of urine volume to kidney and body weight, blood urea nitrogen, chloride ion, nitric oxide, pro- and anti-inflammatory cytokines and the number of leukocytes in the blood and/or renal tissues of infected mice. Additionally, we observed the presence of the parasite in the cortical/medullary and peri-renal region, an increase of inflammatory infiltrate and of vascular permeability of the kidney. Overall, most renal changes occurred mainly in animals infected with high parasitic loads. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that T. cruzi impairs kidney function, and this impairment is more evident in mice infected with high parasitic loads. Moreover, these data suggest that, in addition to the extensively studied cardiovascular effects, renal injury should be regarded as an important indicator for better understanding the pan-infectivity of the parasite and consequently for understanding the disease in experimental models

Relações da força muscular com indicadores de hipertrofia após 32 semanas de treinamento com pesos em mulheres na pós-menopausa

O objectivo do presente estudo foi avaliar o comportamento da força muscular e a participação dos indicadores de hipertrofia, nos ganhos de força após 32 semanas de treinamento com pesos (TP), prescrito por zona alvo de repetições máximas, em mulheres na pós-menopausa. Participaram desta pesquisa 14 mulheres saudáveis e não ativas fisicamente. O TP teve frequência semanal de três vezes, em dias alternados. A composição corporal foi mensurada pela técnica das dobras cutâneas. Os indicadores de hipertrofia foram representados pela massa magra total e regional: área muscular do braço (AMB) e coxa (AMC). A força muscular foi avaliada pelo teste de uma repetição máxima nos exercícios leg press horizontal e rosca direta. Para análise estatística foi utilizado o teste de Friedman. Os resultados mostraram que a força muscular apresentou aumentos graduais e significantes durante a intervenção, que houve aumento da AMB e não houve diferença nos valores de AMC. A rosca direta mostrou forte associação com a AMB durante todos os momentos do estudo. Já o leg press pareceu estar mais efetivamente associado ao componente neural de ganhos de força, visto que a AMC não apresentou modificações significantes. Após 32 semanas de TP a força muscular aumentou significantemente, independentemente dos ganhos de massa magra

Effect of <i>T. cruzi</i> parasite loads on vascular permeability in the kidney tissue.

<p>C57BL/6 mice were challenged with low, medium and high loads of trypomastigotes and at 9 day post-infection, the accumulation of Evans Blue in the renal tissues was assessed. In A–D, a representative image of Evans Blue accumulation in the kidney from each group is demonstrated. E shows the mean percentage ± SEM of Evans Blue accumulation in the renal parenchyma. *p≤0.05 indicates a significant difference when mice from the medium and highly infected groups were compared to the uninfected control mice.</p

Analysis of the presence of <i>T.cruzi</i> amastigotes and inflammatory infiltrates in the renal tissues.

<p>C57BL/6 mice were challenged with low, medium and high loads of trypomastigotes, and at 9 and 18 days post-infection, the inflammatory infiltrate and the presence and location of <i>T. cruzi</i> amastigotes in the renal tissues were evaluated. <i>T. cruzi</i> amastigotes were found in both cortical/medullary (A) and peri-renal (B) tissues. The inflammatory infiltrate was evidenced in the tubular region (C) and in the Bowman’s capsule (D). After demonstrating the presence of nests of <i>T. cruzi</i> amastigotes and the inflammatory infiltrates, we evaluated the comparative percentage of positive antigen labeling for <i>T. cruzi</i> in 5 different slides collected from the different inocula at 9 and 18 days post-infection (E).</p

Effect of <i>T. cruzi</i> parasite loads on cytokine and nitric oxide production in kidney tissues.

<p>C57BL/6 mice were challenged with low, medium and high loads of blood trypomastigotes. At 6, 9, 12 and 18 days post-infection they were euthanized and their kidneys were removed to measure the concentrations of cytokines and nitric oxide. The cytokines TNF-α (A–D), IFN-γ (E–H) and IL-10 (I–L) were measured according to the manufacturer’s instructions, using commercially available ELISA kits. For measurement of nitric oxide, the Griess reaction was used. The absorbance was read at 570 nm. *p≤0.05 indicates a significant difference when animals from the medium and highly infected groups were compared to the uninfected control mice.</p

Parasitemia and survival of mice in the acute stage of <i>T. cruzi</i> infection.

<p>C57BL/6 mice were challenged with 3×10² (low dose), 3×10³ (medium dose) or 3×10⁴ (high dose) blood trypomastigotes. Parasitemia (A) was determined by counting the number of parasites in 5 µL of blood collected from tail snips at the indicated time points. Each point represents the mean of individual values from 10 mice. In the survival curve (B), 10 animals were individually monitored for 30 days of infection. ^δ0p≤0.05 indicates a significant difference when the mice infected with medium-inoculum were compared to the mice infected with high inoculum, ^δ1p≤0.05 indicates a significant difference when the mice from the low-inoculum group were compared to the mice from the high-inoculum group, ^δ2p≤0.05 indicates a significant difference when mice from the low-inoculum group were compared to mice from the medium-inoculum group, and *p≤0.05 indicates a significant difference when animals from the infected groups were compared to the uninfected control mice.</p