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

Population ecology of small rodents and marsupials in a semi-deciduous tropical forest of the southeast Pantanal, Brazil

The Pantanal is a South American biome characterized by extensive plains and stark environmental seasonality. Several habitats are subject to annual flooding, forcing small mammal species to aggregate in dry forest patches, which most likely influences their population dynamics and life history strategies. In order to investigate the seasonal influence on the life history traits of these small mammals, we conducted a 2-year mark-recapture study in the southeastern region of the Brazilian Pantanal (Nhecolândia) and analyzed the population dynamics of the most abundant small mammal species with the jackknife estimator. A trapping effort of 21,560 trap-nights resulted in 615 individuals in 1,171 captures (success = 5.43%). Three species of rodents - Oecomys mamorae (Thomas, 1906), Thrichomys pachyurus (Wagner, 1845), and Clyomys laticeps (Thomas, 1841) - and three species of marsupials - Gracilinanus agilis (Burmeister, 1854), Thylamys macrurus (Olfers, 1818), and Monodelphis domestica (Wagner, 1842) - were obtained. The most abundant species was O. mamorae, followed by G. agilis and T. pachyurus. Oecomys mamorae was more abundant in the wet season and presented an opportunistic reproductive strategy. Gracilianus agilis displayed increased population sizes in the dry season and synchronized, seasonal reproduction during the rainy season. Thrichomys pachyurus had a small population size, delayed response to variations in environmental conditions and higher reproductive rates in the dry season. All species revealed different life history strategies (seasonal, opportunistic or delayed response to environmental variations), coinciding with periods of higher resource availability in order to maximize survival

Multi-Locus Sequencing Reveals Putative Novel Anaplasmataceae Agents, ‘<i>Candidatus</i> Ehrlichia dumleri’ and <i>Anaplasma</i> sp., in Ring-Tailed Coatis (Carnivora: <i>Nasua nasua</i>) from Urban Forested Fragments at Midwestern Brazil

The Anaplasmataceae family encompasses obligate intracellular α-proteobacteria of human and veterinary medicine importance. This study performed multi-locus sequencing to characterize Ehrlichia and Anaplasma in coati’s blood samples in Midwestern Brazil. Twenty-five samples (25/165—15.1%) were positive in the screening PCR based on the dsb gene of Ehrlichia spp. and were characterized using 16S rRNA, sodB, groEL, and gltA genes and the 23S-5S intergenic space region (ITS). Phylogenetic analyses based on all six molecular markers positioned the sequences into a new clade, with a common origin of Ehrlichia ruminantium. Haplotype analyses of 16S RNA sequences revealed the presence of two distinct Ehrlichia genotypes. Six samples (6/165, 3.6%) were positive in the screening nPCR for the 16S rRNA gene of Anaplasma spp. and were submitted to an additional PCR targeting the ITS for molecular characterization. Phylogenetic analyses based on both 16S rRNA gene and ITS positioned the Anaplasma sp. detected in the present study in a large clade with other Anaplasma sp. previously detected in ticks and wild animals and in a clade with ‘Candidatus Anaplasma brasiliensis’, respectively. Based on distinct molecular markers, the present work described a putative novel Anaplasmataceae agent, namely ‘Candidatus Ehrlichia dumleri’, and Anaplasma sp. closely related to the previously described ‘Candidatus Anaplasma brasiliensis’

Distinct <i>Leishmania</i> Species Infecting Wild Caviomorph Rodents (Rodentia: Hystricognathi) from Brazil

<div><p>Background</p><p>Caviomorph rodents, some of the oldest <i>Leishmania</i> spp. hosts, are widely dispersed in Brazil. Despite both experimental and field studies having suggested that these rodents are potential reservoirs of <i>Leishmania</i> parasites, not more than 88 specimens were analyzed in the few studies of natural infection. Our hypothesis was that caviomorph rodents are inserted in the transmission cycles of <i>Leishmania</i> in different regions, more so than is currently recognized.</p><p>Methodology</p><p>We investigated the <i>Leishmania</i> infection in spleen fragments of 373 caviomorph rodents from 20 different species collected in five Brazilian biomes in a period of 13 years. PCR reactions targeting kDNA of <i>Leishmania</i> sp. were used to diagnose infection, while <i>Leishmania</i> species identification was performed by DNA sequencing of the amplified products obtained in the HSP70 (234) targeting. Serology by IFAT was performed on the available serum of these rodents.</p><p>Principal findings</p><p>In 13 caviomorph rodents, DNA sequencing analyses allowed the identification of 4 species of the subgenus <i>L.</i> (<i>Viannia</i>): <i>L. shawi</i>, <i>L. guyanensis</i>, <i>L. naiffi</i>, and <i>L. braziliensis</i>; and 1 species of the subgenus <i>L.</i> (<i>Leishmania</i>): <i>L. infantum</i>. These include the description of parasite species in areas not previously included in their known distribution: <i>L. shawi</i> in <i>Thrichomys inermis</i> from Northeastern Brazil and <i>L. naiffi</i> in <i>T. fosteri</i> from Western Brazil. From the four other positive rodents, two were positive for HSP70 (234) targeting but did not generate sequences that enabled the species identification, and another two were positive only in kDNA targeting.</p><p>Conclusions/Significance</p><p>The infection rate demonstrated by the serology (51.3%) points out that the natural <i>Leishmania</i> infection in caviomorph rodents is much higher than that observed in the molecular diagnosis (4.6%), highlighting that, in terms of the host species responsible for maintaining <i>Leishmania</i> species in the wild, our current knowledge represents only the “tip of the iceberg.”</p></div

Illustrative representation of HSP 70 (234) amplification for <i>Leishmania</i> sp. before and after re-amplification of the PCR products.

<p>(A) PCR products of first amplification of HSP 70 (234) targeting analyzed by electrophoresis polyacrylamide gel stained with silver. Lanes: bp. molecular-weight marker (50 bp DNA ladder); 1. Infected <i>Thrichomys laurentius</i> from São Raimundo Nonato/PI; 2. Negative control of PCR reaction. (B) PCR products of re-amplification of the product obtained in the first PCR reaction. Lanes: bp. molecular-weight marker (50 bp DNA ladder); 1. Negative <i>Thrichomys fosteri</i> from Corumbá/MS (Positive only in kDNA); 2–5. Infected <i>T. laurentius</i> from São Raimundo Nonato/PI; 6. Infected <i>T. fosteri</i> from Corumbá/MS; 7. Negative control of PCR after re-amplification.</p

Main polymorphisms along the HSP70 (234) sequences that allow the distinction of <i>Leishmania</i> species from reference strains.

<p>Main polymorphisms along the HSP70 (234) sequences that allow the distinction of <i>Leishmania</i> species from reference strains.</p

Infected caviomorph rodents and their respective <i>Leishmania</i> species identified by the analysis of similarity between the DNA sequences from the PCR products targeting HSP70 (234) and available sequences from GeneBank.

<p>* Sample with high value between distinct species of <i>Leishmania</i> was considered as a result of hybrid or mixed infection.</p><p>Infected caviomorph rodents and their respective <i>Leishmania</i> species identified by the analysis of similarity between the DNA sequences from the PCR products targeting HSP70 (234) and available sequences from GeneBank.</p

Map of the distribution of <i>Leishmania</i> species infecting caviomorph rodents in Brazil.

<p>Blue markers indicate municipalities where caviomorph rodents were collected, but were all negative in the molecular assay. Red markers indicate municipalities with animals positive for <i>Leishmania</i> infection. * Sample with high value between distinct species of <i>Leishmania</i> was considered as a result of hybrid or mixed infection.</p