-
Donaldson Cunningham posted an update 6 months ago
Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death.
DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4 years of follow-up. PD0166285 Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10 mg/day (n = 2152) or placebo (n = 2152). The mean age was 62 years, 33% were women, the mean eGFR was 43.1 mL/min/1.73 m2, and the median UACR was 949 mg/g. During follow-up, 247 (5.7%) patients died, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio 0.69 ; P = 0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR 0.54 ). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo.
In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.
In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.
As the implementation of sensor-based assessment for sedentary time (ST) and physical activity (PA) has practical limitations when applied on a large-scale, most studies rely on subjective data. We aimed to examine the criterion validity of a single-item question to assess daily breaks in ST and other PA-related outcomes for the first time using sensor-based data as the criterion.
In a sample of 858 adults, breaks in ST and other PA-related parameters were assessed through sensor-based accelerometry and subjective data, which included a comprehensive questionnaire with a specific question (‘During the day, do you usually sit for a long time in a row or interrupt frequently?’) with a three-level closed answer. The Spearman’s rank correlation coefficient was used to determine the agreement between the single-item question and sensor-based data.
Positive correlations were found for self-reported breaks in ST with sensor-based breaks in ST in both women (ρ=0.37; 95% CI=0.29-0.44) and men (ρ=0.15; 95% CI=0.0o replicate these findings.Marinesco-Sjögren syndrome (MSS) is a rare human disorder caused by biallelic mutations in SIL1 characterized by cataracts in infancy, myopathy and ataxia, symptoms that are also associated with a novel disorder caused by mutations in INPP5K. While these phenotypic similarities may suggest commonalties at a molecular level, an overlapping pathomechanism has not been established yet. In this study, we present six new INPP5K patients and expand the current mutational and phenotypical spectrum of the disease showing the clinical overlap between MSS and the INPP5K-phenotype. We applied unbiased proteomic profiling on cells derived from MSS- and INPP5K-patients and identified alterations in D-3-phosphoglycerate dehydrogenase as a common molecular feature. D-3-phosphoglycerate dehydrogenase modulates the production of L-serine and mutations in this enzyme were previously associated with a neurological phenotype, which clinically overlaps with MSS and INPP5K-disease. As, L-serine administration represents a promising therapeutic strategy for D-3-phosphoglycerate dehydrogenase patients, we tested the effect of L-serine in generated sil1, phgdh and inpp5k a + b zebrafish models which showed an improvement in their neuronal phenotype. Thus our study defines a core phenotypical feature underpinning a key common molecular mechanism in three rare diseases and reveals a common and novel therapeutic target for these patients.Tick-borne illnesses pose a serious concern to human and veterinary health and their prevalence is on the rise. The interactions between ticks and the pathogens they carry are largely undefined. However, the genus Anaplasma, a group of tick-borne bacteria, has been instrumental in uncovering novel paradigms in tick biology. The emergence of sophisticated technologies and the convergence of entomology with microbiology, immunology, metabolism and systems biology has brought tick-Anaplasma interactions to the forefront of vector biology with broader implications for the infectious disease community. Here, we discuss the use of Anaplasma as an instrument for the elucidation of novel principles in arthropod-microbe interactions. We offer an outlook of the primary areas of study, outstanding questions and future research directions.Increasing evidence suggests that microglial activation is strongly linked to the initiation and progression of Parkinson’s disease (PD). Cell-to-cell propagation of α-synuclein (α-syn) pathology is a highlighted feature of PD, and the focus of such research has been primarily on neurons. However, recent studies as well as the data contained herein suggest that microglia, the primary phagocytes in the brain, play a direct role in the spread of α-syn pathology. Recent data revealed that plasma exosomes derived from PD patients (PD-EXO) carry pathological α-syn and target microglia preferentially. Hence, PD-EXO is likely a key tool for investigating the role of microglia in α-syn transmission. We showed that intrastriatal injection of PD-EXO resulted in the propagation of exosomal α-syn from microglia to neurons following microglia activation. Toll-like receptor 2 (TLR2) in microglia was activated by exosomal α-syn and acted as a crucial mediator of PD-EXO-induced microglial activation. Additionally, partial microglia depletion resulted in a significant decrease of exogenous α-syn in the substantia nigra (SN).
Please follow & like us :)
All content contained on CatsWannaBeCats.Com, unless otherwise acknowledged,is the property of CatsWannaBeCats.Com and subject to copyright.