Transforming growth factor-β1 in the cerebrospinal fluid of patients with distinct neurodegenerative diseases

A chronic inflammatory condition may underlie neurodegenerative disorders, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). For example, both PD and AD patients show an increase in transforming growth factor-β1 (TGF-β1) levels in their cerebrospinal fluid (CSF). TGF-β1 is a cytokine that inhibits inflammation. In the present study, using an enzyme-linked immunosorbent assay, we tested the hypothesis that the level of TGF-β1 in the CSF of patients with amyotrophic lateral sclerosis (ALS), spinocerebellar degeneration (SCD), or multiple system atrophy-cerebellar subtype (MSA-C) would be elevated compared with that of normal controls. We found that TGF-β1 levels in the CSF were not significantly different between these patients and normal controls. Our data suggest that the level of TGF-β1 in the CSF is an unreliable biomarker of ALS, SCD, and MSA-C

Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome.

The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP

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

The Limited Effect of a History of COVID-19 on Antibody Titers and Adverse Reactions Following BNT162b2 Vaccination: A Single-Center Prospective Study

Background and Objectives: The need for, and ideal frequency of, the vaccination against coronavirus disease 2019 (COVID-19) of previously infected individuals have not yet been sufficiently evaluated. The aim of this study was to examine the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody status and adverse reactions after vaccination among medical staff with or without a history of COVID-19. Materials and Methods: A single-center prospective study was performed at Fukuoka University Chikushi Hospital. We investigated the presence of the anti-SARS-CoV-2 antibody titer among medical staff before and after mRNA vaccination with the BNT162b2. The levels of immunoglobulin G antibody were quantitatively measured at six points—before vaccination, after the first vaccination, at three points after the second vaccination, and finally, after the third vaccination—and the levels were then compared based on the COVID-19 infection history. Results: The previously infected (before the first vaccination) subjects (n = 17) showed a marked increase in antibody titers two weeks after the first vaccination and four weeks after the second vaccination. Although they were able to maintain a certain level of antibody titers until 30 weeks after the second vaccination, the titers fell in the same way as observed in the non-infected subjects. The subjects who did not receive the third vaccination due to adverse reactions to previous vaccines (n = 1) or who were positive for COVID-19 prior to the third vaccination (n = 2) were excluded from the subsequent analyses. Among non-infected subjects (n = 36), smokers had lower peak antibody titers than the others. The previously infected subjects had a significantly higher incidence of adverse reactions after the first vaccination but had a similar incidence of adverse reactions after the second and third vaccinations compared to the non-infected subjects. Conclusions: A history of COVID-19 may influence only the initial increase in anti-SARS-CoV-2 antibody titers and the occurrence of adverse reactions after the first vaccination