A Proposal for New Algorithm that Defines Gait-Induced Acceleration and Gait Cycle in Daily Parkinsonian Gait Disorders

We developed a new device, the portable gait rhythmogram (PGR), to record up to 70 hrs of movement-induced accelerations. Acceleration values induced by various movements, averaged every 10 min, showed gamma distribution, and the mean value of this distribution was used as an index of the amount of overall movements. Furthermore, the PGR algorithm can specify gait-induced accelerations using the pattern-matching method. Analysis of the relationship between gait-induced accelerations and gait cycle duration makes it possible to quantify Parkinson’s disease (PD)-specific pathophysiological mechanisms underlying gait disorders. Patients with PD showed the following disease-specific patterns: (1) reduced amount of overall movements and (2) low amplitude of gait-induced accelerations in the early stages of the disease, which was compensated by fast stepping. Loss of compensation was associated with slow stepping gait, (3) narrow range of gait-induced acceleration amplitude and gait cycle duration, suggesting monotony, and (4) evident motor fluctuations during the day by tracing changes in the above two parameters. Prominent motor fluctuation was associated with frequent switching between slow stepping mode and active mode. These findings suggest that monitoring various movement- and gait-induced accelerations allows the detection of specific changes in PD. We conclude that continuous long-term monitoring of these parameters can provide accurate quantitative assessment of parkinsonian clinical motor signs

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead