Circadian chronotherapies of coronary heart disease and its biological risk factors: A United States Prescribers' Digital Reference-based review.

Chronotherapy is the timing of medications to circadian rhythms to optimize beneficial and minimize adverse outcomes. We reviewed the US Online Prescribers' Digital Reference for the specified administration schedule of medications prescribed to manage coronary heart disease (CHD) and its major risk factors. For arterial hypertension, dosing of terazosin and guanfacine is recommended in the evening and thiazide, thiazide-like, and sulfonamide diuretics morning; Verapamil (Verelan®) morning, its "PM" formulation evening, and long-acting diltiazem (Cardizem® LA), per clinical goal, morning or evening.

Sinefungin, a natural nucleoside analog of S-adenosyl methionine, impairs the pathogenicity of .

, an opportunistic fungal pathogen, causes life-threatening infections in immunocompromised patients. Current antifungals are limited by toxicity, drug-drug interactions, and emerging resistance, underscoring the importance of identifying novel treatment approaches. Here, we elucidate the impact of sinefungin, an analog of S-adenosyl methionine, on the virulence of strain SC5314 and clinical isolates.

A biallelic variant of the RNA exosome gene, EXOSC4, associated with neurodevelopmental defects impairs RNA exosome function and translation.

The RNA exosome is an evolutionarily conserved complex required for both precise RNA processing and decay. Pathogenic variants in EXOSC genes, which encode structural subunits of this complex, are linked to several autosomal recessive disorders. Here, we describe a missense allele of the EXOSC4 gene that causes a collection of clinical features in two affected siblings.

Pioneering new frontiers in circadian medicine chronotherapies for cardiovascular health.

Cardiovascular disease (CVD) is a global health concern. Circadian medicine improves cardiovascular care by aligning treatments with our body's daily rhythms and their underlying cellular circadian mechanisms. Time-based therapies, or chronotherapies, show special promise in clinical cardiology.

The putative RNA helicase DDX1 associates with the nuclear RNA exosome and modulates RNA/DNA hybrids (R-loops).

The RNA exosome is a ribonuclease complex that mediates both RNA processing and degradation. This complex is evolutionarily conserved, ubiquitously expressed, and required for fundamental cellular functions, including rRNA processing. The RNA exosome plays roles in regulating gene expression and protecting the genome, including modulating the accumulation of RNA-DNA hybrids (R-loops).

Primary repair with no flaps for lower lip defects (30-80 %) after cancer excision.

Reconstruction of the lip is a necessary procedure when lip tumors are excised. Although many good techniques have been described, they often have disadvantages such as necrosis and extensive suture lines. In our approach, we aim to minimize the suture line and avoid tissue necrosis for medium-sized lip defects (30-80 %).

A Biallelic Variant of the RNA Exosome Gene Causes Translational Defects Associated with a Neurodevelopmental Disorder.

The RNA exosome is an evolutionarily conserved complex required for both precise RNA processing and decay. Mutations in genes encoding structural subunits of the complex are linked to several autosomal recessive disorders. Here, we describe a missense allele of the gene, which causes a collection of clinical features in two affected siblings.

Comparative analyses of disease-linked missense mutations in the RNA exosome modeled in budding yeast reveal distinct functional consequences in translation.

The RNA exosome is an evolutionarily conserved exoribonuclease complex that consists of a 3-subunit cap, a 6-subunit barrel-shaped core, and a catalytic base subunit. Missense mutations in genes encoding structural subunits of the RNA exosome cause a growing family of diseases with diverse pathologies, collectively termed RNA exosomopathies. The disease symptoms vary and can manifest as neurological defects or developmental disorders.

Sinefungin, a natural nucleoside analog of S-adenosyl methionine, impairs the pathogenicity of .

, an opportunistic fungal human pathogen, is a major threat to the healthcare system due to both infections in immunocompromised individuals and the emergence of antifungal resistance. Fungal infection caused by , candidiasis, is a life-threatening condition in immunocompromised patients and the current treatments are mostly restricted to polyenes, azoles, and echinocandins. Use of these antifungals is limited by toxicity, drug-drug interactions, and the emergence of resistance, underscoring the importance of identifying novel therapeutic targets and the need for new treatment approaches.

RNA structural probing of guanine and uracil nucleotides in yeast.

RNA structure can be essential for its cellular function. Therefore, methods to investigate the structure of RNA in vivo are of great importance for understanding the role of cellular RNAs. RNA structure probing is an indirect method to asess the three-dimensional structure of RNA by analyzing the reactivity of different nucleotides to chemical modifications.

The RNA helicase DDX1 associates with the nuclear RNA exosome and modulates R-loops.

The RNA exosome is a ribonuclease complex that mediates both RNA processing and degradation. This complex is evolutionarily conserved, ubiquitously expressed, and required for fundamental cellular functions, including rRNA processing. The RNA exosome plays roles in regulating gene expression and protecting the genome, including modulating the accumulation of RNA-DNA hybrids (R-loops).

Recommended timing of medications that impact sleep and wakefulness: A review of the American Prescribers' Digital Reference.

An appreciable number of medicines have a recommended unique single time-of-day or asymmetrical or unequal-interval multiple-daily administration schedule. Many prescription and over-the-counter (OTC) products, according to administration time, can exert positive or negative impact on nighttime sleep and daytime wakefulness. Intuitively, medicines used to manage nighttime sleep and daytime wake disorders should be taken, respectively, at night before bedtime and morning after arising.

Interdependency of Core Temperature and Glabrous Skin Blood Flow in Human Thermoregulation Function: A Pilot Study.

Human thermoregulation is governed by a complex, nonlinear feedback control system. The system consists of thermoreceptors, a controller, and effector mechanisms for heat exchange that coordinate to maintain a central core temperature. A principal route for heat flow between the core and the environment is via convective circulation of blood to arteriovenous anastomoses located in glabrous skin of the hands and feet.

Novel temperature-controlled sleep system to improve sleep: a proof-of-concept study.

The sleep-wake cycle is regulated by circadian Process C and homeostatic Process S. Selective thermal stimulation (STS) of the cervical spine region enhances glabrous skin blood flow (GSBF) and augments body heat dissipation to increase distal-to-proximal skin gradient (DPG) causing decrease of core body temperature (CBT), which can shorten sleep onset latency (SOL) and improve sleep quality. A total of 11 young healthy/normal sleeper males challenged to go to bed (lights-off) 2 h earlier than usual were subjected in a randomised order to non-consecutive treatment and control night-time sleep sessions.

Studies of mutations of assembly factor Hit1 in budding yeast suggest translation defects as the molecular basis for PEHO syndrome.

Regulation of protein synthesis is critical for control of gene expression in all cells. Ribosomes are ribonucleoprotein machines responsible for translating cellular proteins. Defects in ribosome production, function, or regulation are detrimental to the cell and cause human diseases, such as progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome.

Bioheat Transfer Basis of Human Thermoregulation: Principles and Applications.

Thermoregulation is a process that is essential to the maintenance of life for all warm-blooded mammalian and avian species. It sustains a constant core body temperature in the face of a wide array of environmental thermal conditions and intensity of physical activities that generate internal heat. A primary component of thermoregulatory function is the movement of heat between the body core and the surface via the circulation of blood.

Ribosomal RNA 2'--methylations regulate translation by impacting ribosome dynamics.

SignificanceThe presence of RNA chemical modifications has long been known, but their precise molecular consequences remain unknown. 2'--methylation is an abundant modification that exists in RNA in all domains of life. Ribosomal RNA (rRNA) represents a functionally important RNA that is heavily modified by 2'--methylations.

Phosphorylation regulates arginine-rich RNA-binding protein solubility and oligomerization.

Posttranslational modifications (PTMs) such as phosphorylation of RNA-binding proteins (RBPs) regulate several critical steps in RNA metabolism, including spliceosome assembly, alternative splicing, and mRNA export. Notably, serine-/arginine- (SR)-rich RBPs are densely phosphorylated compared with the remainder of the proteome. Previously, we showed that dephosphorylation of the splicing factor SRSF2 regulated increased interactions with similar arginine-rich RBPs U1-70K and LUC7L3.

The Circadian Rhythm of Thermoregulation Modulates both the Sleep/Wake Cycle and 24 h Pattern of Arterial Blood Pressure.

Borbély proposed an interacting two-component model of sleep regulation comprising a homeostatic Process S and a circadian Process C. The model has provided understanding of the association between core body temperature (CBT) as a key element of Process C that is deterministic of sleep onset and offset. However, it additionally provides a new perspective of the importance of the thermoregulatory mechanisms of Process C in modulating the circadian rhythm of arterial blood pressure (ABP).

A Conformable Two-Dimensional Resistance Temperature Detector for Measuring Average Skin Temperature.

Thermoregulation research and various medical procedures are accomplished by manipulating skin temperature in a nonuniform pattern. Skin temperature monitoring is essential to assess conformance to protocol specifications and to prevent thermal injury. Existing solutions for skin temperature monitoring include single point sensors, such as thermocouples, and two-dimensional methods of sensing surface temperature, such as infrared thermography, and wearable technology.

Application of deep learning to improve sleep scoring of wrist actigraphy.

Background: Estimation of sleep parameters by wrist actigraphy is highly dependent on performance of the interpretative algorithm (IA) that converts movement data into sleep/wake scores.

Research Questions: (1) Does the actigraphy mode of operation -Proportional Integrating Measure (PIM) or Zero Crossing Mode (ZCM), responsive respectively to intensity and frequency of movements- impact sleep scoring; and (2) Can a better performing sleep scoring IA be developed by a deep learning approach combining PIM/ZCM data.

Study Design And Methods: ZCM and PIM plus electroencephalographic (EEG) data of 40 healthy adults (17 female, mean age: 26.

A comprehensive guideline for Bland-Altman and intra class correlation calculations to properly compare two methods of measurement and interpret findings.

The rapid emergence of new measurement instruments and methods requires personnel and researchers of different disciplines to know the correct statistical methods to utilize to compare their performance with reference ones and properly interpret findings. We discuss the often-made mistake of applying the inappropriate correlation and regression statistical approaches to compare methods and then explain the concepts of agreement and reliability. Then, we introduce the intraclass correlation as a measure of inter-rater reliability, and the Bland-Altman plot as a measure of agreement, and we provide formulae to calculate them along with illustrative examples for different types of study designs, specifically single measurement per subject, repeated measurement while the true value is constant, and repeated measurement when the true value is not constant.

Accuracy of Wristband Fitbit Models in Assessing Sleep: Systematic Review and Meta-Analysis.

Background: Wearable sleep monitors are of high interest to consumers and researchers because of their ability to provide estimation of sleep patterns in free-living conditions in a cost-efficient way.

Objective: We conducted a systematic review of publications reporting on the performance of wristband Fitbit models in assessing sleep parameters and stages.

Methods: In adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we comprehensively searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, Embase, MEDLINE, PubMed, PsycINFO, and Web of Science databases using the keyword Fitbit to identify relevant publications meeting predefined inclusion and exclusion criteria.