A single dose of noradrenergic/serotonergic reuptake inhibitors combined with an antimuscarinic does not improve obstructive sleep apnoea severity.

Previous trials have demonstrated that the combination of noradrenergic reuptake inhibitors with an antimuscarinic can substantially reduce the apnoea-hypopnoea index (AHI) and improve airway collapsibility in patients with obstructive sleep apnoea (OSA). However, some studies have shown that when administered individually, neither noradrenergic or serotonergic agents have been effective at alleviating OSA. This raises the possibility that serotonergic agents (like noradrenergic agents) may also need to be delivered in combination to be efficacious.

A framework for digital health equity.

We present a comprehensive Framework for Digital Health Equity, detailing key digital determinants of health (DDoH), to support the work of digital health tool creators in industry, health systems operations, and academia. The rapid digitization of healthcare may widen health disparities if solutions are not developed with these determinants in mind. Our framework builds on the leading health disparities framework, incorporating a digital environment domain.

Player-labelling as a solution to overcome maturation selection biases in youth football.

The fact that potentially skilled, but biologically later-maturing athletes are less likely to be selected into talent development programmes (TDP) can represent a failure of Talent Identification (TID) in sports. To overcome maturation selection biases, maturation independent TID should be established to include less mature, but talented athletes in TDP more frequently. Using a randomised parallel-group design, this study aimed to evaluate the effect of labelling under-11 (U) Swiss male youth football players ( = 24, age = 11.

Evaluation of two short overlapping rbcL markers for diatom metabarcoding of environmental samples: Effects on biomonitoring assessment and species resolution.

Two short diatom rbcL barcodes, 331 bp and 263 bp in length, have frequently been used in diatom metabarcoding studies. They overlap in a common 263-bp region but differ in the presence or absence of a 68-bp tail at the 5' end. Though the effectiveness of both has been demonstrated in separate biomonitoring and diversity studies, the impact of the 68-bp non-shared region has not been evaluated.

Exploring the experiences of a community palliative care team as services were adapted to meet the demand of the COVID-19 pandemic.

During COVID-19, it was critical that services adapted to meet the high demands of the pandemic. This qualitative study explores the experiences of several staff members of the community palliative care team, as they adapted the delivery of their services to such pressures. Semi-structured interviews via a virtual platform were conducted and four themes were identified: service development, communication, inter-professional relationships and support mechanisms.

Erratum: Evaluation of F-IAM6067 as a sigma-1 receptor PET tracer for neurodegeneration in rodents and in human tissue: Erratum.

[This corrects the article DOI: 10.7150/thno.47585.

"What needs to be seen": An exploration into the visual anticipation behaviour of different skill-level football referees while observing long passes on-field.

It is well established that elite football referees possess superior anticipatory skills in specific game scenarios such as when assessing foul situations. Referees might also have better anticipatory skills in other important scenarios such as when observing a long pass. In these often-occurring situations, a referee has to use visual information to anticipate the outcome of the pass, in particular to foresee any potential infringements that might occur when players battle for ball possession.

Subtyping Evaluation of Enteritidis Using Single Nucleotide Polymorphism and Core Genome Multilocus Sequence Typing with Nanopore Reads.

Whole-genome sequencing (WGS) for public health surveillance and epidemiological investigation of foodborne pathogens predominantly relies on sequencing platforms that generate short reads. Continuous improvement of long-read nanopore sequencing, such as Oxford nanopore technologies (ONT), presents a potential for leveraging multiple advantages of the technology in public health and food industry settings, including rapid turnaround and onsite applicability in addition to superior read length. Using an established cohort of Salmonella Enteritidis isolates for subtyping evaluation, we assessed the technical readiness of nanopore long read sequencing for single nucleotide polymorphism (SNP) analysis and core-genome multilocus sequence typing (cgMLST) of a major foodborne pathogen.

Impact of Kidney Failure Risk Prediction Clinical Decision Support on Monitoring and Referral in Primary Care Management of CKD: A Randomized Pragmatic Clinical Trial.

Rationale & Objective: To design and implement clinical decision support incorporating a validated risk prediction estimate of kidney failure in primary care clinics and to evaluate the impact on stage-appropriate monitoring and referral.

Study Design: Block-randomized, pragmatic clinical trial.

Setting & Participants: Ten primary care clinics in the greater Boston area.

Phylotranscriptomics reveals the reticulate evolutionary history of a widespread diatom species complex.

In contrast to surveys based on a few genes that often provide limited taxonomic resolution, transcriptomes provide a wealth of genomic loci that can resolve relationships among taxonomically challenging lineages. Diatoms are a diverse group of aquatic microalgae that includes important bioindicator species and many such lineages. One example is Nitzschia palea, a widespread species complex with several morphologically defined taxonomic varieties, some of which are critical pollution indicators.

Tolerability of Sacubitril/Valsartan in Patients With Advanced Heart Failure: Analysis of the LIFE Trial Run-In.

Background: The LIFE (LCZ696 In Hospitalized Advanced Heart FailurE) trial, which evaluated sacubitril/valsartan in patients with advanced heart failure (HF) with reduced ejection fraction and recent New York Heart Association functional class IV symptomatology, did not require tolerance to a renin angiotensin system antagonist before initiating sacubitril/valsartan, thus affording an opportunity to study the tolerability of sacubitril/valsartan in advanced HF with reduced ejection fraction.

Objectives: The goal of this analysis of the LIFE trial is to characterize the tolerability of initiating sacubitril/valsartan in patients with chronic advanced HF with reduced ejection fraction.

Methods: In the LIFE trial, 445 subjects with advanced HF entered an unblinded run-in period of 3-7 days with sacubitril/valsartan 24/26 mg twice a day.

TREM-2 plays a protective role in cholestasis by acting as a negative regulator of inflammation.

Background & Aims: Inflammation, particularly that mediated by bacterial components translocating from the gut to the liver and binding to toll-like receptors (TLRs), is central to cholestatic liver injury. The triggering receptor expressed on myeloid cells-2 (TREM-2) inhibits TLR-mediated signaling and exerts a protective role in hepatocellular injury and carcinogenesis. This study aims to evaluate the role of TREM-2 in cholestasis.

The impact of daytime transoral neuromuscular stimulation on upper airway physiology - A mechanistic clinical investigation.

There is a need for alternatives to positive airway pressure for the treatment of obstructive sleep apnea and snoring. Improving upper airway dilator function might alleviate upper airway obstruction. We hypothesized that transoral neuromuscular stimulation would reduce upper airway collapse in concert with improvement in genioglossal muscle function.

A polar bear paleogenome reveals extensive ancient gene flow from polar bears into brown bears.

Polar bears (Ursus maritimus) and brown bears (Ursus arctos) are sister species possessing distinct physiological and behavioural adaptations that evolved over the last 500,000 years. However, comparative and population genomics analyses have revealed that several extant and extinct brown bear populations have relatively recent polar bear ancestry, probably as the result of geographically localized instances of gene flow from polar bears into brown bears. Here, we generate and analyse an approximate 20X paleogenome from an approximately 100,000-year-old polar bear that reveals a massive prehistoric admixture event, which is evident in the genomes of all living brown bears.

Acrylamide fragment inhibitors that induce unprecedented conformational distortions in enterovirus 71 3C and SARS-CoV-2 main protease.

RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional proteins. Many of these proteases exhibit a similar fold and contain an essential catalytic cysteine, offering the opportunity to inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that target the active site cysteine of the 3C protease (3C) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region.

Rare Case of Tracheal Fibromyxoma in Obstructive Tracheal Mass.

A 77-year-old male with a history of chronic obstructive pulmonary disease (COPD) who presented with cough, congestion, and stridor and was found to have a near obstructing tracheal mass. He subsequently underwent excision of the mass. On pathologic examination, it was diagnosed as fibromyxoma of the trachea.

Inadequate pitch-difference sensitivity prevents half of all listeners from discriminating major vs minor tone sequences.

Substantial evidence suggests that sensitivity to the difference between the major vs minor musical scales may be bimodally distributed. Much of this evidence comes from experiments using the "3-task." On each trial in the 3-task, the listener hears a rapid, random sequence of tones containing equal numbers of notes of either a G major or G minor triad and strives (with feedback) to judge which type of "tone-scramble" it was.

The influence of variations in background noise on Florida manatee (Trichechus manatus latirostris) detection of boat noise and vocalizations.

A manatee's primary modality to detect a vessel on a possible collision course is hearing as underwater visibility is limited in many manatee habitats and their visual acuity is poor. We estimate a Florida manatee's ability to detect the sound of an approaching boat and vocalizations in four different soundscapes in Sarasota Bay, FL. Background noise samples were collected every 5 minutes for a two-week period during winter and summer at each location (2019 or 2020).

Advances in Our Clinical Understanding of Autonomic Regulation Therapy Using Vagal Nerve Stimulation in Patients Living With Heart Failure.

The ANTHEM-HF, INOVATE-HF, and NECTAR-HF clinical studies of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) systems have collectively provided dose-ranging information enabling the development of several working hypotheses on how stimulation frequency can be utilized during VNS for tolerability and improving cardiovascular outcomes in patients living with heart failure (HF) and reduced ejection fraction (HFrEF). Changes in heart rate dynamics, comprising reduced heart rate (HR) and increased HR variability, are a biomarker of autonomic nerve system engagement and cardiac control, and appear to be sensitive to VNS that is delivered using a stimulation frequency that is similar to the natural operating frequency of the vagus nerve. Among prior studies, the ANTHEM-HF Pilot Study has provided the clearest evidence of autonomic engagement with VNS that was delivered using a stimulation frequency that was within the operating range of the vagus nerve.