The dual endothelin A and angiotensin II type 1 receptor antagonist sparsentan (FILSPARI®) exhibits a safe nonclinical male fertility toxicity profile.

Marketed endothelin receptor antagonists (ERAs) have been associated with testicular tubular atrophy and decreases in male animal fertility in chronic toxicity studies in rats and dogs. Consistent with these findings, reduced sperm count has been observed in the clinical setting and is considered a potential class risk with chronic administration of ERAs. In contrast, no such effects on male animal fertility are noted with angiotensin II type 1 receptor blocker (ARB) treatment.

Composite Recycling with Biocatalytic Thermoset Reforming.

Carbon fiber reinforced polymers (CFRPs, or composites) are increasingly replacing traditional manufacturing materials used in the automobile, aerospace, and energy sectors. With this shift, it is vital to develop end-of-life processes for CFRPs that retain the value of both the carbon fibers and the polymer matrix. Here we demonstrate a strategy to upcycle pre- and postconsumer polystyrene-containing CFRPs, cross-linked with unsaturated polyesters or vinyl esters, to benzoic acid.

The effect of an acute bout of exercise on circulating vitamin D metabolite concentrations: a randomised crossover study in healthy adults.

The effect of acute exercise on circulating concentrations of vitamin D metabolites is unclear. To address this knowledge gap, we examined the effect of a bout of treadmill-based exercise versus rest on circulating concentrations of 25(OH)D, 25(OH)D, 3-epi-25(OH)D, 24,25(OH)D, 1,25(OH)D, and vitamin D and D in healthy men and women. Thirty-three healthy adults (14 females, 41 (15) years, body mass index 26.

Discovery of Uncommon Tryptophan-Containing Diketopiperazines from CBS 101889 Using an Heterologous Expression System.

Fungal secondary metabolite (SM) biosynthetic gene clusters (BGCs) containing dimethylallyltryptophan synthases (DMATSs) produce structurally diverse prenylated indole alkaloids with wide-ranging activities that have vast potential as human therapeutics. To discover new natural products produced by DMATSs, we mined the Department of Energy Joint Genome Institute's MycoCosm database for DMATS-containing BGCs. We found a DMATS BGC in CBS 101889, which also contains a nonribosomal peptide synthetase (NRPS).

Developing and exploring the validity of a patient reported experience measure for adult inpatient diabetes care.

Aim: To develop and explore the validity of a Patient Reported Experience Measure (PREM) for adult inpatient diabetes care.

Method: 27 in-depth interviews were conducted to inform the development of the 42-item PREM which was cognitively tested with 10 people. A refined 38-item PREM was piloted with 228 respondents completing a paper (n = 198) or online (n = 30) version.

Computer-aided, resistance gene-guided genome mining for proteasome and HMG-CoA reductase inhibitors.

Unlabelled: Secondary metabolites (SMs) are biologically active small molecules, many of which are medically valuable. Fungal genomes contain vast numbers of SM biosynthetic gene clusters (BGCs) with unknown products, suggesting that huge numbers of valuable SMs remain to be discovered. It is challenging, however, to identify SM BGCs, among the millions present in fungi, that produce useful compounds.

A systematic review to determine use of the Endometriosis Health Profiles to measure quality of life outcomes in women with endometriosis.

Background: The Endometriosis Health Profiles (EHPs), the EHP-30 and EHP-5, are patient-reported outcome measures that were developed to measure the health-related quality of life (HRQoL) of women living with endometriosis. Prior to their development, a systematic review was undertaken which identified that the HRQoL of women living with endometriosis was poorly understood, with only three medical and one surgical study identified.

Objective And Rationale: The 20-year anniversary of the EHP-30 provided a timely opportunity to assess how the tools have been used and explore what the findings tell us about the impact of endometriosis and its associated treatments upon women's QoL.

Lysophosphatidic acid receptor 1 antagonist (EPGN2154) causes regression of NASH in preclinical NASH models.

Background: NASH causes a tremendous health care burden in the United States. A glucagon-like peptide-1 agonist, semaglutide (Sema), treatment resulted in hepatic steatosis reduction in clinical trials of NASH. Lysophosphatidic acid receptor 1 antagonists are known to have antifibrotic effects in several organs.

Overcoming training bottlenecks: mixed-methods evaluation of digital training for non-specialists in postnatal depression self-help treatment.

Objectives: This mixed-methods study evaluated the feasibility, acceptability and preliminary effectiveness of an interactive digital training programme for non-specialist supporters providing a guided self-help intervention for postnatal depression (PND).

Methods: A total of 49 non-specialist trainees participated. Six digital training modules were flexibly delivered over a 5-week period.

A heterologous expression platform in for the elucidation of cryptic secondary metabolism biosynthetic gene clusters: discovery of the sartorypyrone biosynthetic pathway.

is a serious human pathogen causing life-threatening Aspergillosis in immunocompromised patients. Secondary metabolites (SMs) play an important role in pathogenesis, but the products of many SM biosynthetic gene clusters (BGCs) remain unknown. In this study, we have developed a heterologous expression platform in , using a newly created genetic dereplication strain, to express a previously unknown BGC from and determine its products.

Allelic prevalence and geographic distribution of cerebrotendinous xanthomatosis.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare recessive genetic disease characterized by disruption of bile acid synthesis due to inactivation of the CYP27A1 gene. Treatment is available in the form of bile acid replacement. CTX is likely underdiagnosed, and prevalence estimates based on case diagnosis are probably inaccurate.

The development of a patient reported outcome measure for fatigue and breathlessness for patients with chronic heart failure (OxFAB).

Background: Fatigue and breathlessness are the two most common and distressing symptoms for patients with chronic heart failure. They affect a patient's quality of life and ability to undertake activities of daily living. Currently there are no symptom specific measures for fatigue and breathlessness available or developed and validated for use with this patient group and no questionnaire that incorporates both symptoms into one measure.

Computerized adaptive testing for the Oxford Hip, Knee, Shoulder, and Elbow scores : accurate measurement from fewer, and more patient-focused, questions.

Aims: The aim of this study was to develop and evaluate machine-learning-based computerized adaptive tests (CATs) for the Oxford Hip Score (OHS), Oxford Knee Score (OKS), Oxford Shoulder Score (OSS), and the Oxford Elbow Score (OES) and its subscales.

Methods: We developed CAT algorithms for the OHS, OKS, OSS, overall OES, and each of the OES subscales, using responses to the full-length questionnaires and a machine-learning technique called regression tree learning. The algorithms were evaluated through a series of simulation studies, in which they aimed to predict respondents' full-length questionnaire scores from only a selection of their item responses.

Heart Transplantation From DCD Donors in Australia: Lessons Learned From the First 74 Cases.

Heart transplantation from donation after circulatory death (DCD) donors has the potential to substantially increase overall heart transplant activity. The aim of this report is to review the first 8 y of our clinical heart transplant program at St Vincent's Hospital Sydney, to describe how our program has evolved and to report the impact that changes to our retrieval protocols have had on posttransplant outcomes. Since 2014, we have performed 74 DCD heart transplants from DCD donors utilizing a direct procurement protocol followed by normothermic machine perfusion.

A qualitative study into the experience of living with acalculia after stroke and other forms of acquired brain injury.

Acalculia, an acquired disability following a brain injury, involves difficulty processing numerical information and/or calculations. Acalculia is not routinely screened for, and as a result there is a lack of understanding about the nature and prevalence and the impact of the condition. This qualitative study was initiated by stroke survivors with a strong interest in acalculia.

Test-retest reliability of the PDQ-Carer.

Introduction: The PDQ-Carer is a 29-item measure of health-related quality of life (QoL) for use with carers of people with Parkinson's (PwP). The measure produces a profile of scores across four domains. Previous validation data indicates that the measure possesses sound psychometric properties in terms of validity and internal consistency.