Hyperphosphatemia Contributes to Skeletal Muscle Atrophy in Mice.

Chronic kidney disease (CKD) is associated with various pathologic changes, including elevations in serum phosphate levels (hyperphosphatemia), vascular calcification, and skeletal muscle atrophy. Elevated phosphate can damage vascular smooth muscle cells and cause vascular calcification. Here, we determined whether high phosphate can also affect skeletal muscle cells and whether hyperphosphatemia, in the context of CKD or by itself, is associated with skeletal muscle atrophy. As models of hyperphosphatemia with CKD, we studied mice receiving an adenine-rich diet for 14 weeks and mice with deletion of Collagen 4a3 (Col4a3-/-). As models of hyperphosphatemia without CKD, we analyzed mice receiving a high-phosphate diet for three and six months as well as a genetic model for klotho deficiency (kl/kl). We found that adenine, Col4a3-/-, and kl/kl mice have reduced skeletal muscle mass and function and develop atrophy. Mice on a high-phosphate diet for six months also had lower skeletal muscle mass and function but no significant signs of atrophy, indicating less severe damage compared with the other three models. To determine the potential direct actions of phosphate on skeletal muscle, we cultured primary mouse myotubes in high phosphate concentrations, and we detected the induction of atrophy. We conclude that in experimental mouse models, hyperphosphatemia is sufficient to induce skeletal muscle atrophy and that, among various other factors, elevated phosphate levels might contribute to skeletal muscle injury in CKD.

Recent Outcomes Research in Helicopter Emergency Medical Services: A Scoping Review of Publication Year 2023 Additions to the Helicopter Outcomes Assessment Research Database.

OBJECTIVE: The purpose of this scoping review was to identify and characterize helicopter emergency medical services (HEMS) outcomes literature from 2023, with the goal of describing updates to the Critical Care Transport Collaborative Outcomes Research Effort HEMS Outcomes Assessment Research Database (HOARD). METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, a multireviewer approach was used to source and review articles published or in preprint databases from 2023. The articles included assessed a patient-centered outcome for HEMS versus a non-HEMS control group. Article characteristics included the journal impact factor (JIF), diagnostic group (trauma or nontrauma), and geographic origin. Categoric analyses comparing 2023 studies with HOARD studies from the previous decade (2013-2022) were executed with the Fisher exact test; nonnormal JIF data were described using median and interquartile range and analyzed (vs 2013-2022) with rank sum testing. RESULTS: Of the initial records (N = 4,486), 4,410 were screened out, leaving 76 for full-text review. Of these, 58 were discarded, and 18 were classified as eligible for addition to HOARD. Most studies (14/18, 78%) focused on trauma, and an equally high proportion (14/18, 78%) came from North America. The median JIF was 2.4 (interquartile range, 1.2-3.6). Compared with HOARD studies from the previous decade, 2023 studies were similar with respect to diagnostic focus (P = .779), geographic origin (P = .171), and JIF (P = .531). CONCLUSION: This scoping review provides information on 18 HEMS outcomes studies new to the evidence base in 2023.

Investigating Substance Use as a Coping Strategy Among Adolescent Psychiatric Inpatients: A Comparative Analysis Before and During the COVID-19 Pandemic.

The COVID-19 pandemic resulted in significant changes in daily life, potentially impacting mental health and substance use behavior. Research on COVID-related changes in adolescent substance use have yielded mixed findings. The current cross-sectional chart review study compared rates of past-year substance use before and during COVID-19 among adolescent psychiatric inpatients, and investigated how motives for coping with COVID-19 changes were related to psychiatric acuity, and past-year substance use. Count models assessed if the number of past-year days of alcohol and cannabis use was higher among adolescents (n = 491, 11-18 years, 61% female) hospitalized during COVID-19 (3/14/20 to 4/5/21) versus adolescents hospitalized before COVID-19 (8/30/2019 to 3/13/20). For a subsample of COVID-19 inpatients (n = 124; 75% female), we evaluated psychiatric correlates of endorsing substances to cope with COVID-19 changes/rules. Results indicated adolescents admitted during COVID-19 reported significantly more past-year alcohol and cannabis use days than adolescents admitted before COVID-19. Adolescents endorsed using alcohol (19%), cannabis (33%), and e-cigarettes/vaping (25%) to cope with COVID-19. E-cigarette/vaping to cope with COVID-19 was significantly related to lifetime suicide attempt. Endorsing alcohol or cannabis to cope with COVID-19 was associated with a significantly greater number of past-year use days for each respective substance. Adolescent psychiatric inpatients admitted during COVID-19 reported more substance use days than adolescents admitted before COVID-19. Using substances to cope was linked to psychiatric correlates (e.g., suicidality). Assessing the presence and function of substance use in this population may be important to identify, treat, and prevent compounding negative outcomes during times of community stress.

No one is going to recess: How children evaluate collective and targeted punishment.

This study examined children's responses to targeted and collective punishment. Thirty-six 4-5-year-olds and 36 6-7-year-olds (36 females; 54 White; data collected 2018-2019 in the United States) experienced three classroom punishment situations: Targeted (only transgressing student punished), Collective (one student transgressed, all students punished), and Baseline (all students transgressed, all punished). The older children evaluated collective punishment as less fair than targeted, whereas younger children evaluated both similarly. Across ages, children distributed fewer resources to teachers who administered collective than targeted punishment, and rated transgressors more negatively and distributed fewer resources to transgressors in Collective and Targeted than Baseline. These findings demonstrate children's increasing understanding of punishment and point to the potential impact of different forms of punishment on children's social lives.

Evolution of DS-1-like G8P[8] rotavirus A strains from Vietnamese children with acute gastroenteritis (2014-21): Adaptation and loss of animal rotavirus-derived genes during human-to-human spread.

Animal rotaviruses A (RVAs) are considered the source of emerging, novel RVA strains that have the potential to cause global spread in humans. A case in point was the emergence of G8 bovine RVA consisting of the P[8] VP4 gene and the DS-1-like backbone genes that appeared to have jumped into humans recently. However, it was not well documented what evolutionary changes occurred on the animal RVA-derived genes during circulation in humans. Rotavirus surveillance in Vietnam found that DS-1-like G8P[8] strains emerged in 2014, circulated in two prevalent waves, and disappeared in 2021. This surveillance provided us with a unique opportunity to investigate the whole process of evolutionary changes, which occurred in an animal RVA that had jumped the host species barrier. Of the 843 G8P[8] samples collected from children with acute diarrhoea in Vietnam between 2014 and 2021, fifty-eight strains were selected based on their distinctive electropherotypes of the genomic RNA identified using polyacrylamide gel electrophoresis. Whole-genome sequence analysis of those fifty-eight strains showed that the strains dominant during the first wave of prevalence (2014-17) carried animal RVA-derived VP1, NSP2, and NSP4 genes. However, the strains from the second wave of prevalence (2018-21) lost these genes, which were replaced with cognate human RVA-derived genes, thus creating strain with G8P[8] on a fully DS-1-like human RVA gene backbone. The G8 VP7 and P[8] VP4 genes underwent some point mutations but the phylogenetic lineages to which they belonged remained unchanged. We, therefore, propose a hypothesis regarding the tendency for the animal RVA-derived genes to be expelled from the backbone genes of the progeny strains after crossing the host species barrier. This study underlines the importance of long-term surveillance of circulating wild-type strains in order to better understand the adaptation process and the fate of newly emerging, animal-derived RVA among the human population. Further studies are warranted to disclose the molecular mechanisms by which spillover animal RVAs become readily transmissible among humans, and the roles played by the expulsion of animal-derived genes and herd immunity formed in the local population.

Resolvins D5 and D1 undergo phase II metabolism by uridine 5'-diphospho-glucuronosyltransferases.

Specialized pro-resolving mediators (SPMs) are oxidized lipid mediators that have been shown to resolve inflammation in cellular and animal models as well as humans. SPMs and their biological precursors are even commercially available as dietary supplements. It has been understood for more than forty years that pro-inflammatory oxidized lipid mediators, including prostaglandins and leukotrienes, are rapidly inactivated via metabolism. Studies on the metabolism of SPMs are, however, limited. Herein, we report that resolvin D5 (RvD5) and resolvin D1 (RvD1), well-studied SPMs, are readily metabolized by human liver microsomes (HLM) to glucuronide conjugated metabolites. We further show that this transformation is catalyzed by specific uridine 5'-diphospho-glucuronosyltransferase (UGT) isoforms. Additionally, we demonstrate that RvD5 and RvD1 metabolism by HLM is influenced by non-steroidal anti-inflammatory drugs (NSAIDs), which can act as UGT inhibitors through cyclooxygenase-independent mechanisms. The results from these studies highlight the importance of considering metabolism, as well as factors that influence metabolic enzymes, when seeking to quantify SPMs in vivo.

Australian Rotavirus Surveillance Program Annual Report, 2022.

Abstract: This report from the Australian Rotavirus Surveillance Program describes the circulating rotavirus genotypes identified in children and adults during the period 1 January to 31 December 2022. After two years of a lower number of stool samples received as a result of the coronavirus disease 2019 (COVID-19) pandemic, this reporting period saw the highest number of samples received since the 2017 surveillance period, with samples received from all states and territories. During this period, 1,379 faecal specimens had been referred for rotavirus G- and P- genotype analysis, of which 1,276 were confirmed as rotavirus positive. In total, 1,119/1,276 were identified as wildtype rotavirus, 155/1,276 identified as the Rotarix vaccine strain and 2/1,276 that could not be confirmed as vaccine or wildtype due to sequencing failure. Whilst G12P[8] was the dominant genotype nationally among wildtype samples (28.2%; 315/1,119), multiple genotypes were identified at similar frequencies including G9P[4] (22.3%; 249/1,119) and G2P[4] (20.3%; 227/1,119). Geographical differences in genotype distribution were observed, largely driven by outbreaks reported in some jurisdictions. Outbreaks and increased reports of rotavirus disease were reported in the Northern Territory, Queensland, and New South Wales. A small number of unusual genotypes, potentially zoonotic in nature, were identified, including: G8P[14]; G10[14]; caninelike G3P[3]; G6P[9]; and G11P[25]. Ongoing rotavirus surveillance is crucial to identify changes in genotypic patterns and to provide diagnostic laboratories with quality assurance by reporting incidences of wildtype, vaccine-like, or false positive rotavirus results.

Management Considerations for Air Medical Transport Programs Transfusing RhD-Positive Red Blood Cell-Containing Products to Females of Childbearing Potential.

Recent years have seen increased discussion surrounding the benefits of damage control resuscitation, prehospital transfusion (PHT) of blood products, and the use of whole blood over component therapy. Concurrent shortages of blood products with the desire to provide PHT during air medical transport have prompted reconsideration of the traditional approach of administering RhD-negative red cell-containing blood products first-line to females of childbearing potential (FCPs). Given that only 7% of the US population has blood type O negative and 38% has O positive, some programs may be limited to offering RhD-positive blood products to FCPs. Adopting the practice of giving RhD-positive blood products first-line to FCPs extends the benefits of PHT to such patients, but this practice does incur the risk of future hemolytic disease of the fetus and newborn (HDFN). Although the risk of future fetal mortality after an RhD-incompatible transfusion is estimated to be low in the setting of acute hemorrhage, the number of FCPs who are affected by this disease will increase as more air medical transport programs adopt this practice. The process of monitoring and managing HDFN can also be time intensive and costly regardless of the rates of fetal mortality. Air medical transport programs planning on performing PHT of RhD-positive red cell-containing products to FCPs should have a basic understanding of the pathophysiology, prevention, and management of hemolytic disease of the newborn before introducing this practice. Programs should additionally ensure there is a reliable process to notify receiving centers of potentially RhD-incompatible PHT because alloimmunization prophylaxis is time sensitive. Facilities receiving patients who have had PHT must be prepared to identify, counsel, and offer alloimmunization prophylaxis to these patients. This review aims to provide air medical transport professionals with an understanding of the pathophysiology and management of HDFN and provide a template for the early management of FCPs who have received an RhD-positive red cell-containing PHT. This review also covers the initial workup and long-term anticipatory guidance that receiving trauma centers must provide to FCPs who have received RhD-positive red cell-containing PHT.

A scoping review on what constitutes a good research culture.

Background: The crisis in research culture is well documented, covering issues such as a tendency for quantity over quality, unhealthy competitive environments, and assessment based on publications, journal prestige and funding. In response, research institutions need to assess their own practices to promote and advocate for change in the current research ecosystem. The purpose of the scoping review was to explore ' What does the evidence say about the 'problem' with 'poor' research culture, what are the benefits of 'good' research culture, and what does 'good' look like?' Aims: To examine the peer-reviewed and grey literature to explore the interplay between research culture, open research, career paths, recognition and rewards, and equality, diversity, and inclusion, as part of a larger programme of activity for a research institution. Methods: A scoping review was undertaken. Six databases were searched along with grey literature. Eligible literature had relevance to academic research institutions, addressed research culture, and were published between January 2017 to May 2022. Evidence was mapped and themed to specific categories. The search strategy, screening and analysis took place between April-May 2022. Results: 1666 titles and abstracts, and 924 full text articles were assessed for eligibility. Of these, 253 articles met the eligibility criteria for inclusion. A purposive sampling of relevant websites was drawn from to complement the review, resulting in 102 records included in the review. Key areas for consideration were identified across the four themes of job security, wellbeing and equality of opportunity, teamwork and interdisciplinary, and research quality and accountability. Conclusions: There are opportunities for research institutions to improve their own practice, however institutional solutions cannot act in isolation. Research institutions and research funders need to work together to build a more sustainable and inclusive research culture that is diverse in nature and supports individuals' well-being, career progression and performance.

The psychosocial impact of prostate cancer screening for BRCA1 and BRCA2 carriers.

OBJECTIVES: To report the long-term outcomes from a longitudinal psychosocial study that forms part of the 'Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted Screening in men at higher genetic risk and controls' (IMPACT) study. The IMPACT study is a multi-national study of targeted prostate cancer (PrCa) screening in individuals with a known germline pathogenic variant (GPV) in either the BReast CAncer gene 1 (BRCA1) or the BReast CAncer gene 2 (BRCA2). SUBJECTS AND METHODS: Participants enrolled in the IMPACT study were invited to complete a psychosocial questionnaire prior to each annual screening visit for a minimum of 5 years. The questionnaire included questions on sociodemographics and the following measures: Hospital Anxiety and Depression Scale, Impact of Event Scale, 36-item Short-Form Health Survey, Memorial Anxiety Scale for PrCa, Cancer Worry Scale, risk perception and knowledge. RESULTS: A total of 760 participants completed questionnaires: 207 participants with GPV in BRCA1, 265 with GPV in BRCA2 and 288 controls (non-carriers from families with a known GPV). We found no evidence of clinically concerning levels of general or cancer-specific distress or poor health-related quality of life in the cohort as a whole. Individuals in the control group had significantly less worry about PrCa compared with the carriers; however, all mean scores were low and within reported general population norms, where available. BRCA2 carriers with previously high prostate-specific antigen (PSA) levels experience a small but significant increase in PrCa anxiety (P = 0.01) and PSA-specific anxiety (P < 0.001). Cancer risk perceptions reflected information provided during genetic counselling and participants had good levels of knowledge, although this declined over time. CONCLUSION: This is the first study to report the longitudinal psychosocial impact of a targeted PrCa screening programme for BRCA1 and BRCA2 carriers. The results reassure that an annual PSA-based screening programme does not have an adverse impact on psychosocial health or health-related quality of life in these higher-risk individuals. These results are important as more PrCa screening is targeted to higher-risk groups.