Inhibition of mitosomal alternative oxidase causes lifecycle arrest of early-stage Trachipleistophora hominis meronts during intracellular infection of mammalian cells.

Mitosomes are highly reduced forms of mitochondria which have lost two of the 'defining' features of the canonical organelle, the mitochondrial genome, and the capacity to generate energy in the form of ATP. Mitosomes are found in anaerobic protists and obligate parasites and, in most of the studied organisms, have a conserved function in the biosynthesis of iron-sulfur clusters (ISC) that are indispensable cofactors of many essential proteins. The genomes of some mitosome-bearing human pathogenic Microsporidia encode homologues of an alternative oxidase (AOX). This mitochondrial terminal respiratory oxidase is absent from the human host, and hence is a potential target for the development of new antimicrobial agents. Here we present experimental evidence for the mitosomal localization of AOX in the microsporidian Trachipleistophora hominis and demonstrate that it has an important role during the parasite's life cycle progression. Using a recently published methodology for synchronising T. hominis infection of mammalian cell lines, we demonstrated specific inhibition of T. hominis early meront growth and replication by an AOX inhibitor colletochlorin B. Treatment of T. hominis-infected host cells with the drug also inhibited re-infection by newly formed dispersive spores. Addition of the drug during the later stages of the parasite life cycle, when our methods suggest that AOX is not actively produced and T. hominis mitosomes are mainly active in Fe/S cluster biosynthesis, had no inhibitory effects on the parasites. Control experiments with the AOX-deficient microsporidian species Encephalitozoon cuniculi, further demonstrated the specificity of inhibition by the drug. Using the same methodology, we demonstrate effects of two clinically used anti-microsporidian drugs albendazole and fumagillin on the cell biology and life cycle progression of T. hominis infecting mammalian host cells. In summary, our results reveal that T. hominis mitosomes have an active role to play in the progression of the parasite life cycle as well as an important role in the biosynthesis of essential Fe/S clusters. Our work also demonstrates that T. hominis is a useful model for testing the efficacy of therapeutic agents and for studying the physiology and cell biology of microsporidian parasites growing inside infected mammalian cells.

Phylogenomic fingerprinting of tempo and functions of horizontal gene transfer within ochrophytes.

Horizontal gene transfer (HGT) is an important source of novelty in eukaryotic genomes. This is particularly true for the ochrophytes, a diverse and important group of algae. Previous studies have shown that ochrophytes possess a mosaic of genes derived from bacteria and eukaryotic algae, acquired through chloroplast endosymbiosis and from HGTs, although understanding of the time points and mechanisms underpinning these transfers has been restricted by the depth of taxonomic sampling possible. We harness an expanded set of ochrophyte sequence libraries, alongside automated and manual phylogenetic annotation, in silico modeling, and experimental techniques, to assess the frequency and functions of HGT across this lineage. Through manual annotation of thousands of single-gene trees, we identify continuous bacterial HGT as the predominant source of recently arrived genes in the model diatom Phaeodactylum tricornutum Using a large-scale automated dataset, a multigene ochrophyte reference tree, and mathematical reconciliation of gene trees, we note a probable elevation of bacterial HGTs at foundational points in diatom evolution, following their divergence from other ochrophytes. Finally, we demonstrate that throughout ochrophyte evolutionary history, bacterial HGTs have been enriched in genes encoding secreted proteins. Our study provides insights into the sources and frequency of HGTs, and functional contributions that HGT has made to algal evolution.

Hundreds of Out-of-Frame Remodeled Gene Families in the Escherichia coli Pangenome.

All genomes include gene families with very limited taxonomic distributions that potentially represent new genes and innovations in protein-coding sequence, raising questions on the origins of such genes. Some of these genes are hypothesized to have formed de novo, from noncoding sequences, and recent work has begun to elucidate the processes by which de novo gene formation can occur. A special case of de novo gene formation, overprinting, describes the origin of new genes from noncoding alternative reading frames of existing open reading frames (ORFs). We argue that additionally, out-of-frame gene fission/fusion events of alternative reading frames of ORFs and out-of-frame lateral gene transfers could contribute to the origin of new gene families. To demonstrate this, we developed an original pattern-search in sequence similarity networks, enhancing the use of these graphs, commonly used to detect in-frame remodeled genes. We applied this approach to gene families in 524 complete genomes of Escherichia coli. We identified 767 gene families whose evolutionary history likely included at least one out-of-frame remodeling event. These genes with out-of-frame components represent ∼2.5% of all genes in the E. coli pangenome, suggesting that alternative reading frames of existing ORFs can contribute to a significant proportion of de novo genes in bacteria.

Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers.

BACKGROUND: Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation. METHOD: 161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α. RESULTS: Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls. CONCLUSIONS: The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).

Inflammatory subgroups of schizophrenia and their association with brain structure: A semi-supervised machine learning examination of heterogeneity.

OBJECTIVE: Immune system dysfunction is hypothesised to contribute to structural brain changes through aberrant synaptic pruning in schizophrenia. However, evidence is mixed and there is a lack of evidence of inflammation and its effect on grey matter volume (GMV) in patients. We hypothesised that inflammatory subgroups can be identified and that the subgroups will show distinct neuroanatomical and neurocognitive profiles. METHODS: The total sample consisted of 1067 participants (chronic patients with schizophrenia n = 467 and healthy controls (HCs) n = 600) from the Australia Schizophrenia Research Bank (ASRB) dataset, together with 218 recent-onset patients with schizophrenia from the external Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism (BeneMin) dataset. HYDRA (HeterogeneitY through DiscRiminant Analysis) was used to separate schizophrenia from HC and define disease-related subgroups based on inflammatory markers. Voxel-based morphometry and inferential statistics were used to explore GMV alterations and neurocognitive deficits in these subgroups. RESULTS: An optimal clustering solution revealed five main schizophrenia groups separable from HC: Low Inflammation, Elevated CRP, Elevated IL-6/IL-8, Elevated IFN-γ, and Elevated IL-10 with an adjusted Rand index of 0.573. When compared with the healthy controls, the IL-6/IL-8 cluster showed the most widespread, including the anterior cingulate, GMV reduction. The IFN-γ inflammation cluster showed the least GMV reduction and impairment of cognitive performance. The CRP and the Low Inflammation clusters dominated in the younger external dataset. CONCLUSIONS: Inflammation in schizophrenia may not be merely a case of low vs high, but rather there are pluripotent, heterogeneous mechanisms at play which could be reliably identified based on accessible, peripheral measures. This could inform the successful development of targeted interventions.

Impact of COVID-19 on the physical activity, quality of life and mental health of adolescent athletes: a 2-year evaluation of over 17 000 athletes.

PURPOSE: To evaluate the changes in mental health, quality of life (QOL) and physical activity (PA) among adolescent athletes during the COVID-19 pandemic as organised sports resumed. METHODS: Adolescent athletes completed surveys including demographic and sport participation information, 7-item Generalized Anxiety Disorder, 9-item Patient Health Questionnaire, Pediatric Quality of Life Inventory and the Hospital for Special Surgery Pediatric Functional Activity Brief Scale in May 2020 following COVID-19-related sport cancellations (Spring20) and after returning to sports in May 2021 (Spring21). The groups were balanced by inverse propensity score weighting and compared using analysis of variance models and ordinal regression models. RESULTS: 17 421 participants were included (Spring20=13 002; Spring21=4419; 16.2±1.2 years; 53% female). Anxiety was significantly lower (better) in Spring21 (Spring20=7.0, 95% CI 6.9 to 7.1; Spring21=4.9, 95% CI 4.8 to 5.0, p<0.001), as was the prevalence of moderate to severe anxiety (Spring20=29.4%, Spring21=17.1%, p<0.001). Depression was significantly improved in Spring21 (Spring20=7.6, 95% CI 7.5 to 7.7; Spring21=4.6, 95% CI 4.5 to 4.8, p<0.001), as was the prevalence of moderate to severe depression (Spring20=32.2%, Spring21=15.4%, p<0.001). Athletes in Spring21 reported higher QOL (Spring20=79.6, 95% CI 79.3 to 79.9; Spring21=84.7, 95% CI 84.4 to 85.0, p<0.001) and increased levels of PA (Spring20=13.8, 95% CI 13.6 to 13.9; Spring21=22.7, 95% CI 22.6 to 22.9, p<0.001). CONCLUSION: Early COVID-19 sports restrictions were associated with worsening mental health in adolescents. In 2021, after returning to sports, athletes reported significant improvements in mental health, QOL and PA, although mental health adversities remain an important priority.

Assessing the energy trap of industrial agriculture in North America and Europe: 82 balances from 1830 to 2012.

Early energy analyses of agriculture revealed that behind higher labor and land productivity of industrial farming, there was a decrease in energy returns on energy (EROI) invested, in comparison to more traditional organic agricultural systems. Studies on recent trends show that efficiency gains in production and use of inputs have again somewhat improved energy returns. However, most of these agricultural energy studies have focused only on external inputs at the crop level, concealing the important role of internal biomass flows that livestock and forestry recirculate within agroecosystems. Here, we synthesize the results of 82 farm systems in North America and Europe from 1830 to 2012 that for the first time show the changing energy profiles of agroecosystems, including livestock and forestry, with a multi-EROI approach that accounts for the energy returns on external inputs, on internal biomass reuses, and on all inputs invested. With this historical circular bioeconomic approach, we found a general trend towards much lower external returns, little or no increases in internal returns, and almost no improvement in total returns. This "energy trap" was driven by shifts towards a growing dependence of crop production on fossil-fueled external inputs, much more intensive livestock production based on feed grains, less forestry, and a structural disintegration of agroecosystem components by increasingly linear industrial farm managements. We conclude that overcoming the energy trap requires nature-based solutions to reduce current dependence on fossil-fueled external industrial inputs and increase the circularity and complexity of agroecosystems to provide healthier diets with less animal products. Supplementary Information: The online version contains supplementary material available at 10.1007/s13593-023-00925-5.

Free fatty acid treatment of mouse preimplantation embryos demonstrates contrasting effects of palmitic acid and oleic acid on autophagy.

Treatment of mouse preimplantation embryos with elevated palmitic acid (PA) reduces blastocyst development, whereas cotreatment with PA and oleic acid (OA) together rescues blastocyst development to control frequencies. To understand the mechanistic effects of PA and OA treatment on early mouse embryos, we investigated the effects of PA and OA, alone and in combination, on autophagy during preimplantation development in vitro. We hypothesized that PA would alter autophagic processes and that OA cotreatment would restore control levels of autophagy. Two-cell stage mouse embryos were placed into culture medium supplemented with 100 µM PA, 250 µM OA, 100 µM PA and 250 µM OA, or potassium simplex optimization media with amino acid (KSOMaa) medium alone (control) for 18-48 h. The results demonstrated that OA cotreatment slowed developmental progression after 30 h of cotreatment but restored control blastocyst frequencies by 48 h. PA treatment elevated light chain 3 (LC3)-II puncta and p62 levels per cell whereas OA cotreatment returned to control levels of autophagy by 48 h. Autophagic mechanisms are altered by nonesterified fatty acid (NEFA) treatments during mouse preimplantation development in vitro, where PA elevates autophagosome formation and reduces autophagosome degradation levels, whereas cotreatment with OA reversed these PA effects. Autophagosome-lysosome colocalization only differed between PA and OA alone treatment groups. These findings advance our understanding of the effects of free fatty acid exposure on preimplantation development, and they uncover principles that may underlie the associations between elevated fatty acid levels and overall declines in reproductive fertility.

Interacting effects of density and temperature on fish growth rates in freshwater protected populations.

Despite the demonstrated benefits of marine protected areas, there has been relatively little dialogue about freshwater protected areas (FPAs) even though some have been established to protect freshwater species from recreational and commercial fishers. After populations recover from fishing pressure, abundances and densities of formerly fished species increase, and we should therefore expect changes in demographic traits compared to those in exploited populations. To test this, we used capture-mark-recapture data for 10 Galaxias maculatus populations across a density gradient mediated by different degrees of fishery closure. We examined the extent to which density-dependent (DD) and density-independent (DI) effects interact to affect specific growth rates in post-recruit populations. We found that population density, stream temperature and individual size interact to affect growth rates. When population densities were high, compensatory responses of far slower growth rates were strongest, indicating that DD growth is a key mechanism regulating post-recruit populations of G. maculatus. This study emphasizes the importance of understanding DD and DI processes, their interactions, function and effectiveness for freshwater fisheries management. For FPAs to be effective, the extent and quality of target species' habitats must serve as key criteria for protection to alleviate competition for limited resources that underpins DD processes.

Effects of palmitic acid on localization of embryo cell fate and blastocyst formation gene products.

As obese and overweight patients commonly display hyperlipidemia and are increasingly accessing fertility clinics for their conception needs, our studies are directed at understanding the effects of hyperlipidemia on early pregnancy. We have focused on investigating palmitic acid (PA) and oleic acid (OA) treatment alone and in combination from the mouse two-cell stage embryos as a model for understanding their effects on the mammalian preimplantation embryo. We recently reported that PA exerts a negative effect on mouse two-cell progression to the blastocyst stage, whereas OA co-treatment reverses that negative effect. In the present study, we hypothesized that PA treatment of mouse embryos would disrupt proper localization of cell fate determining and blastocyst formation gene products and that co-treatment with OA would reverse these effects. Our results demonstrate that PA treatment significantly (P < 0.05) reduces blastocyst development and cell number but did not prevent nuclear localization of YAP in outer cells. PA treatment significantly reduced the number of OCT4+ and CDX2+ nuclei. PA-treated embryos had lower expression of blastocyst formation proteins (E-cadherin, ZO-1 and Na/K-ATPase alpha1 subunit). Importantly, co-treatment of embryos with OA reversed PA-induced effects on blastocyst development and increased inner cell mass (ICM) and trophectoderm (TE) cell numbers and expression of blastocyst formation proteins. Our findings demonstrate that PA treatment does not impede cell fate gene localization but does disrupt proper blastocyst formation gene localization during mouse preimplantation development. OA treatment is protective and reverses PA's detrimental effects. The results advance our understanding of the impact of FFA exposure on mammalian preimplantation development.

Cognitive trajectories following onset of psychosis: a meta-analysis.

BACKGROUND: Cognitive impairment is a core feature of schizophrenia, associated with poor functional outcomes. The course of cognitive function in the years following illness onset has remained a subject of debate, with a previous analysis finding no worsening, providing support for the neurodevelopmental model of schizophrenia. Since then, many more studies have reported on longitudinal cognitive performance in early psychosis, with some indicating deterioration, which does not align with this view. AIMS: This study aims to quantitatively review the literature on the longitudinal trajectory of cognitive deficits in the years following psychosis onset, in comparison with healthy controls. It is the first to also synthesise longitudinal data on social cognition. METHOD: Electronic databases ('PubMed', 'PsycInfo' and 'Scopus') were searched (to end September 2021). Meta-analyses of 25 longitudinal studies of cognition in early psychosis were conducted (1480 patients, 789 health controls). Unlike previous analyses, randomised controlled trials and those with multiple cognitive testing periods within the first year were excluded to minimise bias (PROSPERO, ID: CRD42021241525). RESULTS: Small improvements were observed for global cognition (g = 0.25, 95% CI 0.17-0.33) and individual cognitive domains, but these were comparable with healthy controls and likely an artefact of practice effects. CONCLUSIONS: There is no evidence of continued cognitive decline or improvement in the early years following psychosis onset, with a need for more studies over longer follow-up periods. Practice effects highlight the importance of including control samples in longitudinal and intervention studies. Further data are needed to evaluate the course of social cognition subdomains.

Outcomes of cold snare piecemeal EMR for nonampullary small-bowel adenomas larger than 1 cm: a retrospective study.

BACKGROUND AND AIMS: Nonampullary small-bowel adenomas ≥10 mm are typically resected using cautery-based polypectomy, which is associated with significant adverse events. Studies have demonstrated the safety and efficacy of piecemeal cold snare EMR for removing large colon polyps. Our aim was to assess the safety and efficacy of cold snare EMR for removal of large adenomas in the small bowel. METHODS: A retrospective study of patients who underwent lift and piecemeal cold snare EMR of small-bowel adenomas ≥1 cm between January 2014 and March 2019 was conducted at a tertiary care medical center. Polyp characteristics at the time of index and surveillance endoscopy were collected. Primary outcomes were residual or recurrent adenoma (RRA) seen on surveillance endoscopy, polyp eradication rate, and number of endoscopic procedures required for eradication. Adverse events including immediate and delayed bleeding, perforation, stricture, pancreatitis, and postpolypectomy syndrome were assessed. RESULTS: Of 43 patients who underwent piecemeal cold snare EMR, 39 had follow-up endoscopy. Polyps ranged in size from 10 to 70 mm (mean, 26.5 mm). RRA was found in 18 patients (46%), with increased polyp size correlating with higher recurrence (P < .001). Polyp eradication was observed in 35 patients (89%), requiring a median of 2 (range, 1-6) endoscopic procedures. Only 1 patient (2.3%) had immediate postprocedural bleeding. No cases of perforation or postpolypectomy syndrome were seen. CONCLUSIONS: Piecemeal cold snare EMR may be a feasible, safe, and efficacious technique for small-bowel polyps >10 mm. Prospective, randomized studies are needed to assess how outcomes compare with traditional cautery-based polypectomy.

Transanal excision with adjuvant therapy for pT1N0 rectal tumors with high-risk features offers equivalent survival to radical resection: A National Cancer Database analysis.

BACKGROUND: Current guidelines favor transabdominal radical resection (RR) over transanal local excision (TAX) followed by adjuvant therapy (TAXa) for pT1N0 rectal tumors with high-risk features. Comparison of oncologic outcomes between these approaches is limited, although the former is associated with increased postoperative morbidity. We hypothesize that such treatment strategies result in equivalent long-term survival. METHODS: A retrospective cohort study was conducted using the National Cancer Database (2010-2016) to identify patients with pT1N0 rectal adenocarcinoma with high-risk features who underwent TAX or RR for curative intent. The primary outcome was 5-year overall survival (OS), evaluated with log-rank and Cox-proportional hazards testing. RESULTS: A total of 1159 patients (age 67.4 ± 12.9 years; 56.6% male; 83.3% White) met study criteria, of which 1009 (87.1%) underwent RR and 150 (12.9%) underwent TAXa. Patients undergoing TAXa had shorter lengths of stay (RR = 6.5 days, TAXa = 2.7 days, p < 0.001). The 5-year OS was equivalent between groups. TAX without adjuvant therapy was associated with an increased risk of mortality (hazard ratio 1.81, 95% confidence interval 1.17-2.78, p = 0.01). CONCLUSIONS: This is the largest study to demonstrate equivalent 5-year OS between TAXa and RR for T1N0 rectal cancer with high-risk features. These findings may guide the development of prospective, randomized trials and influence changes in practice recommendations for early-stage rectal cancer.

Differential localization patterns of pyruvate kinase isoforms in murine naïve, formative, and primed pluripotent states.

Mouse embryonic stem cells (mESCs) and mouse epiblast stem cells (mEpiSCs) represent opposite ends of the pluripotency continuum, referred to as naïve and primed pluripotent states, respectively. These divergent pluripotent states differ in several ways, including growth factor requirements, transcription factor expression, DNA methylation patterns, and metabolic profiles. Naïve cells employ both glycolysis and oxidative phosphorylation (OXPHOS), whereas primed cells preferentially utilize aerobic glycolysis, a trait shared with cancer cells referred to as the Warburg Effect. Until recently, metabolism has been regarded as a by-product of cell fate, however, evidence now supports metabolism as being a driver of stem cell state and fate decisions. Pyruvate kinase muscle isoforms (PKM1 and PKM2) are important for generating and maintaining pluripotent stem cells (PSCs) and mediating the Warburg Effect. Both isoforms catalyze the final, rate limiting step of glycolysis, generating adenosine triphosphate and pyruvate, however, the precise role(s) of PKM1/2 in naïve and primed pluripotency is not well understood. The primary objective of this study was to characterize the cellular expression and localization patterns of PKM1 and PKM2 in mESCs, chemically transitioned epiblast-like cells (mEpiLCs) representing formative pluripotency, and mEpiSCs using immunoblotting and confocal microscopy. The results indicate that PKM1 and PKM2 are not only localized to the cytoplasm, but also accumulate in differential subnuclear regions of mESC, mEpiLCs, and mEpiSCs as determined by a quantitative confocal microscopy employing orthogonal projections and airyscan processing. Importantly, we discovered that the subnuclear localization of PKM1/2 changes during the transition from mESCs, mEpiLCs, and mEpiSCs. Finally, we have comprehensively validated the appropriateness and power of the Pearson's correlation coefficient and Manders's overlap coefficient for assessing nuclear and cytoplasmic protein colocalization in PSCs by immunofluorescence confocal microscopy. We propose that nuclear PKM1/2 may assist with distinct pluripotency state maintenance and lineage priming by non-canonical mechanisms. These results advance our understanding of the overall mechanisms controlling naïve, formative, and primed pluripotency.

Emergency Preparedness for Sudden Cardiac Arrest in Amateur Athletic Union Basketball Teams: An Opportunity to Improve Outcomes in Higher Risk Athletes.

OBJECTIVE: To examine sudden cardiac arrest (SCA) awareness and emergency preparedness for SCA in Amateur Athletic Union (AAU) youth basketball teams. DESIGN: Cross-sectional survey of AAU coaches and administrators. SETTING: Random sampling of AAU club teams across the United States. PARTICIPANTS: AAU club coaches and/or administrators. INTERVENTIONS: Electronic survey (Qualtrics) accessed online and by cell phone. Each coach/administrator was invited to participate via email up to 3 times, spaced approximately 5 days apart. MAIN OUTCOME MEASURES: Established and practiced emergency action plan (EAP), cardiopulmonary resuscitation (CPR) training, and automated external defibrillator (AED) access. RESULTS: A total of 53/449 (12%) respondents completed the survey. Only 6% of responding AAU clubs had a written EAP and practiced it on an annual basis. Only 35% of clubs required CPR training for their coaches. Automated external defibrillator were available at practices and games in only 45% and 35% of AAU clubs, respectively. Over 50% of clubs did not have an affiliated athletic trainer or medical director. CONCLUSION: The vast majority of AAU clubs in this study lack proper emergency preparedness for SCA. Given male basketball players are at highest risk of SCA compared with other young athlete populations, urgent interventions are needed to improve awareness, standardize training, establish EAPs, and ensure access to AEDs in AAU clubs.

Reported COVID-19 Incidence in Indoor Winter Sports Among US High-School Athletes.

OBJECTIVE: To evaluate the association between COVID-19 incidence among high-school athletes participating in different indoor winter sports and attending schools with in-person versus virtual instructional delivery. DESIGN: Cross-sectional survey. SETTING: US high schools. PARTICIPANTS: High-school athletic directors. INDEPENDENT VARIABLES: Indoor winter sports, school instructional delivery method, and state COVID-19 incidence. MAIN OUTCOME MEASURES: Surveys were distributed to high-school athletic directors throughout the United States regarding sport reinitiation and COVID-19 cases in winter 2020 to 2021. Separate mixed effects Poisson regression models were developed to evaluate the associations between reported COVID-19 incidence and (1) different sports and (2) school instructional delivery method, while adjusting for the background, state COVID-19 incidence. RESULTS: Four hundred thirty schools had restarted fall sports, representing 31 274 athletes on 1404 teams from 14 states. One thousand four hundred sixty cases of COVID-19 were reported, representing a case rate of 4668 cases per 100 000 athletes and an incidence rate of 58.7 cases per 100 000 player-days. Reported COVID-19 incidence was greatest among girls' hockey (82.1 cases per 100 000 player-days (95% CI, 56.8-115) and boys' hockey [76.7 (61.8-94.2)] and lowest among swimming [39.0 (31.1-48.2)] and gymnastics [28.5 (13.1-54.2)]. No difference in reported COVID-19 incidence was identified among athletes attending schools with virtual versus in-person instruction [incidence rate ratio = 0.86 (0.52-1.4)]. CONCLUSIONS: In this nationwide survey of US high-school athletic directors regarding indoor winter sports, reported COVID-19 incidence was lower in noncontact sports but unrelated to school instructional delivery method. This information may help guide decision-making regarding high-school sport participation during the COVID-19 pandemic.

Contribution of Lean Mass Distribution on Aerobic Fitness and Performance in NCAA Division I Female Rowers.

ABSTRACT: Haraldsdottir, K, Sanfilippo, J, Dawes, S, and Watson, A. Contribution of lean mass distribution on aerobic fitness and performance in NCAA division I female rowers. J Strength Cond Res 36(7): 1956-1960, 2022-The purpose of this study was to determine the relative influence of total lean body mass (LBM), body fat percentage (BF%), upper extremity lean mass (ULM), lower extremity lean mass (LLM), and trunk lean mass (TLM) on maximal aerobic capacity (V̇o2max) and time to exhaustion (Tmax) in female collegiate rowers. One hundred seven female collegiate rowers (aged 18-22 years) performed maximal progressive rowing ergometer testing to determine V̇o2max and Tmax. Body mass, LBM, BF%, ULM, LLM, and TLM were determined by using dual-energy x-ray absorptiometry. Separate multivariable linear regression models were performed to predict V̇o2max and Tmax by using LBM and BF% as predictors. In addition, separate linear regression models were used to predict V̇o2max and Tmax with ULM, LLM, and TLM as covariates. Subjects were aged 20 ± 3 years. V̇o2max was significantly predicted by LBM (r2 = 0.29, p < 0.001), but not BF% (r2 = 0.002, p = 0.79). Similarly, Tmax was significantly predicted by LBM (r2 = 0.25, p < 0.001), but not BF% (r2 = 0.003, p = 0.19). V̇o2max was significantly predicted by LLM (r2 = 0.12, p < 0.01), but not ULM (r2 = 0.08, p = 0.68) or TLM (r2 = 0.09, p = 0.17), and Tmax was significantly predicted by TLM (r2 = 0.09, p = 0.02), but not ULM (r2 = 0.07, p = 0.89) or LLM (r2 = 0.08, p = 32). Among female collegiate rowers, whole body LBM is a significant predictor of both V̇o2max and Tmax. However, LLM is a stronger predictor of V̇o2max while TLM is a stronger predictor Tmax, although each of these relationships has a low coefficient of determination. These findings suggest that aerobic fitness and performance may be influenced by regions of lean mass differently.

The digital divide: factors impacting on uptake of remote therapy in a South London psychological therapy service for people with psychosis.

BACKGROUND: Remote therapy promises a cost-effective way of increasing delivery of psychological-therapy in underserved populations. However, research shows a "digital divide", with some groups experiencing digital exclusion. AIMS: To assess whether technology, accessibility, and demographic factors influence remote therapy uptake among individuals with psychosis, and whether demographic factors are associated with digital exclusion. METHODS: Remote therapy uptake and demographics were assessed in people (n = 51) within a psychology-led service for psychosis, using a survey of access to digital hardware, data and private space. RESULTS: The majority of individuals had access to digital devices, but 29% did not meet minimum requirements for remote therapy. Nineteen (37%) individuals declined remote therapy. Those who accepted were significantly younger and more likely to have access to technology than those who declined. The mean age of those with access to smartphones and large screen devices was younger than those without access. CONCLUSIONS: A subgroup of people with psychosis face barriers to remote therapy and a significant minority are digitally excluded. Older age is a key factor influencing remote therapy uptake, potentially related to less access to digital devices. Services must minimize exclusion through provision of training, hardware and data, whilst promoting individual choice.

Deconstructing depression and negative symptoms of schizophrenia; differential and longitudinal immune correlates, and response to minocycline treatment.

BACKGROUND: Immune dysfunction has been implicated in negative symptoms of schizophrenia and also in depression. These disorders are frequently co-morbid, with some symptoms such as anhedonia and apathy common to both. The anti-inflammatory agent minocycline may be ineffective in schizophrenia, but more positive effects have been seen in depression. Our aim was to investigate the role of immune dysfunction in depression and sub-domains of negative symptoms in schizophrenia by investigating their intercorrelation and the influence of treatment with minocycline. METHODS: We analysed longitudinal data from 207 patients within 5 years of onset of schizophrenia, from the randomised double-blind, placebo-controlled trial of minocycline (BeneMin). Symptom ratings and circulating IL-6, C-reactive protein (CRP) and TNF-α concentrations were collected at baseline and repeated over twelve months. The sample was not stratified by CRP prior to randomisation. Positive and Negative Syndrome Scale composite ratings of avolition-apathy and diminished expression, Calgary Depression Scale total scores, and immune markers were examined cross-sectionally using Spearman's rank, and longitudinally by linear mixed effect models that included body mass index and minocycline. Additionally, post hoc analysis of the sample stratified by elevated CRP (>1 mg/l and <10 mg/l at baseline) was carried out to assess whether minocycline had any effect on specific symptoms in an immune active sub-group of patients. RESULTS: Depression and avolition-apathy were significantly positively related, and depression correlated weakly with IL-6 at baseline. Diminished expression was associated with increased TNF-α both cross-sectionally and longitudinally. CRP was unrelated to any symptom domain. Minocycline did not affect any individual symptom or sub-domain in the full sample or in the immune active sub-group. DISCUSSION: IL-6 may have some specificity to depression in early schizophrenia. TNF-α may be an indicator of immune dysfunction relevant to negative symptoms, and our longitudinal findings add to this evidence. However, minocycline continues to show very little promise as a treatment for any symptom dimension of early schizophrenia.

Extracellular vesicles, microRNA and the preimplantation embryo: non-invasive clues of embryo well-being.

Elective single embryo transfer is rapidly becoming the standard of care in assisted reproductive technology for patients under the age of 35 years with a good prognosis. Clinical pregnancy rates have become increasingly dependent on the selection of a single viable embryo for transfer, and diagnostic techniques facilitating this selection continue to develop. Current progress in elucidating the extracellular vesicle and microRNA components of the embryonic secretome is reviewed, and the potential for these findings to improve clinical embryo selection discussed. Key results have shown that extracellular vesicles and microRNAs are rapidly detectable constituents of the embryonic secretome. Evidence suggests that the vesicular population is largely exosomal in nature, secreted at all stages of preimplantation development and capable of traversing the zona pellucida. Both extracellular vesicle and microRNA concentrations within the secretome are elevated for blastocysts with diminished developmental competence, as indicated either by degeneracy or implantation failure, whereas studies have yet to firmly correlate individual microRNA sequences with pregnancy outcome. These emerging correlations support the viability of extracellular vesicles and microRNAs as the basis for a new diagnostic test to supplement or replace morphokinetic assessment.