Prevention strategies and modifiable risk factors for concussion:A systematic review and meta-analysis for the Female, woman and girl Athlete Injury pRevention (FAIR) consensus

Objective To examine prevention strategies and potential modifiable risk factors (MRFs) for sport-related concussion (SRC) and head impact/head acceleration event (HAE) outcomes in female, woman and/or girl athletes.Design Systematic review with meta-analyses and Grading of Recommendations, Assessment, Development and Evaluation.Data sources Medline, CINAHL, PsycINfo, SportDiscus, ERIC, CENTRAL and CDSR.Eligibility Primary data studies with comparison group(s) assessing the association of prevention interventions and/or MRFs for SRC or HAE with ≥1 female/woman/girl in each study group.Results Of the 108 included studies, 67 evaluated a SRC prevention strategy (equipment n=25, policy/rule n=21, training n=10, management n=11) and 41 evaluated potential MRFs (34 distinct MRFs across nine categories). In total, 40/108 (37%) studies (prevention 19/67; MRF 21/41) included female/woman/girl-specific estimates. Three meta-analyses were conducted: two SRC prevention strategies (headgear, eyewear) and one MRF (artificial turf vs grass) based on availability of female/woman/girl-only estimates and similar outcomes and exposure. Headgear was associated with 30% lower SRC rates in adolescent female/girl lacrosse and soccer (IRR=0.70, 95% CI 0.50 to 0.99; very-low certainty). Eyewear use was not protective for SRC (IRR=1.08, 95% CI 0.69 to 1.68; very-low certainty). SRC rates did not differ by artificial turf versus grass (IRR=0.95, 95% CI 0.62 to 1.45; very-low certainty).Conclusion We found limited evidence for prevention strategies and MRFs in female/woman/girl athletes except for very-low certainty evidence supporting headgear use in adolescent lacrosse and soccer. Future studies should consider the design, implementation and evaluation of SRC prevention strategies that target MRFs to guide safe practice recommendations specifically for female/woman/girl athletes

Gender- and/or sex-specific considerations for sport-related injury: a concept mapping approach for the Female, woman and/or girl Athlete Injury pRevention (FAIR) consensus

Objective: This study aimed to gather and represent experts’ perspectives on the gender- and/or sex-specific factors relevant to injury risk for female/woman/girl athletes. Methods: Mixed-methods concept mapping study. Sixty-six experts including cisgendered (1) athlete/coach/carers, (2) clinicians, (3) sports science/high-performance professional, (4) administrators and (5) researchers brainstormed statements to a prompt (‘What gender-specific and/or sex-specific factors do you think contribute to injury risk among female, woman and girl athletes?’) before thematically sorting and rating the statements/factors for importance and modifiability (5-point Likert scales). Results: Ten clusters were constructed from 101 unique statements/factors. The clusters (number of statements) include: (1) Inequitable organisational funding and support (n=17); (2) Athletes’ lack of, and access to, resources (n=7); (3) Lack of knowledge and expertise among support staff (n=6); (4) Lack of evidence for, and implementation of gender and sex-appropriate injury prevention (n=20); (5) Sex-related factors (n=14); (6) Gendered health (n=8); (7) Gendered expectations to conform to athletic ideals and norms (n=10); (8) Gendered harassment (interpersonal violence) and social biases (n=9); (9) Gendered sport environment (7); (10) Gendered communication (n=3). Lack of knowledge and expertise among support staff was deemed the most important and modifiable cluster to address gender- and/or sex-specific factors relevant to injury prevention for female/woman/girl athletes. Conclusion: Ten gender- and/or sex-specific clusters, ranging from organisational to biological considerations and societal influences, were defined that could impact female/woman/girl athlete injury risk factors. Advancing stronger evidence for gender and sex appropriate injury prevention is urgently needed

EXPOSURE TO MOBILE RADIATION AFFECTS THE SPATIAL MEMORY OF SIBERIAN HAMSTER (PHODOPUS SUNGORUS)

In this modern world, the use of mobile phones is exponentially increasing and becoming an indispensable tool in our daily life. The use of mobile phones, however, is coupled with one’s exposure to electromagnetic radiation. This study investigated  the effects of mobile phone radiation on the spatial memory of hamsters using a modified T-maze. Four groups of hamsters were exposed to electromagnetic radiation ranging from 0 to 850 MHz after task habituation.  Results showed that hamsters exposed  to the high electromagnetic radiation (600-800 MHz) had spent the longest time in finding the reward. This indicates a decrease in the hippocampal-dependent  spatial memory of the hamsters. Generally, the experimental groups had significantly decreased their spatial ability compared with  the control. The results of this study are essential in understanding the subtle effects of electromagnetic radiation on the spatial memory of organisms, especially in humans. &nbsp

Metabolomic signatures associated with weight gain and psychosis spectrum diagnoses: A pilot study

Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data (n = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (≥5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs

Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection

Zoonotic transmission of coronaviruses poses an ongoing threat to human populations. Endemic outbreaks of swine acute diarrhea syndrome coronavirus (SADS-CoV) have caused severe economic losses in the pig industry and have the potential to cause human outbreaks. Currently, there are no vaccines or specific antivirals against SADS-CoV, and our limited understanding of SADS-CoV host entry factors could hinder prompt responses to a potential human outbreak. Using a genomewide CRISPR knockout screen, we identified placenta-associated 8 protein (PLAC8) as an essential host factor for SADS-CoV infection. Knockout of PLAC8 abolished SADS-CoV infection, which was restored by complementing PLAC8 from multiple species, including human, rhesus macaques, mouse, pig, pangolin, and bat, suggesting a conserved infection pathway and susceptibility of SADS-CoV among mammals. Mechanistically, PLAC8 knockout does not affect viral entry; rather, knockout cells displayed a delay and reduction in viral subgenomic RNA expression. In a swine primary intestinal epithelial culture (IEC) infection model, differentiated cultures have high levels of PLAC8 expression and support SADS-CoV replication. In contrast, expanding IECs have low levels of PLAC8 expression and are resistant to SADS-CoV infection. PLAC8 expression patterns translate in vivo; the immunohistochemistry of swine ileal tissue revealed high levels of PLAC8 protein in neonatal compared to adult tissue, mirroring the known SADS-CoV pathogenesis in neonatal piglets. Overall, PLAC8 is an essential factor for SADS-CoV infection and may serve as a promising target for antiviral development for potential pandemic SADS-CoV

SARS-CoV-2 infection of airway cells causes intense viral and cell shedding, two spreading mechanisms affected by IL-13

Muco-obstructive lung diseases are typically associated with high risks of COVID-19 severity; however, allergic asthma showed reduced susceptibility. To investigate viral spread, primary human airway epithelial (HAE) cell cultures were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and host–virus interactions were examined via electron microscopy, immunohistochemistry, RNA in situ hybridization, and gene expression analyses. In HAE cell cultures, angiotensin-converting enzyme 2 (ACE2) expression governed cell tropism and viral load and was up-regulated by infection. Electron microscopy identified intense viral egress from infected ciliated cells and severe cytopathogenesis, culminating in the shedding of ciliated cells packed with virions, providing a large viral reservoir for spread and transmission. Intracellular stores of MUC5AC, a major airway mucin involved in asthma, were rapidly depleted, likely to trap viruses. To mimic asthmatic airways, HAE cells were treated with interleukin-13 (IL-13), which reduced viral titers, viral messenger RNA, and cell shedding, and significantly diminished the number of infected cells. Although mucus hyperproduction played a shielding role, IL-13–treated cells maintained a degree of protection despite the removal of mucus. Using Gene Expression Omnibus databases, bulk RNA-sequencing analyses revealed that IL-13 up-regulated genes controlling glycoprotein synthesis, ion transport, and antiviral processes (albeit not the typical interferon-induced genes) and down-regulated genes involved in cilial function and ribosomal processing. More precisely, we showed that IL-13 reduced ACE2 expression, intracellular viral load, and cell-to-cell transmission while increasing the cilial keratan sulfate coating. In conclusion, intense viral and cell shedding caused by SARS-CoV-2 infection was attenuated by IL-13, which affected viral entry, replication, and spread

Preclinical discovery of candidate genes to guide pharmacogenetics during phase I development: the example of the novel anticancer agent ABT-751

ABT-751, a novel orally available antitubulin agent, is mainly eliminated as inactive glucuronide (ABT-751G) and sulfate (ABT-751S) conjugates. We performed a pharmacogenetic investigation of ABT-751 pharmacokinetics using in-vitro data to guide the selection of genes for genotyping in a phase I trial of ABT-751