Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a clear genetic component. While most SLE patients carry rare gene variants in lupus risk genes, little is known about their contribution to disease pathogenesis. Amongst them, SH2B3-a negative regulator of cytokine and growth factor receptor signaling-harbors rare coding variants in over 5% of SLE patients. Here, we show that unlike the variant found exclusively in healthy controls, SH2B3 rare variants found in lupus patients are predominantly hypomorphic alleles, failing to suppress IFNGR signaling via JAK2-STAT1. The generation of two mouse lines carrying patients' variants revealed that SH2B3 is important in limiting the number of immature and transitional B cells. Furthermore, hypomorphic SH2B3 was shown to impair the negative selection of immature/transitional self-reactive B cells and accelerate autoimmunity in sensitized mice, at least in part due to increased IL-4R signaling and BAFF-R expression. This work identifies a previously unappreciated role for SH2B3 in human B cell tolerance and lupus risk.

Coaches of youth field sports as delivery agents of injury prevention programmes: how are we training the trainers? A scoping review.

OBJECTIVE: To systematically map the coach education (CE) component of injury prevention programmes (IPPs) for youth field sports by identifying and synthesising the design, content and facilitation strategies used to address competency drivers and behaviour change. DESIGN: Scoping review. DATA SOURCES: PubMed, PsycInfo, EMBASE, CINAHL, SportDiscus and Google Scholar electronic databases were searched using keywords related to IPPs and youth field sports. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies of IPPs in youth field sports, that provided 'train-the-trainer' education to coaches as designated delivery agents. RESULTS: 20 studies from two field sports (soccer/football; n=17, Rugby Union; n=3) fulfilled the eligibility criteria. Eleven CE interventions occurred in the preseason and 18 occurred at one time-point (single day). Five studies cited use of a behavioural change theory or model in the design of their CE, most frequently the Health Action Process Approach model (n=5); and use of behavioural change techniques varied. Twelve of twenty studies (60%) reported some form of ongoing support to coaches following the CE primary intervention concurrent with IPP implementation. CONCLUSION: CE that occurs on 1 day (one time-point) is most popular for preparing coaches as delivery agents of IPPs in youth field sports. While recognising pragmatic barriers, more expansive in-service training, support and feedback may enhance the effective implementation of IPPs. TRIAL REGISTRATION NUMBER: https://doi.org/10.17605/OSF.IO/FMHGD.

Safety and efficacy of biological agents in the treatment of Systemic Lupus Erythematosus (SLE).

BACKGROUND: To determine the safety and efficacy of biological agents used in the treatment of systemic lupus erythematosus (SLE) in adults. METHODS: Systematic review and meta-analysis following PRISMA guidelines. DATA SOURCES: MEDLINE (through Pubmed), EMBASE, Cochrane library, Clinicaltrials.gov, Australianclinicaltrials.gov.au, ANZCTR.org.au and WHO International Clinical Trials Registry Platform for studies published from 20 May 2021 and 15 years prior. A grey literature search was performed and completed on 31 May 2021. STUDY CRITERIA: Phase II, III or quasi randomised controlled trials, studies with only cerebral or cutaneous lupus were excluded. DATA EXTRACTION: Two authors independently screened studies for eligibility, extracted, reviewed data for accuracy, and used the Cochrane tool to assess risk of bias. RESULTS: Forty-four studies were identified, consisting of 15 groups of drugs and 25 different biological agents, totalling 16,889 patients. The main outcomes assessed included Systemic Lupus Erythematosus Responder Index (SRI), BILAG-Based Composite Lupus Assessment (BICLA) and combined combined/partial renal remission (CRR/PRR). Four groups of biologics were found to improve outcomes. Anti-interferons: Anifrolumab increased BICLA response and SRI 5 to 8, decreased prednisone dosages, with increased herpes zoster infections, but fewer serious adverse events. Sifalimumab improved SRI but also increased herpes zoster infections. Anti BAFF/BLyS and/or APRIL: Belimumab consistently improved SRI 4, decreased prednisone dosages, increased combined CRR/PRR, and had no adverse safety outcomes. Tabalumab increased SRI 5 at 52 weeks with no steroid sparing effect but was associated with increased infusion related adverse events. Telitacicept improved SRI 4 at 52 weeks, with no increased adverse events, though data was rather sparse. Anti CD-20 monoclonal antibody, Obinutuzumab increased combined CRR/PRR at 1 and 2 years. Anti IL12/23 monoclonal antibody, Ustekinumab, increased SRI 4 to 6, but not BICLA at 24 weeks, with no concerning safety outcomes. CONCLUSION: Multiple biologic agents are shown in high quality studies to have a significant therapeutic impact on outcomes in SLE.

Leptin activation of dorsal raphe neurons inhibits feeding behavior.

Leptin is a homeostatic regulatory element that signals the presence of energy stores -in the form of adipocytes-which ultimately reduces food intake and increases energy expenditure. Similarly, serotonin (5-HT), a signaling molecule found in both the central and peripheral nervous systems, also regulates food intake. Here we use a combination of pharmacological manipulations, optogenetics, retrograde tracing, and in situ hybridization, combined with behavioral endpoints to physiologically and anatomically identify a novel leptin-mediated pathway between 5-HT neurons in the dorsal raphe nucleus (DRN) and hypothalamic arcuate nucleus (ARC) that controls food intake. In this study, we show that microinjecting leptin directly into the DRN reduces food intake in male Sprague-Dawley rats. This effect is mediated by leptin-receptor expressing neurons in the DRN as selective optogenetic activation of these neurons at either their ARC terminals or DRN cell bodies also reduces food intake. Anatomically, we identified a unique population of serotonergic raphe neurons expressing leptin receptors that send projections to the ARC. Finally, by utilizing in vivo microdialysis and high-performance liquid chromatography, we show that leptin administration to the DRN increases 5-HT efflux into the ARC. Overall, this study identifies a novel circuit for leptin-mediated control of food intake through a DRN-ARC pathway, utilizing 5-HT as a mechanism to control feeding behavior. Characterization of this new pathway creates opportunities for understanding how the brain controls eating behavior, as well as opens alternative routes for the treatment of eating disorders. Significance: Leptin and serotonin both play a vital role in the regulation of food intake, yet there is still uncertainty in how these two molecules interact to control appetite. The purpose of this study is to further understand the anatomical and functional connections between leptin receptor expressing neurons in the dorsal raphe nucleus, the main source of serotonin, and the arcuate nucleus of the hypothalamus, and how serotonin plays a role in this pathway to reduce food intake. Insight gained from this study will contribute to a more thorough understanding of the networks that regulate food intake, and open alternative avenues for the development of treatments for obesity and eating disorders.

The Effects of High-Repetition Strength Training on Performance in Competitive Endurance Athletes: A Systematic Review and Meta-Analysis.

ABSTRACT: Nugent, FJ, Flanagan, EP, Darragh, I, Daly, L, and Warrington, GD. The effects of high-repetition strength training on performance in competitive endurance athletes: A systematic review and meta-analysis. J Strength Cond Res 37(6): 1315-1326, 2023-The aim of this systematic review and meta-analysis was to evaluate the effects of high-repetition strength training (HRST) on performance in competitive endurance athletes. The methodology followed the Preferred Reporting Items for Systematic Review and Meta-Analysis protocol. A search of databases was performed until December 2020. Inclusion criteria were (a) competitive endurance athletes, (b) ≥4 weeks HRST intervention, (c) control or comparison group, (d) outcome measures of performance (either physiological or time trial performance), and (e) all experimental designs. Quality assessment was performed using the Physiotherapy Evidence Database (PEDro) scale. Of the 615 studies retrieved, 11 studies were included (216 subjects) and 9 studies provided sufficient data for the meta-analysis (137 subjects). The PEDro scale score had a mean of 5 of 10 points (range: 3-6). There was no significant difference between the HRST and control groups (g = 0.35; 95% confidence interval [CI] = -0.38 to 1.07; p = 0.35) or HRST and low-repetition strength training (LRST) groups (g = 0.24; 95% CI = -0.24 to 0.72; p = 0.33). The findings of this review and meta-analysis indicate that HRST does not result in improved performance over a 4- to 12-week period, and the results seem to be similar to LRST. The majority of studies involved recreational endurance athletes and had a mean duration of 8 weeks, which is a limitation of the findings. Future intervention studies should be > 12 weeks in duration and involve well-trained endurance athletes (maximal oxygen uptake [V̇o2max] of >65 ml·kg-1·min-2).

Risk factors for acute ankle sprains in field-based, team contact sports: a systematic review of prospective etiological studies.

OBJECTIVE: The aim of this systematic review was to identify prospectively measured ankle sprain risk factors in field-based team contact sports. METHODS: Eight databases including SPORTDiscus, CINAHL Complete, MEDLINE (EBSCO), Education Source, Web of Science, Scopus, Embase, and Pubmed were searched using specific Boolean terms. A modified-CASP diagnostic test assessed the quality of the included studies. Extensive data extraction included but was not limited to injury definition, protocols for injury diagnosis and recording, and outcomes associated with ankle sprain. RESULTS: 4012 records were returned from the online search and 17 studies met the inclusion criteria for this review. Twelve different risk factors including anatomic alignment of the foot and ankle, joint laxity, height, mass, BMI (body mass index), age, ankle strength, hip strength, single leg landing performance (ground reaction force, pelvic internal rotation, and knee varus), and single leg reach were all found to be associated with ankle sprain incidence. Injury definitions and methods of diagnosis and recording varied across the 17 studies. CONCLUSION: This review updates the literature on prospective risk factors for ankle sprain in a specific population rather than heterogeneous cohorts previously studied. From more than 20 categories of risk factors investigated for ankle sprain association across 17 studies in field-based team contact sports, 12 variables were found to be associated with increased incidence of ankle sprain. In order to reduce the risk of ankle sprain, BMI, ankle plantar and dorsiflexion strength, hip strength, and single leg landing performance should be factored in to athlete assessment and subsequent program design. More studies utilizing standardized definitions and methods of recording and reporting are needed. Future prospective etiological studies will allow strength and conditioning coaches, physiotherapists, and physicians to apply specific training principles to reduce the risk and occurrence of ankle sprain injuries.

Injury Trends for School Rugby Union in Ireland: The Need for Position-specific Injury-prevention Programs.

BACKGROUND: Concern has been raised over the injury risk to school Rugby union (Rugby) players and the potential long-term health consequences. Despite the increase in studies for this cohort, the influence of playing position on injury incidence and presentation is unclear. PURPOSE: To describe the incidence, nature and severity of match injuries for school Rugby in Ireland overall, and as a function of playing position. STUDY DESIGN: Prospective cohort study. METHODS: Data were collected from 15 male (aged 16-19 years) school Senior Cup teams across 2 seasons. In total, 339 players participated in season 1, whereas 326 players participated in season 2. Injury data were recorded onto a bespoke online platform. Match exposure was also recorded. RESULTS: The incidence rate of match injuries (24-hour time loss) was 53.6 per 1000 hours. Across both seasons, 6810 days were lost from play due to injury. Forwards (65.4 per 1000 hours) sustained significantly more (P < 0.05) injuries than backs (40.5 per 1000 hours). The head, shoulder, knee, and ankle were the most common injured body regions; however, forwards sustained significantly more (P < 0.05) head and shoulder injuries than backs. The tackle was responsible for the majority of injuries in both groups. The highest proportion of injuries occurred during the third quarter. CONCLUSION: Clear differences in injury presentation and incidence were evident when comparing forwards versus backs. The high rate of head and shoulder injuries in the forwards suggest the need for more targeted injury-prevention strategies and further research on education and laws around the tackle event. The spike of injuries in the third quarter suggests that fatigue or inadequate half-time warm-up may be a contributing factor warranting further exploration. CLINICAL RELEVANCE: This study demonstrates clear differences in injury presentation according to playing position in school Rugby and highlights the need for a more tailored approach to the design and implementation of injury-prevention strategies. LEVEL OF EVIDENCE: Level 3.

Effects of long-haul transmeridian travel on physiological, sleep, perceptual and mood markers in Olympic team support staff.

The objective of this study was to holistically examine the impact of long-haul transmeridian travel (LHTT) on perceptual, mood, sleep and physiological markers in Olympic team support staff travelling to Japan for the 2020 Summer Olympic Games. An observational descriptive study design was used. Nine support staff members of the Irish Olympic team (2 M/7 F; age 34.3 ± 8.3 y (mean ±SD)) embarked on a long-haul (LH) eastward flight across eight time-zones from Ireland to Japan (approx. 24 h total travel time), to work at the Irish Team's 2020 Summer pre-Olympic Games camp, postponed to July 2021 due to Covid-19 pandemic. Perceived jet lag and travel fatigue symptoms, mood states and salivary markers for circadian rhythm and stress were assessed in the morning and evening during the week prior to travel as baseline (BL) measures and on days 1 to 8 (C1-C8) and day 15 (C15) post-travel. Night-time sleep (duration and quality) was monitored via actigraphy monitors and self-report sleep diaries. Participants perceived themselves to be significantly jet lagged for six days post-travel (p < .05). Morning sCort decreased by 66% on C1 and remained significantly lower than BL until C6 (p ≤ .03). On arrival participants perceived sleep to be worse than BL on arrival (C1, C2, C4, C5; p ≤ .04), with significantly shorter sleep duration (C2, C3, C6; p ≤ .01) and lower sleep efficiency (C2, C6; p ≤ .04) recorded by actigraphy, all normalizing by C7. Negative changes in mood states were evident in the evening time following LHTT, with significant elevations in confusion (C2, C3, p ≤ .02), fatigue (C2, C3; p ≤ .03) and depression (C3, C7; p < .05) and reduction in vigour (C2, C6, C7; p < .05). Following LHTT in an eastward direction across eight time-zones, it took seven days for perceived jet lag, physiological markers for circadian rhythm and sleep to normalize in Olympic team support staff. Despite alleviation of jet lag and fatigue and return of sleep to normal by C15, vigor remained low, indicating a "submerged" mood profile in these Olympic team support staff. These findings highlight the need to put strategies in place before and after LHTT for the Olympic Games to assist Olympic team support staff to maximize sleep, minimize stress and assist with expediating recovery from jet lag and travel fatigue, allowing them to perform optimally in supporting Olympic athletes in their final preparations for the Games.

Effects of Long-Haul Travel on Recovery and Performance in Elite Athletes: A Systematic Review.

ABSTRACT: Rossiter, A, Warrington, GD, and Comyns, TM. Effects of long-haul travel on recovery and performance in elite athletes: a systematic review. J Strength Cond Res 36(11): 3234-3245, 2022-Elite athletes are often required to travel long-haul (LH) across numerous time zones for training or competition. However, the extent to which LH travel affects elite athlete performance remains largely unknown. The purpose of this systematic literature review was to critically evaluate available evidence on the effects of LH travel on elite athlete psychometric, physiological, sleep, and performance markers. Electronic database searches of PubMed, SPORTDiscus, Scopus, and Web of Science were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were eligible for inclusion if subjects were identified as elite athletes who embarked on a LH flight (>6 hours) and used an outcome measurement of recovery or performance after the flight. Studies that were retrospective, used light therapy or pharmacological interventions were not included. Of 2,719 records assessed, 14 studies comprising a total of 197 athletes from 6 sports met the inclusion criteria. There was an increase in perceived jet lag and disturbance to various physiological markers after LH travel; however, there was minimal disturbance in other psychometric markers. Sleep was not negatively affected by LH travel. Of 10 studies that assessed performance, 3 found decrements in indirect markers of performance. Elite athletes perceived themselves to be jet lagged and experienced disturbance to various physiological mechanisms after LH travel; however, the effect on performance was inconclusive. Future research would benefit from higher quality studies with improved control measures, larger sample sizes from a wider variety of sports, and use of ecologically valid measures of circadian rhythm and athletic performance.

A 19 day earth tide measurement with a MEMS gravimeter.

The measurement of tiny variations in local gravity enables the observation of subterranean features. Gravimeters have historically been extremely expensive instruments, but usable gravity measurements have recently been conducted using MEMS (microelectromechanical systems) sensors. Such sensors are cheap to produce, since they rely on the same fabrication techniques used to produce mobile phone accelerometers. A significant challenge in the development of MEMS gravimeters is maintaining stability over long time periods, which is essential for long term monitoring applications. A standard way to demonstrate gravimeter stability and sensitivity is to measure the periodic elastic distortion of the Earth due to tidal forces-the Earth tides. Here, a 19 day measurement of the Earth tides, with a correlation coefficient to the theoretical signal of 0.975, has been presented. This result demonstrates that this MEMS gravimeter is capable of conducting long-term time-lapse gravimetry, a functionality essential for applications such as volcanology.

Design, synthesis and chemical stability of indolizine derivatives for antidiabetic activity.

Prodrugs of metformin were synthesized with the goal of enhancing biological activity of metformin. They were synthesized by combining metformin with 2-substituted indolizine (C7-C12). The synthesized prodrugs were characterized by IR, 1H NMR, 13C NMR, and mass spectroscopy. The chemical hydrolysis of C7-C12 was carried out at pH 1.2, 6.8, and 7.4. All compounds showed encouraging chemical stability at pH 1.2 and 6.8, whereas mild hydrolysis was shown at pH 7.4. Further prodrugs were screened for antidiabetic activity using a streptozotocin-induced model in rat. These derivatives showed substantial results. Among them C8 showed significant activity in the reduction of streptozotocin-induced blood glucose in rats when compared to that of metformin, indicating the effectiveness of prodrug.

Design, synthesis and chemical stability of indolizine derivatives for antidiabetic activity.

Prodrugs of metformin were synthesized with the goal of enhancing biological activity of metformin. They were synthesized by combining metformin with 2-substituted indolizine (C7-C12). The synthesized prodrugs were characterized by IR, 1H NMR, 13C NMR, and mass spectroscopy. The chemical hydrolysis of C7-C12 was carried out at pH 1.2, 6.8, and 7.4. All compounds showed encouraging chemical stability at pH 1.2 and 6.8, whereas mild hydrolysis was shown at pH 7.4. Further prodrugs were screened for antidiabetic activity using a streptozotocin-induced model in rat. These derivatives showed notable results. Among them C8 showed significant activity in the reduction of STZ-induced blood glucose in rats when compared to that of metformin, indicating the effectiveness of prodrug.

TLR7 gain-of-function genetic variation causes human lupus.

Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease1-7, evidence of lupus-causing TLR7 gene variants is lacking. Here we describe human systemic lupus erythematosus caused by a TLR7 gain-of-function variant. TLR7 is a sensor of viral RNA8,9 and binds to guanosine10-12. We identified a de novo, previously undescribed missense TLR7Y264H variant in a child with severe lupus and additional variants in other patients with lupus. The TLR7Y264H variant selectively increased sensing of guanosine and 2',3'-cGMP10-12, and was sufficient to cause lupus when introduced into mice. We show that enhanced TLR7 signalling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c+ age-associated B cells and germinal centre B cells. Follicular and extrafollicular helper T cells were also increased but these phenotypes were cell-extrinsic. Deficiency of MyD88 (an adaptor protein downstream of TLR7) rescued autoimmunity, aberrant B cell survival, and all cellular and serological phenotypes. Despite prominent spontaneous germinal-centre formation in Tlr7Y264H mice, autoimmunity was not ameliorated by germinal-centre deficiency, suggesting an extrafollicular origin of pathogenic B cells. We establish the importance of TLR7 and guanosine-containing self-ligands for human lupus pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.

Epidemiology of Shoulder Injuries in Schoolboy Rugby Union in Ireland.

BACKGROUND: The shoulder has been reported as a frequent location of injury in adult professional and amateur rugby, with match injury incidence rates ranging from 1.8 to 3 per 1000 player-hours (h). An increased understanding of the incidence and mechanism of shoulder injuries in school rugby players is vital to establish effective injury preventive strategies and advise on appropriate rehabilitation. PURPOSE: To describe the incidence, nature, and severity of shoulder injuries in schoolboy rugby in Ireland. STUDY DESIGN: Descriptive epidemiology study. METHODS: Injury surveillance was carried out for Senior Cup teams across two seasons (N = 665 players aged 17-19 years) in Ireland from 2018 to 2020. Match and training injury data were recorded using an online system by trained nominated injury recorders. Match exposure was also recorded. RESULTS: Shoulder match injury incidence was 12.2 per 1000 h (95% CI, 9.1-16.2), with a mean severity of 47 days' time loss and an overall burden of 573 days per 1000 h. In total, 47 match and 5 training shoulder injuries were recorded. The most common injuries were shoulder dislocations/subluxations (34%), followed by acromioclavicular joint sprains (30%). Shoulder dislocations/subluxations represented the most burdensome injury (280 days per 1000 h). The tackle accounted for the majority (81%) of shoulder injuries. Forwards sustained a significantly higher incidence of shoulder injuries (8.3/1000 h) in comparison with backs (3.9/1000 h), with a rate ratio of 2.13 (95% CI, 1.15-3.94; P = .015). CONCLUSION: We found a notably higher injury incidence rate in schoolboy rugby as compared with the adult amateur and professional game. Shoulder injuries were responsible for more days lost than any other injury, and shoulder dislocations were the most severe. This is of particular concern so early in a player's career and warrants further investigation into potential risk factors and mechanisms associated with shoulder injuries in school-age players.

Increased burden of rare variants in genes of the endosomal Toll-like receptor pathway in patients with systemic lupus erythematosus.

OBJECTIVE: To compare the frequency of rare variants in genes of the pathophysiologically relevant endosomal Toll-like receptor (eTLR) pathway and any quantifiable differences in variant rarity, predicted deleteriousness, or molecular proximity in patients with systemic lupus erythematosus (SLE) and healthy controls. PATIENTS AND METHODS: 65 genes associated with the eTLR pathway were identified by literature search and pathway analysis. Using next generation sequencing techniques, these were compared in two randomised cohorts of patients with SLE (n = 114 and n = 113) with 197 healthy controls. Genetically determined ethnicity was used to normalise minor allele frequencies (MAF) for the identified genetic variants and these were then compared by their frequency: rare (MAF < 0.005), uncommon (MAF 0.005-0.02), and common (MAF >0.02). This was compared to the results for 65 randomly selected genes. RESULTS: Patients with SLE are more likely to carry a rare nonsynonymous variant affecting proteins within the eTLR pathway than healthy controls. Furthermore, individuals with SLE are more likely to have multiple rare variants in this pathway. There were no differences in rarity, Combined Annotation Dependent Depletion (CADD) score, or molecular proximity for rare eTLR pathway variants. CONCLUSIONS: Rare non-synonymous variants are enriched in patients with SLE in the eTLR pathway. This supports the hypothesis that SLE arises from several rare variants of relatively large effect rather than many common variants of small effect.

Comparison of UAV and fixed-wing aerial application for alfalfa insect pest control: evaluating efficacy, residues, and spray quality.

BACKGROUND: Integrating unmanned aerial vehicles (UAV) as a new method of pesticide application into existing commercial crop protection systems requires extensive research and comparison to conventional, proven application technology. Pest control expressed as efficacy against target pests, and spray quality expressed as coverage and chemical residue are three key criteria. We investigated and compared these quantitative parameters between a multi-rotor UAV and conventional piloted airplanes in two commercial alfalfa production systems. RESULTS: Effective and equivalent control of leaf-feeding insect pests was achieved by both methods of aerial application when delivering chlorantraniliprole at the same labeled use rate in different spray volumes (46.8 and 93.5 L ha-1 ) on commercially grown alfalfa in California. Residue levels and spray coverage were also comparable and consistent between the UAV and airplane applications across three sampling techniques, specifically residue levels on alfalfa, insecticide recovery from filter paper, and spray coverage on water sensitive cards. Differences in droplet size and deposit characteristics were more variable for the UAV than airplanes based on analysis of deposition images. CONCLUSION: The results of this study provide confidence supporting the use of small-scale multi-rotor UAVs for pesticide application on agricultural crops. According to the parameters tested, UAV application quality and crop protection performance were comparable to that of the conventional fixed wing airplane application. However, the droplet spectrum and the short-term fate of droplets from unmanned aerial spray system require further optimization for effective and efficient crop protection with minimal risk to the environment.

Injury Trends in Irish Amateur Rugby: An Epidemiological Comparison of Men and Women.

BACKGROUND: Rugby union is a physically demanding sport that carries an inherent risk of injury. Despite being a popular and widely played team sport, little is known about injuries occurring across the male and female amateur game. PURPOSE: To establish and compare injury incidence, nature, and severity in male and female Irish amateur rugby union. STUDY DESIGN: Prospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: Data were collected prospectively from 25 male teams (959 players) and 8 female teams (234 players) over 2 full seasons. Both time-loss (24-hour time-loss injury definition) and non-time-loss match injury reports were collected, alongside match exposure data. RESULTS: Time-loss match injury incidence rates were 49.1/1000 and 35.6/1000 player-hours for male and female players, respectively. Concussion and ankle ligament sprains were the most common diagnoses for male (5.6/1000 and 4.4/1000 player-hours, respectively) and female players (5.5/1000 and 3.9/1000 player-hours, respectively). Anterior cruciate ligament injuries presented the highest injury burden for male and female players with 200.3 and 307.2 days of absence per 1000 player-hours, respectively. In female players, 83% of noncontact injuries occurred in the fourth quarter of match play. CONCLUSION: While female players had a lower overall injury incidence rate compared with male players, concussion and ankle ligament injuries were the most common injuries in both cohorts. In female players, a high rate of noncontact injuries in the second half points to the need for strength and conditioning training programs to reduce fatigue-related injuries. CLINICAL RELEVANCE: Establishing the incidence and burden of rugby-related injuries is an essential step in minimizing injury risk. This epidemiological information will aid the development of future reduction strategies, including education and coaching strategies and strength and conditioning programs, informed by the most common injuries observed and the mechanism of injury.

Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease.

We identify an intronic deletion in VANGL1 that predisposes to renal injury in high risk populations through a kidney-intrinsic process. Half of all SLE patients develop nephritis, yet the predisposing mechanisms to kidney damage remain poorly understood. There is limited evidence of genetic contribution to specific organ involvement in SLE.1,2 We identify a large deletion in intron 7 of Van Gogh Like 1 (VANGL1), which associates with nephritis in SLE patients. The same deletion occurs at increased frequency in an indigenous population (Tiwi Islanders) with 10-fold higher rates of kidney disease compared with non-indigenous populations. Vangl1 hemizygosity in mice results in spontaneous IgA and IgG deposition within the glomerular mesangium in the absence of autoimmune nephritis. Serum transfer into B cell-deficient Vangl1+/- mice results in mesangial IgG deposition indicating that Ig deposits occur in a kidney-intrinsic fashion in the absence of Vangl1. These results suggest that Vangl1 acts in the kidney to prevent Ig deposits and its deficiency may trigger nephritis in individuals with SLE.

Validity of Session-Rate of Perceived Exertion to Quantify Training Loads in Paralympic Swimmers.

ABSTRACT: Sinnott-O'Connor, C, Comyns, TM, and Warrington, GD. Validity of session-RPE to quantify training loads in Paralympic swimmers. J Strength Cond Res 35(9): 2611-2615, 2021-Multiple measures may be used by coaches to quantify training load (TL). The application of heart rate (HR) has limitations in swimming and in Paralympic swimmers, and it may not always be a suitable measure. Therefore, the aim of this study was to determine the validity and reliability of the session-rate of perceived exertion (sRPE) method for quantifying internal TL in Paralympic swimmers. A further aim was to examine the relationship between athlete and coach perceptions of sRPE TL. Four international Paralympic swimmers selected to compete in Rio 2016 Paralympic Games participated in this study. Heart rate, RPE, and session duration were recorded for 30 training sessions of varied intensities across a 6-week home training period to quantify TL. Significant high to very high positive correlations were observed between sRPE and 3 HR-based measures-Banister's, Edwards, and Lucia's TRIMP (r = 0.68, 0.66, 0.74, p < 0.01, respectively). Moderate correlations were observed between sRPE and distance measures (r = 0.53, p < 0.05) but were lower than those observed with HR-based measures. A 2-way analysis of variance identified significant differences in the sRPE ratings between coaches and athletes (F(2, 108) = 170.4, p < 0.01, η2 = 0.75). The results of this study suggest that the sRPE method may be an appropriate monitoring tool for quantifying TL during water-based training using a single measure in Paralympic swimmers.