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Objective: To evaluate the efficacy of the Fédération Internationale de Football Association (FIFA) cooling break policy against alternative cooling configurations in attenuating thermal strain during simulated football in the heat., Methods: 12 males (age: 27±6 years, V̇O 2peak : 61±7 mL/kg/min) completed five 90 min intermittent treadmill football match simulations in 40°C and 41% relative humidity (32°C wet-bulb globe temperature) with different cooling configurations: regular match without cooling breaks (REG), 3 min breaks without cooling (BRK no-cool ), 3 min breaks with cooling (BRK cool : current FIFA policy; chilled fluid ingestion and ice towel across neck and shoulders), 5 min extended half-time without cooling breaks (ExtHT only ) and 3 min cooling breaks with 5 min ExtHT (ExtHT cool ). Rectal temperature (T re ), heart rate, whole-body sweat rate (WBSR) and rating of perceived exertion (RPE) were recorded. Data are presented as mean (95% CIs)., Results: Final T re was lower in BRK no-cool (0.20°C (0.01, 0.39), p=0.038), BRK cool (0.39°C (0.21, 0.57), p<0.001) and ExtHT cool (0.40°C (0.22, 0.58), p<0.001) than REG (39.1°C (38.8, 39.3)). Mean T re was lower in ExtHT cool (38.2°C (38.0, 38.4)) than BRK cool (38.3°C (38.1, 38.5), p=0.018), BRK no-cool and ExtHT only (38.4°C (38.2, 38.6), p<0.001) and REG (38.5°C (38.3, 38.7), p<0.001). Mean heart rate was lower during BRK cool (6 beats/min (4, 7), p<0.001) and ExtHT cool (7 beats/min (6, 8), p<0.001) compared with REG. WBSR was comparable across trials (p ≥ 0.07) and RPE was attenuated during BRK cool (0.4 (0.1, 0.7), p=0.004) and ExtHT cool (0.5 (0.2, 0.7), p=0.002), compared with REG., Conclusion: BRK cool and ExtHT cool attenuated thermal, cardiovascular and perceptual strain during a simulated football match in the heat. Additional strategies may be required in field settings or under harsher conditions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Assess the effect of water dousing on heat strain and performance during self- and fixed-paced exercise in the heat., Design: Crossover, block-randomized controlled trial., Methods: Thirteen trained runners completed a 10-km time trial (TT) and 60-minute fixed-pace run (60% velocity of V˙O2max) in a 30.4 °C, 47.4% relative humidity environment using either water dousing (DOUSE) or no dousing (CON)., Results: Ten-kilometer TT performance was faster in DOUSE compared to CON (44:11 [40:48, 47:34] vs 44:38 [41:21, 47:56] min:s; P = .033). Change in core temperature (Tc) was not different between groups during the TT (+0.02 [-0.04, 0.07] °C in DOUSE; P = .853) or fixed-pace run (+0.02 [-0.15, 0.18] °C; P = .848). Change in mean skin temperature was lower in DOUSE during the TT (-1.80 [-2.15, -1.46] °C; P < .001) and fixed-pace run (-1.38 [-1.81, -0.96] °C; P < .001). Heart rate was lower for DOUSE during the fixed-pace run (-3.5 [-6.8, -0.2] beats/min; P = .041) but not during the TT (-0.2 [-2.5, 2.1] beats/min; P = .853). Thermal sensation was lower for DOUSE during the TT (-49.3 [-72.1, -26.1] mm; P < .001) and fixed-pace run (-44.7 [-59.7, -29.6] mm; P < .001). Rating of perceived exertion was not different between groups for the TT (-0.2 [-0.7, 0.3]; P = .390) or fixed-pace run (-0.2 [-0.8, 0.4]; P = .480). Sweat rate was lower for DOUSE for the TT (-0.37 [-0.53, -0.22] L/h; P < .001) and fixed-pace run (-0.37 [-0.48, -0.26] L/h; P < .001)., Conclusion: Water dousing improves 10-km TT performance in the heat but does not affect Tc. The positive change in thermal perception (via lower skin temperature) during the TT likely drives this benefit.

Objectives: To describe the epidemiology of injuries in sub-elite female Australian Football (AF)., Design: Prospective cohort., Methods: 424 athletes were tracked across a 12-match season. Injury characteristics (location, severity, mechanism) were reported. Injury incidence (injuries per 1000 h) and injury burden (days absent per 1000 h) were calculated. Severity was considered as the number of days missed between injury onset and return to full training. Incidence was compared using incidence rate ratios, and severity using a Mann-Whitney U test., Results: Total injury incidence was 10.8 (95 % confidence interval [CI] = 9.0, 12.8) injuries per 1000 h. Match incidence was 34.6 (95 % CI = 28.0, 42.4) injuries per 1000 h. Ankle sprain injuries (2.2 per 1000 h, 95 % CI = 1.4, 3.1) and concussion (1.6 per 1000 h, 95 % CI = 1.0, 2.5) injuries were the most frequent, followed by anterior cruciate ligament (ACL) injuries (0.9 per 1000 h, 95 % CI = 0.4, 1.6). ACL (40.4 days per 1000 h, 95 % CI = 36.9, 44.1), ankle sprain injuries (31.4 per 1000 h, 95 % CI =28.4, 34.7), and concussion (19.9 per 1000 h, 95 % CI = 17.5, 22.5) injuries were also the most burdensome. There were 78 mild, 34 moderate, and 21 severe injuries. ACL injuries were the most severe injury (56.0 [77.0] in-season days missed)., Conclusions: This research describes the first large-scale injury profile of sub-elite female AF, reporting time-loss measures of incidence and burden for many injury types. Ankle sprain injuries, concussions, and ACL injuries are common and burdensome, and should be prioritised for prevention., Competing Interests: Declaration of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Abstract: Gantzer, C, Huff, D, Butterick, B, Chalmers, S, Marshall, P, Lovell, R, and Siegler, JC. Performing lower-limb strength exercises before or after training does not influence fatigue indices in competitive youth soccer players. J Strength Cond Res XX(X): 000-000, 2024-A multicenter approach was used to conduct a controlled, laboratory-based study (Part A) in conjunction with an ecologically focused, field-based study (Part B) of the influence of timing on hamstring fatigue induced by lower-limb strength exercises. Part A required players to perform the FIFA 11+ warm-up before a simulated soccer training session, whereas the other session involved removing the lower-limb strength exercises from the warm-up and delivering them after the simulated session. For Part B, players completed 2 live training sessions, where one session included the Nordic hamstring exercise (NHE) as part of a standardized warm-up before training and the other session incorporated the NHE at the end of training. Maximal hamstring force (MVC), rate of force development (RFD), countermovement jump (CMJ), and sprint speed (SS) were assessed before, during, and after the simulation and field training, respectively, to quantify fatigue across both study cohorts. There was no suggestion that timing of the intervention had an influence fatigue in either Part A or B, with no condition (MVC [Part A & B]: p > 0.43; RFD: p = 0.43; CMJ: p = 0.10; SS: p = 0.62), time (MVC: p > 0.30; RFD: p = 0.72; CMJ: p = 0.87; SS: p = 0.85), or interactions (MVC: p > 0.93; RFD: p = 0.78; CMJ: p = 0.99; SS: p = 0.94) evident. Our findings suggest youth soccer coaches should not be concerned with the timing of interventions, allowing them to focus instead on adherence and player buy-in., (Copyright © 2024 National Strength and Conditioning Association.)

Rationale: Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives: To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods: Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results: In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV 1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P  < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM ( P  < 0.05). Conclusions: Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM.

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune skin disease which occurs independently and in conjunction with systemic lupus erythematosus. Drug development for CLE is severely lacking. Anandamide (AEA) is a primary endocannabinoid which exhibits immunomodulatory effects through mixed cannabinoid receptor agonism. We evaluated AEA as topical treatment for CLE and assessed benefits of nanoparticle encapsulation (AEA-NP) on cutaneous drug penetration, delivery and biological activity. Compared to untreated controls, AEA-NP decreased IL-6 and MCP-1 in UVB-stimulated keratinocytes (p < 0.05) in vitro. In BALB/c mice, AEA-NP displayed improved cutaneous penetration, extended release and persistence of AEA in the follicular unit extending to the base after 24 h. Utilizing the MRL-lpr lupus murine model, twice weekly treatment of lesions with topical AEA-NP for 10 weeks led to decreased clinical and histologic lesion scores compared to unencapsulated AEA and untreated controls (p < 0.05). Prophylactic application of AEA-NP to commonly involved areas on MRL-lpr mice similarly resulted in decreased clinical and histologic scores when compared to controls (p < 0.05), and reduced C3 and IBA-1 in lesional tissue (p < 0.05). The demonstrated clinical and immunomodulatory effects of treatment with AEA support its potential as therapy for CLE. This work also suggests that encapsulation of AEA improves penetration and treatment efficacy. Future studies will be conducted to assess full therapeutic potential., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Post-COVID Syndrome (also known as Long COVID) refers to the multi-system condition affecting individuals following COVID-19 infection. This can include speech and language therapy (SLT) needs, including voice, swallowing, communication and upper airway difficulties. There is limited published literature in this clinical area of practice, particularly for those receiving input from community SLT services., Aims: To describe and compare demand, typical SLT presentation and service delivery across two National Health Service (NHS) Long COVID multidisciplinary services. Independent retrospective service evaluation was completed for each service. Descriptive statistics were produced and compared across services. This service evaluation followed The Strengthening the Reporting of Observation Studies in Epidemiology guidelines for cohort studies., Outcomes & Results: The findings indicated similarities across the two services in SLT service need and demand, clinical presentations and intervention approaches provided within Long COVID services. There were specific differences in the service provision and delivery of intervention in cognitive communication and upper airways subspecialities., Conclusions & Implications: This study highlights the clinical complexities of SLT needs in individuals with Long COVID and the importance for an appropriately skilled and supported workforce within effective multidisciplinary teams. We call for consensus on SLT practices and a consistent and standardized approach to evaluation for SLT needs in Long COVID., What This Paper Adds: What is already known on this subject SLT needs, including voice, swallowing, communication and upper airway difficulties, are present in individuals presenting with Long COVID, both in those who were or were not hospitalized. SLTs are seeing such individuals in a variety of settings, including community services and Long COVID multidisciplinary teams. There is minimal evidence of the clinical presentations and interventions provided to individuals with SLT needs compared across Long COVID services. What this study adds to existing knowledge This study compares two NHS Long COVID services providing a SLT service pathway. It highlights the similarities and differences in service demand and capacity, patient presentation, and SLT intervention to make suggestions for future practice consideration and priority evaluation. Expert consensus among SLT clinicians is a priority to ensure clinicians are delivering consistent and equitable care for patients, while new evidence and data emerge. A consistent and standardized approach to data collection and outcome measures is essential to ensure future research captures the impact and value of SLT input with individuals with Long COVID. What are the clinical implications of this work? The complexities and multifactorial SLT needs of individual with Long COVID call for appropriate SLT staffing provision, skill and training to fulfil the needs of this population. Speech and language therapists should be integrated with multidisciplinary Long COVID services to provide holistic care for patients and to support the professionals working with individuals with post-COVID voice, swallowing, communication and upper airway symptoms., (© 2023 The Authors. International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.)

Background: Colorectal cancer screenings detect the early, treatable, and often curable stages of the disease. Screenings are now recommended beginning at 45 years of age. Health care providers are expected to have patient's complete screenings, and reimbursement rates can be affected if results are not documented., Local Problem: An independent review of expected organizational core measures revealed inadequate colorectal cancer screenings completed and no formal patient outreach program for patients who had not completed ordered screenings. The lack of a formal reminder to patients resulted in a cumulative completion rate of 19%., Methods: A phone call intervention was designed to notify patients of the need to complete colorectal cancer screenings. A preimplementation and postimplementation design was used to compare completed colorectal cancer screenings., Intervention: Patients with ordered colorectal cancer screenings received one reminder phone call to complete the screening. Preintervention and postintervention completion rates were evaluated using data from the electronic medical record., Results: Results revealed a colorectal cancer screening rate of 19% preimplementation and 43% postimplementation and reflected a 61.9% increase in cumulative completion rates over a 12-week intervention period., Conclusion: The colorectal cancer patient reminder intervention showed clinical significance in improving completion rates of colorectal cancer screenings. The intervention was a successful method to improve patient compliance with the expected screening and helped improve provider core measure expectations., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2023 American Association of Nurse Practitioners.)

Background: Existing evidence suggests that clinician and organization engagement in research can improve healthcare processes of care and outcomes. However, current evidence has considered the relationship across all healthcare professions collectively. With the increase in allied health clinical academic and research activity, it is imperative for healthcare organizations, leaders and managers to understand engagement in research within these specific clinical fields. This systematic review aims to identify the effect of engagement in research by allied health professionals (AHPs) and organizations on healthcare performance., Methods: This systematic review has a two-stage search strategy. The first stage will be to screen a previous systematic review examining the effectiveness of engagement in research in health and social care to identify relevant papers published pre-2012. The search strategy used in the previous review will then be rerun, but with a specific focus on allied health. This multi-database search will identify publications from 2012 to date. Only studies that assessed the effectiveness of allied health engagement in research will be included. All stages of the review will be conducted by two reviewers independently, plus documented discussions with the wider research team when discrepancies occur. This systematic review protocol follows the EQUATOR reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (PRISMA-P)., Discussion: The findings of this review will make a significant contribution to the evidence base around the effect of allied health engagement in research on healthcare performance. It will provide insights for clinicians and managers looking to understand the consequences of developing AHP research capability and capacity. The findings of this review will also aim to make recommendations for future evaluation approaches for engagement in research interventions., Trial Registration: This systematic review protocol has been registered with PROSPERO, registration number CRD42021253461., What This Paper Adds: What is already known on the subject This study will provide valuable evidence for professionals and policymakers seeking to understand engagement in research in the allied health disciplines. Where supported by the data, there may be recommendations for future research regarding specific variables to be considered when planning and evaluating engagement in research in allied health practice. What this paper adds to existing knowledge A previous systematic review identified a positive association between clinician and organization engagement in research and improved processes of care and health outcomes. The reviews' findings have been used as a justification for clinicians and organizations to increase research capacity. That review evaluated literature published before 2012 and the studies that were identified predominantly reported on engagement in research by medics and nurses. An updated review is now required to include research published since 2012. This review will specifically focus on the effect of engagement in research within allied health disciplines. What are the potential or actual clinical implications of this work? Research activity among AHPs is gaining momentum. Given this growth in AHP research activity and the rise in dedicated clinical academic roles, a contemporary review to identify the specific effect of AHP engagement in research on healthcare performance is prudent. The findings will inform clinicians, clinical managers and leaders of the potential impact of research activities by AHP clinicians and organizations. This will support the planning and development of initiatives focused on research capacity, capability and culture within allied health., (© 2022 The Authors. International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.)

Objectives: Concussion increases injury risk. However, this has not been investigated in junior Australian football and it is unknown whether the location, severity, and mechanism of subsequent injuries differ after concussion vs. non-concussion injury., Design: Prospective cohort., Methods: 1455 elite adolescent male Australian footballers were tracked across seven seasons to determine whether subsequent injury risk was greater after concussion compared to non-concussion index injury using multilevel survival analysis. Mixed-effects logistic regression compared location and mechanism. Mixed-effects Poisson regression compared severity., Results: Of 1455 athletes, 632 were injured and included in subsequent-injury analysis. There were no differences in injury incidence after a concussion compared to upper- (hazard ratio = 1.0, 0.6 to 1.9, P = 0.892; trivial effect) and lower (hazard ratio = 1.1, 0.6 to 1.9, P = 0.810; trivial effect) index injury, or in location. Subsequent injuries were more likely to be contact-based after a non-concussion injury than concussion (odds ratio = 4.6, 1.3 to 16.0; P = 0.017; large effect). There was no difference in subsequent injury severity after lower- (3.4 ± 3.0 missed matches; incidence rate ratio = 1.4, 0.9 to 2.1; P ≤ 0.117; small effect) and upper-limb injuries (3.4 ± 3.1 missed matches; incidence rate ratio = 1.4, 0.9 to 2.2; P = 0.189; small effect) compared to concussion (2.4 ± 2.0 missed matches)., Conclusions: Subsequent injury risk, severity, and location in junior Australian football are similar following concussion compared to non-concussion index injuries, although contact injuries are less likely., Competing Interests: Declaration of interest statement The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: High-impact loads have been linked with running injuries. Fatigue has been proposed to increase impact loads, but this relationship has not been rigorously examined, including the associated role of muscle strength, power, and endurance., Purpose: This study aimed to investigate the effect of fatigue on impact loading in runners and the role of muscle function in mediating changes in impact loading with fatigue., Methods: Twenty-eight trained endurance runners performed a fixed-intensity time to exhaustion test at 85% of V̇O 2max . Tibial accelerations were measured using leg-mounted inertial measurement units and sampled every minute until volitional exhaustion. Tests of lower limb muscle strength, power, and endurance included maximal isometric strength (soleus, knee extensors, and knee flexors), single leg hop for distance, and the one leg rise test. Changes in peak tibial acceleration (PTA, g ) were compared between time points throughout the run (0%, 25%, 50%, 75%, and 100%). Associations between the change in PTA and lower limb muscle function tests were assessed (Spearman's rho [ rs ])., Results: PTA increased over the duration of the fatiguing run. Compared with baseline (0%) (mean ± SD, 9.1 g ± 1.6 g ), there was a significant increase at 75% (9.9 g ± 1.7 g , P = 0.001) and 100% (10.1 g ± 1.8 g , P < 0.001), with no change at 25% (9.6 g ± 1.6 g , P = 0.142) or 50% (9.7 g ± 1.7 g , P = 0.053). Relationships between change in PTA and muscle function tests were weak and not statistically significant ( rs = -0.153 to 0.142, all P > 0.05)., Conclusions: Peak axial tibial acceleration increased throughout a fixed-intensity run to exhaustion. The change in PTA was not related to performance in lower limb muscle function tests., (Copyright © 2022 by the American College of Sports Medicine.)

Background: Previous studies suggested that hypernatremia or hyperosmolarity may have protective effects in lung injury. We hypothesized that hypernatremia and/or hyperosmolarity would prevent ARDS., Design: Retrospective cohort study of all admissions at medical, surgical, and multidisciplinary intensive care units in Mayo Clinic, Rochester from the year of 2009 to 2019. The occurrence of ARDS was identified using a validated computerized search strategy. The association between serum sodium/osmolarity and the occurrence of ARDS was analyzed using a multivariable logistic regression model. The relationship between serum sodium/osmolarity and outcomes of ARDS was analyzed using linear and logistic regression models., Results: Among 50,498 patients, the serum sodium level on admission did not have a significant association with the occurrence of ARDS, with an adjusted odds ratio of 0.95 [95% CI (0.86, 1.05)]. There was no significant association between calculated serum osmolarity and the occurrence of ARDS, with an adjusted odds ratio of 1.03 [95% CI (1.00, 1.07)]. 1560 patients developed ARDS during the ICU stay. Their serum sodium level and osmolarity level did not have a significant association with their outcomes., Conclusions: Admission serum sodium or serum osmolarity were not associated with the occurrence or outcomes of ARDS in ICU., Competing Interests: Declaration of Competing Interest All authors have disclosed that they do not have any conflicts of interest related to this study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study aimed to identify whether a revised lower Functional Movement Screen (FMS) composite score threshold would be associated with a greater injury risk for junior athletes than the common threshold of≤14. This prospective cohort study included tracking of 809 elite junior male Australian football players for injuries that resulted in a missed game. All athletes completed pre-season FMS testing and a 12-month self-reported retrospective injury questionnaire. Analyses examined the relationship between composite score thresholds of≤14, ≤13, and≤12 and the risk of injury. The relationship between prospective injury and the common composite threshold score of ≤ 14 was dependent on the presence of a recent injury history (relative risk [RR] = 1.45, p  = 0.004) in comparison to no recent injury history (RR = 0.98, p  = 0.887). Scoring≤12 in the presence of a recent injury history had the greatest diagnostic accuracy but only a trivial increase in injury risk (RR = 1.59, p  = 0.001, sensitivity = 0.35, specificity = 0.80, negative and positive likelihood ratios = 0.81 and 1.75). Whilst some small statistical relationships existed between prospective injury and the FMS composite score thresholds, all three thresholds were not associated with a clinically meaningful relationship with prospective injury and were no more effective than retrospective injury for determining athletes at risk of injury.

Abstract: Bennett, H, Fuller, J, Milanese, S, Jones, S, Moore, E, and Chalmers, S. The relationship between movement quality and physical performance in elite adolescent Australian football players. J Strength Cond Res 36(10): 2824-2829, 2022-The assessment of movement quality is commonplace in competitive sport to profile injury risk and guide exercise prescription. However, the relationship between movement quality scores and physical performance measures is unclear. Moreover, whether improvements in these measures are associated remain unknown. Over a 4-year period, 918 individual elite adolescent Australian Rules Footballers completed the Functional Movement Screen (FMS) and physical performance testing (5- and 20-m sprint, vertical jump, planned agility, and 20-m shuttle run test), allowing the analysis of relationships between FMS parameters and performance measures. In addition, 235 athletes completed testing over 2 consecutive years, allowing the analysis of relationships between changes in these outcomes. Small associations were observed between FMS composite score, hurdle step performance, in-line lunge performance, trunk stability push-up performance, rotary stability, and measures of speed, power, agility, and aerobic fitness (ρ = 0.071-0.238). Across consecutive seasons, significant improvements were observed in the deep squat subtest ( d = 0.21), FMS composite score ( d = 0.17), and 5- ( d = 0.16) and 20-m sprint times ( d = 0.39). A negative association between change in rotary stability and change in jump height (ρ = -0.236) from one season to the next was detected. Results suggest FMS scores have limited relationships with measures of performance in footballers. To optimize athletic performance, once acceptable movement capabilities have been established, training should not prioritize improving movement quality over improvements in strength, power, and change of direction ability., (Copyright © 2021 National Strength and Conditioning Association.)

Emerging evidence suggests that the nasal microbiome may influence host susceptibility to initial development and severity of respiratory viral infections. While not as extensively studied as the microbiota of the alimentary tract, it is now clearly established that the microbial composition of this niche is influenced by medical, social and pharmacological influences, predisposing some sub-populations to respiratory infections. The resulting specific microbial profiles may explain variance in susceptibility to viral infection. This review summaries the evolution and constituents of the commensal nasal microbiome; the bacterial-virus, bacterial-host and interbacterial interactions which potentiate disease; and considers the effects of interventions such as vaccination and probiotics., Competing Interests: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

This systematic review and meta-analysis aimed to synthesise and clarify the effect of running-induced fatigue on impact loading during running. Eight electronic databases were systematically searched until April 2021. Studies that analysed impact loading over the course of a run, in adult runners free of medical conditions were included. Changes in leg stiffness, vertical stiffness, shock attenuation, peak tibial accelerations, peak ground reaction forces (GRF) and loading rates were extracted. Subgroup analyses were conducted depending on whether participants were required to run to exhaustion. Thirty-six studies were included in the review, 25 were included in the meta-analysis. Leg stiffness decreased with running-induced fatigue (SMD -0.31, 95% CI -0.52, -0.08, moderate evidence). Exhaustive and non-exhaustive subgroups were different for peak tibial acceleration (Chi 2  = 3.79, p = 0.05), with limited evidence from exhaustive subgroups showing an increase in peak tibial acceleration with fatigue. Findings for vertical GRF impact peak and peak braking force were conflicting based on exhaustive and non-exhaustive protocols (Chi 2  = 3.83, p = 0.05 and Chi 2  = 5.10, p = 0.02, respectively). Moderate evidence suggests leg stiffness during running decreases with fatigue. Given the non-linear relationship between leg stiffness and running economy, this may have implications for performance.

Purpose: Determine the impact of preseason and between-seasons changes in individual physical performance on injury risk in elite junior Australian football players and if injuries sustained during a season impact subsequent-season performance improvement., Methods: This prospective cohort study assessed individual performance measures (sprint speed, jump, agility, and aerobic endurance) during preseason over 4 consecutive seasons. Injury status (injured/not injured) was tracked weekly to determine the relationship between individual performance and in-season injury occurrence. Mixed models were used to determine the relationship between physical performance and injury, and the effect of injury on physical performance improvement., Results: A total of 206 players played 2 consecutive seasons and were included (17.6 y, 181.9 cm, 75.7 kg). Faster players during preseason experienced higher injury incidence (injuries/season) during that playing season (incidence rate ratio = 0.127; P = .034). Injury incidence was not influenced by between-seasons change in any performance measure. Players injured during their first season maintained their aerobic fitness, which declined in noninjured players (d = 0.39; P = .013). Players who sustained a lower-limb injury during their first season saw smaller improvements in sprint speed than players who did not get injured (d = 0.39; P = .035)., Conclusion: Faster players experience higher injury incidence than slower players and may require specific prevention interventions. Players who experience a lower-limb injury during the playing season do not improve sprint speed between seasons to the same extent as players who do not get injured, highlighting the need for targeted high-speed running ability development as part of rehabilitation.

Objectives: Identify how modified Lower-Quarter Y-Balance Test (mYBT-LQ) and Upper-Quarter Balance Test (mYBT-UQ) scores relate to injury risk and measures of physical performance in elite adolescent Australian Football (AF) athletes., Design: Prospective cohort study., Methods: Pre-season mYBT-LQ, mYBT-UQ, and physical performance measures (speed, jump height, and agility) were obtained in 257 elite adolescent male AF athletes. Injury status was tracked across the 18-game season to determine the relationship between mYBT scores and injury risk based on time-to-event analysis. Cross-sectional analysis of mYBT-LQ scores and performance measures determined the relationships between these variables., Results: There were no significant associations between injury risk and any single mYBT parameter. However, athletes with high posteromedial asymmetry and good agility performance (top 25% of the cohort) had moderately increased injury risk with and tended to without a previous injury history (Hazard Ratio = 3.26 [95% Confidence Interval: 1.01, 10.54; p = 0.048] and 2.69 [95% Confidence Interval = 0.92, 7.82; p = 0.069], respectively). There were significant correlations between faster agility times and higher composite limb-length normalised mYBT-LQ (r = -0.210; CI = -0.324, -0.090), limb-length normalised average posteromedial reach score (r = -0.227; CI = -0.340, -0.108), and limb-length normalised average posterolateral reach score (r = -0.250: CI = -0.361, -0.132)., Conclusion: In isolation, the mYBT is not useful for identifying injury risk in junior AF athletes, and only small correlations between mYBT-LQ and physical performance variables were identified. However, high mYBT-LQ posteromedial asymmetry is associated with increased injury risk for athletes with good agility performance. This should be considered within athlete preparation programs., (Copyright © 2021 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Sophie Chalmers is a clinical academic and registered allied health professional working in collaboration with an NHS Trust and Higher Education Institution to enhance research capacity building across alied health professional teams in Bolton NHS Foundation Trust, with support from the University of Central Lancashire. Sophie describes her experience of transitioning from a full-time clinician to dipping her toes into research through a 2-year research secondment.

Open-water swim racing in warm water is associated with significant physiological strain. However, existing international policy that governs safe participation during competition relies only on a fixed water temperature threshold for event cancellation and has an unclear biophysical rationale. The current policy does not factor other environmental factors or race distance, nor provide a stratification of risk (low, moderate, high, or extreme) prior to the threshold for cancellation. Therefore, the primary aim of this Perspectives article is to highlight considerations for the development of modernized warm-water competition policies. We highlight current accounts (or lack thereof) of thermal strain, cooling interventions, and performance in warm-water swimming and opportunities for advancement of knowledge. Further work is needed that systematically evaluate real-world thermal strain and performance during warm water competition (alongside reports of environmental conditions), novel preparatory strategies, and in-race cooling strategies. This could ultimately form a basis for future development of modernized policies for athlete cohorts that stratifies risk and mitigation strategies according to important environmental factors and race-specific factors (distance)., Competing Interests: SC and OJ have a financial consultancy agreement with Swimming Australia but received no honoraria for this paper. Hence, the authors declare that this article was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chalmers, Shaw, Mujika and Jay.)

Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-L-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1/NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1β, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8 + T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance., (© 2021. The Author(s).)

Background: Tyrosine kinase inhibitors (TKIs) have dramatically improved cancer treatment but are known to cause cardiotoxicity. The pathophysiological consequences of TKI therapy are likely to manifest across different cell types of the heart, yet there is little understanding of the differential adverse cellular effects. Cardiac fibroblasts (CFs) play a pivotal role in the repair and remodeling of the heart following insult or injury, yet their involvement in anti-cancer drug induced cardiotoxicity has been largely overlooked. Here, we examine the direct effects of sunitinib malate and imatinib mesylate on adult rat CF viability, Ca 2+ handling and mitochondrial function that may contribute to TKI-induced cardiotoxicity. In particular, we investigate whether Ca 2+ /calmodulin dependent protein kinase II (CaMKII), may be a mediator of TKI-induced effects. Methods: CF viability in response to chronic treatment with both drugs was assessed using MTT assays and flow cytometry analysis. Calcium mobilization was assessed in CFs loaded with Fluo4-AM and CaMKII activation via oxidation was measured via quantitative immunoblotting. Effects of both drugs on mitochondrial function was determined by live mitochondrial imaging using MitoSOX red. Results: Treatment of CFs with sunitinib (0.1-10 μM) resulted in concentration-dependent alterations in CF phenotype, with progressively significant cell loss at higher concentrations. Flow cytometry analysis and MTT assays revealed increased cell apoptosis and necrosis with increasing concentrations of sunitinib. In contrast, equivalent concentrations of imatinib resulted in no significant change in cell viability. Both sunitinib and imatinib pre-treatment increased Angiotensin II-induced intracellular Ca 2+ mobilization, with only sunitinib resulting in a significant effect and also causing increased CaMKII activation via oxidation. Live cell mitochondrial imaging using MitoSOX red revealed that both sunitinib and imatinib increased mitochondrial superoxide production in a concentration-dependent manner. This effect in response to both drugs was suppressed in the presence of the CaMKII inhibitor KN-93. Conclusions: Sunitinib and imatinib showed differential effects on CFs, with sunitinib causing marked changes in cell viability at concentrations where imatinib had no effect. Sunitinib caused a significant increase in Angiotensin II-induced intracellular Ca 2+ mobilization and both TKIs caused increased mitochondrial superoxide production. Targeted CaMKII inhibition reversed the TKI-induced mitochondrial damage. These findings highlight a new role for CaMKII in TKI-induced cardiotoxicity, particularly at the level of the mitochondria, and confirm differential off-target toxicity in CFs, consistent with the differential selectivity of sunitinib and imatinib., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 McMullen, Chalmers, Wood, Cunningham and Currie.)

To develop and verify a digital twin model of critically ill patient using the causal artificial intelligence approach to predict the response to specific treatment during the first 24 hours of sepsis., Design: Directed acyclic graphs were used to define explicitly the causal relationship among organ systems and specific treatments used. A hybrid approach of agent-based modeling, discrete-event simulation, and Bayesian network was used to simulate treatment effect across multiple stages and interactions of major organ systems (cardiovascular, neurologic, renal, respiratory, gastrointestinal, inflammatory, and hematology). Organ systems were visualized using relevant clinical markers. The application was iteratively revised and debugged by clinical experts and engineers. Agreement statistics was used to test the performance of the model by comparing the observed patient response versus the expected response (primary and secondary) predicted by digital twin., Setting: Medical ICU of a large quaternary- care academic medical center in the United States., Patients or Subjects: Adult (> 18 year yr old), medical ICU patients were included in the study., Interventions: No additional interventions were made beyond the standard of care for this study., Measurements and Main Results: During the verification phase, model performance was prospectively tested on 145 observations in a convenience sample of 29 patients. Median age was 60 years (54-66 d) with a median Sequential Organ Failure Assessment score of 9.5 (interquartile range, 5.0-14.0). The most common source of sepsis was pneumonia, followed by hepatobiliary. The observations were made during the first 24 hours of the ICU admission with one-step interventions, comparing the output in the digital twin with the real patient response. The agreement between the observed versus and the expected response ranged from fair (kappa coefficient of 0.41) for primary response to good (kappa coefficient of 0.65) for secondary response to the intervention. The most common error detected was coding error in 50 observations (35%), followed by expert rule error in 29 observations (20%) and timing error in seven observations (5%)., Conclusions: We confirmed the feasibility of development and prospective testing of causal artificial intelligence model to predict the response to treatment in early stages of critical illness. The availability of qualitative and quantitative data and a relatively short turnaround time makes the ICU an ideal environment for development and testing of digital twin patient models. An accurate digital twin model will allow the effect of an intervention to be tested in a virtual environment prior to use on real patients., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

The Functional Movement Screen (FMS) and physical performance testing are often suggested to be related to sports injury risk. This study explored if the combination of FMS and physical performance testing improved identification of non-contact injury risk over FMS testing alone in an elite junior Australian football cohort. Over a 3-year period, 573 players completed pre-season injury history questionnaires, FMS, physical performance testing (20-m sprint, vertical jump, planned agility testing, and shuttle run test), and subsequent in-season injury surveillance. Results: Neither previous injury or FMS score <14 were related to an increased risk of subsequent injury in isolation. The combination of FMS composite score ≤14 and previous injury moderately increased the risk of injury (Hazard ratio [HR] = 2.22 [1.09-4.54]). None of the physical performance measures improved the ability to predict injuries based on FMS composite score. FMS asymmetry was only associated with injury when combined with previous injury and vertical jump performance. Players with ≥1 FMS asymmetry and history of previous injury experienced a large increase in injury risk when vertical jump was poor (HR = 4.26 [1.35-13.42]) or good (HR = 3.17 [1.08-9.29]). Players with a combination of a good vertical jump, no previous injury, and no FMS asymmetries were also at moderately increased risk of injury (HR = 3.41 [1.11-10.42]). No physical performance tests improved the ability to identify non-contact injury risk using an FMS composite score threshold. However, a U-shaped relationship between vertical jump and injury risk was identified with both poor and good vertical jump height associated with a moderate-large increase in non-contact injury risk in the presence of ≥1 asymmetrical FMS sub-test., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

COVID-19 has provided learning opportunities for medical students, supervisors and the public.

The heart is critically dependent on mitochondrial respiration for energy supply. Ischemia decreases oxygen availability, with catastrophic consequences for cellular energy systems. After a few minutes of ischemia, the mitochondrial respiratory chain halts, ATP levels drop and ion gradients across cell membranes collapse. Activation of cellular proteases and generation of reactive oxygen species by mitochondria during ischemia alter mitochondrial membrane permeability, causing mitochondrial swelling and fragmentation and eventually cell death. The mitochondria, therefore, are important targets of cardioprotection against ischemic injury. We have previously shown that ixazomib (IXA), a proteasome inhibitor used for treating multiple myeloma, effectively reduced the size of the infarct produced by global ischemia in isolated rat hearts and prevented degradation of the sarcoplasmic reticulum calcium release channel RyR2. The aim of this work was to further characterize the protective effect of IXA by determining its effect on mitochondrial morphology and function after ischemia. We also quantified the effect of IXA on levels of mitofusin-2, a protein involved in maintaining mitochondrial morphology and mitochondria-SR communication. We found that mitochondria were significantly preserved and functional parameters such as oxygen consumption, the ability to generate a membrane potential, and glutathione content were improved in mitochondria isolated from hearts perfused with IXA prior to ischemia. IXA also blocked the release of cytochrome c observed in ischemia and significantly preserved mitofusin-2 integrity. These beneficial effects resulted in a significant decrease in the left ventricular end diastolic pressure upon reperfusion and a smaller infarct in isolated hearts., Competing Interests: The authors have declared that no competing interests exist.

Background: Depression impacts the lives of millions of people worldwide. Behavioral activation (BA), derived from cognitive behavioral therapy, has the potential for improving depressive symptoms in patients with depression. Studies evaluating the effectiveness of BA specifically in the context of group therapy programs in a hospital setting for patients with depression are limited. In this study, we report findings from a pilot trial evaluating group BA for major depressive disorder., Objective: The objectives of this pilot trial are to assess the potential of a full trial of BA group therapy in a large-scale tertiary care setting and to provide preliminary information about possible results regarding mood symptoms and quality of life in adults with depression., Methods: Using a parallel single-cohort pragmatic pilot randomized controlled trial design, we evaluated the potential of conducting a large trial of BA effectiveness among adults with depression. Participants were randomized to the intervention (BA in addition to usual care) or control (support group in addition to usual care) groups and were assessed weekly for 18 consecutive weeks. Participants randomized to intervention underwent 28 2-h group BA therapy visits administered by trained therapists and completed assessments to examine treatment outcomes. Feasibility was measured in terms of enrollment rates (min. 20%), completion rates of study (min. 80%), and completion rates of weekly measurement scales (min. 80%). The reporting of this pilot trial is in accordance with the CONSORT extension for randomized pilot and feasibility trials., Results: We randomized 20 individuals of mean age of 48.8 years (standard deviation = 9.7) with a DSM-5 diagnosis of major depressive disorder to intervention ( n  = 10) or control ( n  = 10) groups. Based on our feasibility criteria, our recruitment rate was excellent (20/27; 74%), study completion was found to be a moderate (80% of the total participants in both arms completed the study; BA = 100%, control = 60%), and completeness of measurements on a weekly basis was adequate overall (82%; BA = 86%, control = 79%)., Conclusions: The study has demonstrated the potential feasibility to perform a larger scale trial upon modifications to the control group to avoid the low rate of study completion (60%) in this group., Trial Registration: ClinicalTrials NCT02045771, Registered January 22, 2014., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

We detail key considerations for the development of extreme heat policies in sport and exercise. Policies should account for the four environmental parameters (ambient temperature, humidity, air velocity, and mean radiant temperature) and two personal (activity and clothing) parameters that determine the prevailing thermoregulatory strain during exercise in the heat. Considerations for how to measure environmental stress and convey the level of risk are discussed. Finally, we highlight the need to include feasible cooling strategies that are relevant for the prevailing environmental conditions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent studies have suggested that fatty acid oxidation (FAO) is a key metabolic pathway for the growth of triple negative breast cancers (TNBCs), particularly those that have high expression of MYC. However, the underlying mechanism by which MYC promotes FAO remains poorly understood., Methods: We used a combination of metabolomics, transcriptomics, bioinformatics, and microscopy to elucidate a potential mechanism by which MYC regulates FAO in TNBC., Results: We propose that MYC induces a multigenic program that involves changes in intracellular calcium signalling and fatty acid metabolism. We determined key roles for fatty acid transporters (CD36), lipases (LPL), and kinases (PDGFRB, CAMKK2, and AMPK) that each contribute to promoting FAO in human mammary epithelial cells that express oncogenic levels of MYC. Bioinformatic analysis further showed that this multigenic program is highly expressed and predicts poor survival in the claudin-low molecular subtype of TNBC, but not other subtypes of TNBCs, suggesting that efforts to target FAO in the clinic may best serve claudin-low TNBC patients., Conclusion: We identified critical pieces of the FAO machinery that have the potential to be targeted for improved treatment of patients with TNBC, especially the claudin-low molecular subtype.

Objective: To determine whether systemic lupus erythematosus (SLE) can develop in the absence of BAFF in an SLE-prone host., Methods: Starting with C57BL/6 mice that express a human BCL2 transgene (Tg) in their B cells (thereby rendering B cell survival largely independent of BAFF-triggered signals), we introgressed this Tg into NZM 2328 mice genetically deficient in BAFF (NZM.Baff -/- ) to generate NZM.Baff -/- .Bcl2 Tg mice. Expression of human Bcl-2 and lymphocyte profiles were assessed by fluorescence-activated cell sorting, and serologic profiles were determined by enzyme-linked immunosorbent assay. Immunofluorescence and histologic analyses were performed to assess renal immunopathologic features in the mice, and clinical disease was assessed according to the outcomes of severe proteinuria and death., Results: In comparison to their non-Tg NZM.Baff -/- littermates (n ≥ 7), NZM.Baff -/- .Bcl2 Tg mice (n ≥ 8) overexpressed Bcl-2 in their B cells and developed significantly increased percentages and numbers of B cells and plasma cells, serum levels of IgG autoantibodies, glomerular deposition of IgG and C3, and severity of glomerular and tubulointerstitial inflammation, culminating in severe proteinuria and death (all P < 0.05 versus NZM.Baff -/- littermates). The time course for development of SLE-like features in NZM.Baff -/- .Bcl2 Tg mice was more rapid than has been previously observed in NZM 2328 wild-type mice (median age at death 4.5 months versus 7.5 months). NZM.Baff -/- .Bcl2 Tg mice remained responsive to BAFF, since reintroduction of the Baff gene into these mice further accelerated the course of disease (median age at death 3 months)., Conclusion: The role of BAFF in the development of SLE-like disease may be dispensable as long as B cell survival is preserved via a BAFF-independent pathway. This may help explain the limited and variable clinical success with BAFF antagonists in human SLE. Thus, NZM.Baff -/- .Bcl2 Tg mice may serve as a powerful murine model for the study of BAFF-independent SLE., (© 2019, American College of Rheumatology.)

Objective: To describe the location and severity of pain during Functional Movement Screen (FMS) testing in junior Australian football players and to investigate its effect on FMS composite score and injury risk., Design: Prospective cohort study., Methods: Junior male Australian football players (n = 439) completed preseason FMS testing. Pain location and severity (on a 0-to-10 numeric pain-rating scale [NPRS]) were assessed for painful subtests. The FMS composite score was calculated using 3 scoring approaches: "traditional," a score of zero on painful subtests; "moderate," a score of zero on painful subtests if an NPRS pain severity was greater than 4; and "raw," did not adjust painful FMS subtest scores. Players were monitored throughout the competitive season and considered injured when 1 or more matches were missed due to injury., Results: One hundred seventy players reported pain during FMS testing. The pain-scoring approach affected mean composite score values (raw, 14.9; moderate, 14.5; traditional, 13.6; P <.001). Sixty-eight percent of pain was mildly severe (NPRS of 4 or less). Back pain (50%) was more common than upper-limb (24%) or lower-limb (26%) pain ( P <.001). Upper-limb pain was associated with a small increase in injury risk (hazard ratio = 1.59, P = .023). No other FMS pain location influenced injury risk, nor did pain severity ( P >.280). The FMS composite score was not associated with injury risk, regardless of pain-scoring approach ( P ≥.500)., Conclusion: Pain was common during FMS testing in junior Australian football players and had a notable effect on the FMS composite score, but minimal effect on subsequent injury risk. J Orthop Sports Phys Ther 2020;50(2):75-82. Epub 17 Sep 2019. doi:10.2519/jospt.2020.9168 .

The use of electronic cigarettes, known as vaping, has become increasingly popular over the past decade, particularly in the adolescent and young adult population, often exposing users to harmful chemicals. Vaping has been associated with a heterogeneous group of pulmonary disease. Recently, a multistate epidemic has emerged surrounding vaping-related acute lung injury, prompting the Centers for Disease Control and Prevention to list an official health advisory. In this review, we describe the current literature on the epidemiology, clinical significance, as well as recommended evaluation and treatment of vaping-related lung injury., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Toxoplasma gondii is capable of actively invading almost any mammalian cell type including phagocytes. Early events in phagocytic cells such as dendritic cells are not only key to establishing parasite infection, but conversely play a pivotal role in initiating host immunity. It is now recognized that in addition to changes in canonical immune markers and mediators, alteration in metabolism occurs upon activation of phagocytic cells. These metabolic changes are important for supporting the developing immune response, but can affect the availability of nutrients for intracellular pathogens including T. gondii . However, the interaction of T. gondii with these cells and particularly how infection changes their metabolism has not been extensively investigated. Herein, we use a multi-omics approach comprising transcriptomics and metabolomics validated with functional assays to better understand early events in these cells following infection. Analysis of the transcriptome of T. gondii infected bone marrow derived dendritic cells (BMDCs) revealed significant alterations in transcripts associated with cellular metabolism, activation of T cells, inflammation mediated chemokine and cytokine signaling pathways. Multivariant analysis of metabolomic data sets acquired through non-targeted liquid chromatography mass spectroscopy (LCMS) identified metabolites associated with glycolysis, the TCA cycle, oxidative phosphorylation and arginine metabolism as major discriminants between control uninfected and T. gondii infected cells. Consistent with these observations, glucose uptake and lactate dehydrogenase activity were upregulated in T. gondii infected BMDC cultures compared with control BMDCs. Conversely, BMDC mitochondrial membrane potential was reduced in T. gondii -infected cells relative to mitochondria of control BMDCs. These changes to energy metabolism, similar to what has been described following LPS stimulation of BMDCs and macrophages are often termed the Warburg effect. This metabolic reprogramming of cells has been suggested to be an important adaption that provides energy and precursors to facilitate phagocytosis, antigen processing and cytokine production. Other changes to BMDC metabolism are evident following T. gondii infection and include upregulation of arginine degradation concomitant with increased arginase-1 activity and ornithine and proline production. As T. gondii is an arginine auxotroph the resultant reduced cellular arginine levels are likely to curtail parasite multiplication. These results highlight the complex interplay of BMDCs and parasite metabolism within the developing immune response and the consequences for adaptive immunity and pathogen clearance., (Copyright © 2019 Hargrave, Woods, Millington, Chalmers, Westrop and Roberts.)

Pneumonia and acute respiratory distress syndrome are common and important causes of respiratory failure in the intensive care unit with a significant impact on morbidity, mortality and health care utilization despite early antimicrobial therapy and lung protective mechanical ventilation. Both clinical entities are characterized by acute pulmonary inflammation in response to direct or indirect lung injury. Adjunct anti-inflammatory treatment with corticosteroids is increasingly used, although the evidence for benefit is limited. The treatment decisions are based on radiographic, clinical and physiological variables without regards to inflammatory state. Current evidence suggests a role of biomarkers for the assessment of severity, and distinguishing sub-phenotypes (hyper-inflammatory versus hypo-inflammatory) with important prognostic and therapeutic implications. Although many inflammatory biomarkers have been studied the most common and of interest are C-reactive protein, procalcitonin, and pro-inflammatory cytokines including interleukin 6. While extensively studied as prognostic tools (prognostic enrichment), limited data are available for the role of biomarkers in determining appropriate initiation, timing and dosing of adjunct anti-inflammatory treatment (predictive enrichment)., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article.

Background: Studies investigating the association between the Functional Movement Screen (FMS) and sports injury risk have reported mixed results across a range of athlete populations., Objectives: The purpose of this systematic review was to identify whether athlete age, sex, sport type, injury definition and mechanism contribute to the variable findings., Study Design: Systematic review and meta-analysis., Methods: A systematic search was conducted in October 2018 using PubMed, EBSCOhost, Scopus, EmBase and Web of Science databases. Studies were included if they were peer reviewed and published in English language, included athletes from any competition level, performed the FMS at baseline to determine risk groups based on FMS composite score, asymmetry or pain, and prospectively observed injury incidence during training and competition. Study eligibility assessment and data extraction was performed by two reviewers. Random effects meta-analyses were used to determine odds ratio (OR), sensitivity and specificity with 95% confidence intervals. Sub-group analyses were based on athlete age, sex, sport type, injury definition, and injury mechanism., Results: Twenty-nine studies were included in the FMS composite score meta-analysis. There was a smaller effect for junior (OR = 1.03 [0.67-1.59]; p = 0.881) compared to senior athletes (OR = 1.80 [1.17-2.78]; p = 0.008) and for male (OR = 1.79 [1.08-2.96]; p = 0.024) compared to female (OR = 1.92 [0.43-8.56]; p = 0.392) athletes. FMS composite scores were most likely to be associated with increased injury risk in rugby (OR = 5.92 [1.67-20.92]; p = 0.006), and to a lesser extent American football (OR = 4.41 [0.94-20.61]; p = 0.059) and ice hockey (OR = 3.70 [0.89-15.42]; p = 0.072), compared to other sports. Specificity values were higher than sensitivity values for FMS composite score. Eleven studies were included in the FMS asymmetry meta-analysis with insufficient study numbers to generate sport type subgroups. There was a larger effect for senior (OR = 1.78 [1.16-2.73]; p = 0.008) compared to junior athletes (OR = 1.21 [0.75-1.96]; p = 0.432). Sensitivity values were higher than specificity values for FMS asymmetry. For all FMS outcomes, there were minimal differences across injury definitions and mechanisms. Only four studies provided information about FMS pain and injury risk. There was a smaller effect for senior athletes (OR = 1.28 [0.33-4.96]; p = 0.723) compared to junior athletes (OR = 1.71 [1.16-2.50]; p = 0.006). Specificity values were higher than sensitivity values for FMS pain., Conclusion: Athlete age, sex and sport type explained some of the variable findings of FMS prospective injury-risk studies. FMS composite scores and asymmetry were more useful for estimating injury risk in senior compared to junior athletes. Effect sizes tended to be small except for FMS composite scores in rugby, ice hockey and American football athletes., Protocol Registration: CRD42018092916.

Objectives: The study examined if three feasible strategies involving additional in-play cooling periods attenuate the core (rectal) temperature rise during simulated football matches., Design: Four counterbalanced experimental trials in an environmental chamber set to 35 °C ambient temperature, 55% relative humidity, and 30 °C WBGT., Methods: Twelve healthy well-trained football players completed a regular simulated match (REG), regular simulated match with additional 3-min cooling periods at the 30-min mark of each half inclusive of chilled water consumption (COOL water ), regular simulated match with additional 3-min cooling periods at the 30-min mark of each half inclusive of chilled water consumption and the application of an ice towel around the neck (COOL towel ), regular simulated match with an extended (+5 min; total of 20-min) half-time break (HT extended )., Results: The difference in rectal temperature change was significantly lower in the COOL water (-0.25 °C), COOL towel (-0.28 °C), and HT extended (-0.21 °C) trials in comparison to the REG (all p < 0.05). Exercising heart rate and session rating of perceived exertion was lower in the COOL water (-13 bpm; -1.4 au), COOL towel (-10 bpm; -1.3 au), and HT extended (-8 bpm; -0.9 au) trials in comparison to the REG trial (all p < 0.05). The cooling interventions did not significantly change skin temperature or thermal sensation in comparison to the REG (all p > 0.05)., Conclusions: All three cooling interventions attenuated core body thermal strain during simulated matches. The laboratory-based study supports the use of brief in-play cooling periods as a means to attenuate the rise in core temperature during matches in hot and humid conditions., (Copyright © 2019 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Ciliopathies are a group of genetically heterogeneous disorders, characterized by defects in cilia genesis or maintenance. Mutations in the RPGR gene and its interacting partners, RPGRIP1 and RPGRIP1L , cause ciliopathies, but the function of their proteins remains unclear. Here we show that knockdown (KD) of RPGR, RPGRIP1 or RPGRIP1L in hTERT-RPE1 cells results in abnormal actin cytoskeleton organization. The actin cytoskeleton rearrangement is regulated by the small GTPase RhoA via the planar cell polarity (PCP) pathway. RhoA activity was upregulated in the absence of RPGR, RPGRIP1 or RPGRIP1L proteins. In RPGR, RPGRIP1 or RPGRIP1L KD cells, we observed increased levels of DVl2 and DVl3 proteins, the core components of the PCP pathway, due to impaired proteasomal activity. RPGR, RPGRIP1 or RPGRIP1L KD cells treated with thapsigargin (TG), an inhibitor of sarcoendoplasmic reticulum Ca 2+ - ATPases, showed impaired store-operated Ca 2+ entry (SOCE), which is mediated by STIM1 and Orai1 proteins. STIM1 was not localized to the ER-PM junction upon ER store depletion in RPGR, RPGRIP1 or RPGRIP1L KD cells. Our results demonstrate that the RPGR protein complex is required for regulating proteasomal activity and for modulating SOCE, which may contribute to the ciliopathy phenotype., Competing Interests: CONFLICTS OF INTEREST No conflicts of interest were declared.

An indicator of movement quality and potential injury risk during Functional Movement Screen (FMS) testing is the presence of asymmetry when comparing the left and right sides of the body. The aim of the study was to investigate the reproducibility of the injury risk model proposed in our previous research (Chalmers et al. 2017; derivation study) that showed an increased injury risk for elite junior Australian football players demonstrating ≥2 asymmetrical FMS subtests. We used a direct replication design. Players underwent pre-season FMS testing, and an injury surveillance system monitored 277 male participants during the subsequent regular season competition. Designated club officials monitored the weekly competition participation of players. The definition of an injury was "a trauma or medical condition which caused a player to miss a competitive game". Cox proportional hazards regression models were used to investigate the relationship between asymmetry and number of games played before first injury (ie, survival time). The level of reproducibility was determined according to statistical significance, effect size, and subjective assessment. Demonstrating asymmetry during FMS testing was not associated with a significant increase in prospective injury risk in the replication study (P > .05). Moreover, effect sizes (hazard ratios) from the derivation dataset were not within the 95% confidence intervals of the respective asymmetry predictor in the replication dataset. Subjectively, researchers were in agreement that the findings from the derivation data were not successfully reproduced. Clinicians and researchers should be cautious about using FMS asymmetry findings to derive injury risk for junior football players., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The effects of pre cooling on endurance performance are widely known. In contrast, the approach of cooling during endurance exercise in combination with pre-exercise cooling has been poorly understood. The purpose of the present study was to determine whether the effects of precooling and cooling during exercise enhance exercise performance compared to the ingestion of a thermo-neutral beverage (20 °C) or precooling alone in cycling performance. This was an experimental study using a randomised crossover design in which 7 cyclists underwent three trials comprising of 45 min steady state cycling (SS) at 70% VO 2 max and a subsequent 10 km time trial (TT) in hot conditions (32 °C, 50% relative humidity). Rectal temperature (T re ), heat storage (HS), heart rate (HR), blood lactate concentration (BLA) and thermal sensation (TS) were measured. The intervention consisted of: (1) ingestion of thermo-neutral beverage before and during SS cycling (TN), (2) ingestion of ice slurry beverage and application of iced towels (precooling) prior to exercise, and then ingestion of thermo-neutral beverage during SS (PRE) and (3) precooling strategy as above plus ice slurry ingestion during SS cycling (PRE + MID). The intake of thermo-neutral or ice slurry beverage (14 g/kg) occurred over 30 min before and every 15 min during SS cycling. There was no significant difference in TT performance between all the conditions (P =0.72). However, PRE and PRE + MID caused a significant decrease in T re (P < 0.05) from TN during exercise. Accordingly, both precooling and a combination of precooling and mid-cooling during exercise in hot conditions may be a practical and effective way of reducing core temperature. Future studies should investigate longer distance events and timing of ice slurry ingestion., (Copyright © 2018. Published by Elsevier Ltd.)

Previous research on training health professionals to identify and address unhealthy alcohol and drug use in patients through screening, brief intervention, and referral to treatment (SBIRT) has found that training increases knowledge about substance use and increases students' confidence in addressing substance use in patients. To date, however, there is little information on how health professional students integrate SBIRT into individual practice. Within a U.S. SBIRT training consortium, advanced practice registered nurse (APRN) students were required to practice SBIRT in clinical settings and complete assessment logs for each patient screened. Logs documented results from single item alcohol & drug screening questions; AUDIT or DAST responses; brief intervention (BI)/referral to treatment (RT) steps completed and patients' responses. 113 APRN students completed logs on 538 patients (mean age 44; SD 15.0; 53.5% female). Positive single question alcohol screens were more frequent than positive single question drug screens (55.3% vs. 25.5%). More than one third (36%) of the logs included high-risk AUDIT/DAST scores. The most utilized BI components were discussions regarding consequences of use (76%) and safe levels of use (70%), while the most utilized RT steps included referral to a mutual help group (15%) or a specialty treatment program (8%). Positive screening rates found by APRN students were higher than reported rates in most clinical settings. The logs also demonstrated that APRN students employed many of the SBIRT skills they were taught while also helping identify underutilized SBIRT steps, which may be addressed specifically in future SBIRT trainings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The critical role of calcium signalling in processes related to cancer cell proliferation and invasion has seen a focus on pharmacological inhibition of overexpressed ion channels in specific cancer subtypes as a potential therapeutic approach. However, despite the critical role of calcium in cell death pathways, pharmacological activation of overexpressed ion channels has not been extensively evaluated in breast cancer. Here we define the overexpression of transient receptor potential vanilloid 4 (TRPV4) in a subgroup of breast cancers of the basal molecular subtype. We also report that pharmacological activation of TRPV4 with GSK1016790A reduced viability of two basal breast cancer cell lines with pronounced endogenous overexpression of TRPV4, MDA-MB-468 and HCC1569. Pharmacological activation of TRPV4 produced pronounced cell death through two mechanisms: apoptosis and oncosis in MDA-MB-468 cells. Apoptosis was associated with PARP-1 cleavage and oncosis was associated with a rapid decline in intracellular ATP levels, which was a consequence of, rather than the cause of, the intracellular ion increase. TRPV4 activation also resulted in reduced tumour growth in vivo. These studies define a novel therapeutic strategy for breast cancers that overexpress specific calcium permeable plasmalemmal ion channels with available selective pharmacological activators.

Liver failure, whether arising directly from acute liver failure or from decompensated chronic liver disease is an increasing problem worldwide and results in many deaths. In the UK only 10% of individuals requiring a liver transplant receive one. Thus the need for alternative treatments is paramount. A BioArtificial Liver machine could temporarily replace the functions of the liver, buying time for the patient's liver to repair and regenerate. We have designed, implemented and tested a clinical-scale BioArtificial Liver machine containing a biomass derived from a hepatoblastoma cell-line cultured as three dimensional organoids, using a fluidised bed bioreactor, together with single-use bioprocessing equipment, with complete control of nutrient provision with feedback BioXpert recipe processes, and yielding good phenotypic liver functions. The methodology has been designed to meet specifications for GMP production, required for manufacture of advanced therapy medicinal products (ATMPs). In a porcine model of severe liver failure, damage was assured in all animals by surgical ischaemia in pigs with human sized livers (1.2-1.6 kg liver weights). The BioArtificial liver (UCLBAL) improved important prognostic clinical liver-related parameters, eg, a significant improvement in coagulation, reduction in vasopressor requirements, improvement in blood pH and in parameters of intracranial pressure (ICP) and oxygenation.

Objectives: The Functional Movement Screen (FMS) is a popular screening tool, however, the postulated relationship between prospective injury and FMS scoring remains sparsely explored in adolescent athletes. The aim of the study was to examine the association between pre-season FMS scores and injuries sustained during one regular season competition in elite adolescent Australian football players., Design: Prospective cohort study., Methods: 237 elite junior Australian football players completed FMS testing during the late pre-season phase and had their weekly playing status monitored during the regular season. The definition of an injury was 'a trauma which caused a player to miss a competitive match'., Results: The median composite FMS score was 14 (mean=13.5±2.3). An apriori analysis revealed that the presence of ≥1 asymmetrical sub-test was associated with a moderate increase in the risk of injury (hazard ratio=2.2 [1.0-4.8]; relative risk=1.9; p=0.047; sensitivity=78.4%; specificity=41.0%). Notably, post-hoc analysis identified that the presence of ≥2 asymmetrical sub-tests was associated with an even greater increase in risk of prospective injury (hazard ratio=3.7 [1.6-8.6]; relative risk=2.8; p=0.003; sensitivity=66.7%; specificity=78.0%). Achieving a composite score of ≤14 did not substantially increase the risk of prospective injury (hazard ratio=1.1 [0.5-2.1]; p=0.834)., Conclusions: Junior Australian football players demonstrating asymmetrical movement during pre-season FMS testing were more likely to sustain an injury during the regular season than players without asymmetry. Findings suggest that the commonly reported composite FMS threshold score of ≤14 was not associated with injury in elite junior AF players., (Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Heat acclimation over consecutive days has been shown to improve aerobic-based performance. Recently, it has been suggested that heat training can improve performance in a temperate environment. However, due to the multifactorial training demands of athletes, consecutive-day heat training may not be suitable. The current study aimed to investigate the effect of brief (8×30min) intermittent (every 3-4 days) supplemental heat training on the second lactate threshold point (LT 2 ) in temperate and hot conditions. 21 participants undertook eight intermittent-day mixed-intensity treadmill exercise training sessions in hot (30°C; 50% relative humidity [RH]) or temperate (18°C; 30% RH) conditions. A pre- and post-incremental exercise test occurred in temperate (18°C; 30% RH) and hot conditions (30°C; 50% RH) to determine the change in LT 2 . The heat training protocol did not improve LT 2 in temperate (Effect Size [ES]±90 confidence interval=0.10±0.16) or hot (ES=0.26±0.26) conditions. The primary finding was that although the intervention group had a change greater than the SWC, no statistically significant improvements were observed following an intermittent eight day supplemental heat training protocol comparable to a control group training only in temperate conditions. This is likely due to the brief length of each heat training session and/or the long duration between each heat exposure., (Copyright © 2017 Elsevier Ltd. All rights reserved.)