Selection, engineering, and in vivo testing of a human leukocyte antigen-independent T-cell receptor recognizing human mesothelin.

BACKGROUND: Canonical α/ß T-cell receptors (TCRs) bind to human leukocyte antigen (HLA) displaying antigenic peptides to elicit T cell-mediated cytotoxicity. TCR-engineered T-cell immunotherapies targeting cancer-specific peptide-HLA complexes (pHLA) are generating exciting clinical responses, but owing to HLA restriction they are only able to target a subset of antigen-positive patients. More recently, evidence has been published indicating that naturally occurring α/ß TCRs can target cell surface proteins other than pHLA, which would address the challenges of HLA restriction. In this proof-of-concept study, we sought to identify and engineer so-called HLA-independent TCRs (HiTs) against the tumor-associated antigen mesothelin. METHODS: Using phage display, we identified a HiT that bound well to mesothelin, which when expressed in primary T cells, caused activation and cytotoxicity. We subsequently engineered this HiT to modulate the T-cell response to varying levels of mesothelin on the cell surface. RESULTS: The isolated HiT shows cytotoxic activity and demonstrates killing of both mesothelin-expressing cell lines and patient-derived xenograft models. Additionally, we demonstrated that HiT-transduced T cells do not require CD4 or CD8 co-receptors and, unlike a TCR fusion construct, are not inhibited by soluble mesothelin. Finally, we showed that HiT-transduced T cells are highly efficacious in vivo, completely eradicating xenografted human solid tumors. CONCLUSION: HiTs can be isolated from fully human TCR-displaying phage libraries against cell surface-expressed antigens. HiTs are able to fully activate primary T cells both in vivo and in vitro. HiTs may enable the efficacy seen with pHLA-targeting TCRs in solid tumors to be translated to cell surface antigens.

Development and laboratory validation of a plant-derived repellent blend, effective against Aedes aegypti [Diptera: Culicidae], Anopheles gambiae [Diptera: Culicidae] and Culex quinquefasciatus [Diptera: Culicidae].

Mosquitoes of the genera Aedes, Anopheles and Culex vector a wide range of pathogens seriously affecting humans and livestock on a global scale. Over-reliance on insecticides and repellents has driven research into alternative, naturally-derived compounds to fulfil the same objectives. Steam distilled extracts of four plants with strong, yet attractive, volatile profiles were initially assessed for repellency in a dual-port olfactometer using Aedes aegypti as the model species. Picea sitchensis was found to be the most repellent, proving comparable to leading products when applied at 100% (p = 1.000). Key components of conifer-derived volatile profiles were then screened via electroantennography before those components eliciting an electrophysiological response were assayed individually in the olfactometer; according to WHO protocol. The most promising 5 were selected for reductive analyses to produce an optimised semiochemical blend. This combination, and a further two variations of the blend, were then progressed to a multi-species analysis using the BG-test whereby bite-attempt frequency on hands was assessed under different repellent treatments; assays were compared between Aedes aegypti, Anopheles gambiae and Culex quinquefasciatus. Efficacy was found against all three species, although it was found that Ae. aegypti was the most susceptible to the repellent, with An. gambiae being the least. Here, a novel, naturally-derived blend is presented with weak spatial repellency, as confirmed in laboratory assays. Further work will be required to assess the full extent of the potential of the products, both in terms of field application and species screening; however, the success of the products developed demonstrate that plant metabolites have great capacity for use in the repellent sector; both to improve upon known compounds and to reduce the usage of toxic products currently on the market.

In the heat of the moment: the effects of extreme temperatures on the cognitive functioning of firefighters.

Exposure to high temperatures can have detrimental effects on cognitive processing and this is concerning for firefighters who routinely work in extreme temperatures. Whilst past research has studied the effects of heat on firefighter cognition, findings are mixed, and no work has measured the time course of cognitive recovery. This study compared working memory, vigilance, and cognitive flexibility of 37 firefighters before and after they engaged in a live-fire training exercise with temperatures exceeding 115 °C. To assess recovery, cognition was measured on exiting the fire, then 20- and 40-minutes post-fire. Results showed impaired vigilance and cognitive flexibility (increased errors, slower responses) immediately after the fire, but recovery at 20-minutes. These findings indicate that a live indoor fire negatively impacts cognitive processing, but this effect is relatively short-lived and return to baseline functioning is seen 20-minutes after exiting the fire. The findings could be used to inform re-entry and cooling decisions.

Acute heat stress may affect cognitive processing, posing a health and safety risk to firefighters. This study demonstrates impaired cognition following a firefighter training exercise in temperatures exceeding 115 °C. Cognition recovered as core body temperature returned to normal, providing evidence for a 20-minute cooling period following exposure to extreme heat.

Identification of the odorant binding proteins of Western Flower Thrips (Frankliniella occidentalis), characterization and binding analysis of FoccOBP3 with molecular modelling, molecular dynamics simulations and a confirmatory field trial.

Olfactory systems are indispensable for insects as they, including Western Flower Thrips (Frankliniella occidentalis), use olfactory cues for ovipositing and feeding. F. occidentalis use odorant binding proteins (OBPs) to transport semiochemicals to odorant receptors to induce a behavioural response from the sensillum lymph of the insect's antennae. This study identifies four OBPs of F. occidentalis and analyses their expression at three stages of growth: larvae, adult males and adult females. Further, it investigates the presence of conserved motifs and their phylogenetic relationship to other insect species. Moreover, FoccOBP3 was in silico characterized to analyse its structure along with molecular docking and molecular dynamics simulations to understand its binding with semiochemicals of F. occidentalis. Molecular docking revealed the interactions of methyl isonicotinate, p-anisaldehyde and (S)-(-)-verbenone with FoccOBP3. Moreover, molecular dynamics simulations showed bonding stability of these ligands with FoccOBP3, and field trials validated that Lurem TR (commercial product) and p-anisaldehyde had greater attraction as compared to (S)-(-)-verbenone, given the compound's binding with FoccOBP3. The current study helps in understanding the tertiary structure and interaction of FoccOBP3 with lures using computational and field data and will help in the identification of novel lures of insects in the future, given the importance of binding with OBPs.Communicated by Ramaswamy H. Sarma.

Shifting the Energy Toward Los Angeles: Comparing the Energetic Contribution and Pacing Approach Between 2000- and 1500-m Maximal Ergometer Rowing.

PURPOSE: To compare the energetic contribution and pacing in 2000- and 1500-m maximal rowing-ergometer performances. METHODS: On separate visits (>48 h apart, random order), 18 trained junior (16.7 [0.4] y) male rowers completed 3 trials: a 7 × 4-minute graded exercise test, a 2000-m time trial (TT2000), and a 1500-m TT (TT1500). Respiratory gases were continuously measured throughout each trial. The submaximal power-to-oxygen-consumption relationship from the graded exercise test was used to determine the accumulated oxygen deficit for each TT. Differences in mean power output (MPO), relative anaerobic contribution, percentage of peak oxygen uptake, pacing index, maximum heart rate, rating of perceived exertion, and blood lactate concentration were assessed using linear mixed modeling. RESULTS: Compared to TT2000 (324 [24] W), MPO was 5.2% (3.3%) higher in TT1500 (341 [29 W]; P < .001, ηp2=.70). There was a 4.9% (3.3%) increase (P < .001, ηp2=.71) in anaerobic contribution from 17.3% (3.3%) (TT2000) to 22.2% (4.3%) (TT1500). Compared to TT1500, maximum heart rate, rating of perceived exertion, and blood lactate concentration were all greater (P < .05) in TT2000. The pacing index was not different between trials. Percentage increase in MPO from TT2000 to TT1500 was negatively associated with pacing variance in TT1500 (R2 = .269, P = .027). CONCLUSIONS: Maximal ergometer performance over 1500 m requires a significantly greater anaerobic contribution compared with 2000 m. Junior male athletes adopt a consistent pacing strategy across both distances. However, those who experienced greater percentage increases in MPO over the shorter test adopted a more even pacing strategy. To prepare for 1500-m performance, greater emphasis should be placed on developing capacity for work in the severe domain and completing race simulations with a more even pacing strategy.

Cemented versus uncemented hemiarthroplasty for displaced intracapsular fractures of the hip.

Aims: The aim of this study was to report the three-year follow-up for a series of 400 patients with a displaced intracapsular fracture of the hip, who were randomized to be treated with either a cemented polished tapered hemiarthroplasty or an uncemented hydroxyapatite-coated hemiarthroplasty. Methods: The mean age of the patients was 85 years (58 to 102) and 273 (68%) were female. Follow-up was undertaken by a nurse who was blinded to the hemiarthroplasty that was used, at intervals for up to three years from surgery. The short-term follow-up of these patients at a mean of one year has previously been reported. Results: A total of 210 patients (52.5%) died within three years of surgery. One patient was lost to follow-up. Recovery of mobility was initially significantly better in those treated with a cemented hemiarthroplasty, although by three years after surgery this difference became statistically insignificant. The mortality was significantly lower in those treated with a cemented hemiarthroplasty (p = 0.029). There was no significant difference in pain scores, or in the incidence of implant-related complications or revision surgery, between the two groups. Conclusion: These results further support the use of a cemented hemiarthroplasty for the routine management of elderly patients with a displaced intracapsular fracture of the hip.

Demarcation of Intensity From 3 to 5 Zones Aids in Understanding Physiological Performance Progression in Highly Trained Under-23 Rowing Athletes.

ABSTRACT: Watts, SP, Binnie, MJ, Goods, PSR, Hewlett, J, Fahey-Gilmour, J, and Peeling, P. Demarcation of intensity from 3 to 5 zones aids in understanding physiological performance progression in highly trained under-23 rowing athletes. J Strength Cond Res 37(11): e593-e600, 2023-The purpose of this investigation was to compare 2 training intensity distribution models (3 and 5 zone) in 15 highly trained rowing athletes ( n = 8 male; n = 7 female; 19.4 ± 1.1 years) to determine the impact on primary (2,000-m single-scull race) and secondary (2,000-m ergometer time trial, peak oxygen consumption [V̇O 2 peak], lactate threshold 2 [LT2 power]) performance variables. Performance was assessed before and after 4 months training, which was monitored through a smart watch (Garmin Ltd, Olathe, KS) and chest-strap heart rate (HR) monitor (Wahoo Fitness, Atlanta, GA). Two training intensity distribution models were quantified and compared: a 3-zone model (Z1: between 50% V̇O 2 peak and lactate threshold 1 (LT1); Z2: between LT1 and 95% LT2; Z3: >95% LT2) and a 5-zone model (T1-T5), where Z1 and Z3 were split into 2 additional zones. There was significant improvement in LT2 power for both male (4.08% ± 1.83, p < 0.01) and female (3.52% ± 3.38, p = 0.02) athletes, with male athletes also demonstrating significant improvement in 2,000-m ergometer time trial (2.3% ± 1.92, p = 0.01). Changes in V̇O 2 peak significantly correlated with high-quality aerobic training (percent time in T2 zone; r = 0.602, p = 0.02), whereas changes in LT2 power significantly correlated with "threshold" training (percent time in T4 zone; r = 0.529, p = 0.04). These correlations were not evident when examining intensity distribution through the 3-zone model. Accordingly, a 5-zone intensity model may aid in understanding the progression of secondary performance metrics in rowing athletes; however, primary (on-water) performance remains complex to quantify.

A long term follow-up for a randomised trial of total hip arthroplasty versus hemiarthroplasty for displaced intracapsular fractures.

104 patients with a displaced intracapsular fracture were randomised to surgical treatment with either a cemented hemiarthroplasty or a cemented total hip arthroplasty. All surviving patients were followed up for five years from injury by a blinded observer. No differences in outcome between groups was seen for the degree of residual pain or regain of function or independence. There was a tendency to more complications and re-operations for those treated with the total hip arthroplasty. We continue to recommend that caution should be exercised regarding the increased promotion of THR for intracapsular hip fractures until further studies with long term follow up are completed.

Evaluation of Metarhizium brunneum- and Metarhizium-Derived VOCs as Dual-Active Biostimulants and Pest Repellents in a Wireworm-Infested Potato Field.

Wireworm, the larval stages of click beetles, are a serious pest of tubers, brassicas and other important commercial crops throughout the northern hemisphere. No effective control agent has been developed specifically for them, and many of the pesticides marketed as having secondary application against them have been withdrawn from EU and Asian markets. Metarhizium brunneum, an effective entomopathogenic fungus, and its derived volatile metabolites are known to be effective plant biostimulants and plant protectants, although field efficacy has yet to be validated. Field validation of a combined M. brunneum and derived VOC treatments was conducted in Wales, UK, to assess the effects of each as a wireworm control agent and biostimulant. Plots were treated with Tri-Soil (Trichoderma atroviridae), M. brunneum, 1-octen-3-ol or 3-octanone, or combinations thereof. Treatments were applied subsurface during potato seeding (n = 52), and potatoes were harvested at the end of the growing season. Each potato was weighed individually and scored for levels of wireworm damage. Applications of both the VOCs and the M. brunneum individually were found to significantly decrease wireworm burden (p < 0.001). Combinations of M. brunneum and 3-octanone were also found to significantly decrease wireworm damage (p < 0.001), while no effect on yield was reported, resulting in an increased saleable mass over controls (p < 0.001). Herein, we present a novel 'stimulate and deter' wireworm control strategy that can be used to significantly enhance saleable potato yields and control wireworm populations, even under high pest pressure densities.

Hold me or stroke me? Individual differences in static and dynamic affective touch.

Low-threshold mechanosensory C-fibres, C-tactile afferents (CTs), respond optimally to sensations associated with a human caress. Additionally, CT-stimulation activates brain regions associated with processing affective states. This evidence has led to the social touch hypothesis, that CTs have a key role in encoding the affective properties of social touch. Thus, to date, the affective touch literature has focussed on gentle stroking touch. However, social touch interactions involve many touch types, including static, higher force touch such as hugging and holding. This study aimed to broaden our understanding of the social touch hypothesis by investigating relative preference for static vs dynamic touch and the influence of force on these preferences. Additionally, as recent literature has highlighted individual differences in CT-touch sensitivity, this study investigated the influence of affective touch experiences and attitudes, autistic traits, depressive symptomology and perceived stress on CT-touch sensitivity. Directly experienced, robotic touch responses were obtained through a lab-based study and vicarious touch responses through an online study where participants rated affective touch videos. Individual differences were determined by self-report questionnaire measures. In general, static touch was preferred over CT-non-optimal stroking touch, however, consistent with previous reports, CT-optimal stroking (velocity 1-10 cm/s) was rated most pleasant. However, static and CT-optimal vicarious touch were rated comparably for dorsal hand touch. For all velocities, 0.4N was preferred over 0.05N and 1.5N robotic touch. Participant dynamic touch quadratic terms were calculated for robotic and vicarious touch as a proxy CT-sensitivity measure. Attitudes to intimate touch significantly predict robotic and vicarious quadratic terms, as well as vicarious static dorsal hand touch ratings. Perceived stress negatively predicted robotic static touch ratings. This study has identified individual difference predictors of CT-touch sensitivity. Additionally, it has highlighted the context dependence of affective touch responses and the need to consider static, as well as dynamic affective touch.

Quantifying on-water performance in rowing: A perspective on current challenges and future directions.

Winning times at benchmark international rowing competitions (Olympic Games and World Championships) are known to vary greatly between venues, based on environmental conditions and the strength of the field. Further variability in boat speed for any given effort is found in the training environment, with less controlled conditions (i.e., water flow, non-buoyed courses), fewer world class competitors, and the implementation of non-race specific effort distances and intensities. This combination of external factors makes it difficult for coaches and practitioners to contextualise the performance underpinning boat speed or race results on any given day. Currently, a variety of approaches are referenced in the literature and used in practice to quantify this underpinning performance time or boat speed, however, no clear consensus exists. The use of relative performance (i.e., time compared to other competitors), accounting for influence of the weather (i.e., wind and water temperature), and the novel application of instrumented boats (with power instrumentation) have been suggested as potential methods to improve our understanding of on-water rowing speeds. Accordingly, this perspective article will discuss some of these approaches from recent literature, whilst also sharing experience from current practice in the elite environment, to further stimulate discussion and help guide future research.

Potential of 3-octanone as a lure and kill agent for control of the Brown garden snail.

The brown garden snail (Cornu aspersum) is a major agricultural pest, causing damage to a wide range of economically important crops. Withdrawal or restricted use of pollutant molluscicides like metaldehyde has prompted a search for more benign control products. This study investigated the response of snails to 3-octanone; a volatile organic compound (VOCs) produced by the insect pathogenic fungus Metarhizium brunneum. Concentrations of 1 - 1000 ppm of 3-octanone were first assessed in laboratory choice assays to determine behavioural response. Repellent activity was found at 1000 ppm whereas attractance was found for the lower concentrations of 1, 10 and 100 ppm. These three concentrations of 3-octanone were carried forward in field evaluations to assess potential for use in "lure and kill" strategies. The highest concentration (100 ppm) was the most attractive to the snails but also the most lethal. Even at the lowest concentration this compound proved toxic effects making 3-octanone an excellent candidate for the development as a snail attractant and molluscicide.

Insulin signaling in skeletal muscle during inflammation and/or immobilisation.

BACKGROUND: The decline in the downstream signal transduction pathway of anabolic hormone, insulin, could play a key role in the muscle atrophy and insulin resistance observed in patients with intensive care unit acquired weakness (ICUAW). This study investigated the impact of immobilisation via surgical knee and ankle fixation and inflammation via Corynebacterium parvum injection, alone and in combination, as risk factors for altering insulin transduction and, therefore, their role in ICUAW. RESULTS: Muscle weight was significantly decreased due to immobilisation [estimated effect size (95% CI) - 0.10 g (- 0.12 to - 0.08); p < 0.001] or inflammation [estimated effect size (95% CI) - 0.11 g (- 0.13 to - 0.09); p < 0.001] with an additive effect of both combined (p = 0.024). pAkt was only detectable after insulin stimulation [estimated effect size (95% CI) 85.1-fold (76.2 to 94.0); p < 0.001] irrespective of the group and phosphorylation was not impaired by the different perturbations. Nevertheless, the phosphorylation of GSK3 observed in the control group after insulin stimulation was decreased in the immobilisation [estimated effect size (95% CI) - 40.2 (- 45.6 to - 34.8)] and inflammation [estimated effect size (95% CI) - 55.0 (- 60.4 to - 49.5)] groups. The expression of phosphorylated GS (pGS) was decreased after insulin stimulation in the control group and significantly increased in the immobilisation [estimated effect size (95% CI) 70.6-fold (58.8 to 82.4)] and inflammation [estimated effect size (95% CI) 96.7 (85.0 to 108.5)] groups. CONCLUSIONS: Both immobilisation and inflammation significantly induce insulin resistance, i.e., impair the insulin signaling pathway downstream of Akt causing insufficient GSK phosphorylation and, therefore, its activation which caused increased glycogen synthase phosphorylation, which could contribute to muscle atrophy of immobilisation and inflammation.

Sprint cycling rate of torque development associates with strength measurement in trained cyclists.

PURPOSE: A cyclist's rate of force/torque development (RFD/RTD) and peak force/torque can be measured during single-joint or whole-body isometric tests, or during cycling. However, there is limited understanding of the relationship between these measures, and of the mechanisms that contribute to each measure. Therefore, we examined the: (i) relationship between quadriceps central and peripheral neuromuscular function with RFD/RTD in isometric knee extension, isometric mid-thigh pull (IMTP), and sprint cycling; and (ii) relationship among RFD/RTD and peak force/torque between protocols. METHODS: Eighteen trained cyclists completed two familiarisation and two experimental sessions. Each session involved an isometric knee extension, IMTP, and sprint cycling protocol, where peak force/torque, average and peak RFD/RTD, and early (0-100 ms) and late (0-200 ms) RFD/RTD were measured. Additionally, measures of quadriceps central and peripheral neuromuscular function were assessed during the knee extension. RESULTS: Strong relationships were observed between quadriceps early EMG activity (EMG50/M) and knee extension RTD (r or ρ = 0.51-0.65) and IMTP late RFD (r = 0.51), and between cycling early or late RTD and peak twitch torque (r or ρ = 0.70-0.75). Strong-to-very strong relationships were observed between knee extension, IMTP, and sprint cycling for peak force/torque, early and late RFD/RTD, and peak RFD/RTD (r or ρ = 0.59-0.80). CONCLUSION: In trained cyclists, knee extension RTD or IMTP late RFD are related to measures of quadriceps central neuromuscular function, while cycling RTD is related to measures of quadriceps peripheral neuromuscular function. Further, the strong associations among force/torque measures between tasks indicate a level of transferability across tasks.

Repeated-sprint training in heat and hypoxia: Acute responses to manipulating exercise-to-rest ratio.

The aim of this study was to investigate acute performance and physiological responses to the manipulation of exercise-to-rest ratio (E:R) during repeated-sprint hypoxic training (RSH) in hot conditions. Twelve male team-sport players completed two experimental sessions at a simulated altitude of ∼3000 m (FIO2 0.144), air temperature of 40°C and relative humidity of 50%. Exercise involved either 3 × 5 × 10-s (E:R1:2) or 3 × 10 × 5-s (E:R1:4) maximal cycling sprints interspersed with active recoveries at 120W (20-s between sprints, 2.5 and 5-min between sets for E:R1:2 and E:R1:4 respectively). Sessions were matched for overall sprint and total session duration (47.5-min). Peak and mean power output, and total work were greater in E:R1:4 than E:R1:2 (p < 0.05). Peak core temperature was significantly higher in E:R1:4 than E:R1:2 (38.44 ± 0.33 vs. 38.20 ± 0.35°C, p = 0.028). Muscle deoxygenation magnitude during sprints was greater in E:R1:2 (28.2 ± 1.6 vs. 22.4 ± 4.6%, p < 0.001), while muscle reoxygenation did not differ between conditions (p > 0.05). These results indicate E:R1:4 increased mechanical power output and core temperature compared to E:R1:2. Both protocols had different effects on measures of muscle oxygenation, with E:R1:2 generating greater muscle oxygen extraction and E:R1:4 producing more muscle oxygenation flux, which are both important signals for peripheral adaptation. We conclude that the E:R manipulation during RSH in the heat might be used to target different physiological and performance outcomes, with these findings forming a strong base for future mechanistic investigation.Highlights During a typical repeated-sprint training session conducted in hot and hypoxic conditions, an exercise-to-rest ratio of 1:4 during sprint efforts displayed an increased mechanical power output compared to an exercise-to-rest ratio of 1:2. This represents a potentially useful increase in training stimulus.An exercise-to-rest ratio of 1:2 generated greater muscle oxygen extraction, while an exercise-to-rest ratio of 1:4 resulted in more muscle oxygenation flux and a higher core temperature, indicating key markers of environment-related physiological strain were varied between conditions.Exercise-to-rest ratio manipulation may be used to target different physiological and performance outcomes when prescribing repeated-sprint training in hot and hypoxic conditions.

Assessing the rate of torque development in sprint cycling: a methodological study.

The present study examined (i) the magnitude of the rate of torque development (RTD) and (ii) the between-day reliability of RTD at the start of a cycling sprint when sprint resistance, sprint duration, and the pedal downstroke were altered. Nineteen well-trained cyclists completed one familiarisation and three testing sessions. Each session involved one set of 1-s sprints and one set of 5-s sprints. Each set contained one moderate (0.3 N m kg-1), one heavy (0.6 N m kg-1), and one very heavy (1.0 N m kg-1) resistance sprint. RTD measures (average and peak RTD, RTD 0-100 ms, and RTD 0-200 ms) were calculated for downstroke 1 in the 1-s sprint. For the 5-s sprints, RTD measures were calculated for each of the first three downstrokes, as an average of downstrokes 1 and 2, and as an average of downstrokes 2 and 3. Whilst RTDs were greatest in downstroke 3 at all resistances, the greatest number of reliable RTD measures were obtained using the average of downstrokes 2 and 3 with heavy or very heavy resistances, where average and peak RTD, and RTD 0-200 ms were deemed reliable (ICC ≥ 0.8, CV ≤ 10%). Since only 1-2 downstrokes can be completed within 1 s, the greatest RTD reliability cannot be achieved using a 1-s sprint; therefore, the average of downstrokes 2 and 3 during a >2-s cycling sprint (e.g. 5-s test) with heavy or very heavy resistance is recommended for the assessment of RTD in sprint cyclists.HighlightsWhilst RTD measures were greatest in pedal downstroke 3 at all resistances, the greatest number of reliable RTD measures were obtained using the average of pedal downstrokes 2 and 3 with heavy or very heavy resistances, with average and peak RTD, and RTD 0-200 ms having acceptable reliability.RTD 0-100 ms and all RTD measurements for downstroke 1 were not reliable and should not be used. As only 1-2 downstrokes can be performed in 1 s, the greatest RTD reliability cannot be achieved using a 1-s sprint. Instead, RTD may be evaluated using a 5-s sprint.

Increased air temperature during repeated-sprint training in hypoxia amplifies changes in muscle oxygenation without decreasing cycling performance.

The present study aims to investigate the acute performance and physiological responses, with specific reference to muscle oxygenation, to ambient air temperature manipulation during repeated-sprint training in hypoxia (RSH). Thirteen male team-sport players completed one familiarisation and three experimental sessions at a simulated altitude of ∼3000 m (FIO2 0.144). Air temperatures utilised across the three experimental sessions were: 20°C, 35°C and 40°C (all 50% relative humidity). Participants performed 3 × 5 × 10-s maximal cycle sprints, with 20-s passive recovery between sprints, and 5 min active recovery between sets. There were no differences between conditions for cycling peak power, mean power, and total work (p>0.05). Peak core temperature (Tc) was not different between conditions (38.11 ± 0.36°C). Vastus lateralis muscle deoxygenation during exercise and reoxygenation during recovery was of greater magnitude in 35°C and 40°C than 20°C (p<0.001 for all). There was no condition × time interaction for Tc, skin temperature, pulse oxygen saturation, heart rate, rating of perceived exertion and thermal sensation (P>0.05). Exercise-induced increases in blood lactate concentration were higher in 35°C and 40°C than 20°C (p=0.010 and p=0.001, respectively). Integrating ambient temperatures up to 40°C into a typical RSH session had no detrimental effect on performance. Additionally, the augmented muscle oxygenation changes experienced during exercise and recovery in temperatures ≥35°C may indicate that the potency of RSH training is increased with additional heat. However, alterations to the training session may be required to generate a sufficient rise in Tc for heat training purposes.Highlights Heat exposure (35-40°C) did not affect mechanical performance during a typical RSH session. This indicates hot ambient temperature can be implemented during RSH, without negative consequence to training output.Hotter ambient conditions (35-40°C) likely result in greater muscle oxygenation changes during both exercise and recovery compared to temperate conditions.Although hotter sessions were perceived as more difficult and more thermally challenging, they did not further elevate Tc beyond that of temperate conditions. Accordingly, if intended to be used for heat acclimation purposes, alterations to the session may be required to increase heat load.

Rowing in Los Angeles: Performance Considerations for the Change to 1500 m at the 2028 Olympic Games.

BACKGROUND: World Rowing's decision to support the proposed change from a 2000-m to a 1500-m regatta course at the 2028 Olympic Games in Los Angeles is anticipated to have important implications for athlete preparation and race execution during the 2024-2028 quadrennium. PURPOSE: This commentary aims to provide insight into the expected implications of the reduction in course length heading into the 2028 Games, focusing on the training and monitoring of high-performance rowers, as well as tactical, technical, and pacing considerations for performance. The reduction in event duration (estimated to be ∼90-120 s across all event classes) will lead to an expected ∼5% to 15% increase in relative contribution of anaerobic metabolism. Consequently, adjustment in training periodization priorities toward higher-intensity interventions may be required, especially in the period immediately prior to the games. The critical-power and anaerobic-power-reserve concepts may become more useful tools for structuring exercise programs, evaluating training outcomes, and determining event suitability through individual physiological profiling. Additionally, the adoption of a more constant (flat) pacing strategy, rather than the commonly used reverse J-shaped approach, might be considered for racing over this new distance. Finally, technical aspects, such as stroke rate and gearing, may require adjustment for optimal performance; however, research is clearly required to explore such effects. CONCLUSIONS: Our intention is to stimulate discussion and debate, with the provision of practical recommendations that aim to optimize rowers' preparation for and performance at the 2028 Olympic Games.

Mortality following hip fracture: Trends and geographical variations over the last SIXTY years.

INTRODUCTION: The management of hip fractures has advanced on all aspects from prevention pre-operatively, specialised hip fracture units, early operative intervention and rehabilitation. This is in line with the appropriate recognition over the past years of an important presentation with significant mortality and socioeconomic consequences of ever increasing incidence in an aging population. It is therefore imperative to continue to gather data on the incidence and trends of hip fractures to guide future management planning of this important presentation. METHODS: A review of all articles published on the outcome after hip fracture over a twenty year period (1999-2018) was undertaken to determine any changes that had occurred in the demographics and mortality over this period. This article complements and expands upon the findings of a previous article by the authors assessing a four decade period (1959 - 1998) and attempts to present trends and geographical variations over sixty years. RESULTS: The mean age of patients sustaining hip fractures continues to be steadily increasing at approximately just over 1 year of age for every 5-year time period. The mean age of patients sustaining hip fractures increased from 73 years (1960s) to 81 years (2000s) to 82 years (2010s). Over the six decade period one-year mortality has reduced from an overall mean of 27% (1960s) to 20% (2010s). The proportion of female hip fractures has decreased from 84% (1960s) to 70% (2010s). There is a decreasing trend in the proportion of intracapsular fractures from 54% (1970s) to 49% (2000s) and 48% (2010s). CONCLUSION: Our study indicates that significant progress has been made with preventative planning, medical management, specialised orthogeriatric units and surgical urgency all playing a role in the improvements in mean age of hip fracture incidence and reduction in mortality rates. While geographical variations do still exist there has been an increase in the study of hip fractures globally with results now being published from more widespread institutions indicating appropriate increased attention and commitment to an ever-increasing presentation.

Molecular mechanisms of muscular and non-muscular actions of neuromuscular blocking agents in critical illness: a narrative review.

Despite frequent use of neuromuscular blocking agents in critical illness, changes in neuromuscular transmission with critical illness are not well appreciated. Recent studies have provided greater insights into the molecular mechanisms for beneficial muscular effects and non-muscular anti-inflammatory properties of neuromuscular blocking agents. This narrative review summarises the normal structure and function of the neuromuscular junction and its transformation to a 'denervation-like' state in critical illness, the underlying cause of aberrant neuromuscular blocking agent pharmacology. We also address the important favourable and adverse consequences and molecular bases for these consequences during neuromuscular blocking agent use in critical illness. This review, therefore, provides an enhanced understanding of clinical therapeutic effects and novel pathways for the salutary and aberrant effects of neuromuscular blocking agents when used during acquired pathologic states of critical illness.