Morphine induces inflammatory responses via both TLR4 and cGAS-STING signaling pathways.

BACKGROUND: Opioid activation of the microglia or macrophage Toll-like receptor 4 (TLR4) and associated inflammatory cytokine release are implicated in opioid-induced hyperalgesia and tolerance. The cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS-STING) signaling pathway, activated by double-stranded DNA including mitochondrial DNA (mtDNA), has emerged as another key mediator of inflammatory responses. This study tested the hypothesis that morphine induces immune inflammatory responses in microglia and macrophages involving TLR4 and cGAS-STING pathway. METHODS: BV2 microglia and Raw 264.7 (Raw) macrophage cells were exposed to morphine with and without a STING inhibitor (C176) for 6 h or TLR 4 inhibitor (TAK242) for 24 h. Western blotting and RT-qPCR analyses assessed TLR4, cGAS, STING, nuclear factor-kappa B (NF-κB), and pro-inflammatory cytokine expression. Morphine-induced mitochondria dysfunction was quantified by reactive oxygen species (ROS) release using MitoSOX, mtDNA release by immunofluorescence, and RT-qPCR. Polarization of BV2 and Raw cells was assessed by inducible nitric oxide (iNOS) and CD86 expression. The role of mtDNA on morphine-related inflammation was investigated by mtDNA depletion of the cells with ethidium bromide (EtBr) or cell transfection of mtDNA extracted from morphine-treated cells. RESULTS: Morphine significantly increased the expression of TLR4, cGAS, STING, p65 NF-κB, and cytokines (IL-6 and TNF-α) in BV2 and Raw cells. Morphine-induced mitochondrial dysfunction by increased ROS and mtDNA release; the increased iNOS and CD86 evidenced inflammatory M1-like phenotype polarization. TLR4 and STING inhibitors reduced morphine-induced cytokine release in both cell types. The transfection of mtDNA activated inflammatory signaling proteins, cytokine release, and polarization. Conversely, mtDNA depletion led to the reversal of these effects. CONCLUSION: Morphine activates the cGAS-STING pathway in macrophage cell types. Inhibition of the STING pathway can be an additional method to overcome immune cell inflammation-related morphine tolerance and opioid-induced hyperalgesia.

Powering Toward Los Angeles: Comparing Power Output and Pacing Approach Between Maximal 2000- and 1500-m On-Water Racing in Elite Rowers.

PURPOSE: To compare power output and pacing between maximal 1500- and 2000-m on-water rowing performances. METHODS: Twenty-six (female n = 4, male n = 22) international rowers, across 6 boat classes, completed maximal 1500- and 2000-m on-water races, separated by 24 to 48 hours. Crew combinations and seat orders remained consistent between races. Peach PowerLine instrumentation measured power output and stroke rate. Differences in completion time, mean power output (MPO), percentage prognostic velocity (PPV; percentage of world record velocity in each boat class), stroke rate, and pacing variance were assessed using linear mixed modeling. RESULTS: Compared with 2000-m, completion times were 90.4 (6.1) seconds shorter over 1500 m (-24.7% [0.7%]). Both MPO (P = .255, ηp2=.06) and PPV (P = .340, ηp2=.18) were not different between distances. Broadly, crews adopted a reverse-J-shaped pacing across both distances, demonstrating a reduced variance over 1500 m (P = .035, ηp2=.62). Percentage change in MPO from 2000 to 1500 m demonstrated a strong negative association with pacing variance over 1500 m (R2 = .74, P = .027). CONCLUSIONS: International rowing crews did not increase MPO or PPV when racing maximally over 1500 m compared to 2000 m. Comparable strategies were adopted over both distances, with less variance in pacing observed over 1500 m. The crews that demonstrated greater increases in MPO over the shorter race employed a flatter pacing strategy. To improve 1500-m on-water performance, rowers may need to adopt a more even pacing approach.

Comparative genomics of Metarhizium brunneum strains V275 and ARSEF 4556: unraveling intraspecies diversity.

Entomopathogenic fungi belonging to the Order Hypocreales are renowned for their ability to infect and kill insect hosts, while their endophytic mode of life and the beneficial rhizosphere effects on plant hosts have only been recently recognized. Understanding the molecular mechanisms underlying their different lifestyles could optimize their potential as both biocontrol and biofertilizer agents, as well as the wider appreciation of niche plasticity in fungal ecology. This study describes the comprehensive whole genome sequencing and analysis of one of the most effective entomopathogenic and endophytic EPF strains, Metarhizium brunneum V275 (commercially known as Lalguard Met52), achieved through Nanopore and Illumina reads. Comparative genomics for exploring intraspecies variability and analyses of key gene sets were conducted with a second effective EPF strain, M. brunneum ARSEF 4556. The search for strain- or species-specific genes was extended to M. brunneum strain ARSEF 3297 and other species of genus Metarhizium, to identify molecular mechanisms and putative key genome adaptations associated with mode of life differences. Genome size differed significantly, with M. brunneum V275 having the largest genome amongst M. brunneum strains sequenced to date. Genome analyses revealed an abundance of plant-degrading enzymes, plant colonization-associated genes, and intriguing intraspecies variations regarding their predicted secondary metabolic compounds and the number and localization of Transposable Elements. The potential significance of the differences found between closely related endophytic and entomopathogenic fungi, regarding plant growth-promoting and entomopathogenic abilities, are discussed, enhancing our understanding of their diverse functionalities and putative applications in agriculture and ecology.

Contribution of Physical Characteristics to Game Performance in Male Wheelchair Basketball Athletes at the Tokyo Paralympic Games.

ABSTRACT: Snyder, L, Goods, PSR, Peeling, P, Balloch, A, Peiffer, JJ, Binnie, MJ, and Scott, BR. Contribution of physical characteristics to game performance in male wheelchair basketball athletes at the Tokyo Paralympic Games. J Strength Cond Res XX(X): 000-000, 2024-This investigation explored the physical characteristics of elite male wheelchair basketball (WCB) athletes and their association with game performance during the Tokyo 2020 Paralympic Games. Sixteen male athletes from the Australian national WCB squad were assessed for anthropometrics, speed, change of direction, aerobic power, and upper-body power during a training camp before the 2020 Paralympic Games. Athletes were grouped according to the International Wheelchair Basketball Federation disability classification system (1.0-4.5) as low- (≤2.5, more severe impairments) or high-point (≥3.0, less severe impairments) athletes. Physical and performance characteristics between groups were compared using independent-samples t-tests, and their relationship to game statistics (points, rebounds, assists, and steals) per minute played was explored through stepwise regression. High-point athletes were 13% taller (p = 0.001), 4-9% faster (p < 0.001-0.017), and demonstrated superior change of direction ability (15%, p < 0.001) compared with low-point athletes. Approximately 74% of the variance in points scored per minute was accounted for by athlete classification, whereas the most important modifiable physical characteristic was speed, which contributed significantly to steals (54% of variance) and assists (96% of variance when arm span and sitting reach height were also considered). Low-point athletes with spinal cord injuries generally have impaired trunk control, which is a likely explanation for performance differences between groups. A range of nonmodifiable (classification, sitting reach height, and arm span) and modifiable (speed) physical characteristics contribute to game performance outcomes and should therefore be considered when identifying, developing, and selecting WCB athletes for elite competition.

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.

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.