Performance Benefits of Pre- and Per-cooling on Self-paced Versus Constant Workload Exercise:A Systematic Review and Meta-analysis

BACKGROUND AND OBJECTIVE: Exercise in hot environments impairs endurance performance. Cooling interventions can attenuate the impact of heat stress on performance, but the influence of an exercise protocol on the magnitude of performance benefit remains unknown. This meta-analytical review compared the effects of pre- and per-cooling interventions on performance during self-paced and constant workload exercise in the heat.METHODS: The study protocol was preregistered at the Open Science Framework ( https://osf.io/wqjb3 ). A systematic literature search was performed in PubMed, Web of Science, and MEDLINE from inception to 9 June, 2023. We included studies that examined the effects of pre- or per-cooling on exercise performance in male individuals under heat stress (&gt; 30 °C) during self-paced or constant workload exercise in cross-over design studies. Risk of bias was assessed using the Cochrane Risk of Bias Tool for randomized trials.RESULTS: Fifty-nine studies (n = 563 athletes) were identified from 3300 records, of which 40 (n = 370 athletes) used a self-paced protocol and 19 (n = 193 athletes) used a constant workload protocol. Eighteen studies compared multiple cooling interventions and were included more than once (total n = 86 experiments and n = 832 paired measurements). Sixty-seven experiments used a pre-cooling intervention and 19 used a per-cooling intervention. Average ambient conditions were 34.0 °C [32.3-35.0 °C] and 50.0% [40.0-55.3%] relative humidity. Cooling interventions attenuated the performance decline in hot conditions and were more effective during a constant workload (effect size [ES] = 0.62, 95% confidence interval [CI] 0.44-0.81) compared with self-paced exercise (ES = 0.30, 95% CI 0.18-0.42, p = 0.004). A difference in performance outcomes between protocols was only observed with pre-cooling (ES = 0.74, 95% CI 0.50-0.98 vs ES = 0.29, 95% CI 0.17-0.42, p = 0.001), but not per-cooling (ES = 0.45, 95% CI 0.16-0.74 vs ES = 0.35, 95% CI 0.01-0.70, p = 0.68).CONCLUSIONS: Cooling interventions attenuated the decline in performance during exercise in the heat, but the magnitude of the effect is dependent on exercise protocol (self-paced vs constant workload) and cooling type (pre- vs per-cooling). Pre-cooling appears to be more effective in attenuating the decline in exercise performance during a constant workload compared with self-paced exercise protocols, whereas no differences were found in the effectiveness of per-cooling.</p

Quality assurance of radiotherapy in the ongoing EORTC 22042–26042 trial for atypical and malignant meningioma: Results from the dummy runs and prospective individual case Reviews

BACKGROUND: The ongoing EORTC 22042–26042 trial evaluates the efficacy of high-dose radiotherapy (RT) in atypical/malignant meningioma. The results of the Dummy Run (DR) and prospective Individual Case Review (ICR) were analyzed in this Quality Assurance (QA) study. MATERIAL/METHODS: Institutions were requested to submit a protocol compliant treatment plan for the DR and ICR, respectively. DR-plans (n=12) and ICR-plans (n=50) were uploaded to the Image-Guided Therapy QA Center of Advanced Technology Consortium server (http://atc.wustl.edu/) and were assessed prospectively. RESULTS: Major deviations were observed in 25% (n=3) of DR-plans while no minor deviations were observed. Major and minor deviations were observed in 22% (n=11) and 10% (n=5) of the ICR-plans, respectively. Eighteen% of ICRs could not be analyzed prospectively, as a result of corrupted or late data submission. CTV to PTV margins were respected in all cases. Deviations were negatively associated with the number of submitted cases per institution (p=0.0013), with a cutoff of 5 patients per institutions. No association (p=0.12) was observed between DR and ICR results, suggesting that DR’s results did not predict for an improved QA process in accrued brain tumor patients. CONCLUSIONS: A substantial number of protocol deviations were observed in this prospective QA study. The number of cases accrued per institution was a significant determinant for protocol deviation. These data suggest that successful DR is not a guarantee for protocol compliance for accrued patients. Prospective ICRs should be performed to prevent protocol deviations

Carotid stiffness in young adults: a life-course analysis of its early determinants The Amsterdam Growth and Health Longitudinal Study

Cardiovascular risk factors affecting arterial stiffness in adulthood may develop at different critical periods earlier in life. We examined whether the trajectories, from adolescence to young adulthood, of blood pressure, body fatness and fat distribution, blood lipids, cardiorespiratory fitness, and heart rate determined levels of arterial stiffness in young adults. We investigated 373 apparently healthy adults in whom cardiovascular risk factors were repeatedly examined between the ages of 13 and 36 years and carotid stiffness estimates were obtained at the age of 36 years. Differences in the mean levels and the trajectories of risk factors throughout the 24-year longitudinal period between subjects with different levels of carotid stiffness at age 36 years were analyzed with generalized estimating equations. Compared with individuals with less stiff carotid arteries, those with stiffer carotid arteries at the age of 36 years were characterized from ages 13 to 36 years by greater levels of and steeper increases in blood pressure and central fatness, independently of each other and other risk factors. These increases were already present in adolescence, preceded the development of poorer levels of blood lipids, cardiorespiratory fitness, and heart rate, which were evident during adulthood only, and explained to a great extent the deleterious association between these risk factors and carotid stiffness at the age of 36 years. Multiple and intertwined mechanisms involved in the pathogenesis of arterial stiffness have their origins in early life. Blood pressure and central fatness have a pivotal role herein and should be specifically targeted to prevent arterial stiffening and its cardiovascular sequelae

Training for the HandbikeBattle:an explorative analysis of training load and handcycling physical capacity in recreationally active wheelchair users

Purpose: (1) to analyze training characteristics of recreationally active wheelchair users during handcycle training, and (2) to examine the associations between training load and change in physical capacity. Methods: Former rehabilitation patients (N = 60) with health conditions such as spinal cord injury or amputation were included. Participants trained for five months. A handcycling/arm crank graded exercise test was performed before and after the training period. Outcomes: peak power output per kg (POpeak/kg) and peak oxygen uptake per kg (VO 2peak/kg). Training load was defined as Training Impulse (TRIMP), which is rating of perceived exertion (sRPE) multiplied by duration of the session, in arbitrary units (AU). Training intensity distribution (TID) was also determined (time in zone 1, RPE ≤4; zone 2, RPE 5–6; zone 3, RPE ≥7). Results: Multilevel regression analyses showed that TRIMP sRPE was not significantly associated with change in physical capacity. Time in zone 2 (RPE 5–6) was significantly associated with ΔVO 2peak, %ΔVO 2peak, ΔVO 2peak/kg and %ΔVO 2peak/kg. Conclusion: Training at RPE 5–6 was the only determinant that was significantly associated with improvement in physical capacity. Additional controlled studies are necessary to demonstrate causality and gather more information about its usefulness, and optimal handcycle training regimes for recreationally active wheelchair users.IMPLICATIONS FOR REHABILITATION Monitoring of handcycle training load is important to structure the training effort and intensity over time and to eventually optimize performance capacity. This is especially important for relatively untrained wheelchair users, who have a low physical capacity and a high risk of overuse injuries and shoulder pain. Training load can be easily calculated by multiplying the intensity of the training (RPE 0–10) with the duration of the training in minutes. Results on handcycle training at RPE 5–6 intensity in recreationally active wheelchair users suggests to be promising and should be further investigated with controlled studies

RNA Sequencing Reveals Differential Expression of Mitochondrial and Oxidation Reduction Genes in the Long-Lived Naked Mole-Rat When Compared to Mice

The naked mole-rat (Heterocephalus glaber) is a long-lived, cancer resistant rodent and there is a great interest in identifying the adaptations responsible for these and other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between naked mole-rats and wild-derived mice. Our results indicate that genes associated with oxidoreduction and mitochondria were expressed at higher relative levels in naked mole-rats. The largest effect is nearly 300-fold higher expression of epithelial cell adhesion molecule (Epcam), a tumour-associated protein. Also of interest are the protease inhibitor, alpha2-macroglobulin (A2m), and the mitochondrial complex II subunit Sdhc, both ageing-related genes found strongly over-expressed in the naked mole-rat. These results hint at possible candidates for specifying species differences in ageing and cancer, and in particular suggest complex alterations in mitochondrial and oxidation reduction pathways in the naked mole-rat. Our differential gene expression analysis obviated the need for a reference naked mole-rat genome by employing a combination of Illumina/Solexa and 454 platforms for transcriptome sequencing and assembling transcriptome contigs of the non-sequenced species. Overall, our work provides new research foci and methods for studying the naked mole-rat's fascinating characteristics

Le Web du Goupil.

National audienc

Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III

Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes

99mTc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy

PURPOSE: The purpose of this study was to determine the value of (99m)Tc Hynic-rh-Annexin-V-Scintigraphy (TAVS), a non-invasive in vivo technique to demonstrate apoptosis in patients with head and neck squamous cell carcinoma. METHODS: TAVS were performed before and within 48 h after the first course of cisplatin-based chemoradiation. Radiation dose given to the tumour at the time of post-treatment TAVS was 6-8 Gy. Single-photon emission tomography data were co-registered to planning CT scan. Complete sets of these data were available for 13 patients. The radiation dose at post-treatment TAVS was calculated for several regions of interest (ROI): primary tumour, involved lymph nodes and salivary glands. Annexin uptake was determined in each ROI, and the difference between post-treatment and baseline TAVS represented the absolute Annexin uptake: Delta uptake (DeltaU). RESULTS: In 24 of 26 parotid glands, treatment-induced Annexin uptake was observed. Mean DeltaU was significantly correlated with the mean radiation dose given to the parotid glands (r = 0.59, p = 0.002): Glands that received higher doses showed more Annexin uptake. DeltaU in primary tumour and pathological lymph nodes showed large inter-patient differences. A high correlation was observed on an inter-patient level (r = 0.71, p = 0.006) between the maximum DeltaU in primary tumour and in the lymph nodes. CONCLUSIONS: Within the dose range of 0-8 Gy, Annexin-V-scintigraphy showed a radiation-dose-dependent uptake in parotid glands, indicative of early apoptosis during treatment. The inter-individual spread in Annexin uptake in primary tumours could not be related to differences in dose or tumour volume, but the Annexin uptake in tumour and lymph nodes were closely correlated. This effect might represent a tumour-specific apoptotic respons