Repeated sprint training in hypoxia induces specific skeletal muscle adaptations through S100A protein signaling.

Athletes increasingly engage in repeated sprint training consisting in repeated short all-out efforts interspersed by short recoveries. When performed in hypoxia (RSH), it may lead to greater training effects than in normoxia (RSN); however, the underlying molecular mechanisms remain unclear. This study aimed at elucidating the effects of RSH on skeletal muscle metabolic adaptations as compared to RSN. Sixteen healthy young men performed nine repeated sprint training sessions in either normoxia (FIO2 = 0.209, RSN, n = 7) or normobaric hypoxia (FIO2 = 0.136, RSH, n = 9). Before and after the training period, exercise performance was assessed by using repeated sprint ability (RSA) and Wingate tests. Vastus lateralis muscle biopsies were performed to investigate muscle metabolic adaptations using proteomics combined with western blot analysis. Similar improvements were observed in RSA and Wingate tests in both RSN and RSH groups. At the muscle level, RSN and RSH reduced oxidative phosphorylation protein content but triggered an increase in mitochondrial biogenesis proteins. Proteomics showed an increase in several S100A family proteins in the RSH group, among which S100A13 most strongly. We confirmed a significant increase in S100A13 protein by western blot in RSH, which was associated with increased Akt phosphorylation and its downstream targets regulating protein synthesis. Altogether our data indicate that RSH may activate an S100A/Akt pathway to trigger specific adaptations as compared to RSN.

The impact of regional disparities on the availability of meningococcal vaccines in the US.

BACKGROUND: In the United States (US), three types of vaccines are available to prevent invasive meningococcal disease (IMD), a severe and potentially fatal infection: quadrivalent conjugate vaccines against serogroups A, C, W, Y (MenACWY), and monovalent vaccines against serogroup B (MenB) as well as a newly licensed pentavalent vaccine (MenABCWY) protecting against serogroup A, B, C, W, and Y. The CDC's Advisory Committee on Immunization Practices (ACIP) routinely recommends MenACWY vaccine for all 11- to 12-year-olds with a booster dose at 16 years. MenB vaccination is recommended based on shared clinical decision-making (SCDM) for 16- to 23-year-olds. Recently, the pentavalent meningococcal vaccine (MenABCWY) was recommended by the ACIP. Meningococcal vaccine uptake is suboptimal across the country, particularly among individuals with lower socioeconomic status (SES), despite these recommendations. The objective of the spatial analyses was to assess the relationship between stocking of MenACWY and MenB vaccines, area-level SES, and state-level policies. METHODS: The number of MenACWY and MenB doses stocked by vaccinators was obtained from IQVIA and the CDC's Vaccine for Children (VFC) program and compiled into a county-level dataset from 2016 to 2019. SES, as measured using the CDC's Social Vulnerability Index (SVI), state-level school recommendations, and universal purchasing programs were among the main county-level covariates included to control for factors likely influencing stocking. Data were stratified by public and private market. Bayesian spatial regression models were developed to quantify the variations in rates of stocking and the relative rates of stocking of both vaccines. RESULTS: After accounting for county-level characteristics, lower SES counties tended to have fewer doses of MenB relative to MenACWY on both public and private markets. Lower SES counties tended to have more supply of public vs. private doses. Universal purchasing programs had a strong effect on the markets for both vaccines shifting nearly all doses to the public market. School vaccination strategy was key for improving stocking rates. CONCLUSIONS: Overall, the results show that MenACWY has greater stock relative to MenB across the US. This difference is exacerbated in vulnerable areas without school entry requirements for vaccination and results in inequity of vaccine availability. Beyond state-level policy and SES differences, SCDM recommendations may be a contributing factor, although this was not directly assessed by our model.

Validation of Claims-Based Algorithm for Lyme Disease, Massachusetts, USA.

Compared with notifiable disease surveillance, claims-based algorithms estimate higher Lyme disease incidence, but their accuracy is unknown. We applied a previously developed Lyme disease algorithm (diagnosis code plus antimicrobial drug prescription dispensing within 30 days) to an administrative claims database in Massachusetts, USA, to identify a Lyme disease cohort during July 2000-June 2019. Clinicians reviewed and adjudicated medical charts from a cohort subset by using national surveillance case definitions. We calculated positive predictive values (PPVs). We identified 12,229 Lyme disease episodes in the claims database and reviewed and adjudicated 128 medical charts. The algorithm's PPV for confirmed, probable, or suspected cases was 93.8% (95% CI 88.1%-97.3%); the PPV was 66.4% (95% CI 57.5%-74.5%) for confirmed and probable cases only. In a high incidence setting, a claims-based algorithm identified cases with a high PPV, suggesting it can be used to assess Lyme disease burden and supplement traditional surveillance data.

Hepatitis C coinfection and extrahepatic cancer incidence among people living with HIV.

OBJECTIVES: We assessed the incidence of extrahepatic cancer among people with HIV/HCV coinfection and the potential impact of direct-acting antivirals (DAAs) on extrahepatic cancer risk among people with HIV/HCV coinfection. DESIGN: Our study cohort included adults who initiated HIV care at a CNICS site in the US during 1995-2017, excluding those with previous cancer and without HCV testing. METHODS: We used Cox regression to estimate hazard ratios for extrahepatic cancer incidence among patients with HIV/HCV coinfection compared with those with HIV monoinfection. Standardized morbidity ratio (SMR) weights were used to create a 'pseudopopulation' in which all patients were treated with antiretroviral therapy (ART), and to compare extrahepatic cancer incidence among patients with untreated HIV/HCV coinfection with the incidence that would have been observed if they had been successfully treated for HCV. RESULTS: Of 18 422 adults, 1775 (10%) had HCV RNA and 10 899 (59%) were on ART at baseline. Incidence rates of any extrahepatic cancer among patients with HIV/HCV coinfection and HIV monoinfection were 1027 and 771 per 100 000 person-years, respectively. In SMR-weighted analyses, the risk of any extrahepatic cancer among patients with untreated HCV coinfection at baseline was similar to the risk if they had been successfully treated for HCV. Patients with untreated HCV coinfection at baseline had higher incidence of kidney, lung and inflammation-related cancers than if their HCV had been successfully treated, but these associations were not statistically significant. CONCLUSIONS: We did not find evidence that treating HCV coinfection with DAAs would reduce the incidence of extrahepatic cancers among people with HIV receiving ART.

Can Machine Learning Help Identify Patients at Risk for Recurrent Sexually Transmitted Infections?

BACKGROUND: A substantial fraction of sexually transmitted infections (STIs) occur in patients who have previously been treated for an STI. We assessed whether routine electronic health record (EHR) data can predict which patients presenting with an incident STI are at greatest risk for additional STIs in the next 1 to 2 years. METHODS: We used structured EHR data on patients 15 years or older who acquired an incident STI diagnosis in 2008 to 2015 in eastern Massachusetts. We applied machine learning algorithms to model risk of acquiring ≥1 or ≥2 additional STIs diagnoses within 365 or 730 days after the initial diagnosis using more than 180 different EHR variables. We performed sensitivity analysis incorporating state health department surveillance data to assess whether improving the accuracy of identifying STI cases improved algorithm performance. RESULTS: We identified 8723 incident episodes of laboratory-confirmed gonorrhea, chlamydia, or syphilis. Bayesian Additive Regression Trees, the best-performing algorithm of any single method, had a cross-validated area under the receiver operating curve of 0.75. Receiver operating curves for this algorithm showed a poor balance between sensitivity and positive predictive value (PPV). A predictive probability threshold with a sensitivity of 91.5% had a corresponding PPV of 3.9%. A higher threshold with a PPV of 29.5% had a sensitivity of 11.7%. Attempting to improve the classification of patients with and without repeat STIs diagnoses by incorporating health department surveillance data had minimal impact on cross-validated area under the receiver operating curve. CONCLUSIONS: Machine algorithms using structured EHR data did not differentiate well between patients with and without repeat STIs diagnosis. Alternative strategies, able to account for sociobehavioral characteristics, could be explored.

Relationship between cardiorespiratory phase coherence during hypoxia and genetic polymorphism in humans.

KEY POINTS: High altitude-induced hypoxia in humans evokes a pattern of breathing known as periodic breathing (PB), in which the regular oscillations corresponding to rhythmic expiration and inspiration are modulated by slow periodic oscillations. The phase coherence between instantaneous heart rate and respiration is shown to increase significantly at the frequency of periodic breathing during acute and sustained normobaric and hypobaric hypoxia. It is also shown that polymorphism in specific genes, NOTCH4 and CAT, is significantly correlated with this coherence, and thus with the incidence of PB. Differences in phase shifts between blood flow signals and respiratory and PB oscillations clearly demonstrate contrasting origins of the mechanisms underlying normal respiration and PB. These novel findings provide a better understanding of both the genetic and the physiological mechanisms responsible for respiratory control during hypoxia at altitude, by linking genetic factors with cardiovascular dynamics, as evaluated by phase coherence. ABSTRACT: Periodic breathing (PB) occurs in most humans at high altitudes and is characterised by low-frequency periodic alternation between hyperventilation and apnoea. In hypoxia-induced PB the dynamics and coherence between heart rate and respiration and their relationship to underlying genetic factors is still poorly understood. The aim of this study was to investigate, through novel usage of time-frequency analysis methods, the dynamics of hypoxia-induced PB in healthy individuals genotyped for a selection of antioxidative and neurodevelopmental genes. Breathing, ECG and microvascular blood flow were simultaneously monitored for 30 min in 22 healthy males. The same measurements were repeated under normoxic and hypoxic (normobaric (NH) and hypobaric (HH)) conditions, at real and simulated altitudes of up to 3800 m. Wavelet phase coherence and phase difference around the frequency of breathing (approximately 0.3 Hz) and around the frequency of PB (approximately 0.06 Hz) were evaluated. Subjects were genotyped for common functional polymorphisms in antioxidative and neurodevelopmental genes. During hypoxia, PB resulted in increased cardiorespiratory coherence at the PB frequency. This coherence was significantly higher in subjects with NOTCH4 polymorphism, and significantly lower in those with CAT polymorphism (HH only). Study of the phase shifts clearly indicates that the physiological mechanism of PB is different from that of the normal respiratory cycle. The results illustrate the power of time-evolving oscillatory analysis content in obtaining important insight into high altitude physiology. In particular, it provides further evidence for a genetic predisposition to PB and may partly explain the heterogeneity in the hypoxic response.

More Screening or More Disease? Gonorrhea Testing and Positivity Patterns Among Men in 3 Large Clinical Practices in Massachusetts, 2010-2017.

BACKGROUND: Gonorrhea diagnosis rates in the United States increased by 75% during 2009-2017, predominantly in men. It is unclear whether the increase among men is being driven by more screening, an increase in the prevalence of disease, or both. We sought to evaluate changes in gonorrhea testing patterns and positivity among men in Massachusetts. METHODS: The analysis included men (aged ≥15 years) who received care during 2010-2017 in 3 clinical practice groups. We calculated annual percentages of men with ≥1 gonorrhea test and men with ≥1 positive result, among men tested. Log-binomial regression models were used to examine trends in these outcomes. We adjusted for clinical and demographic characteristics that may influence the predilection to test and probability of gonorrhea disease. RESULTS: On average, 306 348 men had clinical encounters each year. There was a significant increase in men with ≥1 gonorrhea test from 2010 (3.1%) to 2017 (6.4%; adjusted annual risk ratio, 1.12; 95% confidence interval, 1.12-1.13). There was a significant, albeit lesser, increase in the percentage of tested men with ≥1 positive result (1.0% in 2010 to 1.5% in 2017; adjusted annual risk ratio, 1.07; 95% confidence interval, 1.04-1.09). CONCLUSIONS: We estimated significant increases in the annual percentages of men with ≥1 gonorrhea test and men with ≥1 positive gonorrhea test result between 2010 and 2017. These results suggest that observed increases in gonorrhea rates could be explained by both increases in screening and the prevalence of gonorrhea.

Cardio-respiratory, oxidative stress and acute mountain sickness responses to normobaric and hypobaric hypoxia in prematurely born adults.

PURPOSE: We compared the effects of hypobaric and normobaric hypoxia on select cardio-respiratory responses, oxidative stress and acute mountain sickness (AMS) severity in prematurely born individuals, known to exhibit blunted hypoxic ventilatory response. METHODS: Sixteen prematurely born but otherwise healthy males underwent two 8-h hypoxic exposures under: (1) hypobaric hypoxic [HH; terrestrial altitude 3840 m; PiO2:90.2 (0.5) mmHg; BP: 478 (2) mmHg] and (2) normobaric hypoxic [NH; PiO2:90.6 (0.9) mmHg; FiO2:0.142 (0.001)] condition. Resting values of capillary oxyhemoglobin saturation (SpO2), heart rate (HR) and blood pressure were measured before and every 2 h during the exposures. Ventilatory responses and middle cerebral artery blood flow velocity (MCAv) were assessed at rest and during submaximal cycling before and at 4 and 8 h. Plasmatic levels of selected oxidative stress and antioxidant markers and AMS symptoms were also determined at these time points. RESULTS: HH resulted in significantly lower resting (P = 0.010) and exercise (P = 0.004) SpO2 as compared to NH with no significant differences in the ventilatory parameters, HR or blood pressure. No significant differences between conditions were found in resting or exercising MCAv and measured oxidative stress markers. Significantly lower values of ferric-reducing antioxidant power (P = 0.037) were observed during HH as opposed to NH. AMS severity was higher at 8 h compared to baseline (P = 0.002) with no significant differences between conditions. CONCLUSION: These data suggest that, in prematurely born adults, 8-h exposure to hypobaric, as opposed to normobaric hypoxia, provokes greater reductions in systemic oxygenation and antioxidant capacity. Further studies investigating prolonged hypobaric exposures in this population are warranted. REGISTRATION: NCT02780908 (ClinicalTrials.gov).

Characteristics of Out-of-Care Patients Who Required a Referral for Re-engagement Services by Public Health Bridge Counselors Following a Brief Clinic-Based Retention Intervention.

The NC-LINK Project initiated both clinic-based retention services and state public health bridge counselor-based (SBCs) re-engagement services to retain and re-engage people living with HIV infection (PLWH) in care. The goal of this project is to compare efforts between clinic-based retention and SBC re-engagement services to determine whether patients are more or less likely to remain in HIV care services. Clinic appointment data were used to identify patients who were last seen more than 6-9 months prior. Patients either received clinic-based retention services only or were subsequently referred to the SBC re-engagement intervention if the retention services were unsuccessful. The frequency of re-engagement in care (180 days) and HIV suppression (VLS, within 1 year) was examined for patients in these two groups. The SBC group was less likely to have VLS at the visit prior to referral (adjusted OR 2.04, 95% CI 1.53, 2.72). Patients who were referred to the SBC were less likely to re-engage in care within 180 days as compared to those who received clinic-based retention services only (adjusted OR 0.29, 95% CI 0.21, 0.41).

Leg- vs arm-cycling repeated sprints with blood flow restriction and systemic hypoxia.

PURPOSE: The aim was to compare changes in peripheral and cerebral oxygenation, as well as metabolic and performance responses during conditions of blood flow restriction (BFR, bilateral vascular occlusion at 0% vs. 45% of resting pulse elimination pressure) and systemic hypoxia (~ 400 m, FIO2 20.9% vs. ~ 3800 m normobaric hypoxia, FIO2 13.1 ± 0.1%) during repeated sprint tests to exhaustion (RST) between leg- and arm-cycling exercises. METHODS: Seven participants (26.6 ± 2.9 years old; 74.0 ± 13.1 kg; 1.76 ± 0.09 m) performed four sessions of RST (10-s maximal sprints with 20-s recovery until exhaustion) during both leg and arm cycling to measure power output and metabolic equivalents as well as oxygenation (near-infrared spectroscopy) of the muscle tissue and prefrontal cortex. RESULTS: Mean power output was lower in arms than legs (316 ± 118 vs. 543 ± 127 W; p < 0.001) and there were no differences between conditions for a given limb. Arms demonstrated greater changes in concentration of deoxyhemoglobin (∆[HHb], - 9.1 ± 6.1 vs. - 6.5 ± 5.6 µm) and total hemoglobin concentration (∆[tHb], 15.0 ± 10.8 vs. 11.9 ± 7.9 µm), as well as the absolute maximum tissue saturation index (TSI, 62.0 ± 8.3 vs. 59.3 ± 8.1%) than legs, respectively (p < 0.001), demonstrating a greater capacity for oxygen extraction. Further, there were greater changes in tissue blood volume [tHb] during BFR only compared to all other conditions (p < 0.01 for all). CONCLUSIONS: The combination of BFR and/or hypoxia led to increased changes in [HHb] and [tHb] likely due to greater vascular resistance, to which arms were more responsive than legs.

Separate and combined effects of local and systemic hypoxia in resistance exercise.

PURPOSES: This study quantified performance, physiological, and perceptual responses during resistance exercise to task failure with blood flow restriction (BFR), in systemic hypoxia, and with these stimuli combined. METHODS: Fourteen young men were tested for 1-repetition maximum (1RM) in the barbell biceps curl and lying triceps extension exercises. On separate visits, subjects performed exercise trials (4 sets to failure at 70% 1RM with 90 s between sets) in six separate randomized conditions, i.e., in normoxia or hypoxia (fraction of inspired oxygen = 20.9% and 12.9%, respectively) combined with three different levels of BFR (0%, 45%, or 60% of resting arterial occlusion pressure). Muscle activation and oxygenation were monitored via surface electromyography and near-infrared spectroscopy, respectively. Arterial oxygen saturation, heart rate, and perceptual responses were assessed following each set. RESULTS: Compared to set 1, the number of repetitions before failure decreased in sets 2, 3, and 4 for both exercises (all P < 0.001), independently of the condition (P > 0.065). Arterial oxygen saturation was lower with systemic hypoxia (P < 0.001), but not BFR, while heart rate did not differ between conditions (P > 0.341). Muscle oxygenation and activation during exercise trials remained unaffected by the different conditions (all P ≥ 0.206). A significant main effect of time, but not condition, was observed for overall perceived discomfort, difficulty breathing, and limb discomfort (all P < 0.001). CONCLUSION: Local and systemic hypoxic stimuli, or a combination of both, did not modify the fatigue-induced change in performance, trends of muscle activation or oxygenation, nor exercise-related sensations during a multi-set resistance exercise to task failure.

Neuromuscular evaluation of arm-cycling repeated sprints under hypoxia and/or blood flow restriction.

PURPOSE: This study aimed to determine the effects of hypoxia and/or blood flow restriction (BFR) on an arm-cycling repeated sprint ability test (aRSA) and its impact on elbow flexor neuromuscular function. METHODS: Fourteen volunteers performed an aRSA (10 s sprint/20 s recovery) to exhaustion in four randomized conditions: normoxia (NOR), normoxia plus BFR (NBFR), hypoxia (FiO2 = 0.13, HYP) and hypoxia plus BFR (HBFR). Maximal voluntary contraction (MVC), resting twitch force (Db10), and electromyographic responses from the elbow flexors [biceps brachii (BB)] to electrical and transcranial magnetic stimulation were obtained to assess neuromuscular function. Main effects of hypoxia, BFR, and interaction were analyzed on delta values from pre- to post-exercise. RESULTS: BFR and hypoxia decreased the number of sprints during aRSA with no significant cumulative effect (NOR 16 ± 8; NBFR 12 ± 4; HYP 10 ± 3 and HBFR 8 ± 3; P < 0.01). MVC decrease from pre- to post-exercise was comparable whatever the condition. M-wave amplitude (- 9.4 ± 1.9% vs. + 0.8 ± 2.0%, P < 0.01) and Db10 force (- 41.8 ± 4.7% vs. - 27.9 ± 4.5%, P < 0.01) were more altered after aRSA with BFR compared to without BFR. The exercise-induced increase in corticospinal excitability was significantly lower in hypoxic vs. normoxic conditions (e.g., BB motor evoked potential at 75% of MVC: - 2.4 ± 4.2% vs. + 16.0 ± 5.9%, respectively, P = 0.03). CONCLUSION: BFR and hypoxia led to comparable aRSA performance impairments but with distinct fatigue etiology. BFR impaired the muscle excitation-contraction coupling whereas hypoxia predominantly affected corticospinal excitability indicating incapacity of the corticospinal pathway to adapt to fatigue as in normoxia.

Effects of exercise in normobaric hypoxia on hemodynamics during muscle metaboreflex activation in normoxia.

PURPOSE: Little is known about the cardiovascular effects of the transition from exercise in hypoxia (EH) to normoxia. This investigation aimed to assess hemodynamics during the metaboreflex elicited in normoxia after EH. METHODS: Ten trained athletes (four females and six males, age 35.6 ± 8.4 years) completed a cardiopulmonary test to determine the workload at anaerobic threshold (AT). On separate days, participants performed three randomly assigned exercise sessions (10 min pedalling at 80% of AT): (1) one in normoxia (EN); (2) one in normobaric hypoxia with FiO2 15.5% (EH15.5%); and (3) one in normobaric hypoxia with FiO2 13.5% (EH13.5%). After each session, the following protocol was randomly assigned: either (1) post-exercise muscle ischemia after cycling for 3 min, to study the metaboreflex, or (2) a control exercise recovery (CER) session, without any metaboreflex stimulation. RESULTS: The main result were that both EH15.5% and EH13.5% impaired (p < 0.05) the ventricular filling rate response during the metaboreflex (- 18 ± 32 and - 20 ± 27 ml s-1), when compared to EN (+ 29 ± 32 ml s-1), thereby causing a reduction in stroke volume response (- 9.1 ± 3.2, - 10.6 ± 8.7, and + 5 ± 5.7 ml for EH15.5%, EH13.5% and EN test, respectively, p < 0.05). Moreover, systemic vascular resistance was increased after the EH15.5% and the EH13.5% in comparison with the EN test. CONCLUSIONS: These data demonstrate that moderate exercise in hypoxia impairs the capacity to enhance venous return during the metaboreflex stimulated in normoxia. Overall, there is a functional shift from a flow to vasoconstriction-mediated mechanism for maintaining the target blood pressure during the metaboreflex.

Live high-train low guided by daily heart rate variability in elite Nordic-skiers.

PURPOSE: To analyze if live high-train low (LHTL) effectiveness is improved when daily training is guided by heart rate variability (HRV). METHODS: Twenty-four elite Nordic skiers took part in a 15-day LHTL study and were randomized into a HRV-guided training hypoxic group (H-HRV, n = 9, sleeping in normobaric hypoxia, FiO2 = 15.0%) and two predefined training groups sleeping either in hypoxia (H, n = 9, FiO2 = 15.0%) or normoxia (N, n = 6). HRV and training loads (TL) were recorded daily. Prior (Pre), one (Post-1), and 21 days (Post-21) following LHTL, athletes performed a 10-km roller-ski test, and a treadmill test for determination of [Formula: see text] was performed at Pre and Post-1. RESULTS: Some HRV parameters measured in supine position were different between H-HRV and H: low and high (HF) frequency power in absolute (ms2) (16.0 ± 35.1 vs. 137.0 ± 54.9%, p = 0.05) and normalized units (- 3.8 ± 10.1 vs. 53.0 ± 19.5%, p = 0.02), HF(nu) (6.3 ± 6.8 vs. - 13.7 ± 8.0%, p = 0.03) as well as heart rate (3.7 ± 6.3 vs. 12.3 ± 4.1%, p = 0.008). At Post-1, [Formula: see text] was improved in H-HRV and H (3.8 ± 3.1%; p = 0.02 vs. 3.0 ± 4.4%; p = 0.08) but not in N (0.9 ± 5.1%; p = 0.7). Only H-HRV improved the roller-ski performance at Post-21 (- 2.7 ± 3.6%, p = 0.05). CONCLUSION: The daily individualization of TL reduced the decrease in autonomic nervous system parasympathetic activity commonly associated with LHTL. The improved performance and oxygen consumption in the two LHTL groups confirm the effectiveness of LHTL even in elite endurance athletes.

Post-exercise recovery of contractile function and endurance in humans and mice is accelerated by heating and slowed by cooling skeletal muscle.

KEY POINTS: We investigated whether intramuscular temperature affects the acute recovery of exercise performance following fatigue-induced by endurance exercise. Mean power output was better preserved during an all-out arm-cycling exercise following a 2 h recovery period in which the upper arms were warmed to an intramuscular temperature of Ì´ 38°C than when they were cooled to as low as 15°C, which suggested that recovery of exercise performance in humans is dependent on muscle temperature. Mechanisms underlying the temperature-dependent effect on recovery were studied in intact single mouse muscle fibres where we found that recovery of submaximal force and restoration of fatigue resistance was worsened by cooling (16-26°C) and improved by heating (36°C). Isolated whole mouse muscle experiments confirmed that cooling impaired muscle glycogen resynthesis. We conclude that skeletal muscle recovery from fatigue-induced by endurance exercise is impaired by cooling and improved by heating, due to changes in glycogen resynthesis rate. ABSTRACT: Manipulation of muscle temperature is believed to improve post-exercise recovery, with cooling being especially popular among athletes. However, it is unclear whether such temperature manipulations actually have positive effects. Accordingly, we studied the effect of muscle temperature on the acute recovery of force and fatigue resistance after endurance exercise. One hour of moderate-intensity arm cycling exercise in humans was followed by 2 h recovery in which the upper arms were either heated to 38°C, not treated (33°C), or cooled to ∼15°C. Fatigue resistance after the recovery period was assessed by performing 3 × 5 min sessions of all-out arm cycling at physiological temperature for all conditions (i.e. not heated or cooled). Power output during the all-out exercise was better maintained when muscles were heated during recovery, whereas cooling had the opposite effect. Mechanisms underlying the temperature-dependent effect on recovery were tested in mouse intact single muscle fibres, which were exposed to ∼12 min of glycogen-depleting fatiguing stimulation (350 ms tetani given at 10 s interval until force decreased to 30% of the starting force). Fibres were subsequently exposed to the same fatiguing stimulation protocol after 1-2 h of recovery at 16-36°C. Recovery of submaximal force (30 Hz), the tetanic myoplasmic free [Ca2+ ] (measured with the fluorescent indicator indo-1), and fatigue resistance were all impaired by cooling (16-26°C) and improved by heating (36°C). In addition, glycogen resynthesis was faster at 36°C than 26°C in whole flexor digitorum brevis muscles. We conclude that recovery from exhaustive endurance exercise is accelerated by raising and slowed by lowering muscle temperature.

High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation.

Intense exercise training is a powerful stimulus that activates mitochondrial biogenesis pathways and thus increases mitochondrial density and oxidative capacity. Moderate levels of reactive oxygen species (ROS) during exercise are considered vital in the adaptive response, but high ROS production is a serious threat to cellular homeostasis. Although biochemical markers of the transition from adaptive to maladaptive ROS stress are lacking, it is likely mediated by redox sensitive enzymes involved in oxidative metabolism. One potential enzyme mediating such redox sensitivity is the citric acid cycle enzyme aconitase. In this study, we examined biopsy specimens of vastus lateralis and triceps brachii in healthy volunteers, together with primary human myotubes. An intense exercise regimen inactivated aconitase by 55-72%, resulting in inhibition of mitochondrial respiration by 50-65%. In the vastus, the mitochondrial dysfunction was compensated for by a 15-72% increase in mitochondrial proteins, whereas H2O2 emission was unchanged. In parallel with the inactivation of aconitase, the intermediary metabolite citrate accumulated and played an integral part in cellular protection against oxidative stress. In contrast, the triceps failed to increase mitochondrial density, and citrate did not accumulate. Instead, mitochondrial H2O2 emission was decreased to 40% of the pretraining levels, together with a 6-fold increase in protein abundance of catalase. In this study, a novel mitochondrial stress response was highlighted where accumulation of citrate acted to preserve the redox status of the cell during periods of intense exercise.

Exposure to neonicotinoids influences the motor function of adult worker honeybees.

Systemic pesticides such as neonicotinoids are commonly used on flowering crops visited by pollinators, and their use has been implicated in the decline of insect pollinator populations in Europe and North America. Several studies show that neonicotinoids affect navigation and learning in bees but few studies have examined whether these substances influence their basic motor function. Here, we investigated how prolonged exposure to sublethal doses of four neonicotinoid pesticides (imidacloprid, thiamethoxam, clothianidin, dinotefuran) and the plant toxin, nicotine, affect basic motor function and postural control in foraging-age worker honeybees. We used doses of 10 nM for each neonicotinoid: field-relevant doses that we determined to be sublethal and willingly consumed by bees. The neonicotinoids were placed in food solutions given to bees for 24 h. After the exposure period, bees were more likely to lose postural control during the motor function assay and fail to right themselves if exposed to imidacloprid, thiamethoxam, clothianidin. Bees exposed to thiamethoxam and nicotine also spent more time grooming. Other behaviours (walking, sitting and flying) were not significantly affected. Expression of changes in motor function after exposure to imidacloprid was dose-dependent and affected all measured behaviours. Our data illustrate that 24 h exposure to sublethal doses of neonicotinoid pesticides has a subtle influence on bee behaviour that is likely to affect normal function in a field setting.

Comparison between three different endurance tests in professional soccer players.

The aims of this study were (a) to assess and correlate interval shuttle run test (ISRT) performance, maximum oxygen uptake (V[Combining Dot Above]O(2)max), running economy (RE), running velocity at the first rise in blood lactate concentrations above baseline (vLT) and running velocity at 4 mmol·L(-1) blood lactate concentration (v4) in professional soccer players and (b) to investigate whether a correlation exists between the respective results of time to exhaustion (T(lim)) from continuous and intermittent endurance tests, respectively. Eleven male professional field soccer players (mean ± SD: age 23.8 ± 3.0 years, V[Combining Dot Above]O(2)max 58.2 ± 4.9 ml·kg(-1)·min(-1)) completed a continuous Incremental Test with lactate measurements to determine vLT and v4, a continuous Ramp Test with gas exchange analysis to determine V[Combining Dot Above]O(2)max and RE, and an intermittent ISRT to determine intermittent endurance capacity during the first week of preseason preparation. There were significant correlations between ISRT performance and V[Combining Dot Above]O(2)max (r = 0.70, p < 0.05), and between T(lim) in both continuous endurance tests (r = 0.89, p < 0.01). Between all other variables no significant correlations were found overall (best r = 0.60, p > 0.05). The assessment of all values of V[Combining Dot Above]O(2)max, RE, vLT, and v4 should be included when investigating aerobic endurance performance among groups or over time in professional soccer players. Although V[Combining Dot Above]O(2)max, RE, vLT, and v4 have been regarded as important factors of aerobic performance in endurance related sports, the present data revealed that V[Combining Dot Above]O(2)max was the only factor, which correlated with intermittent endurance capacity in professional soccer players. Hence, V[Combining Dot Above]O(2)max should be increased through soccer-specific training interventions including universal agility components. The T(lim) in continuous and intermittent endurance tests differs and is therefore an independent endurance performance factor in professional soccer players.

Hypoxia Does Not Change Performance and Psychophysiological Responses During Repeated Cycling Sprints to Exhaustion With Short Exercise-to-Rest Ratio.

PURPOSE: To compare the acute performance and psychophysiological responses of repeated cycling sprints to exhaustion with a short exercise-to-rest ratio (1:6), between different effort durations and inspired oxygen fractions. METHODS: On separate visits, 10 active participants completed 6 repeated cycling sprint exercises to exhaustion with 3 different effort durations (5, 10, and 20 s) and 2 conditions of inspired oxygen (20.9% and 13.6%). Exercise-to-rest ratio was 1:6 for all trials (ie, 5:30, 10:60, and 20:120). Vastus lateralis muscle oxygenation (near-infrared spectroscopy), blood lactate concentration, and lower-limb and breathing discomfort, using ratings of perceived exertion, were measured. RESULTS: Number of sprints and peak power output decreased while blood lactate increased (all P < .001) during 5:30 compared with 10:60 or 20:120. No condition or interaction effects were reported for blood lactate and exercise-related sensation. Muscle deoxyhemoglobin increased (P < .001) and total hemoglobin decreased (P = .002) during sprint with increasing sprint duration (no condition or interaction). CONCLUSION: During repeated-sprint exercise to exhaustion with a short exercise-to-rest ratio, the psychophysiological responses did not differ between normoxia and moderate hypoxia, probably due to an extended recovery period. It means that hypoxia did not modify repeated-sprint exercise performance with a short exercise-to-rest ratio. The sprint duration was the primary underlying factor of the observed differences in performance and muscle oxygenation reported between the repeated-sprint exercise sessions.

The Oxidative-Glycolytic Balance Influenced by Sprint Duration Is Key during Repeated Sprint in Hypoxia.

PURPOSE: This study investigates the effects of normobaric hypoxia on repeated sprint exercise (RSE) with different balance between oxidative (phosphocreatine and oxidative pathway) and glycolytic contributions. Therefore, performance and psychophysiological responses were compared during RSE to exhaustion with the same exercise-to-rest ratio (1:2) but different sprint durations (5, 10, or 20 s) either in normoxic (RSN) or hypoxic (RSH; F io2 = 0.13) conditions. METHODS: On separate visits, 10 active participants completed in random order three cycling RSN (5:10; 10:20 and 20:40) and three similar RSH sessions to exhaustion. Vastus lateralis muscle oxygenation was recorded by near-infrared spectroscopy. Blood lactate concentration, limb and breathing discomfort, and ratings of perceived exertion were measured. RESULTS: Total sprint number was smaller in hypoxia than in normoxia for 5:10 (20.8 ± 8.6 vs 14.7 ± 3.4; P = 0.014) and 10:20 (13.7 ± 6.3 vs 8.8 ± 2.5; P = 0.018) but not 20:40 (5.6 ± 1.9 vs 5.6 ± 2.5). The fatigue index was larger in hypoxia only for 5:10 (-43.5%, P < 0.001). Irrespective of condition, blood lactate concentration increased with the sprint duration with higher values for 20:40 than 5:10 (13.1 ± 2.7 vs 11.5 ± 2.2 mmoL·L -1 ; P = 0.027). Limb and breathing discomfort and ratings of perceived exertion did not differ in all RSE. Muscle oxygenation was mainly impacted by sprint duration (i.e., main effect of sprint duration on [HHb] min, [tHb] max, Δ[HHb], and Δ[tHb]) but not by hypoxia. The normoxia-to-hypoxia percentage decrease for total sprint number for 5:10 was correlated with the highest power output over 5 s ( R2 = 0.55; P = 0.013) and 10 s ( R2 = 0.53; P = 0.016). CONCLUSIONS: Hypoxia impairs repeated sprint ability when the oxidative but not the glycolytic contribution is substantial. The oxidative-glycolytic balance, influenced partly by sprint duration, is key during repeated sprint in hypoxia.