Background and Aims: Whether exercise training induces plasma volume (PV) expansion and distorts circulating progenitor cell (CPC) assessment in heart failure with preserved ejection fraction (HFpEF) remains unclear, particularly in women, who might have lower CPC concentrations and higher cardiovascular risk due to female-specific risk factors. This study investigated sex-specific differences, skeletal muscle mass (SMM)-normalized baseline values, and exercise-induced changes in intravascular volumes, CPCs, and erythropoietin (EPO). Methods: HFpEF patients completed a 3-months strength-endurance training. Blood volume (BV), PV, red blood cell volume (RBCV), and hemoglobin mass (Hb-mass) were assessed using carbon-monoxide rebreathing, CPCs by flow cytometry, EPO by ELISA. CPC concentrations were adjusted for BV. Training effects, sex interactions, and associations between SMM-normalized CPCs and EPO were examined. Results: At baseline, women had comparable BV, PV, RBCV, Hb-mass, and EPO to men when normalized to SMM (all p > 0.05, uncorrected). After BV adjustment, women showed lower total CPC counts (uncorrected p = 0.031), but this difference disappeared after SMM normalization (uncorrected p = 0.160). Exercise training showed no evidence of affecting SMM-normalized intravascular volumes, Hb-mass, EPO, or BV-(un)adjusted CPC concentrations, with no interaction effects of sex (all p > 0.05, uncorrected). Before SMM normalization, exploratory analysis revealed PV changes being inversely associated with CPC concentration (ρ = -0.57, p = 0.044), but not thereafter. CPC relationships to EPO were non-significant (both p > 0.05). Conclusions: Sex differences in CPCs were evident after adjusting for BV but disappeared after SMM normalization. Exercise training did not increase CPCs, but individual responses depended on CPC expression. Findings require validation in larger HFpEF cohorts.

Introduction: We aimed to investigate the effect of different exercise modes on retinal microvascular endothelial function in patients with HF with preserved ejection fraction (HFpEF). Methods: Twenty-eight patients were randomly allocated to either a moderate (MCT) or high-intensity interval training (HIIT) group for 12 weeks. Retinal microvascular structure and function were investigated by analyzing central retinal arteriolar (CRAE) and venular (CRVE) diameter equivalents, the arteriolar-to-venular diameter ratio (AVR), and the dynamic arteriolar (aFID) and venular (vFID) flicker light-induced dilation response. Results: Twenty patients (mean age 70 ± 9 years) were included in the final analysis. After HIIT, AVR increased (0.80 ± 0.03 vs. 0.83 ± 0.04, p = 0.03) due to arteriolar widening. CRAE increased (157 ± 18 µm vs. 164 ± 18 µm, p = 0.05), but CRVE did not change (196 ± 27 µm vs. 197 ± 24 µm, p = 0.56). After MCT, AVR also increased (0.80 ± 0.08 vs. 0.83 ± 0.06, p = 0.02) without significant changes in CRAE (160 ± 19 µm vs. 165 ± 18 µm, p = 0.07) or CRVE (201 ± 14 µm vs. 199 ± 14 µm, p = 0.40). aFID improved after MCT (2.1 ± 1.6% vs. 3.1 ± 1.8%, p = 0.03) but not after the HIIT intervention (2.1 ± 1.7% vs. 2.4 ± 2.1%, p = 0.60). vFID did not statistically significant change neither in the HIIT (4.4 ± 2.2% vs. 3.4 ± 1.9%, p = 0.06) nor in the MCT (4.3 ± 2.2% vs. 5.5 ± 4.1%, p = 0.26) group. Conclusion: MCT and HIIT are both adequate therapy options to improve microvascular health in patients with HFpEF.

Acute exhaustive exercise acts as a physiological stressor, leading to endothelial activation and the release of circulating progenitor cells (CPC). In heart failure, this CPC response may be blunted. Reactive oxygen species provided by oxidised low density lipoproteins (oxLDL), and nitric oxide metabolites (nitrate, NOm) secreted from activated endothelial cells, could influence endothelial shedding by circulating endothelial cells (CEC) and the mobilisation of CPC - especially in untrained heart failure patients with preserved ejection fraction (HFpEF). MicroRNAs (miRs) such as miR-21-5p, miR-126-3p, miR-138-5p and miR-155-5p regulate CPC and endothelial function influenced by oxidative stress and NOm. This study aimed to investigate the immediate stress, CEC, CPC, and miR-response to an exhaustive incremental exercise test (CPET) in patients with HFpEF (n=43, 14 male; 72.4(9.7) yrs, 26.0(5.2) kg/m2). We assessed the expression of the described miRs by RT-qPCR in peripheral mononuclear cells (MNC), CD34+/CD45dim CPC, CD31+/CD45- CEC by flow cytometry as well as oxLDL and NOm in serum before and directly after the CPET. Data are presented as mean(SE), except patient characteristics as mean(SD). Comparisons pre-to-post exercise were done by Wilcoxon signed-rank test, paired or one-sample t-tests. Parameter associations were evaluated by respective correlation analyses. A two-sided p-value of <0.05 was considered significant. OxLDL did not increase after the exhaustive exercise (63.2(2.7) U/L to 65.3(2.8) U/L, p=0.097, n=37), while NOm decreased (29.8(2.8) µmol/L to 26.0(2.2) µmol/L, p<0.001, n=37). Levels of miR-126 (+2.3(0.5)-fold vs. baseline, p=0.016, n=31), and miR-138 (+2.2(0.4)-fold vs. baseline, p=0.002, n=29) were higher within circulating MNC after the CPET than before. Endothelial shedding by CEC and mobilisation of CPC were enhanced by the CPET (40.0(8.6) CEC/µl to 45.4(10.4) CEC/µl, p=0.021; 0.917(0.178) CPC/µl to 1.252(0.235) CPC/µl, p=0.004, both n=23). Neither miR-155 (+5.7(2.5)-fold vs. baseline, p=0.074, n=31) nor MiR-21 expression were significantly altered (1.8(0.6)-fold vs. baseline, p=0.157, n=30), but miR-21 expression change was linked to the increase in CPC (rho=0.51, p=0.027, n=19 after outlier exclusion, Fig.1), and expression changes in miR-155 (rho=0.52, p=0.007, n=26 after outlier exclusion, Fig.2). Both acute exercise-induced OxLDL and NOm were not related to any cell or miR changes post-CPET (all p>0.05). In HFpEF patients, acute exercise elevates endothelial cell shedding, progenitor cell mobilisation, and MNC miR levels. A non-significant rise in miR-21 correlates with higher CPC, potentially limiting their mobilisation. This effect appears independent of oxidative stress and NOm, but is linked to increased pro-inflammatory miR-155, which negatively affects endothelial cell contacts. This indicates an altered stress response during exhaustive exercise in HFpEF.Fig. 1Correlation miR-21 & CPC changesFig. 2Correlation miR-155 & -21 changes

Background:Bioimpedance cardiography offers a non-invasive and time-efficient method to measure hemodynamic parameters. Previous studies only investigated its reliability under steady-state conditions and at maximum load but not at ventilatory thresholds (VTs). This is the first study that assesses the reliability of measured hemodynamic parameters at different exercise stages during cardiopulmonary exercise testing (CPET) using prespecified strict criteria to assess reliability. Methods:Data from 31 healthy, well-trained adults were analyzed. Each participant completed two CPETs, both following the same ramp protocol, with a 7-day interval between them. Hemodynamic parameters were measured with the PhysioFlow® (Manatec Biomedical, Poissy, France) at characteristic phases and thresholds [VT1, VT2, and peak oxygen uptake (V̇O2peak)]. To ensure comparability, the wattage (power) corresponding to the thresholds in Test 1 (PVT1, PVT2, and PV̇O2peak) was used for Test 2. Results:Heart rate, stroke volume, and cardiac output demonstrated good reliability on a group level (mean intraclass correlation >0.75) at both thresholds (0.91, 0.80, and 0.77 at PVT1; 0.92, 0.80, and 0.77 at PVT2) and at PV̇O2peak (0.93, 0.82, and 0.80). For stroke volume at PV̇O2peak, both individual differences (-39.0 to 36.9 mL for the women and -39.9 to 45.2 mL for the men) and mean detectable change (17.5 mL) were larger than the a priori defined acceptable ranges of agreement (-3.6 to 3.8 mL for the women and -4.5 to 3.3 mL for the men). Conclusion:The PhysioFlow® reliably measures heart rate, stroke volume, and cardiac output during CPET on a group level. However, as shown by the Bland-Altman plots, the reliability is too low to be used for individual comparisons.

BACKGROUND:Cardiac output (CO) is the product of the heart rate (HR) and the stroke volume (SV).over time. It is a direct marker of myocardial function. In healthy subjects, the myocard normally responds well and CO improves after exercise training. However, the effect of exercise on CO in patients with heart failure with preserved ejection fraction (HFpEF) is less clear. Therefore, this study aimed to systematically summarise the current evidence on the effects of an exercise intervention on CO in subjects with HFpEF. MATERIAL AND METHODS:A literature search in Medline, Embase, CENTRAL, and SportDiscus was performed. Included were all RCTs that compared the effect of exercise training on CO in patients with HFpEF and were published before 11 April 2024. Risk of bias assessment was performed by using Cochrane's RoB 2 tool. The review was reported according to preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. RESULTS:We identified 750 abstracts that were screened for eligibility. A total of 11 selected full texts were analysed. One study fulfilled our inclusion criteria. No significant difference in the change of CO between the intervention and control groups at rest or during maximal exercise after the intervention was detected. DISCUSSION:The identification of only one RCT hallmarks the sparse evidence on alterations of CO prior to post an exercise intervention in subjects with HFpEF. This might be because other markers such as V̇O2max are much easier to measure.

BACKGROUND:Patients with heart failure with preserved ejection fraction (HFpEF) commonly experience exercise intolerance, resulting in reduced cardiorespiratory fitness. This is characterised by a decreased maximal oxygen uptake (V̇O2peak), which is determined by the product of cardiac output (CO) and arteriovenous oxygen difference (a-vDO2). While exercise training has been shown to improve V̇O2peak in HFpEF patients, the effects on CO remain unclear. The aim of this study is to systematically review and analyse the current evidence on the effects of supervised exercise training on CO in patients with HFpEF. METHODS:We will systematically search for literature describing the effects of supervised exercise training on CO in patients with HFpEF. All eligible studies published before 30 June 2023 in the following electronic databases will be included: MEDLINE (Ovid), Embase (Ovid), SPORTDiscus (EBSCOhost), and CENTRAL (Cochrane Library). Effect sizes will be extracted for CO before and after a supervised exercise training intervention at rest and maximal exercise. Mass of heterogeneity (I2) will be calculated, and either fixed-effect models or random-effect models will be used for meta-analysis. To detect a potential publication bias, funnel plot analyses will be performed. DISCUSSION:While several studies have reported a positive effect of supervised exercise training on cardiorespiratory fitness, attempts to assess the underlying determinants of V̇O2peak, CO, and a-vDO2 are much scarcer, especially in patients with HFpEF. From a physiological perspective, measuring CO before and after supervised exercise training seems to be a reasonable way to accurately operationalise a potential improvement in cardiac function. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42022361485.

Background: The success of competitive alpine skiers with respective to their world ranking (WR) positions might be associated with prominent gene polymorphisms. Methods: Twenty-six competitive alpine skiers were followed from 2015 to 2019 for their WR positions (FIS-ranking). Using PCR, the genotypes of ACE-I/D, TNC, ACTN3, and PTK2 were identified. The correlations between the discipline-specific WR position (slalom-SL, giant slalom-GS, super G-SG, downhill-DH, and alpine combined-AC) and gene polymorphisms were analyzed concerning an influence with multivariate regression models. Results: The WR position and the ACE gene as well as the copy number of the ACE I-allele exhibited reciprocal relationships for speed specialists (SG and DH) but not for technical specialists (SL and GS). Similarly, the gene polymorphisms ACTN3 and (partly) PTK2 were associated with the WR position in disciplines characterized by a high number of turns (technical specialists-SL and GS) and speed (speed-specialists-SG and DH), respectively. Conclusions: Our findings emphasize the contributions of aerobic and cardiovascular metabolism in fueling muscle work and recovering from muscle fatigue for competitive success in slalom-driven skiing disciplines and highlight the contributions of sequence variants in the genes ACE, TNC, and ACTN3.

Aim: High-altitude mountaineering has become more and more popular, however if female alpinists show different injury pattern is not finally elucidated. Material and methods: A retrospective analysis was therefore conducted from the central registry of the Swiss Alpine Club (SAC) during the observational period from 2009 to 2022 concerning intersex differences of emergencies specific while high-altitude mountaineering. Conclusions: A total of 1252 female (22%) and 4347 male (78%) emergencies while high-altitude mountaineering were elucidated. A significant difference was detected in average NACA score as proxy for the severity of an event for falls, where female cases show a significant lower severity with NACA score 3.0 +/- 1.5 as compared to male cases with NACA score 3.5 +/- 2.0 (p < 0.001). Furthermore, on average men have more often a fatal event. It might be suggested that men choosing routes in rougher terrain, tend to overestimate their abilities more often and have a higher willingness to take risks.

Objectives: One risk while high-altitude mountaineering despite falls or stranding are rock falls. Due to the climatic change such events might have become potentially more common yielding to the research question to elucidate rock falls while high-altitude mountaineering in the Alps of Switzerland. Design: A retrospective analysis was conducted from the central registry of the Swiss Alpine Club (SAC) during the observational period from 2009 to 2020. Results: A total of 266 cases of rock falls was detected during an observational period yielding to in average 22.2 +/- 7 emergency cases per year. No increase nor decrease of the number of cases over time (R2 = 0.0019) was detected. The average age of a victim was 50.2 +/- 18.6 years. The mean of the NACA-Score (NACA = National Advisory Committee for Aeronautics) was 2.7 +/- 1.4 implying a moderate injury, however not life threatening. The NACA-Score slightly decreased over time indicating that emergencies have become less severe (R2 = 0.1379). The injury pattern was relatively equal distributed between upper and lower extremity. Conclusions: The slight decrease in the severity of the events might be a consequence of increasing security standards over the observational period. The fact that the average victim of an emergency action was around 50 years, might indicate that stone falls are a constant risk as it can be suggested that alpinists with this age are more risk averse than younger alpinists. As findings were analyzed in a retrospective design, a quasi-prospective design might be helpful while directly analyzing emergencies after occurrence with interviews of involved persons. These hints could be used constructively in order to improve security recommendations.

Background: Polymorphism rs1049434 characterizes the nonsynonymous exchange of adenosine (A) by thymidine (T) in the gene for monocarboxylate transporter 1 (MCT1). We tested whether T-allele carriers of rs1049434 demonstrate increased accumulation of markers of metabolic strain. Methods: Physically active, healthy, young male subjects (n = 22) conducted a power-matched one-legged cycling exercise to exhaustion. Metabolic substrates in capillary blood, selected metabolic compounds, and indices for the slow oxidative phenotype of vastus lateralis muscle were quantified in samples collected before and after exercise. The genotypes of the rs1049434 polymorphism were determined with polymerase chain reactions. Results: One-legged exercise affected the concentration of muscle metabolites entering the tricarboxylic acid cycle, such as acetyl-co-enzyme A (+448%) and acetyl-L-carnitine (+548%), muscle glycogen (−59%), and adenosine monophosphate (−39%), 30 min post-exercise. Exercise-related variability in the muscular concentration of glycogen, long-chain acyl co-enzyme As and a triglyceride, nicotinamide adenine dinucleotide (NADH), and adenosine monophosphate (AMP) interacted with rs1049434. T-allele carriers demonstrated a 39% lesser reduction in glycogen after exercise than non-carriers when NADH increased only in the non-carriers. Muscle lactate concentration was 150% higher, blood triacyl-glyceride concentration was 53% lower, and slow fiber percentage was 20% lower in T-allele carriers. Discussion: The observations suggest a higher anaerobic glycolytic strain during exhaustive exercise and a lowered lipid handling in T-allele non-carriers.

[This corrects the article DOI: 10.1016/j.cpnec.2023.100196.].

Background and aim: Heart failure is considered as a systemic disease as beside the heart, skeletal muscle is affected.Methods and results: In this retrospective case-control study 64 men and 15 women with heart failure as well as an individually pairwise matched sample by sex, age and body mass index of healthy individuals from the COmPLETE cohort study performed an exhaustive cardiopulmonary exercise test, strength tests and anthropometric measurements. V_O2peak was 28.6% lower in male and 24.6% lower in female patients with heart failure as compared to healthy controls. Strength parameters are significantly higher for counter movement jump in male subjects. In females, significant differences were detected for mid-thigh pull in healthy versus patients with heart failure. Skeletal muscle mass of patients was in male as well as female 3.7% lower than in controls. Furthermore, the function of skeletal muscle seems impaired as the ability to accelerate is significantly lower in affected male with a heart pathology. Conclusion: It seems that severe affections (approx. 25 to 30%) on cardiocirculatory level are associated with moderate to low affections on functional and structural capacity on skeletal muscle level. Further, as in the male cohort with a heart pathology acceleration meaning 'fast' contracting is impaired, it is suggested, that the central limitations respectively the low perfusion of skeletal muscle over years yield to adaptions on muscle cell level ingoing with a decreased ability of fast contracting. It is therefore suggested, that the central circulatory limitations in patients with heart failure, respectively the low perfusion of skeletal muscle over years, promote maladaptation's in the periphery.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background: We recently reported that metformin administration has substantial effects on steroid hormone concentrations. In this study, we specifically explored which enzymatic activities were affected before a first treatment versus after a time of metformin treatment. Material and Methods: Twelve male subjects (54.2 ± 9.1 years, 177.3 ± 4.1 cm, 80 ± 10.4 kg) and seven female subjects (57.2 ± 18.9 years, 162.7 ± 4.1 cm, 76.1 ± 10.4 kg) were recruited based on an indication of metformin. Prior to the first intake of metformin and after 24 h, urine collections were performed. Urine steroid analysis was completed using gas chromatography–mass spectrometry. Results: The average reduction in steroid hormone concentrations after the metformin treatment was substantial and relatively equally distributed in all metabolites and the sum of all metabolites with 35.4%. An exception was dehydroepiandrosterone, with a decrease of almost three hundred percent of average concentration. In addition, the sum of all cortisol metabolites and 18-OH cortisol (indicative of oxidative stress) were lower after the metformin treatment. Furthermore, significant inhibition of 3ß-HSD activity was detectable. Discussion: Effects prior to and after the metformin treatment on inhibiting 3ß-HSD activity were detected in line with findings from others. Furthermore, the pattern of a reduction, for example, in the sum of all glucocorticoids following the metformin treatment supported an effect on oxidative stress, which was further supported by the reduction in 18-OH cortisol. Nevertheless, we do not understand all steps in the complex pattern of the enzymes that affect steroid hormone metabolism and, consequently, further studies are necessary to improve our understanding.

Background: The prominent insertion/deletion polymorphism in the gene for the major modulator of tissue perfusion, angiotensin-converting enzyme (ACE-I/D) is associated with variability in adjustments in cardiac and skeletal muscle performance with standard forms of endurance and strength type training. Here, we tested whether the ACE-I/D genotype would be associated with variability in the effects of interval-type training on peak and aerobic performance of peripheral muscle and cardio-vasculature and post-exercise recovery. Methods: Nine healthy subjects (39.0 ± 14.7 years of age; 64.6 ± 16.1 kg, 173.6 ± 9.9) completed eight weeks of interval training on a soft robotic device based on repeated sets of a pedaling exercise at a matched intensity relative to their peak aerobic power output. Prior to and post-training, peak anaerobic and aerobic power output was assessed, mechanical work and metabolic stress (oxygen saturation and hemoglobin concentrations of Musculus vastus lateralis (VAS) and Musculus gastrocnemius (GAS), blood lactate and factors setting cardiac output such as heart rate, systolic and diastolic blood pressure were monitored during ramp-incremental exercise and interval exercise with the calculation of areas under the curve (AUC), which were put in relation to the produced muscle work. Genotyping was performed based on I- and D-allele-specific polymerase chain reactions on genomic DNA from mucosal swaps. The significance of interaction effects between training and ACE I-allele on absolute and work-related values was assessed with repeated measures ANOVA. Results: Subjects delivered 87% more muscle work/power, 106% more cardiac output, and muscles experienced ~72% more of a deficit in oxygen saturation and a ~35% higher passage of total hemoglobin during single interval exercise after the eight weeks of training. Interval training affected aspects of skeletal muscle metabolism and performance, whose variability was associated with the ACE I-allele. This concerned the economically favorable alterations in the work-related AUC for the deficit of SmO2 in the VAS and GAS muscles during the ramp exercise for the I-allele carriers and opposing deteriorations in non-carriers. Conversely, oxygen saturation in the VAS and GAS at rest and during interval exercise was selectively improved after training for the non-carriers of the I-allele when the AUC of tHb per work during interval exercise deteriorated in the carriers. Training also improved aerobic peak power output by 4% in the carriers but not the non-carriers (p = 0.772) of the ACE I-allele while reducing negative peak power (−27.0%) to a lesser extent in the ACE I-allele carriers than the non-carriers. Variability in cardiac parameters (i.e., the AUC of heart rate and glucose during ramp exercise, was similar to the time to recovery of maximal tHb in both muscles after cessation of ramp exercise, only associated with the ACE I-allele but not training per se. Diastolic blood pressure and cardiac output during recovery from exhaustive ramp exercise demonstrated a trend for training-associated differences in association with the ACE I-allele. Discussion: The exercise-type dependent manifestation of antidromic adjustments in leg muscle perfusion and associated local aerobic metabolism between carriers and non-carriers of the ACE I-allele with the interval-training highlight that non-carriers of the I-allele do not present an essential handicap to improve perfusion-related aerobic muscle metabolism but that the manifestation of responsiveness depends on the produced work. Conclusions: The deployed interval-type of exercise produced ACE I-allele-related differences in the alterations of negative anaerobic performance and perfusion-related aerobic muscle metabolism, which manifestation is exercise specific. The training-invariant ACE I-allele-associated differences in heart rate and blood glucose concentration emphasize that the repeated impact of the interval stimulus, despite a near doubling of the initial metabolic load, was insufficient to overturn ACE-related genetic influences on cardiovascular function.

Background: The training of elite skiers follows a systematic seasonal periodization with a preparation period, when anaerobic muscle strength, aerobic capacity, and cardio-metabolic recovery are specifically conditioned to provide extra capacity for developing ski-specific physical fitness in the subsequent competition period. We hypothesized that periodization-induced alterations in muscle and metabolic performance demonstrate important variability, which in part is explained by gene-associated factors in association with sex and age. Methods: A total of 34 elite skiers (20.4 ± 3.1 years, 19 women, 15 men) underwent exhaustive cardiopulmonary exercise and isokinetic strength testing before and after the preparation and subsequent competition periods of the World Cup skiing seasons 2015–2018. Biometric data were recorded, and frequent polymorphisms in five fitness genes, ACE-I/D (rs1799752), TNC (rs2104772), ACTN3 (rs1815739), and PTK2 (rs7460, rs7843014), were determined with specific PCR reactions on collected DNA. Relative percentage changes of cardio-pulmonary and skeletal muscle metabolism and performance over the two seasonal periods were calculated for 160 data points and subjected to analysis of variance (ANOVA) to identify hypothesized and novel associations between performance alterations and the five respective genotypes and determine the influence of age × sex. A threshold of 0.1 for the effect size (h2) was deemed appropriate to identify relevant associations and motivate a post hoc test to localize effects. Results: The preparation and competition periods produced antidromic functional changes, the extent of which varied with increasing importance for anaerobic strength, aerobic performance, cardio-metabolic efficiency, and cardio-metabolic/muscle recovery. Only peak RER (−14%), but not anaerobic strength and peak aerobic performance, and parameters characterizing cardio-metabolic efficiency, differed between the first and last studied skiing seasons because improvements over the preparation period were mostly lost over the competition period. A number of functional parameters demonstrated associations of variability in periodic changes with a given genotype, and this was considerably influenced by athlete “age”, but not “sex”. This concerned age-dependent associations between periodic changes in muscle-related parameters, such as anaerobic strength for low and high angular velocities of extension and flexion and blood lactate concentration, with rs1799752 and rs2104772, whose gene products relate to sarcopenia. By contrast, the variance in period-dependent changes in body mass and peak VO2 with rs1799752 and rs2104772, respectively, was independent of age. Likely, the variance in periodic changes in the reliance of aerobic performance on lactate, oxygen uptake, and heart rate was associated with rs1815739 independent of age. These associations manifested at the post hoc level in genotype-associated differences in critical performance parameters. ACTN3 T-allele carriers demonstrated, compared to non-carriers, largely different periodic changes in the muscle-associated parameters of aerobic metabolism during exhaustive exercise, including blood lactate and respiration exchange ratio. The homozygous T-allele carriers of rs2104772 demonstrated the largest changes in extension strength at low angular velocity during the preparation period. Conclusions: Physiological characteristics of performance in skiing athletes undergo training period-dependent seasonal alterations the extent of which is largest for muscle metabolism-related parameters. Genotype associations for the variability in changes of aerobic metabolism-associated power output during exhaustive exercise and anaerobic peak power over the preparation and competition period motivate personalized training regimes. This may help to predict and maximize the benefit of physical conditioning of elite skiers based on chronological characteristics and the polymorphisms of the ACTN3, ACE, and TNC genes investigated here.

Background: Evidence exists that steroid hormones are altered in individuals with autism, especially androgens. Despite lower prevalence in girls than boys, evidence of potential alterations in progesterone metabolites is sparse, so the aim of this study was to elucidate different progesterone metabolites in affected children with autism versus healthy controls. Material and Methods: Circadian urine samples from 48 boys and 16 girls with autism spectrum disorders and a matched case–control group were analysed for progesterone metabolites by gas chromatography–mass spectrometry and normalised for creatinine excretion. Results: In boys with autism, the majority of progesterone metabolites were reduced, such as progesterone, 6a-OH-3a5b-TH-progesterone, or 20a-DH-progesterone (p < 0.01 for all). In girls with autism, a similar pattern of reduction in progesterone metabolites was detected; however, potentially due to the relatively small sample, this pattern was only detectable on the level of a trend. Discussion: As stated, androgen levels are higher in boys and girls with autism, but evidence for progesterone metabolites is much sparser. The pattern of a decrease in progesterone metabolites suggests the existence of an altered routing of steroid metabolites, probably in combination with a dysregulation of the HPAG axis. As, recently, increased CYP17A1 activity has been suggested, the stronger routing towards androgens is further implied in line with our findings of lower progesterone concentrations in boys and girls with autism than healthy controls.

Background: Increasing evidence exists that higher levels of androgens can be found in individuals with autism. Evidence yields to a susceptible role of Cytochrome P450 17A1 (CYP17A1) with its catalyzation of the two distinct types of substrate oxidation by a hydroxylase activity (17-alpha hydroxylase) and C17/20 lyase activity. However, to what extent steps are altered in affected children with autism versus healthy controls remains to be elucidated. Methods: Urine samples from 48 boys with autism (BMI 19.1 ± 0.6 kg/m2, age 14.2 ± 0.5 years) and a matched cohort of 48 healthy boys (BMI 18.6 ± 0.3 kg/m2, 14.3 ± 0.5 years) as well as 16 girls with autism (BMI 17.5 ± 0.7 kg/m2, age 13.8 ± 1.0 years) and a matched cohort of 16 healthy girls (BMI 17.2 ± 0.8 kg/m2, age 13.2 ± 0.8 years) were analyzed for steroid hormone metabolites by gas chromatography-mass spectrometry. Results: The activity of 17-alpha Hydroxylase increased by almost 50%, whereas activity of 17/20 Lyase activity increased by around 150% in affected children with autism. Furthermore, the concentration of Cortisol was higher as compared to the average increase of the three metabolites TH-Corticosterone, 5α-TH-Corticosterone and TH-11β-DH-Corticosterone, indicating, in addition, a stimulation by the CRH-ACTH system despite a higher enzymatic activity. Discussion: As it was shown that oxidative stress increases the 17/20-lyase activity via p38α, a link between higher steroid hormone levels and oxidative stress can be established. However, as glucocorticoid as well as androgen metabolites showed higher values in subjects affected with autism as compared to healthy controls, the data indicate, despite higher CYP17A1 activity, the presence of increased substrate availability in line with the Cholesterol theory of autism.

BACKGROUND:Despite a potential high risk of acute mountain sickness (AMS) in the Swiss Alps, there is a lack of analyses concerning its relevance over longer periods. In consequence, the aim of this study is to analyze the prevalence of AMS in comparison to other causes of mountain emergencies in recent years in Switzerland.MATERIAL AND METHODS:Based on the central registry of mountain emergencies of the Swiss Alpine Club (SAC), all cases in the period between 2009 and 2020 were analyzed for AMS including the most severe forms of high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE). Emergencies were assessed for the severity of the event with a National Advisory Committee for Aeronautics (NACA) score.RESULTS:From a total of 4596 high-altitude mountaineering emergencies identified in the observational period, a total number of 352 cases of illnesses were detected. Detailed analysis revealed 85 cases of AMS, 5 cases of HAPE, and 1 case of HACE. The average altitude was 3845 ± 540 m. Most cases were in the canton of Valais, especially in the Monte Rosa region and the mountains of the Mischabel group (Täschhorn, Dom, Südlenz, Nadelhorn, Hohberghorn). There were only three deaths related to high-altitude illnesses; all the other events could be identified as moderate to severe but not life-threatening.DISCUSSION:An emergency due to AMS that requires rescue is unlikely in the Swiss Alps. This does not imply that AMS is not a concern. However, the facts that the maximal altitude is relatively low and that fast self-descents often seem possible probably minimize the likelihood that mountaineers with symptoms contact emergency services.

Fortunately, fatal accidents while high-altitude mountaineering have decreased in recent years, but the number of emergencies has increased. These nonfatal emergencies might represent situations where alpinists are stranded (emergencies in which alpinists are no longer able to continue their tour on their own because of, for example, exhaustion, equipment problems, or weather). We analyzed 4596 cases of high-altitude-mountaineering emergencies in the period 2009 to 2020 from the SAC (Swiss Alpine Club) emergency registry. In total, 1951 cases (41.6%) were due to being stranded, 1348 cases were due to falls (28.7%), and 352 cases were due to illness (7.5%); these were the three most common classes. In cases of being stranded, 90% of alpinists were uninjured or not seriously injured. In addition, we found only eight fatal cases. More than 50% of cases occurred while ascending a summit above 4000 m. The main causes of becoming stranded were exhaustion and weather changes. These findings suggest that alpinists contact rescue organizations before experiencing serious troubles; these situations thus present risks and dangers both to those stranded and to emergency services. Since exhaustion and weather changes are the two main causes, adequate preparation and tour planning may help prevent such emergencies.