Brain-Periphery Interactions in Huntington's Disease: Mediators and Lifestyle Interventions.

Prominent pathological features of Huntington's disease (HD) are aggregations of mutated Huntingtin protein (mHtt) in the brain and neurodegeneration, which causes characteristic motor (such as chorea and dystonia) and non-motor symptoms. However, the numerous systemic and peripheral deficits in HD have gained increasing attention recently, since those factors likely modulate disease progression, including brain pathology. While whole-body metabolic abnormalities and organ-specific pathologies in HD have been relatively well described, the potential mediators of compromised inter-organ communication in HD have been insufficiently characterized. Therefore, we applied an exploratory literature search to identify such mediators. Unsurprisingly, dysregulation of inflammatory factors, circulating mHtt, and many other messenger molecules (hormones, lipids, RNAs) were found that suggest impaired inter-organ communication, including of the gut-brain and muscle-brain axis. Based on these findings, we aimed to assess the risks and potentials of lifestyle interventions that are thought to improve communication across these axes: dietary strategies and exercise. We conclude that appropriate lifestyle interventions have great potential to reduce symptoms and potentially modify disease progression (possibly via improving inter-organ signaling) in HD. However, impaired systemic metabolism and peripheral symptoms warrant particular care in the design of dietary and exercise programs for people with HD.

Hypoxia Sensing and Responses in Parkinson's Disease.

Parkinson's disease (PD) is associated with various deficits in sensing and responding to reductions in oxygen availability (hypoxia). Here we summarize the evidence pointing to a central role of hypoxia in PD, discuss the relation of hypoxia and oxygen dependence with pathological hallmarks of PD, including mitochondrial dysfunction, dopaminergic vulnerability, and alpha-synuclein-related pathology, and highlight the link with cellular and systemic oxygen sensing. We describe cases suggesting that hypoxia may trigger Parkinsonian symptoms but also emphasize that the endogenous systems that protect from hypoxia can be harnessed to protect from PD. Finally, we provide examples of preclinical and clinical research substantiating this potential.

Gender Disparities in Health Biomarkers, Lifestyle Patterns, and Nutritional Status among Bank Staff: A Cross-Sectional Study.

Background and Objectives: Despite the importance of nutritional status and a healthy lifestyle in shaping overall well-being, little is known about examining gender-specific differences and trends in health, lifestyle, and nutritional status. The present study aimed to evaluate blood levels of micronutrients, homocysteine, and CoQ10, as well as physical activity (PA) levels and sedentary behavior, among a cohort of Austrian bank staff, with a particular focus on identifying gender differences as well as gender-specific nutritional deficiencies compared to the reference ranges. Materials and Methods: Following a cross-sectional study design, 123 Austrian bank staff (mean age: 43 years; 51% females) participated in this study. Blood samples were collected to evaluate participants' micronutrient status and serum levels of homocysteine and CoQ10. Whole-blood values of macronutrients were compared to gender-specific reference ranges and categorized into three groups: below, within, or over the range. The WHO's Global Physical Activity Questionnaire was used to assess PA levels and sedentary behaviors. Results: No significant difference between males and females was found for diet types, PA levels, sedentary time, homocysteine levels, or CoQ10 values (p > 0.05). A high PA level was reported by 64% of males and 58% of females. 71% of females and 56% of males were found to have a vitamin D deficiency. 63-98% of females and 72-97% of males showed normal blood levels for the remaining micronutrients, including potassium, calcium, magnesium, copper, iron, zinc, selenium, manganese, molybdenum, B6, B9, and B12. Conclusions: The findings highlight the necessity of implementing tailored strategies to foster healthy lifestyle behaviors, thereby enhancing the overall state of health, particularly in the context of occupational health.

Mechanisms underlying the health benefits of intermittent hypoxia conditioning.

Intermittent hypoxia (IH) is commonly associated with pathological conditions, particularly obstructive sleep apnoea. However, IH is also increasingly used to enhance health and performance and is emerging as a potent non-pharmacological intervention against numerous diseases. Whether IH is detrimental or beneficial for health is largely determined by the intensity, duration, number and frequency of the hypoxic exposures and by the specific responses they engender. Adaptive responses to hypoxia protect from future hypoxic or ischaemic insults, improve cellular resilience and functions, and boost mental and physical performance. The cellular and systemic mechanisms producing these benefits are highly complex, and the failure of different components can shift long-term adaptation to maladaptation and the development of pathologies. Rather than discussing in detail the well-characterized individual responses and adaptations to IH, we here aim to summarize and integrate hypoxia-activated mechanisms into a holistic picture of the body's adaptive responses to hypoxia and specifically IH, and demonstrate how these mechanisms might be mobilized for their health benefits while minimizing the risks of hypoxia exposure.

Effects of Qigong Exercise on Physical and Cognitive Performance in Young Sedentary Females: A Quasi-Experimental Design, Placebo-Controlled Study.

Background: Qigong exercise represents one type of traditional Chinese exercise that might positively affect physical and psychological functioning, slow down disease development and improve quality of life. However, study findings are somewhat conflicting and mechanisms contributing to expected beneficial effects are rather poorly known. Objective: This study aims to evaluate the effects of qigong exercise training for 8 weeks on selected physical, cognitive, and biochemical outcomes in young sedentary females. Method/Design: Quasi-experimental design, placebo-controlled study. Setting: The study was performed at the Department of Physical Therapy, Faculty of Allied Health Science, Burapha University, Bangsean, Chonburi province, Thailand. Participants: Participants were 41 females with sedentary lifestyles. Interventions: 41 sedentary females were allocated to qigong exercise (QG, n = 20) or to the control group (CG, n = 21). Primary Outcome Measures: VO2 max predicted from step testing, aspects of cognitive functions (e.g., digit span forward, DSF, and digit span backward, DSB, task), hematological and biochemical parameters, and body composition were assessed in both groups before and after the 8-week training period. Results: Physical performance (estimated VO2 max) significantly increased after qigong training compared to the CG (P < .001). Working memory (DSB) increased after intervention only within the QG (P = .009) but changes did not reach significance between the groups. Changes in neutrophils (potential mediators of inflammation) tended to be improved in the QG in comparison to the CG (P = .075). Body composition remained unchanged. Conclusion: These findings indicate that 8 weeks of qigong training increased aerobic capacity and tended to improve working memory in otherwise sedentary young females. Neutrophils tended to decrease within the QG. Thus, it was speculated that enhanced oxygen supply to the brain and the decrease of neutrophils adhering to cortical capillaries might have contributed to improved cognitive function.

Impact of Environmental Factors on the ACL Injury Risk in Recreational Alpine Skiing.

In recreational alpine skiing, an ACL injury represents the most common injury. Skiing is a complex activity where the skier interacts with the environment, such as weather, snow conditions, temperature, etc. Thus, the aim of this study was to evaluate the potential impact of environmental factors on ACL injury risk in recreational alpine skiers. Among a cohort of 392 ACL-injured skiers and 392 uninjured controls matched for sex and skiing skill, environmental factors were collected by questionnaire. Factors included weather conditions, snow conditions, perceived temperature, and slope difficulty at the time-point of the accident (ACL-injured skiers) or of questioning during the ski day (uninjured controls).Multiple logistic regression revealed that in addition to age, five environmental factors were significantly predictive of an ACL injury: fresh snow (OR 10.5), grippy snow (OR 7.8), icy slope condition (OR 12.4), very cold/cold perceived temperature (OR 1.6), and skiing on easy slopes (OR 6.9). In conclusion, besides age, environmental factors such as fresh and grippy snow, icy slope conditions, low temperatures, and flat slopes are associated with an increased ACL injury risk in recreational alpine skiing. Those factors are at least partly modifiable and should be taken into consideration for preventive strategies.

Molecular Mechanisms of High-Altitude Acclimatization.

High-altitude illnesses (HAIs) result from acute exposure to high altitude/hypoxia. Numerous molecular mechanisms affect appropriate acclimatization to hypobaric and/or normobaric hypoxia and curtail the development of HAIs. The understanding of these mechanisms is essential to optimize hypoxic acclimatization for efficient prophylaxis and treatment of HAIs. This review aims to link outcomes of molecular mechanisms to either adverse effects of acute high-altitude/hypoxia exposure or the developing tolerance with acclimatization. After summarizing systemic physiological responses to acute high-altitude exposure, the associated acclimatization, and the epidemiology and pathophysiology of various HAIs, the article focuses on molecular adjustments and maladjustments during acute exposure and acclimatization to high altitude/hypoxia. Pivotal modifying mechanisms include molecular responses orchestrated by transcription factors, most notably hypoxia inducible factors, and reciprocal effects on mitochondrial functions and REDOX homeostasis. In addition, discussed are genetic factors and the resultant proteomic profiles determining these hypoxia-modifying mechanisms culminating in successful high-altitude acclimatization. Lastly, the article discusses practical considerations related to the molecular aspects of acclimatization and altitude training strategies.

Comparison of heart rates at fixed percentages and the ventilatory thresholds in patients with interstitial lung disease.

Heart rate (HR) responses to maximal exercise are commonly used for the prescription of training intensities in pulmonary rehabilitation. Those intensities are usually based on fixed percentages of peak HR (HRpeak), heart rate reserve (HRR), or peak work load (Wpeak), and rarely on HRs at the individual ventilatory thresholds (VT1 and VT2) derived from cardiopulmonary exercise testing (CPET). For patients suffering from interstitial lung disease (ILD), data on cardiorespiratory responses to CPET are scarce. Thus, the aim of this study was to record cardiorespiratory responses to CPET and to compare fixed HR percentages with HRs at VT1 and VT2 in ILD patients. A total of 120 subjects, 80 ILD patients and 40 healthy controls, underwent a symptom-limited CPET. From the ILD patient, 32 suffered from idiopathic pulmonary fibrosis (IPF), 37 from connective tissue disease (CTD), and 11 from sarcoidosis. HRs at fixed percentages, that is, at 70%HRpeak, at 70%Wpeak, and at 60%HRR were significantly lower in the ILD patients compared with the control group (p-values: 0.001, 0.044, and 0.011). Large percentages of HR values at 70%Wpeak and 60%HRR ranged between the HRs at VT1 and VT2 in ILD subgroups and controls as well. HRs at 70%HRpeak were lower than HRs at VT1 in 66% of the IPF patients, 54% of the CTD patients, and 55% of patients with sarcoidosis compared with 18% in the control group. Our findings demonstrate a considerable scattering of fixed HR percentages compared with HRs at the individual VTs derived from CPET in ILD patients. These findings may provide valuable information for the prescription of exercise intensity in pulmonary rehabilitation of ILD patients.

Impact of ski geometry data and standing height ratio on the ACL injury risk and its use for prevention in recreational skiers.

OBJECTIVES: To evaluate the impact of ski geometry data and standing height ratio on anterior cruciate ligament (ACL) injury risk of male and female recreational skiers. METHODS: A retrospective questionnaire-based, case-control study of ACL-injured and uninjured recreational skiers was conducted during six consecutive winter seasons. Ski geometry data (ski length, side-cut radius, widths of the tip, waist and tail) were recorded from each participant's skis. Standing heights at the front and rear components of the ski binding were measured with a digital sliding calliper, and the standing height ratio between the front and rear was calculated. RESULTS: A total of 1817 recreational skiers participated in this study, of whom 392 (21.6%) sustained an ACL injury. Multiple logistic regression analysis indicates a higher age, a lower skill level and riskier behaviour as independent individual risk factors associated with an ACL injury. An increase in ski length, tip width of the ski, standing height at the rear ski binding component, and in standing height ratio were found to be independent equipment-related risk factors for an ACL injury. CONCLUSION: Reduced ski length, narrower ski tip width, lower rear standing height and a lower standing height ratio (ie, rear component of the ski binding is more elevated compared with the front component) were associated with a reduced likelihood for ACL injury. When buying or renting skis, these parameters could be considered to reduce the likelihood of ACL injury in recreational skiers.

Acute physiological response to a normobaric hypoxic exposure: sex differences.

Although preliminary studies suggested sex-related differences in physiological responses to altitude/hypoxia, controlled studies from standardised exposures to normobaric hypoxia are largely lacking. Hence, the goals of this study were to provide information on cardiorespiratory responses to a 7-h normobaric hypoxia exposure and to explore potential differences between men and women. In this crossover study, a total of 15 men and 14 women were subjected to a 7-h exposure in normoxia (FiO2: 21%) and normobaric hypoxia (FiO2: 15%). Values of peripheral oxygen saturation, heart rate, systolic and diastolic blood pressure and respiratory gases were recorded every hour (8 time points), and oxygen saturation every 30 min (15 time points). Compared to normoxia, exposure to hypoxia significantly increased minute ventilation from baseline to hour 7 in males (+ 71%) and females (+ 40%), significantly greater in men (p < 0.05). A steeper decrease in peripheral oxygen saturation until 2.5 h in hypoxia was seen in females compared to males (p < 0.05). In conclusion, the ventilatory response to hypoxia was more pronounced in men compared to women. Moreover, during the first hours in hypoxia, peripheral oxygen saturation dropped more markedly in women than in men, likely due an initially lower and/or less efficient ventilatory response to moderate hypoxia. Those findings should be considered when performing interventions for therapy or prevention in normobaric hypoxia. Nevertheless, further large-scaled and well-controlled studies are needed.

Ski-geometric parameters do not differ between ACL injury mechanisms in recreational alpine skiing.

PURPOSE: It is not known so far if ski-equipment-related factors differ between the ACL injury mechanisms, potentially influencing the circumstances and causes of falling, finally resulting in ACL injury. More specifically focusing on the injury mechanisms will provide a deeper understanding of injury causation. The aim of the study was to evaluate whether ACL injury mechanisms in recreational alpine skiing differ with regard to ski-geometric parameters, self-reported circumstances and causes of accident and injury severity. METHODS: Among a cohort of 392 ACL-injured (57.9% females) skiers, age, sex, height, weight, skill level, risk-taking behavior, circumstances and causes of accident, and ACL injury severity were collected by questionnaire. Additionally, patients had to recall their type of fall (ACL injury mechanism) by classifying forward and backward falls with and without body rotation. Ski length, side cut radius and widths of the tip, waist and tail were directly notated from the ski. RESULTS: The forward fall with body rotation was the most common reported ACL injury mechanism (63%). A riskier behavior was associated with forward falls without body rotation. Ski-geometric parameters did not significantly influence the type of ACL injury mechanism. Regarding accident characteristics, catching an edge of the ski was more frequent (p < 0.001) the cause for forward falls (75% and 67%) when compared to the backward falls (46 and 15%) and executing a turn was the most frequent action in all falls (39-68%). A complete rupture of the ACL (66-70%) was more commonly reported than a partial tear (30-34%) among all four non-contact ACL injury mechanisms (n.s.). CONCLUSION: In contrast to risk-taking behavior and accident characteristics, ski-geometric parameters and injury severity do not significantly differ between ACL injury mechanisms in recreational skiing. Thus, an individual skiing style seems to have more impact on ACL injury mechanisms than ski equipment. Future studies should evaluate potential effects of ski geometry on the incidence of ACL injury. LEVEL OF EVIDENCE: III.

Extreme sports performance for more than a week with severely fractured sleep.

PURPOSE: Severely fractured sleep is mostly portrayed negatively, but investigations in extreme sports show that humans can maintain performance with a minimum of sleep. With two cases of long-lasting extreme sports performances, we demonstrate that severely fragmented sleep does not necessarily lead to a deterioration of physical and cognitive performance. METHODS: We performed continuous polysomnography on a 34 year-old skier for 11 days and nights during a world record attempt in long-term downhill skiing and monitored a 32 year-old cyclist during the Race Across America for 8.5 days via sleep and activity logs. RESULTS: The skier slept fractured fashion in 15-16 naps with a daily average of 6 h consisting of 77% in sleep stage 1 and 2, 11% in stage 3, and 13% in stage REM. The cyclist slept a total of 7 h and 52 min in 8.5 days, split up into 11 short naps and 6 sleep periods. The average duration of napping was 8.8 min and of sleep 64.2 min. CONCLUSIONS: These two cases demonstrate that outstanding performances are possible with severely fractured sleep and/or sleep deprivation. In well-trained athletes, breaking new recordsis possible despite extreme sleep habits.

In recreational alpine skiing, the ACL is predominantly injured in all knee injuries needing hospitalisation.

PURPOSE: The knee joint still represents the most frequent anatomical injury location accounting for about one-third of all injuries in recreational alpine skiers. However, comprehensive information on current knee injury patterns in this populations is sparse. METHODS: During the winter seasons 2016/17 and 2019/20, this retrospective questionnaire-based study was conducted in an Austrian sportclinic situated in a large ski area. Among a cohort of 282 recreational skiers (51.8% females), all injuries were diagnosed by the use of magnetic resonance imaging. Additionally, data were recorded on anthropometric characteristics, the perceived speed at the moment of injury, type of fall, physical fitness, self-reported skill level and risk-taking behaviour. RESULTS: The anterior cruciate ligament (ACL) was injured in all knee injuries recorded. Of the total study sample, 64.5% (n = 182) were ACL injuries with concomitant injuries and about 35.5% (n = 100) were isolated ACL injuries, not involving any other structures of the knee joint. In general, most common concomitant injury diagnoses among ACL-injured recreational alpine skiers were injuries of the medial collateral ligament (MCL) (n = 92, 50.5%), medial meniscus (MM) (n = 73, 40.1%) and lateral collateral ligament (LCL) (n = 41, 22.5%). No significant differences regarding additionally recorded characteristics were found between ACL-injured individuals with concomitant injuries and those with isolated ACL injury. CONCLUSIONS: Whereas, before the introduction of carving skis, the MCL was reported being the most common injured part of the knee, currently, the majority of knee injuries are ACL injuries accompanied by injury of other knee joint structures, i.e. the MCL, MM and LCL. LEVEL OF EVIDENCE: Level III.

5-Hydroxymethylfurfural and α-ketoglutaric acid supplementation increases oxygen saturation during prolonged exercise in normobaric hypoxia.

This double-blinded, randomized and placebo-controlled, crossover study investigated whether α-ketoglutaric-acid (α-KG) and 5-hydroxymethylfurfural (5-HMF) supplementation improves exercise performance in hypoxia and affects physiological responses during the exercise task. Eight moderately trained male participants (age: 25.3 ± 2.0 y, VO2max: 48.0 ± 8.3 ml/min/kg) performed an incremental exercise test to exhaustion in normoxia and two 2-hour cycle time trial (TT) tests in hypoxia (3,500 m) each separated by 1-week. Prior to the TT, participants supplemented with either α-KG and 5-HMF or placebo (random order). Supplementation did not improve TT performance at altitude and did not affect heart rate, effort perception and oxidative stress levels (p > 0.05). Oxygen saturation (SpO2) was enhanced during the α-KG and 5-HMF supplementation trial (79.5 ± 3.3 vs. 78.2 ± 3.7%, p = 0.026). Even though TT performance was unaffected, the enhanced SpO2 - possibly originated from changed O2-affinity - deserves further consideration as the exercise performance decline at altitude is strongly linked to the SpO2 decline. The inclusion of moderately fit participants, not specifically cycle trained, might have prevented any visible performance enhancement.

The Use of Pulse Oximetry in the Assessment of Acclimatization to High Altitude.

Background: Finger pulse oximeters are widely used to monitor physiological responses to high-altitude exposure, the progress of acclimatization, and/or the potential development of high-altitude related diseases. Although there is increasing evidence for its invaluable support at high altitude, some controversy remains, largely due to differences in individual preconditions, evaluation purposes, measurement methods, the use of different devices, and the lacking ability to interpret data correctly. Therefore, this review is aimed at providing information on the functioning of pulse oximeters, appropriate measurement methods and published time courses of pulse oximetry data (peripheral oxygen saturation, (SpO2) and heart rate (HR), recorded at rest and submaximal exercise during exposure to various altitudes. Results: The presented findings from the literature review confirm rather large variations of pulse oximetry measures (SpO2 and HR) during acute exposure and acclimatization to high altitude, related to the varying conditions between studies mentioned above. It turned out that particularly SpO2 levels decrease with acute altitude/hypoxia exposure and partly recover during acclimatization, with an opposite trend of HR. Moreover, the development of acute mountain sickness (AMS) was consistently associated with lower SpO2 values compared to individuals free from AMS. Conclusions: The use of finger pulse oximetry at high altitude is considered as a valuable tool in the evaluation of individual acclimatization to high altitude but also to monitor AMS progression and treatment efficacy.

Migraine and aura triggered by normobaric hypoxia.

BACKGROUND: For future experimental studies or the development of targeted pharmaceutical agents, a deeper insight into the pathophysiology of migraine is of utmost interest. Reliable methods to trigger migraine attacks including aura are desirable to study this complex disease in vivo. METHODS: To investigate hypoxia as a trigger for migraine and aura, we exposed volunteers diagnosed with migraine, with (n = 16) and without aura (n = 14), to hypoxia utilizing a hypoxic chamber adjusted to a FiO2 of 12.6%. The occurrence of headache, migraine, aura, and accompanying symptoms were registered and vital signs were collected for 6 hours under hypoxia and 2 hours of follow-up. A binary logistic regression analysis examined the probability of triggering headaches, migraines, aura, photo- and phonophobia. FINDINGS: Of 30 participants, 24 (80.0%) developed headaches and 19 (63.3%) migraine, five (16.7%) reported aura. Two patients that developed aura never experienced aura symptoms before in their life. The increase of mean heart frequency was higher in patients developing headaches or migraine. Mean SpO2 during hypoxia was 83.39%. CONCLUSION: Hypoxia was able to trigger migraine attacks and aura independently of any pharmacological agent.

Is the Effect of Physical Activity on Quality of Life in Older Adults Mediated by Social Support?

Increasing evidence suggests positive associations between physical activity, social support, and quality of life in later life. However, the role of physical activity and social support in the influence on quality of life is unclear. In this viewpoint, definitions of central terms and key research findings on factors influencing quality of life in older adults are provided. We highlight the importance of both a physically active lifestyle and high social support in positively influencing quality of life. However, we question the direct effect of physical activity on quality of life and present data of a cross-sectional study to support the assumption that the effect of physical activity on quality of life might be influenced by perceived social support. In this cross-sectional study, self-reported physical activity, social support, and quality of life were assessed in a nonclinical sample of 100 adults aged between 60 and 80 years. Statistical analyses included correlation analyses and covariate-controlled mediation analyses. The results confirmed the research findings on positive correlations between all domains of quality of life and both physical activity and social support. Mediation analyses indicated that the effect of physical activity on all domains of quality of life was at least partially mediated by social support, when controlled for covariates. Based on the findings of published evidence and this cross-sectional study, a socially and physically active lifestyle is recommended for older adults to positively influence quality of life. However, the well-documented effect of physical activity on quality of might be an at least partially mediated effect by perceived social support. Practical and research-related implications of a potential indirect effect are discussed. Further prospective research is warranted to clarify the relationship between the variables.