Maximal heart rate (HRmax) is a widely used measure of cardiorespiratory fitness. Prediction of HRmax is an alternative to cardiopulmonary exercise testing (CPET), but its accuracy among endurance athletes (EA) requires evaluation. This study aimed to externally validate HRmax prediction models in the EA independently for running and cycling CPET. 4043 runners (age=33.58 (8.12) years; 83.53% males; BMI=23.66 (2.54) kg·m−2) and 1026 cyclists (age=36.88 (9.03) years; 89.67% males; BMI=24.04 (2.65) kg·m−2) underwent maximum CPET. Student t-test, mean absolute percentage error (MAPE), mean absolute error (MAE), and root mean square error (RMSE) were applied to externally validate 8 running and 5 cycling HRmax equations. HRmax was 184.60 (9.79) beats·min−1 and 182.66 (10.28) beats·min−1 respectively for running and cycling, p=0.001. Measured and predicted HRmax differed significantly (p=0.001) for 9 of 13 (69.23%) models. HRmax was overestimated by 8 (61.54%) and underestimated by 5 (38.46%) formulae. Overestimated HRmax ranged 0.08-4.94 beats·min−1 and underestimated HRmax ranged 0.03-4.90 beats·min−1. MAE and RMSE were 0.18-4.94 beats·min−1 and 9.13-10.47, respectively. MAPE ranged 3.95-4.69%. Prediction models do not allow for accurate estimation of HRmax. HRmax was more often underestimated than overestimated. Predicted HRmax can be implemented for EA as a supplemental method but CPET is the preferable approach.

This study presents three forms of interdisciplinary expertise in the healthcare design context to approach a particular multifaceted problem around the current healthcare for older adult patients with chronic low-back pain (LBP). Using an interdisciplinary co-design framework, first, our design approach performs the role of an initiator to define the problem by exploring the current context of healthcare. Second, it facilitates the experiences of experts and patients to reach the roots of the problem by functioning as a mediator. Third, our approach fulfills the primary role of healthcare design in producing new meanings considering the principles of patient-centeredness. These roles significantly contributed to the design of healthcare innovations. Our framework transformed the distributed disciplinary knowledge developed while tackling the multifaceted problem into new forms of expertise for collaboration in healthcare innovation.

The use of whole-body vibration (WBV) for therapeutic purposes is far from being standardized and only very recently an empirical foundation for reporting guidelines for human WBV studies has been published. Controversies about safety and therapeutic dosage stll exist. The present study aimed to investigate the metabolic and mechanical effects of low-intensity WBV in according to the ISO 2631 norm on subjects with obesity. 41 obese subjects (BMI≥ 35 kg/mˆ2) were recruited to participate in a 3-week multidisciplinary inpatient rehabilitation program including fitness training and WBV training. During WBV the posture was monitored with an optoelectronic system with 6 infrared cameras (Vicon, Vicon Motion System, Oxford, UK). The primary endpoints were: variation in body composition, factors of the metabolic syndrome, functional activity (sit-to-stand and 6-min walking test), muscle strength, and quality of life. Secondary endpoints were: modification of irisin, testosterone, growth hormone, IGF1 levels. We observed significant changes in salivary irisin levels, Group 2 (p<0.01) as compared to the control group, while muscle strength, function, and other metabolic and hormonal factors did not change after a 3-week low-intensity WBV training respect control group. Future studies are needed to deeper investigate the potential metabolic effect of low-intensity WBV in managing weight.

The climate crisis is developing to a life-changing event on a global level. Health promotion with the aim to increase the health status of individuals, independent from the present health status has been developed on scientific basis at least for the last eight decades and follows. There are some basic principles, which are prerequisites for both, health promotion and climate protection. Those principles include (1) sustainability, (2) orientation on determinants, and (3) requirement of in-dividual as well as community approaches. People are generally aiming to protect their lifestyle habits (e.g. traveling, consumer habits) and personal properties (e.g. car, house) by easy solution with as little effort as possible, and this can affect both, health and climate. To reduce the emission of greenhouse gases and to protect our environment, changes towards a sustainable lifestyle have to be embed into everybody’s mind. Examples for domains, that need to be addressed in health promotion as well as in climate protection include education/ knowledge/ (health) literacy, physical activity, nutrition and dietary habits, mental health, and social capital. If health promo-tion fails to tackle those domains, this will continue to drive climate crisis. And climate change, in turn, will affect health. On the other hand, developing and promoting health resources in the domains mentioned could again help to mitigate the health-damaging effects of climate change.

Telemedicine and remote survey of physiological parameters may significantly increase the health and safety of people working in extreme environmental conditions, like firefighters, maintain rescuers, soldiers, and others. We highlight this problem and give an overview of the historical development and the actual status of systems available. Ruggedized systems, as small, lightweight, and flexible as possible, are needed to optimize the goal of increasing occupational health and safety of persons at risk and maximizing their performance during missions.

Exercise affects various organs. However, its effects on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training in-creases the expression of carbohydrate digestion and absorption molecules. Exercise was also shown to increase the concentration of blood glucagon like peptide-2(GLP-2), which regulates carbohydrate digestion and absorption in small intestinal epithelium. Therefore, we investigated the effects of exercise on intestinal digestion and absorption molecules and the levels of GLP-2. 6-wk-old of male mice were divided into 2 groups; sedentary (SED) and low-intensity exercise (LEx). LEx mice were required to run on a treadmill (12.5 m/min, 60 min), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest and plasma, jejunum, ileum, and colon were sampled. Samples were analyzed using EIA and immunoblotting. The levels of plasma GLP-2 and the expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter (GLUT2) in the jejunum were increased in LEx group. We showed that acute low-intensity exer-cise affects the intestinal carbohydrate digestion and absorption molecules via GLP-2. Our results suggest that exercise might provide new benefits to the small intestine for people with intestinal frailty.

After a Century it is time to turn the page on understanding of lactate metabolism and appreciate that lactate shuttling as an important component of intermediary metabolism in vivo. Cell-Cell and intracellular Lactate Shuttles fulfill purposes of energy substrate production and distribution as well as cell signaling under fully aerobic conditions. Recognition of lactate shuttling came first in studies of physical exercise where roles of driver and recipient cells and tissues were obvious. Moreover, the presence of lactate shuttling as part of postprandial glucose disposal has been recognized. Mitochondrial respiration creates the physiological sink for lactate disposal in vivo. Repeated lactate exposure from regular exercise results in adaptive processes such as mitochondrial biogenesis and other healthful circulatory and neurological characteristic such as improved physical work capacity, metabolic flexibility and cognition. The importance of lactate and lactate shuttling in healthful living is further emphasized when lactate signaling and shuttling are dysregulated as occur in illness and injury. Like a Phoenix, lactate rises again in importance in 21^st Century Biology.

The lytic bone disease is a hallmark of multiple myeloma, being present in about 80% of patients with newly diagnosed MM, and in more during the disease course. The myeloma associated bone disease (MBD) severely affects the morbidity and quality of life of the patients. MBD defines treatment demanding MM. In recent years, knowledge of the underlying pathophysiology has increased, and novel imaging technologies, medical and non-pharmaceutical treatments have improved. In this review, we highlight the major achievements in understanding, diagnosing and treating MBD. For diagnosing MBD, low-dose whole-body CT is now recommended over conventional skeletal survey, but also more advanced functional imaging modalities, such as diffusion-weighted MRI and PET/CT are increasingly important in the assessment and monitoring of MBD. Bisphosphonates have, for many years, played a key role in management of MBD, but denosumab is now an alternative to bisphosphonates, especially in patients with renal impairment. Radiotherapy is used for uncontrolled pain, for impeding fractures and in treatment of impeding or symptomatic spinal cord compression. Cement augmentation has been shown to reduce pain from vertebral compression fractures. Cautious exercise programs are safe and feasible and may have the potential to improve the status of patients with MM.

Objective: The objective of our study was to explore the potential benefits of combining moderate alcohol consumption with regular vigorous physical activity on HDL-cholesterol levels and its potential positive impact on cardiovascular health. Material and method: The study comprised two groups: group A (102 patients) who consumed 1 gram of alcohol per day, specifically red wine, and increased their exercise levels in addition to their standard medical treatment, and group B (108 patients) who adhered only to their standard medical treatment. The patients were monitored for a year, during which various clinical parameters were observed. Results:Our study showed that moderate alcohol consumption, particularly red wine, along with increased physical activity levels, was associated with enhancements in exercise tolerance and elevated levels of HDL-cholesterol. Our findings suggest the efficacy of the intervention in improving lipid profiles, with the group that consumed alcohol as part of their treatment scheme, generally experiencing more pronounced positive effects. Statistically significant differences between groups in terms of angina evolution, AMI recurrence, or arrhythmias evolution were not found. However, there were important differences in terms of EF improvement and quality of life, with the alcohol consuming group displaying greater improvements in both aspects. Conclusions:In conclusion, our study emphasizes the potential benefits of combining moderate alcohol consumption, specifically red wine, with increased physical activity levels for improving exercise tolerance and enhancing HDL-cholesterol levels. However, further research and clinical trials are essential to fully understand the mechanisms and optimize the integration of these lifestyle elements for improved cardiovascular health outcomes.

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for recruitment of transcriptional complexes, and interaction of enhancers and promoters all contribute to acute and chronic adaptations of cells, tissues and organs to internal and external perturbations. Similarly, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is activated by stimuli that alter the cellular energetic demand, and subsequently controls complex transcriptional networks responsible for cellular plasticity. It thus is of no surprise that PGC-1α is under the control of epigenetic mechanisms, and constitutes a mediator of epigenetic changes in various tissues and contexts. In this review, we summarize the current knowledge of the link between epigenetics and PGC-1α in health and disease.

Background: Depression, a multifaceted mental health condition, necessitates a multidimensional approach to treatment. This study aimed to elucidate the potential efficacy of various mitochondrial interventions, ranging from pharmacological treatments to lifestyle modifications, in alleviating depressive symptoms and enhancing overall mental well-being and assess the diverse range of mitochondrial assessments for managing depression by synthesizing findings from selected studies. Methods: A systematic compilation of studies, employing observational, interventional, and animal-based designs, was undertaken to elucidate the intricate relationship between mitochondrial function and depression as well as depressive signs and symptoms. The PRISMA guidelines were employed for conducting this review and a specific set of selection criterion were formulated by a team of reviewers for selection of relevant papers. Results: The synthesized results from the 21 selected papers highlighted the potential of these interventions to target diverse aspects of depression. Hyperbaric oxygen therapy and psychotherapy demonstrated significant reductions in depression and anxiety scores, with hyperbaric oxygen therapy particularly effective in improving nerve function and daily living activities. Whole-body cryotherapy displayed substantial improvements in depressive symptoms and quality of life. Frequent sauna bathing exhibited a lower risk of depressive symptoms in males. Dietary patterns, including Paleolithic and Mediterranean diets, showcased potential protective effects against depression, anxiety, and stress. The ketogenic diet revealed promise in ameliorating depression and psychosis symptoms alongside positive metabolic changes. Fasting interventions, though challenging, were associated with lower anxiety and depression levels without increased fatigue. Bright white light therapy enhanced remission rates and reduced depression scores in bipolar depression. Probiotic supplementation exhibited potential in reducing depression scores and improving metabolic markers, although further investigation is warranted. Conclusion: The diverse array of interventions explored in this study underlines the multifaceted nature of depression treatment. While these findings offer hope for more personalized and effective approaches, it is imperative to consider the variability in study designs, sample sizes, and methodologies among the selected papers. The mechanisms underlying the observed effects remain partially understood, emphasizing the need for continued mechanistic research. This study sets the stage for future investigations and clinical practices, showcasing the potential of various interventions in mitigating the challenges posed by depression and paving the way for more effective treatment strategies.

The worldwide prevalence of type 2 diabetes (T2D) and prediabetes is rapidly increasing, particularly in children, adolescents, and young adults. Oxidative stress (OxS) has emerged as a likely initiating factor in T2D. The role of natural antioxidant products in combating T2D is best evaluated in the context of the complex physiological processes that modulate T2D-OxS such as glycemic control and exercise. The role of natural antioxidant compounds such as vitamin E in T2D must likewise be considered beyond their roles as inhibitors of OxS. In addition to antioxidant properties, vitamin E vitamers (tocopherols and tocotrienols) also exhibit distinct abilities to regulate cellular signal transduction pathways important to T2D progression. Most research on the role of vitamin E in T2D or prediabetes has been limited to tocopherols (Ts) but emerging trials with tocotrienols (T3s) show promise. Minimizing factors that induce chronic damaging OxS and maximizing natural antioxidant protective factors may provide a means of preventing or slowing T2D progression. This “optimal redox” (OptRedox) approach also provides a framework in which to discuss the potential benefits of natural antioxidant factors such as antioxidant products. Since early, effective intervention is critical, the OptRedox strategy would be optimally effective if implemented in the pediatric population.

Back pain is a common symptom that affects all age groups across the globe, when left untreated may eventually lead to disability. A convenient sample selection method was used in this study due to the global Covid-19 pandemic lockdown which was effective in Turkey during the investigation period. Thus, virtual data collection and health education including some health risks were employed. A total population of two hundred adult women was involved in the study but one hundred and twenty-one responses were collected. Findings show that, for socio-demographic characteristics, the pain was found highest in women between the ages of 41-50 and obese/overweight individuals. Although, there was no significant difference recorded in the marital status category. Moreover, statistical mean differences were detected between the scales for ODI (4.18) and BPFS (6.09). Also, p<0.05, paired sample t-test was 0.001 ODI and 0.001 BPFS after the training exercise. This suggests that exercise training is inversely correlated with pain severity which implies that training has a significant influence on pain intensity. Thus, it could be concluded that there is a relationship between the training exercise and ODI/BPFS.

ABSTRACTBackground: Crohn's disease (CD) is a chronic inflammatory bowel disorder with limited treatment options. Mitochondrial dysfunction has been implicated in CD pathogenesis, and mitochondrial-based interventions have emerged as a potential therapeutic avenue. This systematic review aimed to assess the efficacy of mitochondrial-based interventions in the management of CD.Methods: A systematic search of multiple databases was conducted to identify relevant studies in accordance with the PRISMA protocol. Inclusion criteria encompassed studies investigating mitochondrial-targeted interventions in CD patients. Methodological quality and risk of bias assessments were performed. Data synthesis involved both quantitative meta-analysis and qualitative narrative synthesis.Results: A total of 23 studies were included in this review, comprising randomized controlled trials, observational studies, and case reports. Mitochondrial-based interventions encompassed nutraceuticals, probiotics, exercise, and dietary modifications. However, the overall quality of evidence was moderate, primarily due to methodological limitations in some studies.Conclusion: This systematic review suggests that mitochondrial-based interventions hold promise as adjunctive therapies for CD management. They appear to contribute to clinical remission and amelioration of disease activity. Nevertheless, the moderate quality of evidence underscores the need for further well-designed clinical trials to substantiate these findings and delineate optimal intervention strategies.

Course-based Undergraduate Research Experiences (CUREs) in high-enrollment, introductory classes are a 37 potentially transformative approach to retaining more students in STEM majors. We developed and piloted a CURE 38 in the introductory biology courses at the University of Washington. This CURE focuses on analyzing experimental 39 evolution of antibiotic resistance in Escherichia coli and generates data on two topics relevant to clinical practice: 40 compensatory mutations and cross-drug effects. By studying mutations in central cellular machinery that confer drug 41 resistance, students not only gain insight into fundamental cellular phenomena, but also recognize the molecular 42 basis of a medically important form of evolutionary change, connecting genetics, microbiology, and evolution.

Throughout this paper the effects of injuries on athletes are highlighted in different aspects. Exertional compartment syndrome is a specific injury related to athletes that is thoroughly explored in this paper through an analysis of the anatomy, symptoms, diagnosis and treatments of the syndrome. Exertional compartment syndrome is an exercise-induced muscle and nerve condition that causes pain, swelling as well as disability in the affected muscles of the lower leg. This syndrome commonly develops in young athletes involved in sports with excessive running and repetitive impact such as track and field, soccer, basketball and lacrosse. Exertional compartment syndrome is commonly misdiagnosed as other less severe injuries such as shin splints, which is symptomatic of pain along the tibia bone of the lower leg caused by overuse. The misdiagnosis of exertional compartment syndrome allows the syndrome to worsen and intensify resulting in the only effective treatment to be fasciotomy, a surgical procedure to release the pressure within the compartment of the lower leg. There is no definitive protocol developed for patients after fasciotomy is performed. Athletes experiencing similar symptoms after surgery are usually treated for their symptoms rather than the syndrome as a whole, which does not have a high degree of success. The development of a definitive protocol utilizing the techniques of manual therapy, mobility stretching and corrective strength training can improve the adverse effects of exertional compartment syndrome as well as restore functionality to the athlete. Raising awareness of this syndrome in athletics will be effective in treating the athlete early on in order to avoid severe effects and invasive procedures.

We examined special roles of the Central Nervous System (CNS) in an attempt to resolve the puzzle that chronic diseases cannot be cured by medicine. By exploring a skill-learning model, we found that the CNS is able to remember certain information reflecting biochemical and cellular (B&C) processes in the body. From the skill using ability, we found that the CNS is able to control basic B&C processes that drive and power the skill. From the ability to adjust forces and force direction of a physical act, we found that the CNS is able to adjust B&C processes that drive the physical act. From this adjustment capability, we further inferred that the CNS must also store information on the baseline B&C processes. As a whole, we found that the CNS can maintain information on baseline B&C processes, up-regulate or down-regulate the processes, and make comparisons in performing its regulatory functions. We found that chronic diseases are the results of deviated baseline B&C processes. Per the proved hypothesis, the CNS maintains deviated baseline B&C processes, and thus protects the body states of fully developed diseases. We then used the three CNS roles to explain that cancer progresses with increasing malignancy, cancer quickly returns after a surgery, cancer cells repopulate after chemotherapy and radiotherapy, cancer develops drug resistance inevitably, immune cells rebound after suppression, generally poor benefits of cancer drugs such as beta-blockers, etc. We further showed that long-term exercises generally push most, if not all, baseline B&C processes in diametrical opposing directions against the diseased B&C processes, implying that exercises play unique roles in reversing chronic diseases. Finally, we proposed several strategical approaches to resetting the CNS’ state memory as the essential condition for curing chronic diseases.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID Syndrome (PCS). A fraction of the PCS patients develops the full clinical picture of ME/CFS. New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure. Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing constriction of resistance vessels and of precapillary sphincters which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion. The detrimental coincidence of the microcirculatory with the precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in pre-disposed patients because the interaction causes a particular kind of perfusion disturbance - capillary ischemia-reperfusion - which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter in turns worsens the vascular situation by the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.

Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but literature on long-term recovery of young adults after mild-to-moderate infection is lacking. Heart rate variability (HRV) allows observation of autonomic nervous system (ANS) modulation post SARS-CoV-2 infection. Additionally, physical activity (PA) helps improve ANS modulation, where investigation of PA influence on ANS recovery is vital to reduce risk and severity of symptoms. Clinicians may use this research to aid development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were observed where general amnamnesis was performed, followed by HRV and PA assessment. 10 CT and 7 PCOV subjects returned for follow-up (FU) evaluation 6 weeks after complete immunization (2 doses) and assessments were repeated. Over the follow-up period, decrease in sympathetic (SNS) activity (mean heart rate: p=0.0024, CI=-24.67- -3.26; SNS index: p=0.0068, CI=-2.50- -0.32) and increase in parasympathetic (PNS) activity (mean RR:p=0.0097, CI=33.72-225.51; PNS index: p=0.0091, CI=-0.20-1.47) were observed. At follow-up, HRV was not different between groups (p>0.05). Additionally, no differences were observed in PA between moments and groups. This study provides evidence of ANS recovery after SARS-CoV-2 insult in young adults over a follow-up period, independent of changes in PA.

Breast Cancer Associated Susceptibility Proteins Type 1/2 (BRCA1/2) promote cellular functioning by modulating NRF2-mediated antioxidant signaling. Redox failure in women with BRCA1/2 insufficiency increases the risk for breast/ovarian/uterine cancers. Risk‐reducing salpingo‐oophorectomy (RRSO) is a prophylactic surgery of the reproductive organs, which is frequently conducted by the age of 40 to lower the occurrence of cancer in women with BRCA1/2 mutations. However, abrupt estrogen decline following RRSO causes ovarian failure, which implicates various cellular physiological processes, resulting in increased release of free radicals and subsequent severe onset of menopausal symptoms. Comfort measures (e.g., hormonal replacement therapy (HRT) and mindfulness-based stress reduction (MBSR)) may improve chronological menopause-related quality of life, but their specific effects are not clear in women with gene mutations. Aiming to fill the gap, this study used path analysis to examine the effects of HRT and MBSR on menopausal symptoms among RRSO patients (N = 199, mean age = 50.5 ± 6.7 years). HRT alleviated menopausal symptoms in BRCA2 carriers and women who were physically active, premenopausal at the time of RRSO, had a high BMI, and had no history of breast cancer. It increased the severity of urogenital symptoms in those with a history of cancer. MBSR, on the other hand, was associated with increased intensity of most menopausal symptoms. The results suggest that young women undergoing recent RRSO may benefit from HRT at an individual level while their need for extensive measures to optimize their psychological wellbeing is ongoing. Adverse effects of MBSR, which are captured in the present study imply that MBSR may interfere with redox sensitivity associated with estradiol fluctuations in BRCA1/2 carriers. Investigations are needed to test this hypothesis and elaborate on the underlying mechanisms in those women.