Metabolic Consequences of Anabolic Steroids, Insulin, and Growth Hormone Abuse in Recreational Bodybuilders: Implications for the World Anti-Doping Agency Passport.

BACKGROUND: Hormonal doping in recreational sports is a public-health concern. The World Anti-Doping Agency (WADA) promoted the creation of the Athlete Biological Passport, aiming to monitor athlete's biological variables over time to facilitate indirect detection of doping. Detection tests for anabolic androgenic steroids (AAS) and growth hormone (GH) are available while insulin abuse cannot be revealed. We have determined in recreational bodybuilders the metabolic effects associated with different patterns of hormone abuse. All analyses were conducted using Statistical Package for Social Sciences (SPSS) 21.0 software (SPSS Chicago, IL). RESULTS: We have assessed plasma concentrations of selected metabolic markers and fatty acid content in erythrocyte membranes of 92 male bodybuilders and in 45 healthy controls. Hormonal abuse was identified by anonymous questionnaires. 43% (%) of recruited bodybuilders regularly abused hormones, i.e., anabolic androgenic steroids (95%) often associated with GH (30%) and/or insulin (38%). HDL-cholesterol was lower in insulin and/or GH abusers. Alanine (ALT) and aspartic (AST) transaminases were greater in hormone abusing bodybuilders than in non-doping bodybuilders and controls. Insulin doping was selectively associated with increased plasma ALT-to-AST ratio. In erythrocyte membranes, elongase activity (i.e., stearic-to-palmitic ratio) was lower in insulin and/or growth hormone doping, whereas increased Δ-9 desaturase activity (i.e., palmitoleic-to-palmitic ratio) was selectively associated with insulin doping. CONCLUSIONS: In conclusion, our study demonstrates that insulin and GH abuse are characterized by multiple alterations of specific metabolic markers. Although further studies are needed to test whether longitudinal monitoring of selected metabolic marker such as muscle contraction time, HDL levels, ALT-AST ratio as well as the activities of selected enzymes (e.g. Δ-9 desaturase and elongase), could contribute to the detection of insulin and GH abuse in sport.

Retinal venular vessel diameters are smaller during ten days of bed rest.

Older individuals experience cardiovascular dysfunction during extended bedridden hospital or care home stays. Bed rest is also used as a model to simulate accelerated vascular deconditioning occurring during spaceflight. This study investigates changes in retinal microcirculation during a ten-day bed rest protocol. Ten healthy young males (22.9 ± 4.7 years; body mass index: 23.6 ± 2.5 kg·m-2) participated in a strictly controlled repeated-measures bed rest study lasting ten days. High-resolution images were obtained using a hand-held fundus camera at baseline, daily during the 10 days of bed rest, and 1 day after re-ambulation. Retinal vessel analysis was performed using a semi-automated software system to obtain metrics for retinal arteriolar and venular diameters, central retinal artery equivalent and central retinal vein equivalent, respectively. Data analysis employed a mixed linear model. At the end of the bed rest period, a significant decrease in retinal venular diameter was observed, indicated by a significantly lower central retinal vein equivalent (from 226.1 µm, CI 8.90, to 211.4 µm, CI 8.28, p = .026), while no significant changes in central retinal artery equivalent were noted. Prolonged bed rest confinement resulted in a significant (up to 6.5%) reduction in retinal venular diameter. These findings suggest that the changes in retinal venular diameter during bedrest may be attributed to plasma volume losses and reflect overall (cardio)-vascular deconditioning.

Participation in youth sports influences sarcopenia parameters in older adults.

Background: The degree of deterioration in sarcopenia parameters may be affected by a person's level of physical activity (PA) and sedentary behavior (SB). Our study focused on examining the PA and SB of active older adults including those with and without history of sports in youth. Methods: Forty-four participants (20 men and 24 women, mean age of total sample 76.1 ± 5.2 years) were included in analysis of PA, SB habits and sarcopenia parameters, determined by skeletal muscle index, hand-grip strength, gait speed, Timed Up and Go tests (TUG). PA and SB were recorded with accelerometers. Our primary aim was to compare participants with (AH) or without a sport history in youth (NAH), in their sarcopenia parameters and PA and SB habits. Results: When divided participants in two groups (AH and NAH) and adjusting for age, we have detected the differences for skeletal muscle index (p = 0.007) and hand-grip strength (p = 0.004) in favor of participants who were engaged in sports in youth. We did not find any differences in PA and SB habits between the AH and NAH groups. After adjusting for age, participants with a higher number of daily steps, longer moderate to vigorous physical activity (MVPA) bouts, a higher number of MVPA bouts in a day and higher overall MVPA engagement achieved better results in hand-grip strength and TUG. Participants with lower SB had better TUG and gait speed results. Conclusions: Our findings suggest that engaging in sports activities in youth can make a difference with sarcopenia parameters. Although we found no differences in PA and SB habits between participants with AH and NAH, participants with an athlete history performed better results in sarcopenia parameters.

Environmental enrichment through virtual reality as multisensory stimulation to mitigate the negative effects of prolonged bed rest.

Prolonged bed rest causes a multitude of deleterious physiological changes in the human body that require interventions even during immobilization to prevent or minimize these negative effects. In addition to other interventions such as physical and nutritional therapy, non-physical interventions such as cognitive training, motor imagery, and action observation have demonstrated efficacy in mitigating or improving not only cognitive but also motor outcomes in bedridden patients. Recent technological advances have opened new opportunities to implement such non-physical interventions in semi- or fully-immersive environments to enable the development of bed rest countermeasures. Extended Reality (XR), which covers augmented reality (AR), mixed reality (MR), and virtual reality (VR), can enhance the training process by further engaging the kinesthetic, visual, and auditory senses. XR-based enriched environments offer a promising research avenue to investigate the effects of multisensory stimulation on motor rehabilitation and to counteract dysfunctional brain mechanisms that occur during prolonged bed rest. This review discussed the use of enriched environment applications in bedridden patients as a promising tool to improve patient rehabilitation outcomes and suggested their integration into existing treatment protocols to improve patient care. Finally, the neurobiological mechanisms associated with the positive cognitive and motor effects of an enriched environment are highlighted.

Functional characteristics and subjective disease perception in patients with COVID-19 two months after hospital discharge.

Introduction: Although early inpatient and post-hospital rehabilitation is recognized as necessary, not all COVID-19 patients have access to rehabilitation. There are no published reports in the literature that investigate the outcomes of patients who do not receive rehabilitation after COVID-19. Our aim was to evaluate possible improvements in determinate functional and psychological parameters in COVID-19 patients two months after their hospital discharge. Methods: On both time points various motor, cognitive, and clinical measurements such as body composition, tensiomyography, blood pressure, spirometry, grip strength test, Timed Up and Go test, gait speed, 30-second chair-stand test, and Montreal Cognitive Assessment, were performed. Additionally, questionnaires such as the SARC-CalF test, Edmonton frail scale, International Physical Activity questionnaire andThe Mediterranean Lifestyle index were conducted to assess lifestyle characteristics. Results: A total of 39 patients (87.2% male; mean age of 59.1 ± 10.3 years), who were hospitalized due to COVID-19 at the Izola General Hospital (IGH), Slovenia between December 2020 and April 2021, were included. Patients were assessed at two time points (T1 and T2): T1 was taken after receiving a negative COVID-19 test and T2 was taken two months after T1. After two months of self-rehabilitation, we have detected a BMI increase (p < .001), fat free mass increase (p < .001), better Edmonton frail scale (p < .001), SARC-CalF score (p = .014) and MoCA score (p = .014). There were no detected changes in lifestyle habits nor in physical performance tests. Discussion: It is already known that COVID-19 has long-term negative consequences regardless of the stage of the disease. Our findings support the notion that patients cannot fully regain all their functions within a two-month period without receiving structured or supervised rehabilitation. Therefore, it is crucial to offer patients comprehensive and structured rehabilitation that incorporates clinical, cognitive, and motor exercises.

A pilot study: Exploring the influence of COVID-19 on cardiovascular physiology and retinal microcirculation.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the cardiovascular system. The current study investigated changes in heart rate (HR), blood pressure (BP), pulse wave velocity (PWV), and microcirculation in patients recovering from Coronavirus disease 2019 (COVID-19) infection. METHODOLOGY: Out of 43 initially contacted COVID-19 patients, 35 (30 males, 5 females; age: 60 ± 10 years; and body mass index (BMI): 31.8 ± 4.9) participated in this study. Participants were seen on two occasions after hospital discharge; the baseline measurements were collected, either on the day of hospital discharge if a negative PCR test was obtained, or on the 10th day after hospitalization if the PCR test was positive. The second measurements were done 60 days after hospitalization. The vascular measurements were performed using the VICORDER® device and a retinal blood vessel image analysis. RESULTS: A significant increase in systolic BP (SBP) (from 142 mmHg, SD: 15, to 150 mmHg, SD: 19, p = 0.041), reduction in HR (from 76 bpm, SD: 15, to 69 bpm, SD: 11, p = 0.001), and narrower central retinal vein equivalent (CRVE) (from 240.94 µm, SD: 16.05, to 198.05 µm, SD: 17.36, p = 0.013) were found. Furthermore, the trends of increasing PWV (from 11 m/s, SD: 3, to 12 m/s, SD: 3, p = 0.095) and decreasing CRAE (from 138.87 µm, SD: 12.19, to 136.77 µm, SD: 13.19, p = 0.068) were recorded. CONCLUSION: The present study investigated cardiovascular changes following COVID-19 infection at two-time points after hospital discharge (baseline measurements and 60 days post-hospitalization). Significant changes were found in systolic blood pressure, heart rate, and microvasculature indicating that vascular adaptations may be ongoing even weeks after hospitalization from COVID-19 infection. Future studies could involve conducting additional interim assessments during the active infection and post-infection periods.

Effects of COVID-19 on cognition and mood after hospitalization and at 2-month follow-up.

A plethora of evidence links SARS-CoV-2 infection with concomitant cognitive dysfunction, which often persists weeks to months after the acute stages of illness and affects executive function, attention, memory, orientation, and movement control. It remains largely unclear which conditions or factors exacerbate the recovery. In a cohort of N=37 Slovenian patients (5 females, aged M = 58, SD = 10.7 years) that were hospitalized because of COVID-19, the cognitive function and mood states were assessed immediately after discharge and 2-months later to investigate the early post-COVID recovery changes. We assessed the global Montreal Cognitive Assessment (MoCA), Simple and Choice Reaction Times, executive functions (Trail-Making Test - TMT-A and TMT-B), short-term memory (Auditory Verbal Learning Test - AVLT), and visuospatial memory. We monitored depressive and anxiety symptoms and applied general self-efficacy and cognitive complaints questionnaires. Our results showed a global cognitive impairment (MoCA, Z = 332.5; p = 0.012), poorer performance on executive functions (TMT-A, Z = 188; p = 0.014; and TMT-B, Z = 185; p = 0.012), verbal memory (AVLT, F = 33.4; p < 0.001), and delayed recall (AVLT7, F = 17.1; p < 0.001), and higher depressive (Z = 145; p = 0.015) and anxiety (Z = 141; p = 0.003) symptoms after hospital discharge compared to 2-month follow-up, indicating that SARS-CoV-2 may transiently impair cognitive function and adversely affect the mood. No improvement in MoCA was observed in 40.5% of the patients at follow-up, indicating possible long-term effects of COVID-19 on global cognitive performance. Medical comorbidities (p = 0.035) significantly predicted the change in MoCA score over time, while fat mass (FM, p = 0.518), Mediterranean diet index (p = .0.944), and Florida Cognitive Activities Score (p = 0.927) did not. These results suggest that the patients' medical comorbidities at the time of SARS-CoV-2 infection could importantly contribute to the acute impairment of cognitive function and stress the importance of systemic implementation of countermeasures to limit the negative consequences on public health.

Pathophysiological mechanisms of reduced physical activity: Insights from the human step reduction model and animal analogues.

Physical inactivity represents a heavy burden for modern societies and is spreading worldwide, it is a recognised pandemic and is the fourth cause of global mortality. Not surprisingly, there is an increasing interest in longitudinal studies on the impact of reduced physical activity on different physiological systems. This narrative review focuses on the pathophysiological mechanisms of step reduction (SR), an experimental paradigm that involves a sudden decrease in participants' habitual daily steps to a lower level, mimicking the effects of a sedentary lifestyle. Analogous animal models of reduced physical activity, namely, the "wheel-lock" and the "cage reduction" models, which can provide the foundation for human studies, are also discussed. The empirical evidence obtained thus far shows that even brief periods of reduced physical activity can lead to substantial alterations in skeletal muscle health and metabolic function. In particular, decrements in lean/muscle mass, muscle function, muscle protein synthesis, cardiorespiratory fitness, endothelial function and insulin sensitivity, together with an increased fat mass and inflammation, have been observed. Exercise interventions seem particularly effective for counteracting these pathophysiological alterations induced by periods of reduced physical activity. A direct comparison of SR with other human models of unloading, such as bed rest and lower limb suspension/immobilisation, is presented. In addition, we propose a conceptual framework aiming to unravel the mechanisms of muscle atrophy and insulin resistance in the specific context of reduced ambulatory activity. Finally, methodological considerations, knowledge gaps and future directions for both animal and human models are also discussed in the review.

Sarcopenia parameters in active older adults - an eight-year longitudinal study.

BACKGROUD: Sarcopenia is a common skeletal muscle syndrome that is common in older adults but can be mitigated by adequate and regular physical activity. The development and severity of sarcopenia is favored by several factors, the most influential of which are a sedentary lifestyle and physical inactivity. The aim of this observational longitudinal cohort study was to evaluate changes in sarcopenia parameters, based on the EWGSOP2 definition in a population of active older adults after eight years. It was hypothesized that selected active older adults would perform better on sarcopenia tests than the average population. METHODS: The 52 active older adults (22 men and 30 women, mean age: 68.4 ± 5.6 years at the time of their first evaluation) participated in the study at two time points eight-years apart. Three sarcopenia parameters were assessed at both time points: Muscle strength (handgrip test), skeletal muscle mass index, and physical performance (gait speed), these parameters were used to diagnose sarcop0enia according to the EWGSOP2 definition. Additional motor tests were also performed at follow-up measurements to assess participants' overall fitness. Participants self-reported physical activity and sedentary behavior using General Physical Activity Questionnaire at baseline and at follow-up measurements. RESULTS: In the first measurements we did not detect signs of sarcopenia in any individual, but after 8 years, we detected signs of sarcopenia in 7 participants. After eight years, we detected decline in ; muscle strength (-10.2%; p < .001), muscle mass index (-5.4%; p < .001), and physical performance measured with gait speed (-28.6%; p < .001). Similarly, self-reported physical activity and sedentary behavior declined, too (-25.0%; p = .030 and - 48.5%; p < .001, respectively). CONCLUSIONS: Despite expected lower scores on tests of sarcopenia parameters due to age-related decline, participants performed better on motor tests than reported in similar studies. Nevertheless, the prevalence of sarcopenia was consistent with most of the published literature. TRIAL REGISTRATION: The clinical trial protocol was registered on ClinicalTrials.gov, identifier: NCT04899531.

Interleukin-18 Is a Potential Biomarker Linking Dietary Fatty Acid Quality and Insulin Resistance: Results from a Cross-Sectional Study in Northern Italy.

Dietary lipids are pivotal in modulating metabolic inflammation. Among the inflammatory mediators characterizing metabolic inflammation, interleukin 18 (IL-18) has been consistently associated with obesity and insulin resistance. This study aims to evaluate whether the quality of lipid intake impacts upon IL-18 plasma levels and the implications on insulin resistance computed by the homeostatic model assessment for insulin resistance (HOMA-IR). Using a cross-sectional design, this study confirmed that IL-18 correlated positively with insulin resistance and individuals with a HOMA-IR ≥ 2.5 displayed higher circulating IL-18 levels compared with their insulin-sensitive counterparts. In terms of the effect of the quality of dietary lipids on IL-18 circulating levels, the ratio between monounsaturated, omega-3, polyunsaturated and saturated fatty acids as well as the intake of eicosapentaenoic and docosahexaenoic acids correlated negatively with IL-18. Despite this, IL-18 circulating levels, but not dietary fatty acid quality, predicted insulin resistance. Nevertheless, the ratio between omega 3 and saturated fatty acids was a predictor of IL-18 plasma levels. Thus, the downregulation of IL-18 may underpin, at least partially, the beneficial metabolic effects of substituting omega 3 for saturated fatty acids with this cytokine potentially representing a biomarker linking dietary lipids and metabolic outcomes.

Sarcopenia, obesity, and their association with selected behavioral factors in active older adults.

Introduction: The number of obese people in the world is increasing, as is the number of sarcopenic people among the older adults. Although both states are concerning, they can be positively influenced by selected behavioral factors such as adequate nutrition and physical activity. We were interested in the prevalence of sarcopenic obesity in active older people and the influence of behavioral factors on this phenomenon. Methods: The study included 38 older adults (21 women) with a mean age of 75.3 ± 5.0 years. Sarcopenic parameters were determined with different tests: Handgrip Test, Chair Stand Test, Gait Speed, Timed Up and Go Test, and Short Physical Performance Battery. Body composition was measured by dual-energy x-ray absorptiometry. Physical activity level was measured using accelerometers, and nutritional status was assessed using the Mini-Nutritional Assessment and MEDLIFE Index questionnaire. Results: Of all included active participants (the average number of steps per day was 8,916 ± 3,543), 47.4% of them were obese. Of all included women, 52.4% were obese. Sarcopenic obesity was found in three (7.9%) participants. Nutritional status correlated with strength of lower extremities and physical performance tests (gait speed, Timed Up and Go Test and Short Physical performance battery). Higher number of steps per day positively correlates with physical performance. Discussion: Interestingly, we did not find any correlation between the main obesity parameter such as percent body fat or body mass index (and thus sarcopenic obesity) and any of the selected behavioral factors (physical activity, sedentary behavior, or dietary habits). In conclusion, reaching the recommended levels of physical activity in older adults may not be sufficient to prevent the occurrence of obesity and sarcopenic obesity.

Impact of 10-day bed rest on serum levels of irisin and markers of musculoskeletal metabolism.

The bed rest (BR) is a ground-based model to simulate microgravity mimicking skeletal-muscle alterations as in spaceflight. Molecular coupling between bone and muscle might be involved in physiological and pathological conditions. Thus, the new myokine irisin and bone-muscle turnover markers have been studied during and after 10 days of BR. Ten young male individuals were subjected to 10 days of horizontal BR. Serum concentrations of irisin, myostatin, sclerostin, and haptoglobin were assessed, and muscle tissue gene expression on vastus lateralis biopsies was determined. During 10-days BR, we observed no significant fluctuation levels of irisin, myostatin, and sclerostin. Two days after BR (R+2), irisin serum levels significantly decreased while myostatin, sclerostin, and haptoglobin were significantly increased compared with BR0. Gene expression of myokines, inflammatory molecules, transcription factors, and markers of muscle atrophy and senescence on muscle biopsies were not altered, suggesting that muscle metabolism of young, healthy subjects is able to adapt to the hypomobility condition during 10-day BR. However, when subjects were divided according to irisin serum levels at BR9, muscle ring finger-1 mRNA expression was significantly lower in subjects with higher irisin serum levels, suggesting that this myokine may prevent the triggering of muscle atrophy. Moreover, the negative correlation between p21 mRNA and irisin at BR9 indicated a possible inhibitory effect of the myokine on the senescence marker. In conclusion, irisin could be a prognostic marker of hypomobility-induced muscle atrophy, and its serum levels could protect against muscle deterioration by preventing and/or delaying the expression of atrophy and senescence cellular markers.

Irisin Attenuates Muscle Impairment during Bed Rest through Muscle-Adipose Tissue Crosstalk.

The detrimental effect of physical inactivity on muscle characteristics are well known. Irisin, an exercise-induced myokine cleaved from membrane protein fibronectin type III domain-containing protein-5 (FNDC5), mediates at least partially the metabolic benefits of exercise. This study aimed to assess the interplay between prolonged inactivity, circulating irisin, muscle performance, muscle fibers characteristics, as well as the FNDC5 gene expression (FNDC5ge) in muscle and adipose tissue among healthy subjects. Twenty-three healthy volunteers were tested before and after 14 days of Bed Rest, (BR). Post-BR circulating levels of irisin significantly increased, whereas body composition, muscle performance, and muscle fiber characteristics deteriorated. Among the subjects achieving the highest post-BR increase of irisin, the lowest reduction in maximal voluntary contraction and specific force of Fiber Slow/1, the highest increase of FNDC5ge in adipose tissue, and no variation of FNDC5ge in skeletal muscle were recorded. Subjects who had the highest FNDC5ge in adipose tissue but not in muscle tissue showed the highest circulating irisin levels and could better withstand the harmful effect of BR.

Does an active lifestyle matter? A longitudinal study of physical activity and health-related determinants in older adults.

Introduction: It is well-known that regular physical activity, and thus an active lifestyle, has positive effects on aging and general wellbeing. However, the question remains as to whether regular or increased physical activity can improve self-perception of health status and quality of life in older adults. Methods: We conducted a longitudinal study on a group of active older adults between 2013 and 2021. At baseline, i.e., the 1st measurements (baseline), 147 participants were enrolled (mean age 68.4 ± 5.6). After 8 years, in 2021 (follow up), 52 older adults (mean age 75.9 ± 5.3 years) were measured. For the purpose of this study, we included 52 older adults participated at both time-points. For both measurements, participants reported their physical activity and sedentary behavior using the Global physical activity questionnaire (GPAQ), socio-demographic and environmental determinants, recording their self-perception in terms of overall wellbeing. Furthermore, we conducted a qualitative study using semi-structured interviews to obtain subjective data on the changes and events that may have affected physical abilities and general health over an 8-year period. Results: At the follow up, participants reported lower physical activity and sedentary behavior compared to baseline, but still met health-enhancing physical activity (HEPA) standards for total self-reported physical activity (>3,000 METmin/week). In addition, they rated their overall health (p < 0.001), physical fitness (p < 0.001), psychological wellbeing (p < 0.001) and overall quality of life (p < 0.001) as better. The qualitative data confirmed that the 8-year period involved changes in physical activity. Specifically, they have continued to carry out physical work (gardening, working in the vineyards, olive groves), but previously organized physical activities were replaced by walks in nature, which probably also influenced the reduction of sedentary behavior. Conclusion: After 8 years, as expected, participants reported a decrease in physical activity and a lower level of sedentary behavior. It appears from the interview that healthy older adults filled their days with daily tasks and found more time for walking. Individuals who were more active in the past 8 years also reported better overall health and wellbeing. Selected variables correlated with an active lifestyle and better perceptions of quality of life.

The reliability, validity and usefulness of the 30-15 intermittent fitness test for cardiorespiratory fitness assessment in military personnel.

The objectives of this study were to investigate the reliability, validity, and usefulness of the 30-15 intermittent fitness test (30-15IFT) in soldiers. The 34 infantry members of the Slovenian armed forces were recruited as participants. Participants performed the continuous incremental treadmill test (TR), a 2-mile run (2MR) test, and two 30-15IFT tests. Additionally, participants were divided into a highest-scoring group (HSG) and a lowest-scoring group (LSG) based on their scores on the Army Physical Fitness Test. A very high reliability ratings were observed for 30-15IFT measures, as follows: end-running speed (ERS) ERSIFT (ICC = 0.971), maximal heart rate (HRmax) HRmaxIFT (IC = 0.960), and maximal relative oxygen consumption (VO2max) VO2max-IFT (ICC = 0.975). Although 30-15IFT measures demonstrated high correlations (r = 0.695-0.930) to the same measures of TR test, ERS, HRmax and VO2max were higher in the 30-15IFT (p > 0.05). Furthermore, ERSIFT and predicted VO2maxIFT were higher in HSG compared to LSG, whereas HRmax did not differ. The results of this study show that the 30-15IFT test is a reliable, valid and useful tool for assessing cardiorespiratory fitness in the armed forces. Moreover, the ERS and predicted VO2max values derived from the 30-15IFT could be considered more sensitive markers of combat readiness than the parameters derived from the TR and 2MR tests.Trial registration number: NCT05218798.

Reliability and validity of 30-15 intermittent fitness test for cardiorespiratory fitness assessment among infantry members of Slovenian armed forces: A study protocol.

Introduction: Cardiorespiratory fitness (CRF) testing is routinely performed by most armed and tactical forces around the world as part of their recruitment process for new members or simply as an annual examination of their personnel. A 2-mile run (2MR) test is among the most commonly used. However, as it is performed outdoors, weather, climate, and terrain can influence the results and often limit the maximum performance. Also, this test has been shown to be difficult for individuals because the pacing strategy is self-paced. As such, it does not reflect the real situation on the battlefield, where most activities are externally driven by the environment and the enemy. Therefore, we believe that the 30-15 Intermittent Fitness Test (30-15IFT) may be a suitable tool for measuring CRF and battle readiness of military personnel. Moreover, given the importance of visual attention to military personnel we aim to investigate the differences in visual attention between better and less physically prepared infantry members and its corresponding response to maximal endurance running test. Methods and analysis: This randomized cross-over study using a within-subjects test-retest design will enroll 32 infantry members of the Slovenian Armed Forces. To investigate the reliability and validity of the 30-15IFT test, an incremental treadmill test (TR), a 2MR test, and two identical 30-15IFT will be performed in randomized order. Additionally, participants will be subsequently divided into two groups based on their score on the Army Physical Fitness Test (APFT), whereas differences in visual attention will be assessed by using the d2 test. The primary analysis will assess differences in key physiological outcomes between the different CRF tests (TR vs. 2MR vs. 30-15IFT). In addition, the relative reliability of all dependent variables between two 30-15IFT trials will be estimated by interclass correlation coefficient (ICC), while relationship between maximal oxygen uptake, heart rate and maximal running speed of 30-15IFT, TR and 2MR will be assessed using Pearson's correlation. Ethics and dissemination: Ethical approval was obtained from the National Medical Ethics Committee (reference number: 0120-495/2021/6). The results of the proposed study will be disseminated through publication in peer-reviewed journals. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT05218798].

Neural Bases of Age-Related Sensorimotor Slowing in the Upper and Lower Limbs.

With advanced age, there is a loss of reaction speed that may contribute to an increased risk of tripping and falling. Avoiding falls and injuries requires awareness of the threat, followed by selection and execution of the appropriate motor response. Using event-related potentials (ERPs) and a simple visual reaction task (RT), the goal of our study was to distinguish sensory and motor processing in the upper- and lower-limbs while attempting to uncover the main cause of age-related behavioral slowing. Strength (amplitudes) as well as timing and speed (latencies) of various stages of stimulus- and motor-related processing were analyzed in 48 healthy individuals (young adults, n = 24, mean age = 34 years; older adults, n = 24, mean age = 67 years). The behavioral results showed a significant age-related slowing, where the younger compared to older adults exhibited shorter RTs for the upper- (222 vs. 255 ms; p = 0.006, respectively) and the lower limb (257 vs. 274 ms; p = 0.048, respectively) as well as lower variability in both modalities (p = 0.001). Using ERP indices, age-related slowing of visual stimulus processing was characterized by overall larger amplitudes with delayed latencies of endogenous potentials in older compared with younger adults. While no differences were found in the P1 component, the later components of recorded potentials for visual stimuli processing were most affected by age. This was characterized by increased N1 and P2 amplitudes and delayed P2 latencies in both upper and lower extremities. The analysis of motor-related cortical potentials (MRCPs) revealed stronger MRCP amplitude for upper- and a non-significant trend for lower limbs in older adults. The MRCP amplitude was smaller and peaked closer to the actual motor response for the upper- than for the lower limb in both age groups. There were longer MRCP onset latencies for lower- compared to upper-limb in younger adults, and a non-significant trend was seen in older adults. Multiple regression analyses showed that the onset of the MRCP peak consistently predicted reaction time across both age groups and limbs tested. However, MRCP rise time and P2 latency were also significant predictors of simple reaction time, but only in older adults and only for the upper limbs. Our study suggests that motor cortical processes contribute most strongly to the slowing of simple reaction time in advanced age. However, late-stage cortical processing related to sensory stimuli also appears to play a role in upper limb responses in the elderly. This process most likely reflects less efficient recruitment of neuronal resources required for the upper and lower extremity response task in older adults.

Dietary Acid Load but Not Mediterranean Diet Adherence Score Is Associated With Metabolic and Cardiovascular Health State: A Population Observational Study From Northern Italy.

Diet plays a pivotal role in shaping the trajectory of chronic diseases. In this regard, the Mediterranean diet has been widely shown to exert beneficial effects on cardiometabolic health. On the contrary, the Western diet, which has also been reported to be an acidogenic dietary pattern, elicits detrimental effects on both metabolic and cardiovascular (CV) health. However, the role of dietary acid load (DAL) as a predictor of cardiometabolic prognosis remains to be elucidated. Thus, this study aims to compare Mediterranean diet adherence (MDA) and DAL focusing on their relationship with metabolic and CV prognosis. A total of 448 individuals aged 55-80 years were grouped depending on their MDA, assessed using food frequency questionnaires, or DAL, evaluated using potential renal load acid (PRAL) and net-endogenous acid production (NEAP). Study participants underwent anthropometric and biochemical measurements. The metabolic syndrome (MetS) prevalence was evaluated according to the National Cholesterol Education Program-Adult Treatment Panel III. Finally, the CV risk was evaluated using three independent algorithms: atherosclerotic cardiovascular disease (ASCVD), European Systematic COronary Risk Evaluation (SCORE), and Cuore risk scores. Mediterranean diet adherence was negatively associated with PRAL and NEAP. Individuals in the higher MDA tertile group had higher HDL cholesterol as well as lower homeostasis model assessment index (HOMA-IR) and fat mass relative to the lowest MDA tertile. However, in the high-MDA tertile group, there was neither a significantly lower MetS prevalence nor CV risk. Instead, both the MetS prevalence and CV risk were higher in individuals in the higher acid PRAL quartile relative to the lower alkaline PRAL quartile. Dietary acid load, especially assessed using PRAL but not MDA, was associated with indices of metabolic and CV prognosis. Thus, DAL assessed by 24-h dietary recalls may represent a better predictor of cardiometabolic health if compared to MDA evaluated using food frequency questionnaires.

Decrease in work rate in order to keep a constant heart rate: biomarker of exercise intolerance following a 10-day bed rest.

Aerobic exercise prescription is often set at specific heart rate (HR) values. Previous studies demonstrated that during exercise carried out at a HR slightly above that corresponding to the gas exchange threshold (GET), work rate (WR) has to decrease in order to maintain HR constant. We hypothesized a greater WR decrease at a fixed HR after simulated microgravity/inactivity (bed rest, BR). Ten male volunteers (23 ± 5 yr) were tested before (PRE) and after (POST) a 10-day horizontal BR and performed on a cycle ergometer 1) incremental exercise; b) 15-min HRCLAMPED exercise, in which WR was continuously adjusted to maintain a constant HR, corresponding to that at 120% of GET determined in PRE; 3) two moderate-intensity constant WR (MOD) exercises. Breath-by-breath O2 uptake (V̇o2), HR, and other variables were determined. After BR, peak V̇o2 (V̇o2peak) and GET significantly decreased, by ∼10%. During HRCLAMPED (145 ± 11 beats·min-1), the decrease in WR needed to maintain a constant HR was greater in POST versus PRE (-39 ± 10% vs. -29 ± 14%, P < 0.01). In six subjects the decreased WR switched from the heavy- to the moderate-intensity domain. The decrease in WR during HRCLAMPED, in PRE versus POST, was significantly correlated with the V̇o2peak decrease (R2 = 0.52; P = 0.02). A greater amplitude of the slow component of the HR kinetics was observed during MOD following BR. Exercise at a fixed HR is not associated with a specific WR or WR domain; the problem, affecting exercise evaluation and prescription, is greater after BR. The WR decrease during HRCLAMPED is a biomarker of exercise intolerance after BR.NEW & NOTEWORTHY During a 15-min exercise carried out at a heart rate (HR) slightly above that corresponding to the gas exchange threshold, to keep HR constant work rate significantly decreased; the decrease was more pronounced after a 10-day horizontal bed rest. The work rate decrease at a fixed HR can be considered a systemic biomarker of exercise intolerance during microgravity/inactivity and could also be easily and reliably determined during spaceflights or in patients.

Early Biomarkers of Altered Renal Function and Orthostatic Intolerance During 10-day Bedrest.

Exposure to actual or simulated microgravity results in alterations of renal function, fluid redistribution, and bone loss, which is coupled to a rise of urinary calcium excretion. We provided evidence that high calcium delivery to the collecting duct reduces local Aquaporin 2 (AQP2)-mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration to reduce calcium saturation. To investigate early renal adaptation into simulated microgravity, we investigated the effects of 10 days of strict bedrest in 10 healthy volunteers. We report here that 10 days of inactivity are associated with a transient, significant decrease (day 5) in vasopressin (copeptin) paralleled by a decrease in AQP2 excretion, consistent with an increased central volume to the heart, resulting in reduced water reabsorption. Moreover, bedrest caused a significant increase in calciuria secondary to bone demineralization paralleled by a decrease in PTH. Urinary osteopontin, a glycoprotein exerting a protective effect on stone formation, was significantly reduced during bedrest. Moreover, a significant increase in adrenomedullin (day 5), a peptide with vasodepressor properties, was observed at day 5, which may contribute to the known reduced orthostatic capacity post-bedrest. We conclude that renal function is altered in simulated microgravity and is associated with an early increase in the risk of stone formation and reduced orthostatic capacity post-bedrest within a few days of inactivity.