Lower Body Research Articles

7284 Ablation of hexose-6-phosphate dehydrogenase in mice causes skeletal muscle atrophy and dramatically impairs exercise capacity

Abstract Disclosure: M. Zogg: None. A.D. Grötsch: None. J. Birk: None. P. Pelczar: None. J. Bouitbir: None. A. Odermatt: None. Hexose-6-phosphate dehydrogenase (H6PD) catalyzes the first two steps of the pentose-phosphate pathway (PPP) within the endoplasmic reticulum (ER), generating the redox equivalent NADPH. It has been shown that mice lacking H6PD develop defects mainly in skeletal muscles [1]. Nevertheless, the mechanisms underlying the myopathy in H6PD KO mice is unknown. Here, we further assessed muscle responses to H6PD deficiency and aimed to uncover the mechanisms that may cause myopathy in mice. We conducted a detailed characterization of the muscle structure and function as well as energy metabolism in oxidative and glycolytic muscles of H6PD KO mice. At the age of 15 weeks, H6PD KO mice displayed lower body weight than WT mice, despite similar food and water intake. Grip strength was significantly lower in H6PD KO than in WT mice. This was associated with decreased weight of the mixed (gastrocnemius, quadriceps) and fast fiber type rich muscles of the hind leg (extensor digitorum longus, tibialis anterior) in H6PD KO animals. Atrogin1 and Murf1 mRNA expression, markers of atrophy, increased only in the white (glycolytic) quadriceps. In this context, fast-twitch fibers in WT mice displayed higher H6pd mRNA expression than slow-twitch fibers. Electron microscopy analysis of red and white gastrocnemius muscles displayed the presence of large intramyofibrillar vacuoles, and morphologic changes of the sarcoplasmic reticulum and mitochondria in H6PD KO muscle. Metabolically, H6PD KO muscles presented an accumulation of glycogen granules and significantly decreased mRNA expression of glucose transporter Glut4, glucose-6-phosphate transporter G6pt and glycogen phosphorylase Pygm. The exercise capacity, measured by maximal running distance, decreased by more than 50% in H6PD KO mice. Upon exercise, both WT and H6PD KO animals were able to mobilize the majority of glycogen stored in their muscles. However, immediately after exercise, there was a significant increase in plasma lactate and glucose levels in H6PD KO animals. Disturbances in glucose metabolism were further supported by in vitro experiments using stable C2C12 H6PD KO myoblasts, revealing a shift in basal state mitochondrial fuel oxidation usage from glucose to fatty acid and glutamine in metabolic dependency assays. In conclusion, our findings revealed that H6PD seems to play a key role in proper function and energy metabolism of skeletal muscles.

Thermal-biomechanical manikin applied in turbulent airflow and vibration systems in transient conditions

This paper applied a thermal-biomechanical manikin in turbulent airflow and vibration systems in transient conditions. This numerical model evaluated the thermal and biomechanical components to which the human body is subjected. The first one considers the first-order equations systems based on the thermal numerical model, while the second one considers the second-order equations systems based on the vibration numerical model. This second-order equations system is converted into a first-order equation system. The resolution of the thermal and biomechanical numerical models is made through the Runge-Kutta-Fehlberg method with error control. The thermal numerical model is used in the study of the steady-state and transient conditions when the skin is subjected to mean and turbulent airflow. The biomechanical numerical model is used in the study of the human body vibrations applied to the feet, that a standing person is subjected, using periodical and random vibration signals of the floor. The thermal analysis shows that with an air fluctuation velocity, the skin temperature reduces slightly. The amplitude of the vibration in the lower body section is higher than in the upper body section. The introduction of the randomised vibration, in the periodical vibration, the human body vibration increases the fluctuation level.

Predation of eggs and incubating females in willow ptarmigan Lagopus l. lagopus

Nest predation is a major cause of reproductive loss in many ground-nesting birds. During 15 consecutive years the predation of nests and females throughout the incubation season were recorded in a willow ptarmigan Lagopus l. lagopus population in central Norway. The temporal predation patterns, factors affecting the predation probability and age-specific nesting patterns in this species were studied. There was a large annual variation in predation rate of both nests (0-50%) and incubating females (0-29%) in this area during the study period. The mean annual predation rate of nests (15%) was on average three times higher than the predation of incubating willow ptarmigan females (5%). Predation rate was not constant throughout the incubation season, and the nest predation rate increased with increasing number of available nests. The predation events started after the mean initiation day of incubation, and coincided with the highest number of available nests. None of the parameters we tested in a logistic regression analysis (physical condition, nest cover, experience and date for initiation of egg-laying) could predict the predation probability of nests and incubating females. However, “good” nest cover tended to have some predictive value on the predation probability. Yearling incubating females had significantly lower physical body condition than adults, and also there were differences in choice of nest site in relation to cover between the two age groups. Initiation of egg-laying in adult females tended to be distributed more evenly over the season, whereas yearling females had a more aggregated egg-laying pattern, compared to adults.

Moderate hypothermia circulatory arrest as a brain-protective strategy for type a aortic dissection.

Brain protective strategies for acute type A aortic dissection (TAAD) remain controversial. Moderate hypothermia circulatory arrest (MHCA) without cerebral perfusion is not commonly used. However, we aimed to assess its safety and efficacy in 358 patients who underwent hemiarch replacement with MHCA for acute type A aortic dissection at our institution from August 2012 to August 2022. Clinical outcomes were compared according to circulatory arrest time (≤15 min [S group, n = 52] vs ≥ 16 min [L group, n = 306]). The primary outcome was postoperative stroke. The S group had more older patients (72.5 vs 68.8 years; p = 0.04), a greater incidence of carotid artery malperfusion (21% vs 11%; p = 0.043), and a lower body mass index (21.7 vs 23.6 kg/m2; p < 0.01) and haemodynamic instability (3.8% vs 16%; p = 0.02) than the L group. The incidence of postoperative stroke (7.7% vs 12%; p = 0.33) and the rate of 30-day mortality (5.8% vs 6.5%; p = 0.83) did not significantly differ between groups. After adjusting for all potential confounding factors pre- and intraoperatively, there was no significant difference in postoperative outcomes between groups. MHCA alone for TAAD had comparable postoperative outcomes with circulatory arrest times under and over 15 min. However, longer arrest times were associated with a higher risk of stroke.

Small-molecule mediated MuRF1 inhibition protects from doxorubicin-induced cardiac atrophy and contractile dysfunction

Cancer chemotherapy induces cell stress in rapidly dividing cancer cells to trigger their growth arrest and apoptosis. However, adverse effects related to cardiotoxicity underpinned by a limited regenerative potential of the heart limits clinical application: In particular, chemotherapy with doxorubicin (DOXO) causes acute heart injury that can transition to persisting cardiomyopathy (DOXO-CM). Here, we tested if MuRF1 inhibition (“MuRFi”) was able to attenuate DOXO-CM. To mimic DOXO chemotherapy, we treated mice over four weeks with five DOXO injections, resulting in a cumulative dosage of 25 mg/kg. At day 28, mice had lower body and heart weights, reduced cardiac cross-sectional myofibrillar areas (CSAs), and disturbed functional ejection fractions (EFs) and fractional shortenings (FS) as indicated by echocardiography (ECHO). In contrast, mice with a 1 g/kg Myomed#205 spiked diet, a previously described experimental MuRFi therapy, showed lower DOXO-CM at day 28, and also reduced acute DOXO cardiac injury at day 7 (single DOXO dose; 15 mg/kg). Underlying molecular signatures using Western blot (WB) assays showed at day 28 reduced phospho-AKT (AKTp) and phospo-4EBP1 (4 EBP1p) levels following DOXO that were normalized following MuRFi treatment. Taken together, our data suggest that MuRFi treatment is suitable to attenuate DOXO-CM by preserving AKTp and 4 EBP1p levels in DOXO stressed cardiomyocytes, thereby supporting de novo protein translation and cardiomyocyte survival under translational arrest stress.

Association of a composite trait for anthropometrics, adiposity and energy expenditure with cardiometabolic diseases: An age-stratified cohort and genetic risk score analysis.

Various anthropometric measures capture distinct as well as overlapping characteristics of an individual's body composition. To characterize independent body composition measures, we aimed to reduce easily-obtainable individual measures reflecting adiposity, anthropometrics and energy expenditure into fewer independent constructs, and to assess their potential sex- and age-specific relation with cardiometabolic diseases. Analyses were performed within European ancestry participants from UK Biobank (N = 418,963, mean age 58.0 years, 56% women). Principal components (PC) analyses were used for the dimension reduction of 11 measures of adiposity, anthropometrics and energy expenditure. PCs were studied in relation to incident type 2 diabetes mellitus (T2D) and coronary artery disease (CAD). Multivariable-adjusted Cox regression analyses, adjusted for confounding factors, were performed in all and stratified by age. Genome-wide association studies were performed in half of the cohort (N = 156,295) to identify genetic variants as instrumental variables. Genetic risk score analyses were performed in the other half of the cohort stratified by age of disease onset (N = 156,295). We identified two PCs, of which PC1 reflected lower overall adiposity (negatively correlated with all adiposity aspects) and PC2 reflected more central adiposity (mainly correlated with higher waist-hip ratio, but with lower total body fat) and increased height, collectively capturing 87.8% of the total variance. Similar to that observed in the multivariable-adjusted regression analyses, we found associations between the PC1 genetic risk score and lower risks of CAD and T2D [CAD cases <50 years, odds ratio: 0.91 (95% confidence interval 0.87, 0.94) per SD; T2D cases <50 years, odds ratio: 0.76 (0.72, 0.81)], which attenuated with higher age (p-values 8.13E-4 and 2.41E-6, respectively). No associations were found for PC2. The consistently observed weaker associations of the composite traits with cardiometabolic disease suggests the need for age-specific cardiometabolic disease prevention strategies.

Effects of Preoperative Training on Static and Dynamic Balance among Female Athletes with Injured ACL

Aims: The purpose of this research was to study the effects of preoperative training on static and dynamic balance among female athletes with injured ACLs. Methods: This semi-experimental study involved a 2-group pretest-post-test design. Subjects were 36 (19 control and 17 experimental) female athletes with injured ACLs, that were chosen with the available sampling method. The experimental group did the preoperative training in the eight weeks and the control group did not participate in any training program during this period. Static and dynamic balance and lower body muscle strength were measured. The paired sample T-test was used to compare pre and post-test results and the independent sample T-test achieved comparisons between the two groups. Results: The results indicated that static (with eyes opened and closed) dynamic balance and muscle strength were improved significantly (p &lt; 0.05) in the exercise group, but no significant change (p &gt; 0.05) was found in the control group. Also, significant differences were found in improvement changes results between the two groups (p &lt; 0.05). Conclusion: Results of the study confirmed that preoperative training can have a beneficial effect on improving static and dynamic balance among female athletes with injured ACLs.

Patterns of girdle shape and their correlates in Australian limb-reduced skinks.

The evolution of limb reduction in squamates is a classic example of convergence, but the skeletal morphological patterns associated with it are underexplored. To provide insights on the biomechanical and developmental consequences of transitions to limb reduction, we use geometric morphometrics to examine the morphology of pectoral and pelvic girdles in 90 species of limb-reduced skinks and their fully limbed relatives. Clavicle shapes converge towards an acute anterior bend when forelimbs are lost but hindlimbs are retained-a morphology typical of sand-swimmers. This may either indicate functional adaptations to locomotion in fine substrates, or a developmental consequence of complete limb loss. The shape of limb-bearing elements of both girdles (coracoid and pelvis) instead closely mirrors limb reduction, becoming more simplified as undulation replaces limbed locomotion. Integration between girdles decreases in taxa lacking elements of the forelimbs but not hindlimbs, indicating differential selection on each girdle in response to distinct locomotory strategies. However, this pattern becomes less clear when considering phylogenetic history, perhaps because it is limited to one specific clade (Lerista). We show how the functional demands of locomotion can induce changes at different levels of organismal organization, including both external and internal structures.

Detection and Coil Embolisation of Pelvic Venous Incompetence for Chronic Pain in the Female Pelvis: A Development Phase Economic Analysis

Detection and Coil Embolisation of Pelvic Venous Incompetence for Chronic Pain in the Female Pelvis: A Development Phase Economic Analysis

Associations Between Pelvis, Trunk, and Shoulder Girdle Muscle Activity; Age; and Scores During the Closed Kinetic Chain Upper Extremity Stability Test in Baseball Pitchers

OBJECTIVE: To evaluate associations between muscle activity, age, and scores on the Closed Kinetic Chain Upper Extremity Stability Test (CKCUEST). DESIGN: Quasi-experimental. METHODS: Pelvic, trunk, and shoulder girdle surface electromyography (sEMG) and kinematic data were measured in 21 high school and college male baseball pitchers (17.4 ± 2.0 years, 184.4 ± 5.7 cm, 78.4 ± 14.2 kg) while they performed the CKCUEST. Mean sEMG data were computed while in sole support on the throwing-arm side (TS) as the glove-arm side (GS) was horizontally translating. Correlations and local regressions were used to assess associations and general patterns between mean sEMG data, age, and scores. RESULTS: TS serratus anterior, TS external oblique, GS serratus anterior, and TS gluteus medius had the highest mean sEMG data. Low-to-high significant correlations were found between proximal muscle groups. Correlations with the highest magnitudes in descending order were TS external oblique and TS gluteus maximus, TS external oblique and TS serratus anterior, and GS external oblique and TS gluteus medius. Small significant associations were observed between other muscle groups and age; there were no associations between muscle activity and test performance. CONCLUSION: Associations were observed between mean muscle activity among muscle groups and age but not test outcome. J Orthop Sports Phys Ther 2024;2(4):1-9. Epub 7 June 2024. doi:10.2519/jospt.2024.1023

Maternal low-dose caffeine intake during the perinatal period promotes short- and long-term sex-dependent hormonal and behavior changes in the offspring.

Maternal caffeine crosses the placenta and mammary barriers, reaching the baby and, because his/her caffeine metabolism is immature, our hypothesis is that even a low caffeine intake (250 mg/day), lower than the dose limit recommended by the World Health Organization, can promote caffeine overexposure in the offspring, leading to short- and long-term changes. Pregnant Wistar rats received intragastric caffeine (CAF) (25 mg/Kg/day) or vehicle during the gestation and lactation periods. We evaluated morphometrical, metabolic, hormonal, and behavioral parameters of male and female offspring at different ages. Even a low caffeine intake promoted lower maternal body mass and adiposity, higher plasma cholesterol and lower plasma T3, without changes in plasma corticosterone. Female CAF offspring exhibited lower birth weight, body mass gain and food intake throughout life, and hyperinsulinemia at weaning, while male CAF offspring showed reduced food intake and lower plasma T3 at weaning. At puberty and adulthood, male CAF showed higher preference for palatable food, aversion to caffeine intake and higher locomotor activity, while female CAF only showed lower preference for high fat diet (HFD) and lower anxiety-like behavior. At adulthood, both male and female offspring showed higher plasma T3. Male CAF showed hypertestosteronemia, while female CAF showed hypoinsulinemia without effect on glucose tolerance. A low caffeine intake during the perinatal period affects rat's offspring development, promoting sex-dependent hormonal and behavior changes. Current data suggest the need to review caffeine recommendations during the perinatal period.

Breastfeeding in infancy and cardiovascular disease in middle-aged and older adulthood: a prospective study of 0.36 million UK Biobank participants

BackgroundCardiovascular disease originates in early life. We aimed to investigate the association between breastfeeding in infancy and cardiovascular disease in adult life. MethodsWe followed 364,240 participants from UK Biobank aged 40–73 years from 2006 – 2010 to 2021. Information on breastfeeding in infancy was self-reported by questionnaire. Cox proportional hazard regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between breastfeeding and cardiovascular disease in middle-aged and older adulthood. The multivariable Cox models were used by adjusting for the age (used as the time scale), sex, ethnicity, assessment centre, birth weight, multiple birth status, maternal smoking during pregnancy, Townsend deprivation index, smoking status, alcohol drinker status, physical activity, and menopausal status for women. Binary and multinomial multivariable logistic regression models were used to explore the associations of breastfeeding in infancy with cardiovascular disease risk factors including obesity, body composition, metabolic and inflammatory disorders. ResultsDuring a median of 12.6 years of follow-up, we documented 29,796 new cases of cardiovascular disease, including 24,797 coronary heart disease and 6229 stroke. The multivariable adjusted HRs for breastfed versus non-breastfed were 0.94 (95% CI: 0.91, 0.96) for cardiovascular disease, 0.94 (95% CI: 0.91, 0.96) for coronary heart disease, and 0.95 (95% CI: 0.89, 1.01) for stroke. Furthermore, the strength of observed association between breastfeeding and cardiovascular disease seems to decrease with age (P for interaction <0.001), and increase with polygenic risk for cardiovascular disease (P for interaction <0.001). Consistently, breastfeeding in infancy was associated with cardiovascular disease risk factors including lower body mass index 0.92 (95% CI: 0.89, 0.95), body fat percentage 0.85 (95% CI: 0.83, 0.87), android to gynoid fat ratio 0.89 (95% CI: 0.83, 0.96), visceral adipose tissue 0.92 (95% CI: 0.84, 1.01), as well as lower C-reactive protein level 0.95 (95% CI: 0.94, 0.97) and a lower risk of metabolic syndrome 0.89 (95% CI: 0.85, 0.92). ConclusionsBreastfeeding in infancy was associated with a lower risk of cardiovascular disease in middle-aged and older adulthood. Promoting breastfeeding is vital not only for promoting child health, but also for halting the increasing trend of cardiovascular disease in adults.

Regional Phase Angle As An Indicator Of Upper And Lower Body Strength Performance In Youth

Regional Phase Angle As An Indicator Of Upper And Lower Body Strength Performance In Youth

Impact Of Basketball Floor Stiffness On Lower Body Biomechanics During Landing

Impact Of Basketball Floor Stiffness On Lower Body Biomechanics During Landing

A service evaluation of weight management for glycaemic control and remission of type 2 diabetes using traditional food in Nepal (Ho-DIRECT NEPAL): a single-arm trial

Remission of early type 2 diabetes (T2D) is possible; however, diet programmes proven effective are unaffordable in many southeast Asian populations where T2D is more frequent and more aggressive at lower body weight and younger age. We evaluate an entirely food-based service. This study employed a single-arm intervention and follow-up design for intervention evaluation in existing hospital people with T2D of under 5 years known duration. Individuals attending a diabetes clinic in Kathmandu with early T2D (<5 years) aged 30-70 years, BMI ≥23kg/m2, were offered a low-cost nutritionally complete diet-programme, using traditional Nepali foods to provide 8-weeks ∼850kcal/day weight loss induction, and then weight maintenance. The participants received 4-weekly dietetic appointments (30-45min) and verbo-pictorial leaflets using household measures. Glucose-lowering medications (49/70at baseline) were stopped at baseline or soon after. The study was registered as ISRCTN10671396, testing a traditional food-based intervention for weight loss and T2D remission. For 70 individuals (45 female) invited between March 19, 2022 and September 19, 2023, baseline mean (SD) age was 48.6 (9.9) years, bodyweight 74.6 (9.5) kg, BMI 29.7 (3.6) kg/m2, known diabetes duration 2.5 (1.9) years, HbA1c on treatment 8.1 (1.6) %. At 12, 24 and 52 weeks respectively, evaluating n=44, 46, 45, bodyweight was 70.1 (8.5), 69.8 (8.9), 70.0 (8.8) kg, HbA1c 6.8 (0.9), 6.9 (1.5), 7.1 (1.3) %; HbA1c<6.5% was recorded for 46%, 48% and 36% and remission of T2D (HbA1c<6.5% off medication >3 months) in 43%, 39% and 29%. The main reported adherence barriers were fears of weakness, hunger, and inconvenience during travel. Incentives were ease of the diet, reduced doses and costs of medications, and improved appearance. Traditional food-based weight management can valuably improve control, reduce medication needs, and generate remissions of established T2D, but adherence barriers must be overcome to optimise outcomes. All Saints Educational Trust, England.

Modeling and numerical analysis of Kangaroo lower body based on constrained dynamics of hybrid serial-parallel floating-base systems

This paper presents the modeling and numerical analysis of the Kangaroo lower body prototype, a novel bipedal humanoid robot developed and manufactured by PAL Robotics. Kangaroo features high-power linear electric actuators combined with unique serial-parallel hybrid chains, which allow for the positioning of all the leg actuators near the base of the robot to improve the overall mass distribution. To model and analyze such complex nonlinear mechanisms, we employ a constrained formulation that is extended to account for floating-base systems in contact with the environment. A comparison is made to demonstrate the significant improvements achieved with TALOS, another humanoid bipedal robot designed by PAL Robotics, in terms of equivalent Cartesian inertia at the feet and centroidal angular momentum. Finally, the paper includes numerical experiments conducted through simulation and preliminary tests performed on the actual Kangaroo platform.

The Difference In Fitness And Lower Body Power Based On Mobility Status In First Responders

The Difference In Fitness And Lower Body Power Based On Mobility Status In First Responders

Effects Of Upper And Lower Body Blood Flow Restriction Training On Subjective Assessments

Effects Of Upper And Lower Body Blood Flow Restriction Training On Subjective Assessments

Risk factors of post-irradiation carotid blowout syndrome in patients with nasopharyngeal carcinoma.

Carotid blowout syndrome (CBS) is a severe complication of radiotherapy in patients with nasopharyngeal carcinoma (NPC). This study is aimed at analyzing risk factors of post-irradiation CBS in patients with NPC. We retrospectively analyzed 660 patients with NPC between 2006 and 2019. The patients were divided into those with and without CBS, and their characteristics and outcomes were evaluated. Independent predictors of CBS were determined by multivariate logistic regression analysis. We identified 17 NPC patients with CBS in our study. In multivariate logistic regression analysis, lower body mass index (BMI) (P = 0.018), tumor encasement (P = 0.039), local recurrence (P = 0.006), and skull base osteoradionecrosis (P < 0.001) were independent predictors of CBS, and a predictive equation model was established. Log-rank test revealed that patients with low BMI, tumor encasement of carotid vessels, local recurrence, and skull base osteoradionecrosis all exhibited shorter CBS-free time (all P < 0.001). We demonstrated that low BMI, tumor encasement, local recurrence, and skull base osteoradionecrosis were independent predictors for CBS in NPC patients. Physicians can use these factors for the early detection and prevention of CBS.

Rehospitalizaciones precoces y tardías tras el cierre percutáneo de la orejuela izquierda

Introduction and objectives: Percutaneous left atrial appendage closure (LAAC) has emerged as a nonpharmacological alternative for the prevention of thromboembolic events in patients with nonvalvular atrial fibrillation. However, there are few data on readmissions after LACC. The aim of this study was to determine the rate of early (≤ 30 days) and late (31-365 days) readmission after LAAC, and to assess the predictors and clinical impact of rehospitalization.Methods: This multicenter study included 1419 consecutive patients who underwent LAAC. The median follow-up was 33 [17-55] months, and follow-up was complete in all but 54 (3.8%) patients. The primary endpoint was readmissions for any cause. Logistic regression and Cox regression analysis were performed to determine the predictors of readmission and its clinical impact.Results: A total of 257 (18.1%) patients were readmitted within the first year after LAAC (3.2% early, 14.9% late). The most common causes of readmission were bleeding (24.5%) and heart failure (20.6%). A previous gastrointestinal bleeding event was associated with a higher risk of early readmission (OR, 2.65; 95%CI, 1.23-5.71). The factors associated with a higher risk of late readmission were a lower body mass index (HR, 0.96-95%CI, 0.93-0.99), diabetes (HR, 1.38-95%CI, 1.02-1.86), chronic kidney disease (HR, 1.60; 95%CI, 1.21-2.13), and previous heart failure (HR, 1.69; 95%CI, 1.26-2.27). Both early (HR, 2.12-95%CI, 1.22-3.70) and late (HR, 1.75; 95%CI, 1.41-2.17) readmissions were associated with a higher risk of 2-year mortality.Conclusions: Readmissions within the first year after LAAC were common, mainly related to bleeding and heart failure events, and associated with patients’ comorbidity burden. Readmission after LAAC confered a higher risk of mortality during the first 2 years after the procedure.