α-Tocopherol Depletion Exacerbates Lipopolysaccharide-Induced Reduction of Grip Strength.

BACKGROUND: α-Tocopherol (αT) deficiency causes several neurologic disorders, such as spinocerebellar ataxia, peripheral neuropathy, and myopathy. Furthermore, decreased antibody production, impaired ex vivo T cell function, and elevated cytokine production are observed in humans and mice with αT deficiency. Although modeling αT deficiency in animals is challenging, αT depletion can be more readily achieved in α-tocopherol transfer protein-null (Ttpa-/-) mice than wild-type (WT) mice. Thus, the Ttpa-/- mouse model is a useful tool for studying metabolic consequences of low αT status. Optimizing this mouse model and selecting the reliable indicators/markers of deficiency are still needed. OBJECTIVE: Our objective was to assess whether αT depletion alters lipopolysaccharide (LPS)-induced inflammatory response in the brain and/or grip strength used as a proxy for fatigue. METHODS: WT and Ttpa-/- weanling littermates (n = 37-40/genotype) were fed an αT deficient diet ad libitum for 9 wk. Mice were then injected with LPS (10 µg/mouse) or saline (control) intraperitoneally and killed 4 h later. Concentrations of αT in diet and tissues were measured via high-pressure liquid chromatography. Grip strength was evaluated via a grip strength meter apparatus 2 d before and 3.5 h after LPS injection. Cerebellar and serum interleukin-6 (IL-6) concentrations were measured via enzyme-linked immunosorbent assay. RESULTS: αT concentrations in the liver, heart, and adipose tissue of WT mice were higher than Ttpa-/- mice. Although αT was detected in the brain, muscle, and serum of WT mice, it was undetectable in these tissues of Ttpa-/- mice. Cerebellar and serum concentrations of IL-6 were increased in LPS-treated groups but were not significantly affected by genotype. Grip strength was reduced in LPS-treated groups, an effect that was more pronounced in Ttpa-/- mice. CONCLUSIONS: Systemic LPS administration caused an acute inflammatory response with a concomitant decline in grip strength, especially in Ttpa-/- mice. αT depletion appears to exacerbate reductions in grip strength brought on by systemic inflammation.

Association Between Dietary Acid Load and Grip Strength in Adults 50 Years and Older: A Cross-Sectional Study.

Minimal data exist on whether the acid-base balance of the diet is linked to muscle strength. The aim of this study was to determine if dietary acid load is associated with grip strength in a nationally representative sample of middle- to older-age adults. We examined the cross-sectional association of grip strength with dietary acid load quantified through potential renal acid load (PRAL) and net endogenous acid production (NEAP) in 4,059 adults aged 50 years and older in the 2011-2014 NHANES survey cycles. PRAL and NEAP were estimated from two 24-h recalls and categorized into sex-specific quartiles. Grip strength was measured on a dynamometer. Multiple linear regression models were used to determine the associations of PRAL and NEAP (as quartiles) with grip strength for men and women separately, adjusting for total energy, age, race/ethnicity, weight, physical activity, smoking, serum 25-hydroxyvitamin D, and estimated glomerular filtration rate. Mean grip strength was 26.8 ± 0.2 kg in women and 43.0 ± 0.4 kg in men. Adjusted grip strength was inversely associated with quartiles of PRAL (ptrend = 0.049) and NEAP (ptrend = 0.034) in women with quartile 4 vs 1 differences of - 1.21 and - 1.08 kg (both p < 0.05), respectively. Adjusted grip strength was not associated with PRAL or NEAP in men. Overall, we found inverse associations between dietary acid load and grip strength in middle- and older-age women, suggesting that an alkaline diet may be important in maintaining muscle strength in this population. There was no association between dietary acid load and grip strength in men.

The Relationship Among Probable SARCopenia, Osteoporosis and SuprasPinatus Tendon Tears in Postmenopausal Women: The SARCOSP Study.

We aimed to investigate the relationship among probable sarcopenia, osteoporosis (OP) and supraspinatus tendon (SSP) tears in postmenopausal women. Postmenopausal women screened/followed for OP were recruited. Demographic data, comorbidities, exercise/smoking status, and handgrip strength values were recorded. Probable sarcopenia was diagnosed as handgrip strength values < 20 kg. Achilles and SSP thicknesses were measured using ultrasound. Among 1443 postmenopausal women, 268 (18.6%) subjects had SSP tears. Unilateral tears were on the dominant side in 146 (10.1%) and on the non-dominant side in 55 women (3.8%). In contrast to those without, women with SSP tears had older age, lower level of education, thinner SSP and lower grip strength (all p < 0.05). In addition, they had higher frequencies of hypertension, hyperlipidemia, DM, OP and probable sarcopenia, but lower exercise frequency (all p < 0.05). Binary logistic regression modeling revealed that age [odds ratio (OR): 1.046 (1.024-1.067 95% CI)], hypertension [OR: 1.560 (1.145-2.124 95% CI)], OP [OR: 1.371 (1.022-1.839 95% CI)] and probable sarcopenia [OR: 1.386 (1.031-1.861 95% CI)] were significant predictors for SSP tears (all p < 0.05). This study showed that age, presence of hypertension, probable sarcopenia and OP were related with SSP tears in postmenopausal women. To this end, although OP appeared to be related to SSP tears, SSP tear/thickness evaluation can be recommended for OP patients, especially those who have other risk factors such as older age, higher BMI, hypertension, and probable sarcopenia.

Physical activity-induced alterations of the gut microbiota are BMI dependent.

Physical inactivity is one of the leading causes of chronic metabolic disease including obesity. Increasing physical activity (PA) has been shown to improve cardiometabolic and musculoskeletal health and to be associated with a distinct gut microbiota composition in trained athletes. However, the impact of PA on the gut microbiota is inconclusive for individuals performing PA in their day-to-day life. This study examined the role of PA and hand-grip strength on gut microbiome composition in middle-aged adults (40-65 years, n = 350) with normal (18.5-24.9 kg/m2 ) and overweight (25-29.9 kg/m2 ) body mass index (BMI). PA was recorded using the International Physical Activity Questionnaire, and hand-grip strength was measured using a dynamometer. Serum samples were assessed for lipidomics while DNA was extracted from fecal samples for microbiome analysis. Overweight participants showed a higher concentration of triacylglycerols, and lower concentrations of cholesteryl esters, sphingomyelin, and lyso-phosphotidylcholine lipids (p < .05) compared with those with normal BMI. Additionally, overweight participants had a lower abundance of the Oscillibacter genus (p < .05). The impact of PA duration on the gut microbiome was BMI dependent. In normal but not overweight participants, high PA duration showed greater relative abundance of commensal taxa such as Actinobacteria and Proteobacteria phyla, as well as Collinsella and Prevotella genera (p < .05). Furthermore, in males with normal BMI, a stronger grip strength was associated with a higher relative abundance of Faecalibacterium and F. prausnitzii (p < .05) compared with lower grip strength. Taken together, data suggest that BMI plays a significant role in modeling PA-induced changes in gut microbiota.

Outcome measures in pediatric chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION/AIMS: Objective outcome measures in children undergoing treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are lacking. The aim of the study was to record serial grip strength and motor nerve conduction studies to assess interval change. METHODS: This was a retrospective review of 16 children (8 females and 8 males; median age, 9.7 years; interquartile range, 6-13 years) with CIDP followed at a tertiary children's hospital from 2013 to 2021. Subjects were treated with intravenous immunoglobulin (IVIG). Right and left grip strength measurements were obtained at each clinic visit using a handheld dynamometer. Annual right median motor nerve conduction study data were recorded during the study period. RESULTS: Mean duration of follow-up was 2.9 years. Grip strength (right: 0.19 kg/month, p < 0.001; left 0.23 kg/month, p < 0.001) and median F-wave latencies (-0.23/month, p = 0.015) showed significant improvement over time. Akaike information criterion showed time + IVIG frequency <21 days as best fit for grip strength and distal compound muscle action potential amplitude. DISCUSSION: Our study results indicate serial grip strength measurements are a feasible and objective way to assess motor strength improvement in children with CIDP receiving immunotherapy.

Genetically Proxied Sarcopenia-Related Muscle Traits and Depression: Evidence from the FinnGen Cohort.

BACKGROUND: Sarcopenia and depression are common and often coexist in the elderly. This study aims to determine the impact of sarcopenia-related muscle traits on depression. METHODS: A two-sample Mendelian randomization (MR) study was performed on the summary-level data from the FinnGen cohort to estimate the causal association of appendicular lean mass (ALM), walking pace, or low hand grip strength with depression. Additionally, multivariable MR (MVMR) was performed to assess the dependence of each muscle trait in the causality and adjust the effect of body mass index (BMI). Supplementary backward MR analyses were performed to estimate the effect of depression on sarcopenia-related muscle traits. RESULTS: Univariable MR analyses demonstrated that there were causal associations of ALM (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.88-0.99), walking pace (OR: 0.53; 95% CI: 0.32-0.88), and low hand grip strength (OR: 1.20; 95% CI: 1.05-1.38) with depression. MVMR analyses showed that ALM was the only trait that had a significant causal relationship with depression (OR: 0.91; 95% CI: 0.85-0.98) after accounting for the other two muscle traits. Moreover, the independent association of ALM with depression remained (OR: 0.92; 95% CI: 0.85-0.99) after being adjusted by BMI. The backward MR analyses showed no causal associations of depression with any sarcopenia-related muscle traits. CONCLUSION: Low muscle mass independently increases the risk of depression. This study determined the muscle-related risk factors of depression, which may help establish the causality between sarcopenia and depression and provide evidence-based recommendations for improving mental health in the elderly.

What Happens to Frailty in the First Year After Lung Transplantation?

BACKGROUND: Frailty is prevalent in lung transplant (LTx) candidates, but the impact and subsequent frailty trajectory is unclear. This study aimed to investigate frailty over the first year after LTx. METHOD: Post-LTx recipients completed a thrice weekly 12-week directly supervised exercise rehabilitation program. Edmonton Frail Scale (EFS) was used to assess frailty. Primary outcome was 6-Minute Walk Distance (6MWD) measured at pre-LTx, prerehabilitation, postrehabilitation, and 1 year post-LTx. RESULTS: 106 of 139 recruited participants underwent LTx: mean age 58 years, 48% male, 52% with chronic obstructive pulmonary disease. Mean (± SD) frailty scores pre-LTx and 1 year post-LTx were 5.54 ± 2.4 and 3.28 ±1.5. Mean 6MWD improved significantly for all: prerehabilitation 326 m (SD 116), versus postrehabilitation 523 m (SD 101) (p < 0.001) versus 1 year 512 m (SD 120) (p < 0.001). There were significant differences between an EFS > 7 (frail) and EFS ≤ 7 (not frail) for 6MWD, grip strength (GS), anxiety, and depression. Postrehabilitation, there were no significant differences in 6MWD, GS, anxiety, or depression while comparing EFS > 7 versus ≤ 7. At 1 year, there was a significant difference in depression but not 6MWD, GS, or anxiety between those EFS ≤ 7 and > 7 (p = 0.017). CONCLUSION: Participants in a structured post-LTx rehabilitation program improved in functional exercise capacity (6MWD), GS, depression, and anxiety. For frail participants exercise capacity, depression, anxiety, and GS were well managed in rehabilitation with no significant differences between those who were not frail. Pre-LTx frailty may be reversible post-LTx and should not be an absolute contraindication to LTx.

Mendelian randomization study on association between grip strength and BMD in different age groups.

INTRODUCTION: This study aimed to use the Mendelian randomization study method to verify the causal relationship between grip strength and bone mineral density (BMD) in different ages and different parts of the body. MATERIALS AND METHODS: The analysis was based on pooled data from genome-wide association studies (GWAS). Hand grip strength (right) was used as the exposure variable and total body bone mineral density (BMD) of different age groups was used as the outcome variable. Single-nucleotide polymorphisms highly correlated with exposure variables were used as instrumental variables. The inverse variance weighted (IVW) method was used as the primary analysis method, and the Mendelian randomization Egger (MR-Egger) regression and weighted median methods were used as supplementary evidence for the IVW results. Horizontal pleiotropy and heterogeneity tests were conducted to ensure the stability of the results. RESULTS: Analyzing the GWAS data on osteoporosis as the outcome variable, the IVW analysis showed that osteoporosis risk was associated with decreased grip strength in the 45-60 age group and the risk of declining lumbar spine BMD was associated with decreased grip strength. However, there was no significant correlation between the risk of osteoporosis in other age groups and changes in grip strength. CONCLUSION: A causal relationship exists between decreased grip strength and osteoporosis risk in people aged 45-60 years. The risk of BMD declining in the lumbar spine was associated with reduced grip strength.

Association of diet quality with hand grip strength weakness and asymmetry in a multi-ethnic Asian cohort.

Hand grip strength (HGS) is an important diagnostic tool for sarcopenia and a reliable predictor for age-related chronic diseases and mortality. Interventions in nutrition have been shown as a low-cost strategy to maintain muscular strength and mass. However, there are limited data on the effect of diet on HGS in Southeast Asian populations. This study aims to investigate the association of diet quality with HGS weakness and asymmetry in a multi-ethnic population in Singapore. This cross-sectional study used data from the Singapore Multi-Ethnic Cohort (n = 1547). Dietary data were collected using a validated semi-quantitative FFQ and summarised as the Dietary Quality Index - International (DQI-I). HGS was calculated as the maximum value of six measurements from both hands. HGS weakness and asymmetry were defined using well-recognised criteria. Multivariable linear regression and logistic regression were utilised for continuous and binary outcomes, respectively, adjusting for age, sex, ethnicity, physical activity and smoking status. It was found that the highest quartile of DQI-I was significantly associated with higher HGS (ß = 1·11; 95 % CI 0·41, 1·82; Pfor trend < 0·001) and lower odds of HGS asymmetry (OR = 0·71; 95 % CI 0·53, 0·94; Pfor trend = 0·035) and both HGS weakness and asymmetry (OR = 0·50; 95 % CI 0·32, 0·76; Pfor trend = 0·004). Among the different components of DQI-I, only dietary adequacy was significantly associated with higher HGS (Pfor trend < 0·001) and lower odds for both HGS weakness and asymmetry (Pfor trend = 0·006). Our findings support that DQI-I, an indicator of overall diet quality, can be used to provide dietary guidelines for prevention and management of muscle wasting, sarcopenia and frailty.

The impact of iron deficiency on patients under evaluation for colorectal cancer, a prospective cross-sectional study.

BACKGROUND AND OBJECTIVE: Iron deficiency affects more than 60% of colorectal cancer patients at the time of diagnosis. Iron deficiency ultimately leads to anemia, but additionally, iron deficiency might impact other domains of colorectal cancer patients' health and well-being. The aim of this study was to evaluate the impact of iron deficiency on fatigue, quality of life, cognition, and physical ability in patients undergoing evaluation for colorectal cancer. METHODS: Multicenter, prospective, observational cross-sectional study (2021-2023). Fatigue was the primary outcome, measured using the Focused Assessment of Cancer Treatment-Anemia questionnaire (FACT-An). Quality of Life, Cognition, Aerobe capacity, mobility, and peripheral muscle strength were tested as secondary outcomes. Multivariate analysis was performed to estimate the impact of iron deficiency on all outcomes. RESULTS: Two hundred and one patients were analyzed, 57% being iron deficient. In multivariate regression analysis, iron deficiency was not associated with fatigue: FACT-An (r = -1.17, p = 0.57, 25% CI: -5.27 to 2.92). Results on quality of life, cognition, and mobility were non-significant and with small regression coefficients. Iron deficiency showed a nearly significant association with reduced hand-grip-strength (r = -3.47 kg, p = 0.06, 25%CI -7.03 to 0.08) and reduced 6 min walking distance (r = -40.36 m, p = 0.07, 25%CI: -84.73 to 4.00). CONCLUSION: Iron deficiency in patients undergoing evaluation for colorectal cancer was not associated with fatigue, quality of life, or cognition, but might affect aerobic endurance and peripheral muscle strength to a degree that is clinically relevant.

Grip strength complements performance status in assessing general condition in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

AIM: An accurate assessment of the general condition of patients with hepatocellular carcinoma (HCC) is essential. We evaluated the impact of grip strength (GS) and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) on the clinical outcomes of patients with unresectable HCC (u-HCC) treated with atezolizumab plus bevacizumab. METHODS: This observational cohort study analyzed 89 patients with u-HCC treated with atezolizumab plus bevacizumab between October, 2020 and October, 2023. A Cox proportional hazards model and Kaplan-Meier curve were used to identify the prognostic factors associated with survival outcomes. RESULTS: There were 33 patients who had low GS and 16 had an ECOG-PS ≥1. The frequency of patients with low GS increased as the ECOG-PS score increased. The overall survival of the normal GS group was significantly higher than that of the low GS group (p < 0.01). There was no significant difference in progression-free survival between the normal GS group and low-GS group (p = 0.28). Among the patients in the ECOG-PS 0 groups, the overall survival in the normal GS group was significantly higher than that in the low GS group (p < 0.01). A multivariate analysis revealed that modified albumin-bilirubin 2b (HR 2.24; 95% confidence interval [CI] 1.06-4.73), α-fetoprotein ≥100 ng/mL (HR 2.35; 95% CI 1.20-4.58), and low GS (HR 2.87; 95% CI 1.31-6.27) were independently associated with a poor overall survival. CONCLUSIONS: The present study demonstrated that GS is a sensitive marker for detecting a subclinical decline in the general condition and is therefore a potential predictor of the outcome of u-HCC patients treated with atezolizumab plus bevacizumab.

Preoperative bioelectrical impedance, measured phase angle, and hand-grip strength as predictors of postoperative outcomes in patients undergoing cardiac surgery: a systematic review.

BACKGROUND: Postoperative problems are a major danger for patients after heart surgery. Predicting postoperative outcomes for cardiac surgery is limited by current preoperative evaluations. Handgrip strength (HGS) testing and bioelectrical impedance analysis (BIA) may provide extra ways to identify individuals at risk of surgical problems, enhancing risk assessment and results. OBJECTIVE: The purpose of this systematic review is to assess the utility of measured phase angle (PA), HGS, and bioelectrical impedance as perioperative risk markers in adult patients undergoing elective heart surgery. METHOD: The PRISMA principles were followed in this review. We searched all available electronic databases, including the Science Direct search engine and PubMed, MEDLINE, EMBASE, Cochrane Library, Web of Science, PsycINFO, CINAHL, Google Scholar, Scopus, and the Science Direct search engine, from their creation to the present, as well as the medRxiv pre-print site. We considered studies with adult subjects undergoing elective heart surgery who were monitored for problems after surgery and had perioperative BIA and HGS testing. RESULTS: As a result, out of the 1544 pieces of research that were discovered, eight studies were deemed suitable for inclusion in the review and supplied data from 2781 people. The findings demonstrated a substantial correlation between poor preoperative PA and a higher risk of serious postoperative morbidity, as well as prolonged hospital stays. Furthermore, poor HGS and low PA were linked to greater death rates. Additionally, there was a strong correlation found between low PA and HGS and longer stays in the ICU, as well as an increased chance of dying from all causes in a year. In conclusion these results imply that preoperative HGS and PA may be significant indicators of postoperative results and may assist in identifying patients who are more vulnerable to problems and death.

Grip strength predicts postoperative ileus among patients undergoing abdominal minimally invasive surgery: a prospective multicenter cohort study.

BACKGROUND: Postoperative ileus (POI) is a prevalent complication following abdominal surgery, leading to extended hospitalization and escalated medical expenses. Few studies have investigated the association between grip strength and POI after abdominal minimally invasive surgery (MIS). METHODS: A prospective multicenter cohort study was conducted using data from a prospectively registered database of patients undergoing abdominal MIS from March to December 2022. Grip strength levels were categorized and analyzed for their association with POI using multiple regression analysis with demographic adjustments. A smooth curve was generated to visualize the linear relationship. RESULTS: Out of 501 eligible patients, 393 were analyzed, with 67 (17.05%) developing POI. Grip strength was significantly and independently associated with POI, with each 1 kg and 8.57 kg (SD) increase in grip strength resulting in ORs of 0.94 and 0.61, respectively. Grip strength categories specific to sex and age were significantly associated with POI incidence, with individuals in the high grip strength group having a lower risk. Subgroup analysis showed grip strength as a significant predictor of POI risk, especially for males and older individuals. Higher grip strength was associated with a significantly lower risk of POI in males (OR = 0.29, 95% CI 0.09-0.90, p = 0.031) and older adults over 60 years old (OR = 0.31, 95% CI 0.10-0.98, p = 0.046). CONCLUSION: Grip strength can predict the occurrence of POI in patients undergoing abdominal MIS. This can help identify high-risk individuals and improve perioperative management for better outcomes.

Body surface scan anthropometrics are associated with grip strength in the general population.

BACKGROUND AND AIM: Body shape and anthropometrics are well-known risk factors for cardiovascular diseases (CVD) and mortality. Hand-grip strength (HGS) is also a meaningful marker of health and a promising predictor of CVD and mortality. There is a lack of studies that have systematically investigated associations between body shape and anthropometrics with HGS. In a population-based study, we investigated if anthropometric markers derived from 3D body scanning are related to HGS. METHODS AND RESULTS: We used the data of 1,599 individuals aged 36 to 93 years, who participated in the Study of Health in Pomerania. A total of 87 anthropometric markers, determined by a 3D body scanner, were included in the analysis. Anthropometric measurements were standardized and used as exposure variables. HGS was measured with a hand dynamometer and used as outcome. Sex-stratified linear regression models adjusted for age and height were used to relate standardized anthropometrics and HGS. Anthropometric markers were ranked according to -log-p-values. In men, left and right forearm circumference, left arm length to neck (C7), left forearm length, and forearm-fingertip length were most strongly related to HGS. In women, right forearm circumference, forearm-fingertip length, shoulder breadth, left forearm circumference, and right wrist circumference showed the most significant associations with HGS. The final prediction models contained 13 anthropometric markers in males (R2=0.54) and eight anthropometric markers in females (R2=0.37). CONCLUSIONS: The identified parameters may help estimate HGS in the clinical setting. However, studies in clinical settings are essential to validating our findings.

Safety and efficacy of monthly high-dose vitamin D3 supplementation in children and adolescents with sickle cell disease.

Little is known about the impact of vitamin D supplementation on hand grip strength (HGS) and health-related quality of life (HRQoL) in children and adolescents with sickle cell disease (SCD). We aimed to evaluate the safety and efficacy of monthly high-dose vitamin D3 supplementation and its implications on bone mineral density (BMD), HGS, and HRQoL in patients with SCD and healthy controls. The study included 42 children with SCD and 42 healthy matched controls. The study participants were supplemented with high-dose monthly oral vitamin D3. Changes in the serum level of 25(OH) vitamin D3, maximum HGS, and BMD from baseline to 6 months were assessed, and the HRQoL questionnaire and Childhood Health Assessment Questionnaire (CHAQ) were used to evaluate the functional capacity. At baseline, SCD subjects had poorer growth status indicated by negative Z scores. Suboptimal BMD was detected by significantly lower Z score, and lower HGS and worse HRQL parameters were found compared to the controls (P < 0.001). Median 25(OH) vitamin D3 was significantly lower in SCD patients compared to controls (16.5 vs. 28 ng/mL, respectively (P < 0.001)). After 6 months of vitamin D supplementation, there was significant improvement in the DEXA Z-score (P < 0.001), limitation of physical health (P = 0.02), pain scores (P < 0.001), and CHAQ grades (P = 0.01) in SCD patients. A significant improvement in HGS (P < 0.001 and P = 0.005) as well as the CHAQ score (P < 0.001 and P = 0.003) was detected in the SCD group and controls, respectively. There were no reported clinical adverse events (AEs) or new concomitant medications (CMs) during the study duration, and safe levels of Ca and 25 (OH) D3 were observed at 3 and 6 months for both groups. There was a significant positive correlation between HGS and total physical score (r = 0.831, P < 0.001) and a negative correlation with CHAQ score (r = - 0.685, P < 0.001). We also detected a significant positive correlation between vitamin D levels at 6 months and HGS (r = 0.584, P < 0.001), pain score (r = 0.446, P < 0.001), and a negative correlation with CHAQ score (r = - 0.399, P < 0.001).   Conclusion: Monthly oral high-dose vitamin D supplementation was safe and effective in improving vitamin D levels, HGS, and HRQoL in SCD children and healthy subjects, and BMD scores in SCD patients. Further randomized controlled trials are warranted to assess an optimal dosing strategy and to investigate the impact on clinically significant outcomes in children and adolescents with SCD and their healthy counterparts.   Trial registration: ClinicalTrials.gov , identifier NCT06274203, date of registration: 23/02/2024, retrospectively registered. What is known: • Several studies have reported a high prevalence of vitamin D deficiency and suboptimal bone mineral density (BMD) in sickle cell disease (SCD) patients. • Musculoskeletal dysfunction is reported in SCD patients with a negative impact on physical activity and health-related quality of life (HRQL). • Little is known regarding the impact of vitamin D3 supplementation in children and adolescents with SCD. What is new: • We found that monthly oral high-dose vitamin D3 supplementation was safe, tolerated, and effective in improving serum vitamin D levels, HGS, BMD scores, and HRQL in SCD patients.

Adherence to the Mediterranean diet is associated with handgrip strength in postmenopausal women.

OBJECTIVE: This study aimed to assess the possible association of adherence to the Mediterranean diet (MD) with muscle strength and body composition. METHODS: The cross-sectional study evaluated 112 postmenopausal women (aged 41-71 years). Fasting blood samples were obtained for biochemical/hormonal assessment. The Mediterranean Dietary Score (MedDietScore) was calculated and used to stratify adherence by tertiles (low [T1], moderate [T2] or high [T3]). Handgrip strength (HGS) was measured by dynamometry and body composition with dual-X-ray absorptiometry. RESULTS: Women with low-moderate MedDietScore (T1/T2) had lower HGS values than those with higher scores (19.5 ± 4.9 kg vs. 21.9 ± 3.9 kg, p = 0.023). A linear stepwise increase of HGS values per MedDietScore tertile was found (T1 vs. T2 vs. T3: 18.4 ± 4.4 kg vs. 20.6 ± 5.2 kg vs. 21.9 ± 3.9 kg, ANOVA p-value for linear trend = 0.009, ANCOVA p-value = 0.026). Multivariable models confirmed that HGS values were independently associated with the MedDietScore (ß-coefficient = 0.266, p = 0.010). Lean mass values were associated with the MedDietScore (ß-coefficient = 0.205, p = 0.040). All models were adjusted for age and cardiometabolic risk factors. CONCLUSIONS: The data suggest that the higher the adherence to the MD, the better the muscle strength and lean mass in postmenopausal women. Prospective studies are required to evaluate the significance of these observations in cardiovascular prevention strategies at midlife.

Pharmacological Doses of Thiamine Benefit Patients with the Charcot-Marie-Tooth Neuropathy by Changing Thiamine Diphosphate Levels and Affecting Regulation of Thiamine-Dependent Enzymes.

Charcot-Marie-Tooth (CMT) neuropathy is a polygenic disorder of peripheral nerves with no effective cure. Thiamine (vitamin B1) is a neurotropic compound that improves neuropathies. Our pilot study characterizes therapeutic potential of daily oral administration of thiamine (100 mg) in CMT neuropathy and its molecular mechanisms. The patient hand grip strength was determined before and after thiamine administration along with the blood levels of the thiamine coenzyme form (thiamine diphosphate, ThDP), activities of endogenous holo-transketolase (without ThDP in the assay medium) and total transketolase (with ThDP in the assay medium), and transketolase activation by ThDP [1 - (holo-transketolase/total transketolase),%], corresponding to the fraction of ThDP-free apo-transketolase. Single cases of administration of sulbutiamine (200 mg) or benfotiamine (150 mg) reveal their effects on the assayed parameters within those of thiamine. Administration of thiamine or its pharmacological forms increased the hand grip strength in the CMT patients. Comparison of the thiamin status in patients with different forms of CMT disease to that of control subjects without diagnosed pathologies revealed no significant differences in the average levels of ThDP, holo-transketolase, or relative content of holo and apo forms of transketolase. However, the regulation of transketolase by thiamine/ThDP differed in the control and CMT groups: in the assay, ThDP activated transketolase from the control individuals, but not from CMT patients. Thiamine administration paradoxically decreased endogenous holo-transketolase in CMT patients; this effect was not observed in the control group. Correlation analysis revealed sex-specific differences in the relationship between the parameters of thiamine status in both the control subjects and patients with the CMT disease. Thus, our findings link physiological benefits of thiamine administration in CMT patients to changes in their thiamine status, in particular, the blood levels of ThDP and transketolase regulation.

High hand grip strength is a significant risk factor and a useful predictor of postoperative pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most critical complications of pancreaticoduodenectomy (PD). Studies on predictive factors for POPF that can be identified preoperatively are limited. Recent reports have highlighted the association between the preoperative nutritional status, including sarcopenia, and postoperative complications. We examined preoperative risk factors for POPF after PD, focusing on nutritional indicators. METHODS: A total of 153 consecutive patients who underwent PD at our institution were enrolled in this study. Preoperative nutritional parameters, including hand grip strength (HGS) and skeletal muscle mass as components of sarcopenia, were incorporated into the analysis. POPFs were categorized according to the International Study Group of Pancreatic Fistula (ISGPF) definition as biochemical (grade A) or clinically relevant (CR-POPF; grades B and C). RESULTS: Thirty-seven of the 153 patients (24.1%) fulfilled the ISGPF definition of CR-POPF postoperatively. In the univariate analysis, the incidence of CR-POPF was associated with male sex, non-pancreatic tumor diseases, a high body mass index, a high HGS and a high skeletal muscle mass index. In the multivariate analysis, non-pancreatic tumor diseases and an HGS ≥23.0 kg were selected as independent risk factors for CR-POPF (P <0.05). CONCLUSIONS: A high HGS, a screening tool for sarcopenia, was a risk factor for CR-POPF. It can accurately serve as a useful predictor of POPF risk in patients undergoing PD. These results highlight the potential of sarcopenia to reduce the incidence of POPF and highlight the need to clarify the mechanism of POPF occurrence.

Sex-specific dose-response effects of a 24-week supervised concurrent exercise intervention on cardiorespiratory fitness and muscular strength in young adults: The ACTIBATE randomized controlled trial.

Concurrent training has been postulated as an appropriate time-efficient strategy to improve physical fitness, yet whether the exercise-induced adaptations are similar in men and women is unknown. An unblinded randomized controlled trial was conducted to investigate sex-specific dose-response effects of a 24-week supervised concurrent exercise training program on cardiorespiratory fitness and muscular strength in young adults. One hundred and forty-four sedentary adults aged 18-25 years were assigned to either (i) a control group (n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 46), or (iii) a vigorous intensity exercise group (VIG-EX, n = 44) by unrestricted randomization. Cardiorespiratory fitness (VO2max ), hand grip strength, and one-repetition maximum of leg press and bench press were evaluated at baseline and after the intervention. A total of 102 participants finished the intervention (Control, n = 36; 52% women, MOD-EX, n = 37; 70% women, and VIG-EX, n = 36; 72% women). In men, VO2max significantly increased in the MOD-EX (~8%) compared with the control group and in the VIG-EX group after the intervention (~6.5%). In women, VO2max increased in the MOD-EX and VIG-EX groups (~5.5%) compared with the control group after the intervention. There was a significant increment of leg press in the MOD-EX (~15.5%) and VIG-EX (~18%) groups compared with the control group (~1%) in women. A 24-week supervised concurrent exercise was effective at improving cardiorespiratory fitness and lower body limbs muscular strength in young women-independently of the predetermined intensity-while only at moderate intensity improved cardiorespiratory fitness in men.

Different sedentary behaviors, genetic susceptibility of hypertension, and new-onset hypertension: Mediating effects of body mass index and grip strength.

BACKGROUND: The association between different sedentary behaviors and hypertension risk remains unclear. We aimed to explore the relationship between different domains of sedentary behaviors and new-onset hypertension, investigate whether genetic susceptibility to hypertension modifies the relationship, and examine the extent to which the relationship is mediated by body mass index (BMI) and grip strength. METHODS: 212 714 participants without baseline hypertension in the UK Biobank were enrolled. The three major sedentary behaviors (TV-watching, nonoccupational computer use, and driving) were measured using touch screen questionnaires. The primary outcome was new-onset hypertension. RESULTS: During a median follow-up of 11.9 years, 13 983 participants developed hypertension. There was a linear positive association between TV-watching time and new-onset hypertension (p for nonlinearity =0.868). A J-shaped association was found for nonoccupational computer use time and driving time with new-onset hypertension, with an inflection point of 0.5 h/day for both (both p for nonlinearity <0.001). Polygenetic risk scores for hypertension (based on 118 related single-nucleotide polymorphisms) did not significantly modify these associations (all p-interactions >0.05). Furthermore, the detrimental effects of long-term sedentary behaviors on hypertension were mediated by BMI by 21%-30%, and the beneficial effects of limited sitting time (within 0.5 h/day) for driving and nonoccupational computer use were mediated by grip strength by 6-25%. CONCLUSIONS: There was a positive association for hands-independence sedentary behavior (TV-watching), and a J-shaped association for hands-dependence sedentary behaviors (nonoccupational computer use and driving) with new-onset hypertension, regardless of genetic risks of hypertension. These relationships were partly mediated by BMI and grip strength.