Reduced Muscle Strength Research Articles

Modulation of Brain Kynurenic Acid by N-Acetylcysteine Prevents Cognitive Impairment and Muscular Weakness Induced by Cisplatin in Female Rats

Cisplatin (CIS) is a potent chemotherapeutic agent primarily used to treat hematologic malignancies and solid tumors, including lymphomas, sarcomas, and some carcinomas. Patients receiving this treatment for tumors outside the nervous system develop cognitive impairment. Alterations in the kynurenine pathway (KP) following CIS treatment suggest that certain KP metabolites may cross the blood–brain barrier, leading to increased production of the neuromodulator kynurenic acid (KYNA), which is associated with cognitive impairment. This study aimed to evaluate the effects of modulating brain KYNA levels by the administration of N-acetylcysteine (NAC), an inhibitor of kynurenine aminotransferase II (KATII), an enzyme responsible for KYNA biosynthesis on the cognitive and neuromuscular deficits induced by CIS. Female Wistar rats were divided into four groups: control, NAC (300 mg/day/8 days), CIS (3 mg/kg i.p/5 days), and NAC + CIS (both treatments co-administered in parallel). Seven days after the last CIS administration, cognitive performance, muscle strength, brain KYNA levels, KATII activity, and brain tissue redox profile (lipid peroxidation and oxidized/reduced glutathione (GSH/GSSG) ratio) were assessed. CIS did not affect short-term memory but induced long-term memory deficits and reduced muscle strength, effects which were prevented by NAC co-administration. CIS decreased the GSH/GSSG ratio and the number of cells in the brain cortex while it increased lipid peroxidation, KYNA levels, and marginal KATII activity. All these effects were attenuated by the co-administration of NAC. These findings suggest that NAC mitigates the side effects of CIS, such as chemo-brain and muscle weakness, by improving the redox imbalance and modulating KYNA levels by limiting its non-enzymatic production by reactive oxygen species (ROS).

Muscular strength, endothelial function and cognitive disorders: state of the art.

In recent years, the ageing population has increasingly grown. This process carries a range of pathophysiological changes involving alterations in the skeletal muscle, vascular endothelium and brain function, becoming an important risk factor for developing cognitive disorders and cardiovascular diseases. With ageing, there is a decrease in muscle mass and muscle strength, and a relationship between muscle strength decrease and cognitive decline has been shown. Lower handgrip strength has been linked to memory impairment, lower global cognitive function, decreased attention and reduced visuospatial abilities in the elderly, but understanding of the underlying mechanisms that explain the link between altered skeletal muscle function and structure, endothelial dysfunction, and the role of endothelial dysfunction in the onset of cognitive disorders has been scarcely explored. This review aims to detail the cellular and molecular mechanisms by which the progressive changes associated with ageing can alter healthy skeletal muscle and endothelial function, creating an environment of oxidative stress, inflammation and mitochondrial dysfunction. These changes can lead to reduced muscle strength, and the secretion of detrimental endothelial factors, resulting in endothelial dysfunction, blood-brain barrier disruption, and damage to neurons and microglia, ultimately accelerating the onset of cognitive disorders in the elderly. In addition, we aimed to describe the mechanisms that potentially explain how preserving muscular function with resistance training could prevent brain function deterioration, including the production of different factors that allow an improved endothelial function, haemodynamic parameters and brain plasticity, ultimately delaying the onset of cognitive impairment and chronic diseases.

A Study of Body Composition as a Predictor of Muscle Quality and Endurance- A Cross-Sectional Study

Background: The alarming rise in sarcopenic obesity is compromising the quality of life for millions, underscoring the urgent need to unravel the factors contributing to muscle decline. Sarcopenic obesity, characterized by the concurrent loss of muscle mass and accumulation of excess fat, is a growing public health concern. This condition, often exacerbated by aging and poor lifestyle, negatively impacts muscle quality and contributes to a multitude of comorbidities. Previous research has demonstrated a significant association between obesity and reduced muscle strength compared to non-obese individuals, hindering activities of daily living such as stair climbing and walking. This study aims to investigate the predictive role of body composition on muscle quality and endurance. Methods: This cross-sectional study was carried out on 385 healthy male and female subjects aged between 18-67 years. The staff and students of JMMC and RI were selected for the study based on the inclusion and exclusion criteria, after obtaining the Institutional Ethical Clearance. Handgrip strength (HGS) and endurance (HE) was measured using handgrip dynamometer while body composition was assessed using Omron body fat analyser. Comparisons were done between age and gender. Statistical analysis was done using Independent T test, One-Way ANOVA and Mann Whitney test on SPSS version 20.Results: As age advances, there is statistically significant increase in BMI and BFP (body fat percentage) in both the genders. Increase in BMI and BFP is more pronounced in females with significant decrease in muscle mass percentage and HGS. Females had significant decline in endurance in all age groups (p<0.001).Conclusion: As the BMI and BFP increase with age, the muscle quality deteriorates. Females have more adiposity, poor muscle strength and endurance even though BMI remains same in both genders. To identify the early onset of decrease in muscle quality and endurance, a combination of parameters like BMI, BFP, HGS and HE should form a part of routine clinical screening.

Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular disease

Psychological stress contributes to cardiovascular disease (CVD) and sudden cardiac death, yet its molecular basis remains obscure. RNA binding protein RBM24 plays a critical role in cardiac development, rhythm regulation, and cellular stress. Here, we show that psychological stress activates RBM24 S181 phosphorylation through eIF4E2-GSK3β signaling, which causally links psychological stress to CVD by promoting APOE translation (apolipoprotein E). Using an Rbm24 S181A KI mouse model, we show that impaired S181 phosphorylation leads to cardiac contractile dysfunction, atrial fibrillation, dyslipidemia, reduced muscle strength, behavioral abnormalities, and sudden death under acute and chronic psychological stressors. The impaired S181 phosphorylation of RBM24 inhibits cardiac translation, including APOE translation. Notably, cardiomyocyte-specific expression of APOE rescues cardiac electrophysiological abnormalities and contractile dysfunction, through preventing ROS stress and mitochondrial dysfunction. Moreover, RBM24-S181 phosphorylation acts as a serum marker for chronic stress in human. These results provide a functional link between RBM24 phosphorylation, eIF4E-regulated APOE translation, and psychological-stress-induced CVD.

Epidermal growth factor receptor contributes to indirect regulation of skeletal muscle mass by androgen.

Androgen is widely acknowledged to regulate skeletal muscle mass. However, the specific mechanism driving muscle atrophy resulting from androgen deficiency remains elusive. Systemic androgen receptor knockout (ARKO) mice exhibit reduction in both muscle strength and muscle mass while skeletal muscle fiber specific ARKO mice have decreased muscle strength without affecting skeletal muscle mass in the limbs. Therefore, androgens may indirectly regulate skeletal muscle mass through effects on non-myofibers. Considering this, our investigation focused on blood fluid factors that might play a role in the regulation of skeletal muscle mass under the influence of androgens. Using a male mouse model of sham, orchidectomy and DHT replacement, mass spectrometry for serum samples of each group identified epidermal growth factor receptor (EGFR) as a candidate protein involving the regulation of skeletal muscle mass affected by androgens. Egfr expression in both liver and epididymal white adipose tissue correlated with androgen levels. Furthermore, Egfr expression in these tissues was predominantly elevated in male compared to female mice. Interestingly, male mice exhibited significantly elevated serum EGFR concentrations compared to their female counterparts, suggesting a connection with androgen levels. Treatment of EGFR to C2C12 cells promoted phosphorylation of AKT and its downstream S6K, and enhanced the protein synthesis in vitro. Furthermore, the administration of EGFR to female mice revealed a potential role in promoting an increase in skeletal muscle mass. These findings collectively enhance our understanding of the complex interplay among androgens, EGFR, and the regulation of skeletal muscle mass.

Genetic factors associated with changes in muscle strength and mass during corticosteroid therapy

BACKGROUND: Corticosteroid use is associated with loss of muscle mass and strength, which is associated with an unfavorable prognosis of the underlying disease, as well as an increased risk of cardiovascular disease. Patients with multiple sclerosis (MS) have a higher baseline susceptibility to cardiovascular disease and a higher risk of adverse effects due to corticosteroid use. In clinical practice, different degrees of severity of side effects of corticosteroids are reported. This may be related to the presence of a genetic predisposition, the identification of which should allow a personalized approach to therapy. AIM: To evaluate the association of polymorphic variants of the glucocorticoid receptor gene NR3C1, the FTO gene, and the melatonin receptor genes MTNR1A, MTNR1B with the development of changes in muscle mass and strength in the context of corticosteroid use in patients with MS. MATERIALS AND METHODS: The study included 80 patients (mean age 36.3±10.0 years) with MS receiving pulse corticosteroid therapy: 4 (3; 4) g methylprednisolone. Patients were enrolled over the course of one year. To assess the primary endpoint (reduction in muscle mass and strength), muscle strength and mass were monitored before and after therapy using wrist dynamometry, the time-up-and-go test, and bioimpedancemetry. Polymorphic variants of the glucocorticoid receptor gene NR3C1, the FTO gene, and the melatonin receptor genes MTNR1A and MTNR1B were identified by real-time polymerase chain reaction. Intergenic interactions were evaluated using the multifactor dimensionality reduction (MDR) method. R (v. 3.2, R Foundation for Statistical Computing, Austria) was used for statistical analysis. RESULTS: In women with loss of muscle mass after corticosteroid therapy, there was an increased incidence of depression (p=0.01) for polymorphic variant BclI (rs41423247) of the NR3C1 gene (p=0.005). Reduced dominant arm strength in women was associated with a variant of the BclI gene (rs41423247) (p=0.02), genotypes including BclI (rs41423247) and N363S (rs56149945) (p=0.03). Men with decreased strength in the non-dominant arm were more likely to be smokers (p=0.03). Combinations of genotypes of the NR3C1, FTO, MTNR1B genes were identified with increased and decreased risk of muscle mass loss in women after corticosteroid therapy. Analysis of intergenic interactions showed a strong synergism between the polymorphic variant rs993960 of the FTO gene and rs10830963 of the MTNR1B gene. CONCLUSION: The presence of polymorphic variants BclI (rs41423247), N363S (rs56149945) of the glucocorticoid receptor gene NR3C1 is associated with loss of muscle strength and mass in women receiving corticosteroid therapy for MS. Combinations of genotypes of the NR3C1, FTO, MTNR1B genes have been identified with an increased risk of muscle mass loss in women after corticosteroid therapy. Modifiable factors associated with loss of muscle mass and strength and cardiovascular risk (depression, smoking) were identified. The data obtained can be used to personalize corticosteroid therapy and prevent cardiovascular and metabolic disorders.

Muscle strength, functional mobility, and performance in activities of daily living in children and adolescents with cancer.

During and after childhood cancer treatment, impairments in physical fitness are observed, such as reduced muscle strength, fatigue, and changes in body functions. These aspects may result in limitations and restrictions inperformance of daily activities. To analyze the relationship between upper and lower limb muscle strength, functional mobility, and performance in activities daily living in children, adolescents, and young adults with cancer, compared to their healthy peers. The cross-sectional observational study involves 45 participants, 15 in the cancer group and 30 in the control group. Personal, environmental, and health data were collected. Participants from both groups were evaluated for upper and lower limb muscle strength, functional mobility (timed up and go test-TUG and five times sit-to-Stand test-5xSTS), and performance in activities of daily living (Pediatric Evaluation Of Disability Inventory-Computer Adaptive Test-PEDI-CAT). The participants were 30 females and 15 males (13.67 ± 5.78years: cancer group; 13.07 ± 5.11years: control group). Acute lymphoblastic leukemia (n = 7), chronic myeloid leukemia (n = 2)andHodgkin's lymphoma (n=2) were the main diagnoses in the cancer group. No significant differences were found in upper and lower limb muscle strength between groups (p > 0.05). However, significant differences were observed in functional mobility (TUG and 5xSTS) and performance (PEDI-CAT-mobility) in activities of daily living, with the cancer group showing worse performance compared to the control group (p ≤ 0.001). Conclusion: Children and adolescents with cancer showed lower functional mobility and performance in activities of daily living compared to the control group. These difficulties were not associated with muscle weakness or level of physical activity. Therefore, it is recommended that physiotherapeutic treatment and follow-up include activities focused on mobility and functional independence.

Abstract 4137985: Impaired Skeletal Muscle Condition and Stroke Volume Reserve Characterize Poor Exercise Performance in Childhood Cancer Survivors

Background: Childhood cancer survivors (CCS) frequently show poor exercise performance, but its pathophysiology and clinical significance are poorly understood. Methods: Poor exercise performers, defined as peak oxygen consumption (VO2)/kg < 80% of predicted maximum VO2/kg, were enrolled, including 40 CCS (20 males, 20 females) and 32 controls (15 males, 17 females) from 79 CCS and 147 age-matched controls, respectively. Peak and submaximal CPET parameters were compared between CCS and controls with poor exercise performance. Submaximal slope parameters represent a trend up to anaerobic threshold (AT). Results: Ages and anthropometric measurements (weight, height, and body mass index) were comparable between CCS and controls in both sexes (Table 1). Both resting and peak heart rate (HR) were significantly higher in CCS than in controls in males. There was no significant difference in peak VO2/kg, peak oxygen pulse (OP)/kg, peak respiratory exchange ratio, or VO2/kg at AT (VAT/kg) between CCS and controls in both sexes. Peak work rate (WR/kg) was significantly lower in CCS compared with that in controls in both sexes, suggesting reduced muscle strength in CCS. Figure 1 demonstrates decreased muscle mass/strength in CCS than in controls. In males, Δ[VO2/kg]/ ΔHR was significantly lower in CCS than in controls, indicating limited stroke volume reserve (SVR) in male CCS. In female, although there was no significant difference in Δ[VO2/kg]/ΔHR between CCS and controls, HR-dependency expressed by ΔHR/Δ[WR/kg] was significantly higher in CCS than in controls, suggesting impaired SVR. ΔVO2/ΔWR, a marker for physical conditioning, was comparable between CCS and controls in both sexes. Conclusions: Poor exercise performance in CCS is characterized mainly by decreased muscle mass/strength and impaired SVR for both sexs. Impaired SVR may be an early sign of subclinical cardiotoxicity. Poor exercise performance in CCS should be improved to prevent future cardiovascular complications.

Effects of Creatine Monohydrate Supplementation on Muscle, Bone and Brain- Hope or Hype for Older Adults?

Sarcopenia, generally characterized by the age-related reduction in muscle strength, lean/muscle mass and functional ability, is also associated with reduced bone mass and strength and impaired brain health and function. One potential intervention which has received much 'hype' over the past few decades to countermeasure these negative consequences of biological aging is creatine monohydrate supplementation. From a skeletal muscle perspective, the combination of creatine monohydrate supplementation and resistance training provides 'hope' for older adults as it improves measures of lean mass, regional (limb) muscle thickness, upper- and lower-body muscle strength and functional ability. Further, there is some evidence that creatine (supplementation or habitual diet) provides a ray of 'hope' for improving some aspects of cognitive function. The majority of research suggests that creatine is more 'hype' than 'hope' for improving measures of bone mass in older adults. Creatine monohydrate supplementation provides some anti-sarcopenic benefits for older adults.

Effect of Lumbar Spinal Stabilization Exercises Along With Neural Tissue Mobilization on Pain and Spinal Dysfunction in Failed Back Surgery Syndrome.

Background Failed back surgery syndrome (FBSS) mainly involves back pain radiating to the lower limb after back-related surgeries. It can develop various complications around the operation site and its surrounding area. This study evaluates the effect of lumbar spinal stabilization exercises and neural tissue mobilization on pain and spinal dysfunction in FBSS. Objectives To study the impact of lumbar spinal stabilization exercises and neural tissue mobilization on pain and spinal dysfunction in FBSS. To compare the impact of lumbar spinal stabilization exercises and neural tissue mobilization with conventional therapy on pain and spinal dysfunction in FBSS. Methods The study included 76 participants aged 45-60 with back pain radiating to lower limbs after back-related surgeries within the past six months. Participants were randomly assigned to either a conventional treatment group (Group A) or an experimental exercise program group (Group B). The treatment duration was six weeks and data were analyzed by a paired t-test for within-group analysis and an unpaired t-test for between-group analysis. Results Both groups A and B showed significant differences in all three outcome measures. However, Group B showed extremely significant improvement (<0.0001) in outcome measures, including pain, lumbar muscle strength by manual muscle testing, and modified Oswestry index assessment compared to Group A. Conclusion Both conventional and experimental groups showed a significant impact on the pain and level of function in failed back surgery syndrome patients. However, lumbar stabilization exercises along with neural tissue mobilization (Group B) showed a more pronounced impact on all outcomes such as pain reduction and improvement in lumbar flexor, rotator, and extensor muscle strength and modified Oswestry index compared to the conventional treatment group (Group A).

The Benefits of a Rehabilitation Program Following Medial Patellofemoral Ligament Reconstruction.

The medial patellofemoral ligament (MPFL) is critical for patellar stability. This study investigates the efficacy of a one-year physical therapy rehabilitation program following MPFL reconstruction using Synthetic Graft (SG) and Quadriceps Tendon Autograft (QTA). Thirty-five patients aged 18-38 underwent MPFL reconstruction (20 SG, 15 QTA). They participated in a structured rehabilitation program to improve their range of motion (ROM), muscle strength, pain management, and overall quality of life (QoL). The program included physiotherapy and MLS laser, Game Ready Therapy, EMS, TENS, TECAR, and lymphatic drainage. Before and after the program, assessments included knee flexion and extension using goniometry, muscle strength via the Medical Research Council (MRC) scale, knee circumference, pain intensity on the Visual Analogue Scale (VAS), and QoL with the EQ-5D instrument. Significant improvements were observed in knee flexion (37.57° vs. 114.71°, p < 0.001), muscle strength (MRC scale 1-4 points vs. 4-5 points, p < 0.001), and pain reduction (VAS 6.66 vs. 0.46, p < 0.001). The functional coefficient of mobility and QoL scores also markedly increased. Patients with QTA improved some parameters better than those with SG. These findings support the effectiveness of a comprehensive rehabilitation program in enhancing knee functionality, reducing pain, and improving QoL post-MPFL reconstruction. Personalized rehabilitation protocols are recommended to optimize recovery outcomes.

Improvements in upper extremity isometric muscle strength, dexterity, and self-care independence during the sub-acute phase of stroke recovery: an observational study on the effects of intensive comprehensive rehabilitation.

Stroke often impairs upper extremity motor function, with recovery in the sub-acute phase being crucial for regaining independence. This study examines changes in isometric muscle strength, dexterity, and self-care independence during this period, and evaluates the effects of a comprehensive intensive rehabilitation (COMIRESTROKE). Individuals in sub-acute stroke recovery and age- and sex-matched controls were assessed for pre- and post-rehabilitation differences in primary outcomes (grip/pinch strength, Nine Hole Peg Test [NHPT], Action Research Arm Test [ARAT]). COMIRESTROKE's effects on primary and secondary outcomes (National Institute of Health Stroke Scale [NIHSS], Modified Rankin Scale [MRS], Functional Independence Measure [FIM]) were evaluated. Outcomes were analyzed for dominant and non-dominant limbs, both regardless of impairment and with a focus on impaired limbs. Fifty-two individuals with stroke (NIHSS 7.51 ± 5.71, age 70.25 ± 12.66 years, 21.36 ± 12.06 days post-stroke) and forty-six controls participated. At baseline, individuals with stroke showed significantly lower strength (dominant grip, key pinch, tip-tip pinch, p adj < 0.05), higher NHPT scores (p adj < 0.05), and lower ARAT scores (p adj < 0.001). COMIRESTROKE led to improvements in dominant key pinch, non-dominant tip-tip pinch, NHPT, and both dominant and non-dominant ARAT (p adj < 0.05). Notably, non-dominant key pinch improved significantly when considering only impaired hands. Pre- and post-test differences between groups were significant only for ARAT (both limbs), even after adjustment (p adj < 0.05). All secondary outcomes (NIHSS, MRS, FIM) showed significant improvement post-COMIRESTROKE (p adj < 0.001). Individuals with stroke exhibit reduced muscle strength and dexterity, impairing independence. However, comprehensive intensive rehabilitation significantly improves these functions. Data are available from the corresponding author upon request and are part of a sub-study of NCT05323916.

The impact of anterior knee displacement on knee joint load during the forward bow step in Tai Chi.

While the forward bow step is a crucial component of Tai Chi (TC) practice, little research has been conducted on its impact on knee joint load and muscle coordination. This study aims to investigate the effects of three different knee forward positions during the TC forward bow step on knee joint loading. Twenty TC practitioners were recruited, and motion capture systems, force platforms, and surface electromyography were utilized to synchronously collect biomechanical parameters of three types of forward bow steps: knee joint not exceeding the tip of the foot (NETT), knee joint forward movement level with the tip of the foot (LTT), and knee joint forward movement exceeding the tip of the foot (ETT). Ligament and muscle forces were calculated using OpenSim software for musculoskeletal modeling and simulation. One-way ANOVA was used to analyze the variations of the indicators during the peak anterior displacement of the knee joint in three movements. Additionally, spm1d one-way ANOVA was employed to examine the variations in the one-dimensional curve of the indicators throughout the entire movement process. Compared with LTT and ETT, the NETT posture was associated with significantly decreased knee flexion angle (F = 27.445, p = 0.001), knee anterior-posterior translation (F = 36.07, p < 0.001), flexion-extension torque (F = 22.232, p = 0.001), ligament force (F = 9.055, p = 0.011). Additionally, there was also a significant reduction in muscle strength, including quadriceps (F = 62.9, p < 0.001), long biceps femoris (F = 18.631, p = 0.002), lateral gastrocnemius (F = 24.933, p = 0.001) and soleus (F = 7.637, p = 0.017). This study further confirms that in the forward lunge movement of Tai Chi, the knee joint load is mainly concentrated during the forward movement phase. Compared to the knee joint load at the NETT position, the load is greater at the LTT position; and compared to the LTT position, the load is even greater at the ETT position.

Head and Neck Cancer and Sarcopenia: An Integrative Clinical and Functional Review

Sarcopenia is recognized as a crucial factor impacting the prognosis, treatment responses, and quality of life of HNC patients. This review discusses various mechanisms, including common etiological factors, such as aging, chronic inflammation, and metabolic dysregulation. Cancer-related factors, including tumor locations and treatment modalities, contribute to the development of sarcopenia. The clinical implications of sarcopenia in HNC patients extend beyond reduced muscle strength; it affects overall mobility, reduces quality of life, and increases the risk of falls and fractures. Sarcopenia serves as an independent predictor of postoperative complications, chemotherapy dose-limiting toxicity, and treatment outcomes, which affect therapy planning and perioperative management decisions. Methods to assess sarcopenia in HNC patients encompass various techniques. A sarcopenia assessment offers a potentially efficient and readily available tool for clinical practice. Interventions and management strategies for sarcopenia involve exercise interventions as a cornerstone; however, challenges arise due to patient-specific limitations during cancer treatment. A routine body composition analysis is proposed as a valuable addition to HNC patient management, with ongoing research required to refine preoperative exercise and nutrition programs for improved treatment outcomes and survival.

Feasibility and safety of two weeks of blood flow restriction exercise in individuals with spinal cord injury

Context Reduced muscle strength and function are common after spinal cord injury (SCI). While low-load blood flow restriction exercise (BFRE) enhances muscle strength in healthy and clinical populations, its safety and feasibility in individuals with SCI remain underexplored. Objectives To investigate the feasibility and safety of low-load BFRE in individuals with incomplete SCI. Study Design Case series. Setting SCI rehabilitation center. Participants Six participants with motor incomplete SCI were enrolled in the study. Intervention A two-week BFRE intervention for the lower limbs was conducted twice weekly at 40% total arterial occlusion pressure, using 30-40% of 1-repetition maximum loads. Outcome Measures Feasibility measures, specifically recruitment and eligibility rates and intervention acceptability, were collected. Blood pressure (BP) responses and specific coagulation markers for deep vein thrombosis (DVT) were assessed as safety measures. Results Recruitment and eligibility rates were 2.8% and 6.6% for individuals admitted for first-time rehabilitation (subacute SCI) and 8.3% and 13.9% for 4-week readmission rehabilitation stays (chronic SCI), respectively. Intervention acceptability was high, characterized by 95.8% training adherence and low-to-moderate self-reported pain levels. BP responses and changes in C-reactive protein, Fibrinogen, and D-dimer during the intervention remained within clinically acceptable levels. Conclusion BFRE was feasible in an SCI rehabilitation setting despite a low recruitment rate. BFRE imposed no heightened risk of DVT or severe BP fluctuations in the present case series. Additionally, no severe adverse events occurred, and only mild complaints were reported. More extensive safety considerations warrant larger-scale exploration. Trial registration ClinicalTrials.gov identifier: NCT03690700.

Application of 3D-Slicer Software in the Treatment of Gliomas.

To explore the application of 3D-Slicer multimodal image fusion technology in the surgical treatment of gliomas. A retrospective analysis of clinical data from 48 cases of intracranial gliomas treated with 3D-Slicer multimodal image fusion technology from September 2021 to February 2023. Preoperative cranial CT, MRI, TOF-MRA, DTI, and MRV sequence examinations were completed. DICOM format medical imaging data were processed using the 3D-Slicer software. Multimodal fusion and 3-dimensional reconstruction of the tumor and surrounding structures were conducted to clarify the relationship between the tumor and surrounding structures. The surgery path was simulated through 3D virtual visualization images, enabling precise preoperative planning and assisting in surgical treatment. Out of 48 patients, complete tumor resection was achieved in 45 cases. One case encountered severe postoperative cerebral edema, no infections were reported, 1 patient had slightly reduced muscle strength after surgery compared with before, and no cases of severe neurological function damage or surgical death were recorded. 3D-Slicer multimodal image fusion technology can assist in detailed preoperative planning for the surgical treatment of intracranial glioma, reducing surgical complications, improving the rate of total tumor resection, and reducing postoperative complications.

The effect of tongue-to-palate on deep neck flexor activity

Deep neck flexor (DNF) muscles contribute to cervical stability and proprioception. Reduced muscle strength and endurance lead to faulty movement patterns, muscle imbalances, and dysfunction. Potentially, the orofacial muscles contribute to cervical strength by providing stability through muscular connections. This study examined effects of tongue muscle activity on cervical spine muscular stiffness. Twenty-three healthy subjects assumed three supine positions [at rest (AR), chin tuck (CT), and head lift (HL)] with and without tongue-to-palate pressure. The DNF stiffness was measured using shear wave elastography. Without tongue-to-palate, stiffness increased with CT and HL compared to AR (p <0.001) but not between CT and HL (p = 0.22). Tongue-to-palate increased stiffness AR (p <0.001) but not during CT (p = 0.95) or HL (p = 0.67). Stiffness levels between the AR and HL conditions during tongue-to-palate performance did not differ (p = 0.734), but CT stiffness was significantly greater than AR (p = 0.029) with tongue-to-palate. Tongue-to-palate AR increases DNF stiffness to a similar level as HL with or without tongue-to-palate, while CT with or without tongue-to-palate resulted in the highest stiffness levels. Tongue-to-palate pressure AR or with CT performance may be alternatives to HL strengthening in healthy necks. This may be a useful strategy to increase cervical stability during loads on the cervical spine.

6427 Impact of Adrenalectomy On Frailty And Muscle Function In Patients With Mild Autonomous Cortisol Secretion: A Prospective Longitudinal Study

Abstract Disclosure: J. Saini: None. V. Fell: None. B. Atkinson: None. S. Achenbach: None. I. Bancos: None. Background: Patients with mild autonomous cortisol secretion (MACS) have a higher prevalence of frailty and reduced muscle strength as compared to patients with nonfunctioning adrenal adenomas or subjects without adrenal disorders. Objective: To determine the impact of adrenalectomy on frailty and parameters of functional strength in patients with MACS. Methods: We conducted a single-center prospective longitudinal study of adults with MACS scheduled for adrenalectomy and referent subjects evaluated between 2018 and 2023. MACS was defined as serum cortisol&amp;gt;1.8 mcg/dL after 1 mg dexamethasone suppression test in patients with adrenal adenomas and no features of overt hypercortisolism. Referent subjects were included if they had abdominal imaging and had no adrenal disorders. Patients and referent subjects had a baseline and a follow-up evaluation at least 10 months later. Differences were assessed using paired t-tests for (1) Frailty Index (FI)--calculated using a questionnaire containing 47 variables on comorbidities, symptoms, and daily living activities (frailty defined as FI&amp;gt;0.25) (2) physical function assessed using handgrip strength (Jamar Plus digital hand dynamometer), timed up-and-go test (time taken to rise from a chair, walk to and from 3 m, and sit down), gait speed, 6-minute walk test, and (3) Advanced Glycation End (AGE) Product (using AGE reader). Results: We evaluated 41 patients before and after adrenalectomy, and 31 referent subjects at baseline and follow-up visit, at a similar interval (median 1.6, IQR 1.2-2.0 vs 1.5 years, IQR 1.0-2.2, P=0.759). While sex distributions were no different between the 2 groups (women, 66% vs 84%, P=0.086), patients with MACS were older than the referent group (median age 57.3, IQR 48.8-66.9 vs 49.0, IQR 41.7-57.9 years, P=0.005). Post-adrenalectomy, FI decreased by a mean of 0.057 (SD 0.08), P&amp;lt;0.001 in patients, and remained unchanged in the referent group. AGE decreased in patients by 0.148 (SD 0.45), P=0.04 but not in referent subjects (-0.047, SD 0.242, P=0.5). Patients demonstrated no improvement in parameters of muscle strength: gait speed (mean change 0.305 m/s, P=0.453), 6-minute walk test (mean change 16.4 meters, P=0.201), dominant (mean Z score change -0.055, P=0.72) and nondominant (mean Z score change -0.199, P=0.192) hand grip muscle strength. At follow-up, both patients (mean change 1.897 seconds, P&amp;lt;0.001) and referent subjects (mean change=1.475 seconds, P&amp;lt;0.001) demonstrated a deterioration on the timed up-and-go test. Conclusions: While no improvement was seen in the parameters of muscle strength, adrenalectomy improved the frailty index in patients with MACS. In addition, AGE, a biomarker associated with cardiovascular morbidity, decreased after adrenalectomy, suggesting a beneficial cardiovascular impact of MACS reversal. Presentation: 6/1/2024

Ferroptosis and Sarcopenia-Osteoporosis after Menopause: Research Status, Traditional Chinese Medicine Strategies, and Prospects

Ferroptosis, a precisely regulated cell death mechanism, is distinguished by its intimate link to iron overload and lipid peroxidation processes, playing a pivotal role in the pathological progression of a wide range of diseases. In postmenopausal women suffering from osteoporosis, reduced muscle strength and impaired balance lead to a heightened risk of fragility fractures, markedly diminishing their quality of life. Recent groundbreaking research has underscored the crucial role of the ferroptosis mechanism in the initiation and progression of musculoskeletal diseases. This discovery not only enriches our understanding of disease mechanisms but also heralds ferroptosis pathways as novel and promising therapeutic targets for treating these conditions. Traditional Chinese Medicine (TCM) has exhibited remarkable efficacy in managing musculoskeletal diseases, with studies validating its ability to modulate ferroptosis mechanisms and profoundly impact disease regulation. This portends vast research potential and significant therapeutic promise for the future. By delving deeper into the interplay between ferroptosis and sarcopenia-osteoporosis in postmenopausal women, and by developing innovative therapeutic strategies and TCM interventions, we aspire to forge new pathways for the treatment of sarcopenia-osteoporosis in this patient population.

LRRK2G2019S Gene Mutation Causes Skeletal Muscle Impairment in Animal Model of Parkinson's Disease

ABSTRACTBackgroundWhile the gradually aggravated motor and non‐motor disorders of Parkinson's disease (PD) lead to progressive disability and frequent falling, skeletal muscle impairment may contribute to this condition. The leucine‐rich repeat kinase2 (LRRK2) is a common disease‐causing gene in PD. Little is known about its role in skeletal muscle impairment and its underlying mechanisms.MethodsTo investigate whether the mutation in LRRK2 causes skeletal muscle impairment, we used 3‐month‐old (3mo) and 14‐month‐old (14mo) LRRK2G2019S transgenic (TG) mice as a model of PD, compared with the age‐matched littermate wild‐type (WT) controls. We measured the muscle mass and strength, ultrastructure, inflammatory infiltration, mitochondrial morphology and dynamics dysfunction through behavioural analysis, electromyography (EMG), immunostaining, transmission electron microscopy (TEM) and other molecular biology techniques.ResultsThe 3mo‐TG mice display mild skeletal muscle impairment with spontaneous potentials in EMG (increased by 130%, p &lt; 0.05), myofibre necrosis (p &lt; 0.05) and myosin heavy chain‐II changes (reduced by 19%, p &lt; 0.01). The inflammatory cells and macrophage infiltration are significantly increased (CD8a+ and CD68+ cells up 1060% and 579%, respectively, both p &lt; 0.0001) compared with the WT mice. All of the above pathogenic processes are aggravated by aging. The 14mo‐TG mice EMG examinations show a reduced duration (by 31%, p &lt; 0.01) and increased polyphasic waves of motor unit action potentials (by 28%, p &lt; 0.05). The 14mo‐TG mice present motor behavioural deficits (p &lt; 0.05), muscle strength and mass reduction by 37% and 8% (p &lt; 0.05 and p &lt; 0.01, respectively). A remarkable increase in inflammatory infiltration is accompanied by pro‐inflammatory cytokines in the skeletal muscles. TEM analysis shows muscle fibre regeneration with the reduced length of sarcomeres (by 6%;p &lt; 0.05). The muscle regeneration is activated as Pax7+ cells increased by 106% (p &lt; 0.0001), andmyoblast determination protein elevated by 71% (p &lt; 0.01). We also document the morphological changes and dynamics dysfunction of mitochondria with the increase of mitofusin1 by 43% (p &lt; 0.05) and voltage‐dependent anion channel 1 by 115% (p &lt; 0.001) in the skeletal muscles of 14mo‐TG mice.ConclusionsTaken together, these findings may provide new insights into the clinical and pathogenic involvement of LRRK2G2019 mutation in muscles, suggesting that the diseases may affect not only midbrain dopaminergic neurons, but also other tissues, and it may help overall clinical management of this devastating disease.