-
Scientific Reports Jul 2024The aim of this study were to estimate associations of sarcopenic status with depressive symptoms. We used mixed-effects linear model to estimate longitudinal...
The aim of this study were to estimate associations of sarcopenic status with depressive symptoms. We used mixed-effects linear model to estimate longitudinal association between sarcopenic status and rate of change in 10-item Center for Epidemiologic Studies Depression (CES-D) scores, and used Cox regression model to estimate the association between sarcopenic status and incident depression (CES-D ≥ 10). Stratification analyses were performed when the interactions between sarcopenic status and covariates were significant. A total of 6522 participants were ultimately included. After adjusting for covariates, participants with possible sarcopenia (β = 0.117; 95% CI 0.067 to 0.166; P < 0.001) and sarcopenia (β: 0.093; 95% CI 0.027-0.159; P < 0.001) had a faster increase in CES-D scores compared with normal individuals. Interactions between smoking and sarcopenic status were significant (P < 0.05). We found significantly positive associations of sarcopenic status with CES-D scores in nonsmokers, but not in current and past smokers. Besides, compared with normal participants, those with possible sarcopenia (HR 1.15; 95% CI 1.05 to 1.27) and sarcopenia (HR 1.28; 95% CI 1.12 to 1.46) (P < 0.001) had elevated risks of incident depression. Sarcopenia is associated with a faster increase in CES-D scores and increased risks of depression among Chinese middle-aged and older adults. Stronger associations between sarcopenia and trajectory of CES-D scores were found in nonsmokers than in smokers.
Topics: Humans; Sarcopenia; Male; Female; Depression; Middle Aged; Aged; Smoking; Risk Factors; China
PubMed: 38956420
DOI: 10.1038/s41598-024-65343-3 -
Scientific Reports Jul 2024The INSPIRE randomized clinical trial demonstrated that a high protein diet (HPRO) combined with neuromuscular electrical stimulation (NMES) attenuates muscle atrophy... (Randomized Controlled Trial)
Randomized Controlled Trial
Identification of metabolites associated with preserved muscle volume after aneurysmal subarachnoid hemorrhage due to high protein supplementation and neuromuscular electrical stimulation.
The INSPIRE randomized clinical trial demonstrated that a high protein diet (HPRO) combined with neuromuscular electrical stimulation (NMES) attenuates muscle atrophy and may improve outcomes after aneurysmal subarachnoid hemorrhage We sought to identify specific metabolites mediating these effects. Blood samples were collected from subjects on admission prior to randomization to either standard of care (SOC; N = 12) or HPRO + NMES (N = 12) and at 7 days. Untargeted metabolomics were performed for each plasma sample. Sparse partial least squared discriminant analysis identified metabolites differentiating each group. Correlation coefficients were calculated between each metabolite and total protein per day and muscle volume. Multivariable models determined associations between metabolites and muscle volume. Unique metabolites (18) were identified differentiating SOC from HPRO + NMES. Of these, 9 had significant positive correlations with protein intake. In multivariable models, N-acetylleucine was significantly associated with preserved temporalis [OR 1.08 (95% CI 1.01, 1.16)] and quadricep [OR 1.08 (95% CI 1.02, 1.15)] muscle volume. Quinolinate was also significantly associated with preserved temporalis [OR 1.05 (95% CI 1.01, 1.09)] and quadricep [OR 1.04 (95% CI 1.00, 1.07)] muscle volume. N-acetylserine and β-hydroxyisovaleroylcarnitine were associated with preserved temporalis or quadricep volume. Metabolites defining HPRO + NMES had strong correlations with protein intake and were associated with preserved muscle volume.
Topics: Humans; Male; Female; Middle Aged; Subarachnoid Hemorrhage; Diet, High-Protein; Muscle, Skeletal; Metabolomics; Muscular Atrophy; Electric Stimulation Therapy; Aged; Metabolome; Dietary Supplements
PubMed: 38956192
DOI: 10.1038/s41598-024-64666-5 -
Journal of Neurology Jul 2024Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common genetically inherited myopathies in adults. It is characterized by incomplete penetrance and... (Review)
Review
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common genetically inherited myopathies in adults. It is characterized by incomplete penetrance and variable expressivity. Typically, FSHD patients display asymmetric weakness of facial, scapular, and humeral muscles that may progress to other muscle groups, particularly the abdominal and lower limb muscles. Early-onset patients display more severe muscle weakness and atrophy, resulting in a higher frequency of associated skeletal abnormalities. In these patients, multisystem involvement, including respiratory, ocular, and auditory, is more frequent and severe and may include the central nervous system. Adult-onset FSHD patients may also display some degree of multisystem involvement which mainly remains subclinical. In 95% of cases, FSHD patients carry a pathogenic contraction of the D4Z4 repeat units (RUs) in the subtelomeric region of chromosome 4 (4q35), which leads to the expression of DUX4 retrogene, toxic for muscles (FSHD1). Five percent of patients display the same clinical phenotype in association with a mutation in the SMCHD1 gene located in chromosome 18, inducing epigenetic modifications of the 4q D4Z4 repeated region and expression of DUX4 retrogene. This review highlights the complexities and challenges of diagnosing and managing FSHD, underscoring the importance of standardized approaches for optimal patient outcomes. It emphasizes the critical role of multidisciplinary care in addressing the diverse manifestations of FSHD across different age groups, from skeletal abnormalities in early-onset cases to the often-subclinical multisystem involvement in adults. With no current cure, the focus on alleviating symptoms and slowing disease progression through coordinated care is paramount.
PubMed: 38955828
DOI: 10.1007/s00415-024-12538-3 -
Neurospine Jun 2024To evaluate C2 muscle preservation effect and the radiological and clinical outcomes after C2 recapping laminoplasty.
OBJECTIVE
To evaluate C2 muscle preservation effect and the radiological and clinical outcomes after C2 recapping laminoplasty.
METHODS
Fourteen consecutive patients who underwent C2 recapping laminoplasty around C1-2 level were enrolled. To evaluate muscle preservation effect, the authors conducted a morphological measurement of extensor muscles between the operated and nonoperated side. Two surgeons measured the cross-sectional area (CSA) of obliquus capitis inferior (OCI) and semispinalis cervicis (SSC) muscle before and after surgery to determine atrophy rates (ARs). Additionally, we examined range of motion (ROM), sagittal vertical axis (SVA), neck visual analogue scale (VAS), Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) score to assess potential changes in alignment and consequent clinical outcomes following posterior cervical surgery.
RESULTS
We measured the CSA of OCI and SSC before surgery, and at 6 and 12 months postoperatively. Based on these measurements, the AR of the nonoperated SSC was 0.1% ± 8.5%, the AR of the operated OCI was 2.0% ± 7.2%, and the AR of the nonoperated OCI was -0.7% ± 5.1% at the 12 months after surgery. However, the AR of the operated side's SSC was 11.2% ± 12.5%, which is a relatively higher value than other measurements. Despite the atrophic change of SSC on the operated side, there were no prominent changes observed in SVA, C0-2 ROM, and C2-7 ROM between preoperative and 12 months postoperative measurements, which were 11.8 ± 10.9 mm, 16.3° ± 5.9°, and 48.7° ± 7.7° preoperatively, and 14.1 ± 11.6 mm, 16.1° ± 7.2°, and 44.0° ± 10.3° at 12 months postoperative, respectively. Improvement was also noted in VAS, NDI, and JOA scores after surgery with JOA recovery rate of 77.3% ± 29.6%.
CONCLUSION
C2 recapping laminoplasty could be a useful tool for addressing pathologies around the upper cervical spine, potentially mitigating muscle atrophy and reducing postoperative neck pain, while maintaining sagittal alignment and ROM.
PubMed: 38955529
DOI: 10.14245/ns.2347270.635 -
ACS Chemical Biology Jul 2024Drug candidates that fail in clinical trials for efficacy reasons might still have favorable safety and bioavailability characteristics that could be exploited. A failed...
Drug candidates that fail in clinical trials for efficacy reasons might still have favorable safety and bioavailability characteristics that could be exploited. A failed drug candidate could be repurposed if a receptor, such as an aptamer, were created that binds the compound with high specificity. Branaplam is a small molecule that was previously in development to treat spinal muscular atrophy and Huntington's disease. Here, we report the development of a small (48-nucleotide) RNA aptamer for branaplam with a dissociation constant of ∼150 nM. Starting with a combinatorial RNA pool integrating the secondary and tertiary structural scaffold of a Guanine-I riboswitch aptamer interspersed with regions of random sequence, in vitro selection yielded aptamer candidates for branaplam. Reselection and rational design were employed to improve binding of a representative branaplam aptamer candidate. A resulting variant retains the pseudoknot and two of the paired elements (P2 and P3) from the scaffold but lacks the enclosing paired element (P1) that is essential for the function of the natural Guanine-I riboswitch aptamer. A second combinatorial RNA pool based on the scaffold for TPP (thiamin pyrophosphate) riboswitches also yielded a candidate offering additional opportunities for branaplam aptamer development.
PubMed: 38954594
DOI: 10.1021/acschembio.4c00358 -
Journal of Neurology Jul 2024To evaluate the effectiveness and safety of nusinersen for the treatment of 5q-spinal muscular atrophy (SMA) among Chinese pediatric patients.
OBJECTIVE
To evaluate the effectiveness and safety of nusinersen for the treatment of 5q-spinal muscular atrophy (SMA) among Chinese pediatric patients.
METHODS
Using a longitudinal, multi-center registry, both prospective and retrospective data were collected from pediatric patients with 5q-SMA receiving nusinersen treatment across 18 centers in China. All patients fulfilling the eligibility criteria were included consecutively. Motor function outcomes were assessed post-treatment by SMA type. Safety profile was evaluated among patients starting nusinersen treatment post-enrollment. Descriptive analyses were used to report baseline characteristics, effectiveness, and safety results.
RESULTS
As of March 2nd, 2023, 385 patients were included. Most patients demonstrated improvements or stability in motor function across all SMA types. Type II patients demonstrated mean changes [95% confidence interval (CI)] of 4.4 (3.4-5.4) and 4.1 (2.8-5.4) in Hammersmith Functional Motor Scale-Expanded (HFMSE), and 2.4 (1.7-3.1) and 2.3 (1.2-3.4) in Revised Upper Limb Module (RULM) scores at months 6 and 10. Type III patients exhibited mean changes (95% CI) of 3.9 (2.5-5.3) and 4.3 (2.6-6.0) in HFMSE, and 2.1 (1.2-3.0) and 1.5 (0.0-3.0) in RULM scores at months 6 and 10. Of the 132 patients, 62.9% experienced adverse events (AEs). Two patients experienced mild AEs (aseptic meningitis and myalgia) considered to be related to nusinersen by the investigator, with no sequelae.
CONCLUSIONS
These data underscore the significance of nusinersen in Chinese pediatric patients with SMA regarding motor function improvement or stability, and support recommendations on nusinersen treatment by Chinese SMA guidelines and continuous coverage of nusinersen by basic medical insurance.
PubMed: 38954034
DOI: 10.1007/s00415-024-12442-w -
Cancer Medicine Jul 2024Sarcopenic obesity (SO) in patients with gastrointestinal cancer is associated with a poor prognosis. We aimed to investigate the prognostic impact of SO in patients...
BACKGROUND
Sarcopenic obesity (SO) in patients with gastrointestinal cancer is associated with a poor prognosis. We aimed to investigate the prognostic impact of SO in patients with gastrointestinal cancer, as well as the diagnostic cut-off value of SO in patients with gastrointestinal cancer among Chinese population.
METHODS
We conducted a consecutive cohort study. Between January 2017 and January 2019, 289 patients diagnosed with gastrointestinal cancer were included in our study. Skeletal muscle area, total fat area, and subcutaneous fat area were measured by CT scan. All patients were followed up for 5 years. Receiver operating characteristic curves (ROC) were adopted to determine the cut-off values of visceral fat obesity for the prediction of sarcopenia. Based on the cut-off values, patients with sarcopenia combined with visceral fat obesity were divided into the SO group, and the others were divided into the non-sarcopenic obesity (NSO) group. Kaplan-Meier curves and univariate and multivariate Cox proportional hazard models were employed to explore the associations of body composition profiles with 5-year overall survival and disease-specific survival.
RESULTS
Obtained from Youden's Index for ROC for the prediction of 5-year survival, skeletal muscle mass index (SMI) ≤40.02 cm/m with VFA ≥ 126.30 cm in men and SMI ≤32.05 cm/m with VFA ≥72.42 cm in women indicate a risk of poor prognosis in patients diagnosed with gastrointestinal cancer. Patients with SO had poorer 5-year overall survival (OS) than patients with NSO (6.74% vs. 82.84%, p < 0.001), and poorer 5-year DFS (6.74% vs. 81.82%, p < 0.001). In multivariate analysis, we found that the long-term mortality risk was approximately 13-fold higher among patients in the SO group compared to those with no conditions.
CONCLUSIONS
Preoperative assessment of SO is useful not only for monitoring nutritional status but also for predicting 5-year OS in gastrointestinal cancer patients.
Topics: Humans; Sarcopenia; Male; Female; Gastrointestinal Neoplasms; Prognosis; Middle Aged; Obesity; Aged; Body Composition; ROC Curve; Muscle, Skeletal; Kaplan-Meier Estimate; Intra-Abdominal Fat
PubMed: 38953401
DOI: 10.1002/cam4.7452 -
BMC Geriatrics Jul 2024Dietary intervention is an important method to manage sarcopenic obesity, but the implementation in real world is difficult to achieve an ideal condition. This study... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Dietary intervention is an important method to manage sarcopenic obesity, but the implementation in real world is difficult to achieve an ideal condition. This study aimed to the experiences of older people with sarcopenic obesity during the implementation of dietary behavioural change (DBC) intervention.
METHODS
This study is a semi-structured individual interview embedded within a pilot randomized controlled trial on community-dwelling older people with sarcopenic obesity. Purposive sampling was applied to invite 21 participants who had received a 15-week DBC intervention. The interviews were audio-recorded and transcribed verbatim. Content analysis was performed to analyze the data.
RESULTS
The themes for facilitators included: (a) Attach importance to self's health; (b) Family's support; (c) Concern self's body shape; (d) Instructor's support; (e) Regular food diary taken. The themes for barriers included: (a) Difficulties of taking food diary; (b) Difficulties of calculating the food amount; (c) Yield to offspring's appetite; (d) Misjudging self's or family's appetite.
CONCLUSION
Support from family members and instructor, caring about self's health and body image facilitated the intervention implementation. The complication of food amount estimation and diary record, personal sacrifice for next generations, and previous living experience were barriers for implementing the intervention. Overall, the older people with sarcopenic obesity can accept the design of DBC intervention program and have great willing to join.
Topics: Humans; Aged; Female; Male; Obesity; Sarcopenia; Qualitative Research; Feeding Behavior; Aged, 80 and over; Pilot Projects; Independent Living
PubMed: 38951785
DOI: 10.1186/s12877-024-05157-0 -
Zhonghua Nei Ke Za Zhi Jul 2024To summarize the clinical, imaging, and pathological characteristics of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) to...
To summarize the clinical, imaging, and pathological characteristics of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) to improve the diagnosis of this rare disease. A retrospective case series was conducted to collect the clinical data and results of genetic testing, muscle biopsy, and imaging studies including computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS) of 35 patients with MELAS admitted to the Nanjing Drum Tower Hospital from 2012 to 2021. Descriptive statistical analysis including mean, standard deviation, and frequency percentage were carried out. The average age of onset of the patients was 30.2±2.3 years; the prevalence of family history was 20%. The two main initial symptoms were limb weakness and convulsions. The clinical manifestations of the neuromuscular system were proximal muscle weakness and exercise intolerance. The endocrine system is the most affected outside the neuromuscular system, with diabetes being the most common condition. Among the five patients who underwent brain CT, four showed hypodense lesions and two had calcified lesions. Brain MRI in 26 patients showed that the lesions more often affected the parietal lobe, basal ganglia, temporal lobe, occipital lobe, and frontal lobe than the infratentorial areas. Twelve of these individuals exhibited different levels of brain atrophy. Among the 10 patients who underwent H-MRS, nine showed a decrease in N-acetylaspartate (NAA) levels, eight exhibited abnormal lactate elevation (Lac peaks), whereas six had both reduced NAA levels and the presence of Lac peaks. Thirty-one patients underwent genetic testing; among them, 25 were found to have the mt.3243A>G mutation, while the remaining six exhibited rare gene alterations. Muscle biopsies were performed in 21 patients, and 15 showed abnormal mitochondrial proliferation manifested by ragged red fibers and defective oxidative phosphorylation manifested by cytochrome C oxidase (COX) enzyme-deficient muscle fibers. The clinical manifestations of MELAS syndrome are variable and complex, and early atypical symptoms could be missed or misdiagnosed. A detailed clinical history, imaging MRS analysis, muscle biopsy, and genetic testing are necessary to confirm the accurate diagnosis of MELAS.
Topics: Humans; MELAS Syndrome; Retrospective Studies; Adult; Magnetic Resonance Imaging; Brain; Tomography, X-Ray Computed; Male; Female; Magnetic Resonance Spectroscopy
PubMed: 38951091
DOI: 10.3760/cma.j.cn112138-20231227-00411 -
Journal of Visualized Experiments : JoVE Jun 2024Sepsis is a major cause of in-hospital deaths. Improvements in treatment result in a greater number of sepsis survivors. Approximately 75% of the survivors develop...
Sepsis is a major cause of in-hospital deaths. Improvements in treatment result in a greater number of sepsis survivors. Approximately 75% of the survivors develop muscle weakness and atrophy, increasing the incidence of hospital readmissions and mortality. However, the available preclinical models of sepsis do not address skeletal muscle disuse, a key component for the development of sepsis-induced myopathy. Our objective in this protocol is to provide a step-by-step guideline for a mouse model that reproduces the clinical setting experienced by a bedridden septic patient. Male C57Bl/6 mice were used to develop this model. Mice underwent cecal ligation and puncture (CLP) to induce sepsis. Four days post-CLP, mice were subjected to hindlimb suspension (HLS) for seven days. Results were compared with sham-matched surgeries and/or animals with normal ambulation (NA). Muscles were dissected for in vitro muscle mechanics and morphological assessments. The model results in marked muscle atrophy and weakness, a similar phenotype observed in septic patients. The model represents a platform for testing potential therapeutic strategies for the mitigation of sepsis-induced myopathy.
Topics: Animals; Sepsis; Mice; Disease Models, Animal; Male; Mice, Inbred C57BL; Muscular Diseases; Muscular Atrophy; Muscle, Skeletal; Hindlimb Suspension
PubMed: 38949310
DOI: 10.3791/66685