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Voprosy Kurortologii, Fizioterapii, I... 2024The number of middle-aged and elderly population is increasing every year. At the same time, the course of most chronic diseases worsens with age, which can be explained...
UNLABELLED
The number of middle-aged and elderly population is increasing every year. At the same time, the course of most chronic diseases worsens with age, which can be explained by significant changes in body composition, including redistribution and increase of fat mass and decrease in muscle and skeletal mass. Thus, a decrease in muscle mass becomes intrinsic for the body from the age of 40 and develops on average by 0.5-1.0% per year. The prevalence of patients with sarcopenia is estimated to be between 11 and 50% in different age groups of population: middle, elderly and senile. In addition, the decline in physical activity associated with the urbanization and automation of labor exacerbates the disease at a younger age, which predicts an increase in the number of such patients in the future.
OBJECTIVE
To determine the role of physical rehabilitation in sarcopenia.
MATERIAL AND METHODS
A systematic review including studies found in PubMed, MedLine, Scopus and Web of Science Core Collections databases for 2019-2022 was conducted. The used enrollment criteria were the following: systematic reviews, including cross-over or cohort studies targeting at persons aged from 40 to 90 years of both sexes, with available data on sarcopenia, its severe form or other combinations of physical performance markers called sarcopenia. The mandatory parameter for inclusion in the study was the presence of the effectiveness assessment of physical rehabilitation without limiting its parameters. The systematic review was performed in accordance with the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020.
RESULTS
The best kind of training are 30-60-minute comprehensive methods with predominance of resistance exercises with minimum duration of the course of 3 months and frequency of 3 inconsistent in-person trainings per week under the supervision of a specialist for patients with sarcopenia in order to increase muscle strength and mass, as well as performance. The intensity should consist of the following parameters: start with fewer sets but more repetitions (12-15) with less intensity (55% of maximum) and move to more sets with less repetition (4-6) and greater intensity (>80% of maximum).
CONCLUSION
This article describes the parameters of exercises that are most effective in terms of muscle strength and mass increase and safe for patients. The compilation and further study of this complex in practice are needed.
Topics: Sarcopenia; Humans; Female; Male; Aged; Middle Aged; Adult; Aged, 80 and over
PubMed: 38934959
DOI: 10.17116/kurort202410103156 -
Neural Regeneration Research Jun 2024Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor (AR) gene, which encodes a...
Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology.
Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor (AR) gene, which encodes a ligand-dependent transcription factor. The mutant AR protein, characterized by polyglutamine expansion, is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in SBMA patients. These aggregates alter protein-protein interactions and compromise transcriptional activity. In this study, we reported that in both cultured N2a cells and mouse brain, mutant AR with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-derived neurotrophic factor (MANF). Overexpression of MANF ameliorated the neurotoxicity of mutant AR through the inhibition of mutant AR aggregation. Conversely, knocking down endogenous MANF in the mouse brain exacerbated neuronal damage and mutant AR aggregation. Our findings suggest that inhibition of MANF expression by mutant AR is a potential mechanism underlying neurodegeneration in SBMA.
PubMed: 38934406
DOI: 10.4103/NRR.NRR-D-23-01666 -
Neural Regeneration Research Jun 2024Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target...
Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury-specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research (in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc (AXER-204), fasudil, phosphatase and tensin homolog protein (PTEN) antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide, (-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.
PubMed: 38934397
DOI: 10.4103/NRR.NRR-D-24-00176 -
Neural Regeneration Research Jun 2024Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness. It is one of the most common genetic causes of...
Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness. It is one of the most common genetic causes of mortality among infants aged less than 2 years. Biomarker research is currently receiving more attention, and new candidate biomarkers are constantly being discovered. This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons. We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy, which are classified as either specific or non-specific biomarkers. This review provides new insights into the pathogenesis of spinal muscular atrophy, the mechanism of biomarkers in response to drug-modified therapies, the selection of biomarker candidates, and would promote the development of future research. Furthermore, the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.
PubMed: 38934395
DOI: 10.4103/NRR.NRR-D-24-00067 -
Acta Endocrinologica (Bucharest,... 2023Hashimoto thyroiditis (HT) is an autoimmune disorder associated with hypothyroidism. Lymphocyte infiltration leading to thyroid follicular cell destruction is...
BACKGROUND
Hashimoto thyroiditis (HT) is an autoimmune disorder associated with hypothyroidism. Lymphocyte infiltration leading to thyroid follicular cell destruction is counteracted by increased collagen production, deposition and scarring. However, only recently a specific subpopulation of modified fibroblasts with contractile properties, namely "myofibroblasts" (MFBs) have been linked to HT.
AIM
Our ultrastructural study aims to delineate the presence and contribution of MFBs to the fibrotic milieu of HT.
MATERIAL AND METHODS
Tissue biopsies were obtained from 5 HT-diagnosed patients and specimens were examined using a Transmission Electron Microscope (TEM).
RESULTS
Histopathological examination indicated extensive microvilli atrophy and atypical vacuolations of the thyroid follicular cells in the HT samples. In addition to interstitial extravasated lymphocytes, capillaries were encircled by MFBs (mean distance from lumen 1.248± 0.43µm) with the characteristic electron-dense α-smooth muscle actin (α-SMA), confirmable in higher magnifications. Myofibroblastic projections were found to have significantly higher representation near the capillary lumen compared to the impaired endothelial lining (P < 0.01).
CONCLUSION
Our TEM findings suggest that the intrusion of endothelia by myofibroblastic projections can be a significant factor towards the malfunction of follicular cells in HT patients and offer a paradigmal understanding of the ultrastructural interactions that may underlie the HT pathology.
PubMed: 38933253
DOI: 10.4183/aeb.2023.415 -
Neurology. Clinical Practice Jun 2024Nusinersen has shown significant functional motor benefit in the milder types of spinal muscular atrophy (SMA). Less is known on the respiratory outcomes in patients...
BACKGROUND AND OBJECTIVES
Nusinersen has shown significant functional motor benefit in the milder types of spinal muscular atrophy (SMA). Less is known on the respiratory outcomes in patients with nusinersen-treated SMA. The aim of this study was to describe changes in respiratory function in pediatric patients with SMA type 2 and 3 on regular treatment with nusinersen within the iSMAc international cohort and to compare their trajectory with the natural history (NH) data published by the consortium in 2020.
METHODS
This is a 5-year retrospective observational study of pediatric SMA type 2 and nonambulant type 3 (age ≤18 years) treated with nusinersen. The primary objective was to compare the slopes of decline in forced vital capacity % predicted (FVC% pred.), FVC, and age when FVC dropped below 60% between the treated patients and a control group from the natural history cohort. Data on peak cough flow and the use of noninvasive ventilation (NIV) and cough assist were collected.
RESULTS
Data were available for 69 treated patients, 53 were SMA type 2 and 16 type 3. The mean (SD) age at first injection was 8.5 (3.2) and 9.7 (3.7) years, respectively. The median (interquartile range) treatment duration was 1 (0.7; 1.9) and 1.2 (0.9; 1.9) years, respectively. At the time of the first nusinersen injection, 24 of 52 (46%) patients with SMA type 2 and 2 of 16 (13%) patients with SMA type 3 were on NIV. Forty-three of 53 (81%) and 4 of 16 (25%) patients used cough device. FVC% pred. in treated patients with SMA type 2 declined annually by 2.3% vs 3.9% in NH ( = 0.08) and in treated patients with type 3 by 2.6% vs 3.4% NH ( = 0.59). Patients treated reached FVC <60% later than untreated (12.1 vs 10 years, = 0.05). A higher percentage of treated vs untreated patients maintained FVC% pred. equal/above their baseline after 12 (65% vs 36%) and 24 (50% vs 24%) months, respectively. NIV use among treated did not significantly change throughout 1-year follow-up.
DISCUSSION
This study included the largest real-world cohort of pediatric patients with milder SMA types. The results suggest a positive role of nusinersen in delaying the respiratory decline in patients treated longer than 1 year when compared with natural history. Larger cohorts and longer observation are planned.
CLASSIFICATION OF EVIDENCE
This study provided Class III evidence that nusinersen slows progression for patients with SMA types 2 and 3 compared with a natural history cohort.
PubMed: 38932995
DOI: 10.1212/CPJ.0000000000200298 -
Sensors (Basel, Switzerland) Jun 2024Conventional passive ankle foot orthoses (AFOs) have not seen substantial advances or functional improvements for decades, failing to meet the demands of many...
Conventional passive ankle foot orthoses (AFOs) have not seen substantial advances or functional improvements for decades, failing to meet the demands of many stakeholders, especially the pediatric population with neurological disorders. Our objective is to develop the first comfortable and unobtrusive powered AFO for children with cerebral palsy (CP), the DE-AFO. CP is the most diagnosed neuromotor disorder in the pediatric population. The standard of care for ankle control dysfunction associated with CP, however, is an unmechanized, bulky, and uncomfortable L-shaped conventional AFO. These passive orthoses constrain the ankle's motion and often cause muscle disuse atrophy, skin damage, and adverse neural adaptations. While powered orthoses could enhance natural ankle motion, their reliance on bulky, noisy, and rigid actuators like DC motors limits their acceptability. Our innovation, the DE-AFO, emerged from insights gathered during customer discovery interviews with 185 stakeholders within the AFO ecosystem as part of the NSF I-Corps program. The DE-AFO is a biomimetic robot that employs artificial muscles made from an electro-active polymer called dielectric elastomers (DEs) to assist ankle movements in the sagittal planes. It incorporates a gait phase detection controller to synchronize the artificial muscles with natural gait cycles, mimicking the function of natural ankle muscles. This device is the first of its kind to utilize lightweight, compact, soft, and silent artificial muscles that contract longitudinally, addressing traditional actuated AFOs' limitations by enhancing the orthosis's natural feel, comfort, and acceptability. In this paper, we outline our design approach and describe the three main components of the DE-AFO: the artificial muscle technology, the finite state machine (the gait phase detection system), and its mechanical structure. To verify the feasibility of our design, we theoretically calculated if DE-AFO can provide the necessary ankle moment assistance for children with CP-aligning with moments observed in typically developing children. To this end, we calculated the ankle moment deficit in a child with CP when compared with the normative moment of seven typically developing children. Our results demonstrated that the DE-AFO can provide meaningful ankle moment assistance, providing up to 69% and 100% of the required assistive force during the pre-swing phase and swing period of gait, respectively.
Topics: Cerebral Palsy; Humans; Foot Orthoses; Child; Robotics; Ankle; Elastomers; Gait; Equipment Design; Biomechanical Phenomena
PubMed: 38931570
DOI: 10.3390/s24123787 -
Nutrients Jun 2024Sarcopenia is an age-related condition characterized by progressive loss of muscle mass, strength, and function. The occurrence of sarcopenia has a huge impact on...
BACKGROUND
Sarcopenia is an age-related condition characterized by progressive loss of muscle mass, strength, and function. The occurrence of sarcopenia has a huge impact on physical, psychological, and social health. Therefore, the prevention and treatment of sarcopenia is becoming an important public health issue.
METHOD
35 six-week-old male C57BL/6 mice were randomly divided into five groups, one of which served as a control group, while the rest of the groups were constructed as a model of sarcopenia by intraperitoneal injection of D-galactose. The intervention with lactoferrin, creatine, and their mixtures, respectively, was carried out through gavage for 8 weeks. Muscle function was assessed based on their endurance, hanging time, and grip strength. The muscle tissues were weighed to assess the changes in mass, and the muscle RNA was extracted for myogenic factor expression and transcriptome sequencing to speculate on the potential mechanism of action by GO and KEGG enrichment analysis.
RESULT
The muscle mass (lean mass, GAS index), and muscle function (endurance, hanging time, and grip strength) decreased, and the size and structure of myofiber was smaller in the model group compared to the control group. The intervention with lactoferrin and creatine, either alone or combination, improved muscle mass and function, restored muscle tissue, and increased the expression of myogenic regulators. The combined group demonstrated the most significant improvement in these indexes. The RNA-seq results revealed enrichment in the longevity-regulated pathway, MAPK pathway, focal adhesion, and ECM-receptor interaction pathway in the intervention group. The intervention group may influence muscle function by affecting the proliferation, differentiation, senescence of skeletal muscle cell, and contraction of muscle fiber. The combined group also enriched the mTOR-S6K/4E-BPs signaling pathway, PI3K-Akt signaling pathway, and energy metabolism-related pathways, including Apelin signaling, insulin resistance pathway, and adipocytokine signaling pathway, which affect energy metabolism in muscle.
CONCLUSIONS
Lactoferrin and creatine, either alone or in combination, were found to inhibit the progression of sarcopenia by influencing the number and cross-sectional area of muscle fibers and muscle protein synthesis. The combined intervention appears to exert a more significant effect on energy metabolism.
Topics: Animals; Lactoferrin; Male; Sarcopenia; Mice, Inbred C57BL; Creatine; Disease Models, Animal; Muscle, Skeletal; Mice; Muscle Strength; Signal Transduction
PubMed: 38931310
DOI: 10.3390/nu16121958 -
Nutrients Jun 2024Handgrip strength (HGS) is an indicator of muscular strength, used in the diagnosis of sarcopenia, undernutrition, and physical frailty as well as recovery. Typically,... (Review)
Review
BACKGROUND
Handgrip strength (HGS) is an indicator of muscular strength, used in the diagnosis of sarcopenia, undernutrition, and physical frailty as well as recovery. Typically, the maximum HGS value is used; however, recent evidence suggests the exploration of new indicators provided based on the force-time curve to achieve a more comprehensive assessment of muscle function. Therefore, the objective was to identify indicators of the HGS profile beyond maximum HGS, based on force-time curves, and to systematize knowledge about their applications to various types of samples, health issues, and physical performance.
METHODS
A systematic review was performed including studies whose participants' HGS was assessed with a digital or adapted dynamometer. The outcome measures were HGS profile indicators calculated from the force-time curve.
RESULTS
a total of 15 studies were included, and the following indicators were identified: grip fatigue, fatigability index, fatigue rate, fatigue resistance, time to 80% maximal voluntary contraction, plateau coefficient of variability, time to maximum value, T-90%, release rate, power factor, grip work, average integrated area, endurance, cycle duration, time between cycles, maximum and minimum force-velocity, rate of grip force, final force, inflection point, integrated area, submaximal control, and response time.
CONCLUSIONS
Various indicators based on the force-time curve can be assessed through digital or adapted dynamometers. Future research should analyze these indicators to understand their implications for muscle function assessment, to standardize evaluation procedures, to identify clinically relevant measures, and to clarify their implications in clinical practice.
Topics: Humans; Hand Strength; Muscle Strength Dynamometer; Female; Male; Muscle Fatigue; Aged; Muscle, Skeletal; Muscle Strength; Middle Aged; Sarcopenia; Time Factors; Adult
PubMed: 38931305
DOI: 10.3390/nu16121951 -
Nutrients Jun 2024(1) Background: The assessment of muscle mass is crucial in the nutritional evaluation of patients with colorectal cancer (CRC), as decreased muscle mass is linked to... (Observational Study)
Observational Study
(1) Background: The assessment of muscle mass is crucial in the nutritional evaluation of patients with colorectal cancer (CRC), as decreased muscle mass is linked to increased complications and poorer prognosis. This study aims to evaluate the utility of AI-assisted L3 CT for assessing body composition and determining low muscle mass using both the Global Leadership Initiative on Malnutrition (GLIM) criteria for malnutrition and the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria for sarcopenia in CRC patients prior to surgery. Additionally, we aim to establish cutoff points for muscle mass in men and women and propose their application in these diagnostic frameworks. (2) Methods: This retrospective observational study included CRC patients assessed by the Endocrinology and Nutrition services of the Regional University Hospitals of Malaga, Virgen de la Victoria of Malaga, and Vall d'Hebrón of Barcelona from October 2018 to July 2023. A morphofunctional assessment, including anthropometry, bioimpedance analysis (BIA), and handgrip strength, was conducted to apply the GLIM criteria for malnutrition and the EWGSOP2 criteria for sarcopenia. Body composition evaluation was performed through AI-assisted analysis of CT images at the L3 level. ROC analysis was used to determine the predictive capacity of variables derived from the CT analysis regarding the diagnosis of low muscle mass and to describe cutoff points. (3) Results: A total of 586 patients were enrolled, with a mean age of 68.4 ± 10.2 years. Using the GLIM criteria, 245 patients (41.8%) were diagnosed with malnutrition. Applying the EWGSOP2 criteria, 56 patients (9.6%) were diagnosed with sarcopenia. ROC curve analysis for the skeletal muscle index (SMI) showed a strong discriminative capacity of muscle area to detect low fat-free mass index (FFMI) (AUC = 0.82, 95% CI 0.77-0.87, < 0.001). The identified SMI cutoff for diagnosing low FFMI was 32.75 cm/m (Sn 77%, Sp 64.3%; AUC = 0.79, 95% CI 0.70-0.87, < 0.001) in women, and 39.9 cm/m (Sn 77%, Sp 72.7%; AUC = 0.85, 95% CI 0.80-0.90, < 0.001) in men. Additionally, skeletal muscle area (SMA) showed good discriminative capacity for detecting low appendicular skeletal muscle mass (ASMM) (AUC = 0.71, 95% CI 0.65-0.76, < 0.001). The identified SMA cutoff points for diagnosing low ASMM were 83.2 cm (Sn 76.7%, Sp 55.3%; AUC = 0.77, 95% CI 0.69-0.84, < 0.001) in women and 112.6 cm (Sn 82.3%, Sp 58.6%; AUC = 0.79, 95% CI 0.74-0.85, < 0.001) in men. (4) Conclusions: AI-assisted body composition assessment using CT is a valuable tool in the morphofunctional evaluation of patients with colorectal cancer prior to surgery. CT provides quantitative data on muscle mass for the application of the GLIM criteria for malnutrition and the EWGSOP2 criteria for sarcopenia, with specific cutoff points established for diagnostic use.
Topics: Humans; Sarcopenia; Male; Female; Body Composition; Colorectal Neoplasms; Aged; Malnutrition; Tomography, X-Ray Computed; Retrospective Studies; Middle Aged; Electric Impedance; Nutrition Assessment; Aged, 80 and over; Predictive Value of Tests; Muscle, Skeletal; Hand Strength
PubMed: 38931224
DOI: 10.3390/nu16121869