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International Journal of Molecular... Mar 2023Mitochondria are key structures providing most of the energy needed to maintain homeostasis. They are the main source of adenosine triphosphate (ATP), participate in... (Review)
Review
Mitochondria are key structures providing most of the energy needed to maintain homeostasis. They are the main source of adenosine triphosphate (ATP), participate in glucose, lipid and amino acid metabolism, store calcium and are integral components in various intracellular signaling cascades. However, due to their crucial role in cellular integrity, mitochondrial damage and dysregulation in the context of critical illness can severely impair organ function, leading to energetic crisis and organ failure. Skeletal muscle tissue is rich in mitochondria and, therefore, particularly vulnerable to mitochondrial dysfunction. Intensive care unit-acquired weakness (ICUAW) and critical illness myopathy (CIM) are phenomena of generalized weakness and atrophying skeletal muscle wasting, including preferential myosin breakdown in critical illness, which has also been linked to mitochondrial failure. Hence, imbalanced mitochondrial dynamics, dysregulation of the respiratory chain complexes, alterations in gene expression, disturbed signal transduction as well as impaired nutrient utilization have been proposed as underlying mechanisms. This narrative review aims to highlight the current known molecular mechanisms immanent in mitochondrial dysfunction of patients suffering from ICUAW and CIM, as well as to discuss possible implications for muscle phenotype, function and therapeutic approaches.
Topics: Humans; Critical Illness; Muscular Diseases; Muscle, Skeletal; Intensive Care Units; Muscle Weakness; Mitochondria; Critical Care
PubMed: 36982590
DOI: 10.3390/ijms24065516 -
International Journal of Molecular... Jul 2022Skeletal muscle is a highly adaptable organ, and its amount declines under catabolic conditions such as critical illness. Aging is accompanied by a gradual loss of... (Review)
Review
Skeletal muscle is a highly adaptable organ, and its amount declines under catabolic conditions such as critical illness. Aging is accompanied by a gradual loss of muscle, especially when physical activity decreases. Intensive care unit-acquired weakness is a common and highly serious neuromuscular complication in critically ill patients. It is a consequence of critical illness and is characterized by a systemic inflammatory response, leading to metabolic stress, that causes the development of multiple organ dysfunction. Muscle dysfunction is an important component of this syndrome, and the degree of catabolism corresponds to the severity of the condition. The population of critically ill is aging; thus, we face another negative effect-sarcopenia-the age-related decline of skeletal muscle mass and function. Low-grade inflammation gradually accumulates over time, inhibits proteosynthesis, worsens anabolic resistance, and increases insulin resistance. The cumulative consequence is a gradual decline in muscle recovery and muscle mass. The clinical manifestation for both of the above conditions is skeletal muscle weakness, with macromolecular damage, and a common mechanism-mitochondrial dysfunction. In this review, we compare the molecular mechanisms underlying the two types of muscle atrophy, and address questions regarding possible shared molecular mechanisms, and whether critical illness accelerates the aging process.
Topics: Critical Illness; Humans; Intensive Care Units; Muscle Weakness; Muscle, Skeletal; Muscular Atrophy; Muscular Diseases; Sarcopenia
PubMed: 35955530
DOI: 10.3390/ijms23158396 -
PloS One 2024Adolescent childbirth is associated with worse physical function over the long-term. Differential loss of muscle strength during pregnancy and postpartum for adolescents...
Adolescent childbirth is associated with worse physical function over the long-term. Differential loss of muscle strength during pregnancy and postpartum for adolescents compared to adults may be one explanation for this, but research examining these differences is lacking. The objective of this study as to assess hand grip strength and hip adduction muscle strength in adolescents and adults during pregnancy and postpartum. A prospective cohort study was carried out with adolescent (13 to 18 years) and adult (23 to 28 years) primigravid women. Assessments were performed at three timepoints: before the 16th gestational week, during the third trimester, and between the fourth and sixth week postpartum. Hand grip strength (continuous and muscle weakness if ≤ 20.67 kgf) and hip adductor measures (continuous and muscle weakness if ≤ 13.8 kgf) were assessed using dynamometry. Generalized estimating equations modelled longitudinal relationships between muscle weakness and age group. More adolescents had hip adductor weakness than adults in the third trimester of pregnancy (62.5% vs. 31.8%, p < 0.005), which was corroborated by the longitudinal analyses. For all women, there were higher odds of hip adductor weakness in the third trimester (OR = 4.35; p< 0.001) and postpartum (OR = 9.45; p < 0.001) compared to the 16th gestational week. No significant difference in HGS was observed between age groups or across the different timepoints. The higher proportion of hip adductor weakness among adolescents may indicate a need for resistance training during and after pregnancy and physical therapy if weakness or injury is noted.
Topics: Adult; Pregnancy; Humans; Adolescent; Female; Hand Strength; Prospective Studies; Muscle Strength; Postpartum Period; Muscle Weakness
PubMed: 38536784
DOI: 10.1371/journal.pone.0300062 -
Gait & Posture Jan 2021Children with cerebral palsy (CP) present with a pathological gait pattern due to musculoskeletal impairments, such as muscle weakness and altered bony geometry....
BACKGROUND
Children with cerebral palsy (CP) present with a pathological gait pattern due to musculoskeletal impairments, such as muscle weakness and altered bony geometry. However, the effect of these impairments on gait performance is still unknown. Research aim:This study aimed to explore the effect of hip muscle weakness and femoral deformities on the gait performance of CP and typical developing (TD) subjects.
METHODS
6400 musculoskeletal models were created by weakening the hip extensors, abductors, adductors and flexors from 0% to 75 % and increasing the femoral anteversion angle (FAA) and neck shaft angle (NSA) from 20° to 60° and 120° to 160°, respectively. One TD and five CP gait patterns were imposed to each model and muscle forces were calculated. The effect of weakness and bony deformities on the capability gap (CG) at the hip, i.e. the lack in hip moment generating capacity to perform the gait pattern, was investigated using regression analysis.
RESULTS
The CG of apparent equinus, stiff knee gait, TD gait, jump gait and true equinus increased with 0.080, 0.038, 0.015, 0.023 and 0.005 Nm/kg per 10 percent hip abductor weakness increase, with 0.211, 0.130, 0.056, 0.045 and 0.011 Nm/kg per 10 degrees FAA increase and with 0.163, 0.080, 0.036, 0.043 and 0.011 Nm/kg per 10 degrees NSA increase, respectively. Combined weakness and bony deformities explained 96 %, 85 %, 82 %, 65 %, 40 % and 35 % of the variance in the CG of apparent equinus, TD gait, stiff knee gait, jump gait, true equinus and crouch gait, respectively.
SIGNIFICANCE
The results suggest that surgical correction of femoral deformities is more likely to be effective than strength training of hip muscles in enhancing CP gait performance. Jump gait, true equinus and especially crouch were more robust, while apparent equinus and stiff knee gait were limited by hip weakness and femoral deformities.
Topics: Cerebral Palsy; Child; Female; Femur; Gait; Gait Disorders, Neurologic; Hip Joint; Humans; Male; Muscle Weakness
PubMed: 33227606
DOI: 10.1016/j.gaitpost.2020.10.022 -
Molecular Aspects of Medicine Jun 2024Skeletal muscle weakness is a debilitating consequence of many malignancies. Muscle weakness has a negative impact on both patient wellbeing and outcome in a range of... (Review)
Review
Skeletal muscle weakness is a debilitating consequence of many malignancies. Muscle weakness has a negative impact on both patient wellbeing and outcome in a range of cancer types and can be the result of loss of muscle mass (i.e. muscle atrophy, cachexia) and occur independently of muscle atrophy or cachexia. There are multiple cancer specific triggers that can initiate the progression of muscle weakness, including the malignancy itself and the tumour environment, as well as chemotherapy, radiotherapy and malnutrition. This can induce weakness via different routes: 1) impaired intrinsic capacity (i.e., contractile dysfunction and intramuscular impairments in excitation-contraction coupling or crossbridge cycling), 2) neuromuscular disconnection and/or 3) muscle atrophy. The mechanisms that underlie these pathways are a complex interplay of inflammation, autophagy, disrupted protein synthesis/degradation, and mitochondrial dysfunction. The current lack of therapies to treat cancer-associated muscle weakness highlight the critical need for novel interventions (both pharmacological and non-pharmacological) and mechanistic insight. Moreover, most research in the field has placed emphasis on directly improving muscle mass to improve muscle strength. However, accumulating evidence suggests that loss of muscle function precedes atrophy. This review primarily focuses on cancer-associated muscle weakness, independent of cachexia, and provides a solid background on the underlying mechanisms, methodology, current interventions, gaps in knowledge, and limitations of research in the field. Moreover, we have performed a mini-systematic review of recent research into the mechanisms behind muscle weakness in specific cancer types, along with the main pathways implicated.
Topics: Humans; Neoplasms; Muscle Weakness; Muscle, Skeletal; Muscular Atrophy; Cachexia; Animals
PubMed: 38457901
DOI: 10.1016/j.mam.2024.101260 -
Experimental Gerontology Sep 2021The objective of this study was to use nationally-representative data on Americans greater than 50 years of age to determine the association between grip strength and...
BACKGROUND
The objective of this study was to use nationally-representative data on Americans greater than 50 years of age to determine the association between grip strength and inflammation as independent predictors of incident disability, chronic multimorbidity and dementia.
METHODS
Middle age and older adults (n = 12,618) from the 2006-2008 waves of the Health and Retirement Study with 8-years of follow-up were included. Longitudinal modeling was performed to examine the association between baseline grip strength (normalized to body mass: NGS) and high sensitivity C-reactive protein (hs-CRP) (≥3.0 mg/L) with incident physical disabilities (i.e., ≥2 limitations to activities of daily living), chronic multimorbidity (≥2 of chronic conditions), and dementia.
RESULTS
The odds of incident disability were 1.25 (95% CI: 1.20-1.30) and 1.31 (95% CI: 1.26-1.36) for men and women respectively, for each 0.05-unit lower NGS. The odds of incident chronic multimorbidity were 1.14 (95% CI: 1.08-1.20) and 1.14 (95% CI: 1.07-1.21) for men and women respectively for each 0.05-unit lower NGS. The odds of incident dementia were 1.10 for men (95% CI: 1.02-1.20) for each 0.05-unit lower NGS, but there was no significant association for women. Elevated hs-CRP was only associated with chronic multimorbidity among men (OR = 1.29; 95% CI: 1.00-1.73) and women (OR = 1.60; 95% CI: 1.26-2.02).
CONCLUSIONS
Our findings indicate a robust inverse association between NGS and disability and chronic, multimorbidity in older men and women, and dementia in men. Elevated hs-CRP was only associated with chronic multimorbidity in men and women. Healthcare providers should implement measures of grip strength in routine health assessments and discuss the potential dangers of weakness as well as interventions to improve strength with their patients.
Topics: Activities of Daily Living; Aged; Chronic Disease; Female; Hand Strength; Humans; Male; Multimorbidity; Muscle Weakness; Prognosis; United States
PubMed: 34224846
DOI: 10.1016/j.exger.2021.111462 -
Annals of Physical and Rehabilitation... Nov 2019This paper revisits the taxonomy of the neurophysiological consequences of a persistent impairment of motor command execution in the classic environment of sensorimotor... (Review)
Review
This paper revisits the taxonomy of the neurophysiological consequences of a persistent impairment of motor command execution in the classic environment of sensorimotor restriction and muscle hypo-mobilization in short position. Around each joint, the syndrome involves 2 disorders, muscular and neurologic. The muscular disorder is promoted by muscle hypo-mobilization in short position in the context of paresis, in the hours and days after paresis onset: this genetically mediated, evolving myopathy, is called spastic myopathy. The clinician may suspect it by feeling extensibility loss in a resting muscle, although long after the actual onset of the disease. The neurologic disorder, promoted by sensorimotor restriction in the context of paresis and by the muscle disorder itself, comprises 4 main components, mostly affecting antagonists to desired movements: the first is spastic dystonia, an unwanted, involuntary muscle activation at rest, in the absence of stretch or voluntary effort; spastic dystonia superimposes on spastic myopathy to cause visible, gradually increasing body deformities; the second is spastic cocontraction, an unwanted, involuntary antagonist muscle activation during voluntary effort directed to the agonist, aggravated by antagonist stretch; it is primarily due to misdirection of the supraspinal descending drive and contributes to reducing movement amplitude; and the third is spasticity, one form of hyperreflexia, defined by an enhancement of the velocity-dependent responses to phasic stretch, detected and measured at rest (another form of hyperreflexia is "nociceptive spasms", following flexor reflex afferent stimulation, particularly after spinal cord lesions). The 3 main forms of overactivity, spastic dystonia, spastic cocontraction and spasticity, share the same motor neuron hyperexcitability as a contributing factor, all being predominant in the muscles that are more affected by spastic myopathy. The fourth component of the neurologic disorder affects the agonist: it is stretch-sensitive paresis, which is a decreased access of the central command to the agonist, aggravated by antagonist stretch. Improved understanding of the pathophysiology of deforming spastic paresis should help clinicians select meaningful assessments and refined treatments, including the utmost need to preserve muscle tissue integrity as soon as paresis sets in.
Topics: Humans; Motor Neurons; Muscle Contraction; Muscle Spasticity; Muscle, Skeletal; Paresis
PubMed: 30500361
DOI: 10.1016/j.rehab.2018.10.004 -
International Journal of Environmental... Feb 2020Sarcopenia is a physiopathological process associated with aging, caused by reduction of muscle strength, muscle quality and physical performance, and associated with an... (Review)
Review
Sarcopenia is a physiopathological process associated with aging, caused by reduction of muscle strength, muscle quality and physical performance, and associated with an increased risk of falls, physical disability and premature death. There is no effective treatment for sarcopenia, but physical exercise seems to be highly effective at counteracting the decline in muscle mass and strength associated with aging. Recently, sarcopenia has been recognized as an emerging issue in people living with HIV (PLWH). Despite adequate treatment with combination antiretroviral therapy (cART), PLWH may exhibit an early occurrence of some aging-related conditions, including sarcopenia, frailty and falls, and this is likely resulting from high rates of comorbidities, high-risk behaviours, chronic immune activation and cART-specific factors. In this review, we discuss the potential mechanisms and the clinical relevance of sarcopenia in PLWH, and present data from longitudinal studies of physical activity in this population. Despite none of these studies having specifically addressed the benefits of physical exercise on sarcopenia, there is evidence that exercise is effective to increase aerobic capacity and muscle strength, and to improve body composition and inflammatory outcomes in PLWH. Therefore, the expected benefits of physical exercise are likely to translate into a successful and specific intervention for prevention and treatment of sarcopenia in this population.
Topics: Aging; Anti-HIV Agents; Exercise; Female; HIV Infections; Humans; Male; Muscle Strength; Muscle Weakness; Muscle, Skeletal; Sarcopenia
PubMed: 32079244
DOI: 10.3390/ijerph17041283 -
The Clinical Respiratory Journal Feb 2022Although COPD patients commonly present respiratory complaints despite pharmacological treatment, dyspnea does not correlate directly and linearly with spirometric data,...
INTRODUCTION
Although COPD patients commonly present respiratory complaints despite pharmacological treatment, dyspnea does not correlate directly and linearly with spirometric data, a fact that makes it difficult to select patients for pulmonary rehabilitation. Thus, seems logical that the measurement of respiratory muscle strength could help in this initial assessment if it presents a good correlation with exercise capacity. The aim of this study is to assess whether patients with muscle weakness, characterized as a reduction in maximal inspiratory pressure (PImax) below 70% of predicted value, have a good relationship between the assessed respiratory muscle strength and the exercise capacity measured by the 6-min walk test (6MWT) in patients with COPD.
METHODS
Patients diagnosed with COPD according to the 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) on regular use of their medications, without exacerbations for 3 months or more and with respiratory muscle weakness (PImax < 70% of predicted) performed 6MWT in a 30-m-long flat corridor.
RESULTS
Data from 81 patients were analyzed. There was a strong correlation between the distance of the 6MWD with the PImax (r = 0.764, p < 0.0001). When separating the sample by the 350-m cut in the 6MWD, we found that the patients with the worst performance in the test are those who present the greatest respiratory muscle weakness.
CONCLUSION
PImax correlates well with exercise capacity, and patients with respiratory muscle weakness could be referred to a pulmonary rehabilitation protocol tied to inspiratory muscle training.
Topics: Breathing Exercises; Exercise Test; Exercise Tolerance; Humans; Muscle Weakness; Pulmonary Disease, Chronic Obstructive; Respiratory Muscles
PubMed: 34551459
DOI: 10.1111/crj.13449 -
BMJ Case Reports May 2022Tumour-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is an uncommon paraneoplastic syndrome which poses a diagnostic challenge. The hallmark feature...
Tumour-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is an uncommon paraneoplastic syndrome which poses a diagnostic challenge. The hallmark feature is severe acquired hypophosphataemic osteomalacia due to renal phosphate wasting because of increased secretion of fibroblast growth factor 23 (FGF-23). A man in his 30s, presented with a 4-year history of severe muscle aches, bone pain and proximal muscle weakness, was referred for evaluation. His laboratory examination revealed severe hypophosphataemia as a result of urinary phosphate wasting, low 1,25-dihydroxyvitamin D, high alkaline phosphatase and elevated FGF-23. We could localise the tumour to his right femur and the biopsy showed a mesenchymal origin. The treatment with pharmacotherapy and radiofrequency ablation helped in the normalisation of blood chemistry and resulted in significant clinical improvement. Hypophosphataemia, phosphaturia, elevated FGF-23 and low 1,25-dihydroxyvitamin D level with severe musculoskeletal pain and muscle weakness necessitate careful evaluation of TIO.
Topics: Fibroblast Growth Factors; Humans; Hypophosphatemia; Male; Muscle Weakness; Osteomalacia; Pain; Paraneoplastic Syndromes; Phosphates
PubMed: 35589273
DOI: 10.1136/bcr-2022-249200