Muscle and joint mechanics during maximum force biting following total temporomandibular joint replacement surgery.

Total temporomandibular joint replacement (TMJR) surgery is the established treatment for severe temporomandibular joint disorders. While TMJR surgery is known to increase mouth-opening capacity, reduce pain and improve quality of life, little is known about post-surgical jaw function during activities of daily living such as biting and chewing. The aim of this study was to use subject-specific 3D bite force measurements to evaluate the magnitude and direction of joint loading in unilateral total TMJR patients and compare these data to those in healthy control subjects. An optoelectronic tracking system was used to measure jaw kinematics while biting a rubber sample for 5 unilateral total TMJR patients and 8 controls. Finite element simulations driven by the measured kinematics were employed to calculate the resultant bite force generated when compressing the rubber between teeth during biting tasks. Subject-specific musculoskeletal models were subsequently used to calculate muscle and TMJ loading. Unilateral total TMJR patients generated a bite force of 249.6 ± 24.4 N and 164.2 ± 62.3 N when biting on the contralateral and ipsilateral molars, respectively. In contrast, controls generated a bite force of 317.1 ± 206.6 N. Unilateral total TMJR patients biting on the contralateral molars had a significantly higher lateral TMJ force direction (median difference: 63.6°, p = 0.028) and a significantly lower ratio of working TMJ force to bite force (median difference: 0.17, p = 0.049) than controls. Results of this study may guide TMJ prosthesis design and evaluation of dental implants.

A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15.

Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Pro-inflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed regeneration-promoting program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-ß superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and on muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARγ. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is coexpressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (growth factor-expressing macrophages [GFEMs]).

Mitochondrial Dysfunction in Cancer Cachexia: Impact on Muscle Health and Regeneration.

Cancer cachexia is a frequently neglected debilitating syndrome that, beyond representing a primary cause of death and cancer therapy failure, negatively impacts on patients' quality of life. Given the complexity of its multisystemic pathogenesis, affecting several organs beyond the skeletal muscle, defining an effective therapeutic approach has failed so far. Revamped attention of the scientific community working on cancer cachexia has focused on mitochondrial alterations occurring in the skeletal muscle as potential triggers of the complex metabolic derangements, eventually leading to hypercatabolism and tissue wasting. Mitochondrial dysfunction may be simplistically viewed as a cause of energy failure, thus inducing protein catabolism as a compensatory mechanism; however, other peculiar cachexia features may depend on mitochondria. On the one side, chemotherapy also impacts on muscle mitochondrial function while, on the other side, muscle-impaired regeneration may result from insufficient energy production from damaged mitochondria. Boosting mitochondrial function could thus improve the energetic status and chemotherapy tolerance, and relieve the myogenic process in cancer cachexia. In the present work, a focused review of the available literature on mitochondrial dysfunction in cancer cachexia is presented along with preliminary data dissecting the potential role of stimulating mitochondrial biogenesis via PGC-1α overexpression in distinct aspects of cancer-induced muscle wasting.

Coordination of tumor growth and host wasting by tumor-derived Upd3.

yki-induced gut tumors in Drosophila are associated with host wasting, including muscle dysfunction, lipid loss, and hyperglycemia, a condition reminiscent of human cancer cachexia. We previously used this model to identify tumor-derived ligands that contribute to host wasting. To identify additional molecular networks involved in host-tumor interactions, we develop PathON, a web-based tool analyzing the major signaling pathways in Drosophila, and uncover the Upd3/Jak/Stat axis as an important modulator. We find that yki-gut tumors secrete Upd3 to promote self-overproliferation and enhance Jak/Stat signaling in host organs to cause wasting, including muscle dysfunction, lipid loss, and hyperglycemia. We further reveal that Upd3/Jak/Stat signaling in the host organs directly triggers the expression of ImpL2, an antagonistic binding protein for insulin-like peptides, to impair insulin signaling and energy balance. Altogether, our results demonstrate that yki-gut tumors produce a Jak/Stat pathway ligand, Upd3, that regulates both self-growth and host wasting.

Curcumin and Resveratrol Improve Muscle Function and Structure through Attenuation of Proteolytic Markers in Experimental Cancer-Induced Cachexia.

Muscle wasting and cachexia are prominent comorbidities in cancer. Treatment with polyphenolic compounds may partly revert muscle wasting. We hypothesized that treatment with curcumin or resveratrol in cancer cachectic mice may improve muscle phenotype and total body weight through attenuation of several proteolytic and signaling mechanisms in limb muscles. In gastrocnemius and soleus muscles of cancer cachectic mice (LP07 adenocarcinoma cells, N = 10/group): (1) LC-induced cachexia, (2) LC-cachexia+curcumin, and (3) LC-cachexia + resveratrol, muscle structure and damage (including blood troponin I), sirtuin-1, proteolytic markers, and signaling pathways (NF-κB and FoxO3) were explored (immunohistochemistry and immunoblotting). Compared to nontreated cachectic mice, in LC-cachexia + curcumin and LC-cachexia + resveratrol groups, body and muscle weights (gastrocnemius), limb muscle strength, muscle damage, and myofiber cross-sectional area improved, and in both muscles, sirtuin-1 increased, while proteolysis (troponin I), proteolytic markers, and signaling pathways were attenuated. Curcumin and resveratrol elicited beneficial effects on fast- and slow-twitch limb muscle phenotypes in cachectic mice through sirtuin-1 activation, attenuation of atrophy signaling pathways, and proteolysis in cancer cachectic mice. These findings have future therapeutic implications as these natural compounds, separately or in combination, may be used in clinical settings of muscle mass loss and dysfunction including cancer cachexia.

Analysis of ultrasound image biological image algorithm in the restoration of muscle group movement function / Análise do algoritmo de imagem biológica por ultrassom na restauração da função de movimento do grupo muscular / Análisis del algoritmo de imágenes biológicas de imágenes de ultrasonido en la restauración de la función de movimiento del grupo muscular

ABSTRACT Objective: By studying the recognition effect of ultrasonic biological image data analysis on muscle group motion function, the evaluation value and significance of ultrasonic biomedical image combination algorithm on muscle group motion function are discussed. Methods: A Gabor filtering algorithm is proposed to smooth the original image. The MVEF algorithm is used to enhance the ultrasonic image and binary further the image again. Using the principle of the Hove transform, the thickness of the muscle is automatically estimated. Results: The square of correlation coefficients of the manual measurement method, Gabor filtering algorithm and MVEF algorithm are 91.3%, 91.3% and 87.8%, respectively. The difference between the manual measurement and the estimation based on the Gabor filtering algorithm is 1.45 ± 0.48mm. The difference between the results of manual measurement and the MVEF algorithm is 1.38 ± 0.56mm. The computation time of the MVEF algorithm and Gabor algorithm are 5 seconds and 0.3 seconds, respectively. Conclusions: The algorithm proposed in this study can effectively measure the muscle thickness, fast, convenient and accurate, and can reflect the contractility of skeletal muscle well, which is of great value for the recognition and evaluation of muscle group movement function. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Objetivo: Ao estudar o efeito de reconhecimento da análise de dados de imagem biológica ultrassônica na função de movimento do grupo muscular, o valor de avaliação e a importância do algoritmo de combinação de imagem biomédica ultrassônica na função de movimento do grupo muscular são discutidos. Métodos: Um algoritmo de filtragem Gabor é proposto para suavizar a imagem original. O algoritmo MVEF é usado para aprimorar ainda mais a imagem ultrassônica e binar a imagem novamente. Usando o princípio da transformada de H ove, a espessura do músculo é automaticamente estimada. Resultados: O quadrado dos coeficientes de correlação do método de medição manual, algoritmo de filtragem Gabor e algoritmo MVEF são 91,3%, 91,3% e 87,8%, respectivamente. A diferença entre a medição manual e a estimativa baseada no algoritmo de filtragem Gabor é 1,45 ± 0,48 mm. A diferença entre os resultados da medição manual e o algoritmo MVEF é de 1,38 ± 0,56 mm. O tempo de cálculo do algoritmo MVEF e do algoritmo Gabor é de 5 segundos e 0,3 segundos, respectivamente. Conclusões: O algoritmo proposto neste estudo pode medir efetivamente a espessura muscular, de forma rápida, conveniente e precisa, e pode refletir bem a contratilidade do músculo esquelético, o que é de grande valor para o reconhecimento e avaliação da função de movimento do grupo muscular. Nível de evidência II; Estudos terapêuticos- investigação dos resultados do tratamento.

RESUMEN Objetivo: Al estudiar el efecto de reconocimiento del análisis de datos de imágenes biológicas ultrasónicas sobre la función del movimiento del grupo muscular, se discuten el valor de evaluación y la importancia del algoritmo de combinación de imágenes biomédicas ultrasónicas sobre la función del movimiento del grupo muscular. Métodos: Se propone un algoritmo de filtrado de Gabor para suavizar la imagen original. El algoritmo MVEF se utiliza para mejorar aún más la imagen ultrasónica y volver a binar la imagen. Utilizando el principio de la transformada de H ove, el grosor del músculo se estima automáticamente. Resultados: El cuadrado de los coeficientes de correlación del método de medición manual, el algoritmo de filtrado de Gabor y el algoritmo MVEF son 91,3%, 91,3% y 87,8%, respectivamente. La diferencia entre la medición manual y la estimación basada en el algoritmo de filtrado de Gabor es de 1,45 ± 0,48 mm. La diferencia entre los resultados de la medición manual y el algoritmo MVEF es 1,38 ± 0,56 mm. El tiempo de cálculo del algoritmo MVEF y el algoritmo de Gabor son 5 segundos y 0,3 segundos respectivamente. Conclusiones: El algoritmo propuesto en este estudio puede medir eficazmente el grosor muscular, de forma rápida, conveniente y precisa, y puede reflejar bien la contractilidad del músculo esquelético, lo cual es de gran valor para el reconocimiento y evaluación de la función del movimiento de grupos musculares. Nivel de evidencia II; Estudios terapéuticos- investigación de los resultados del tratamiento.

Analysis of the Muscular Activity, Peak Torque in the Lower Limbs, and Static Balance after Virtual Rehabilitation in Women with Fibromyalgia: A Randomized Controlled Study.

Objective: To analyze the effect of the exergaming on muscular activity at rest and on maximum voluntary isometric contraction by electromyography (EMG) at peak torque, widespread pressure hyperalgesia identified using a tender point count, and static balance in fibromyalgia. Materials and Methods: Thirty-five women were divided into two groups: Wii™ (virtual rehabilitation, n = 16) and control (stretching exercises, n = 19), through simple randomization. The volunteers were evaluated by means of EMG, dynamometry by load cell, baropodometry, and algometry before interventions and reevaluated after the 10th and 20th sessions. The subjects participated fully in three 1-hour treatment sessions per week of 20 sessions. Results: The Wii group showed significant benefits for the peak torque of dorsiflexion movement after 20 sessions and for movement plantarflexion after 10 sessions. The control group showed bilateral improvement in muscular activity in the tibialis anterior muscle after 20 sessions. Both groups showed a significant decrease in tender point count, suggesting improved hyperalgesia after 10 sessions and 20 sessions. No significant improvement was found in static baropodometry in the two evaluated groups. Conclusion: Exergaming have the potential to increase the peak torque for dorsiflexion and plantarflexion movement in women with fibromyalgia. It also produces a decrease in tender point count equal to that with flexibility exercises and does not produce changes in the static balance.

AGEs accumulation is related to muscle degeneration and vascular calcification in peritoneal dialysis patients / O acúmulo de AGEs está relacionado à degeneração muscular e calcificação vascular em pacientes em diálise peritoneal

Abstract Background: Patients with chronic kidney disease (CKD) are affected by dynapenia, sarcopenia, and vascular calcification. Advanced glycation end products (AGEs) may accumulate in peritoneal dialysis (PD) patients and favor sarcopenia via changes in collagen cross-linking, muscle protein breakdown, and the calcification of arterial smooth muscle cells via p38-MAPK activation. The aim of this study is to explore the relationships between AGEs, muscle degeneration, and coronary artery calcification. Methods: This was a clinical observational study in patients with CKD undergoing PD, in which serum and skin AGEs (AGEs-sAF), cumulative glucose load, muscle strength and functional tests, muscle ultrasounds with elastography, coronary artery calcium (CAC) quantification, and muscle density by multislice computed tomography were measured. Results: 27 patients aged 48±16 years, dialysis vintage of 27±17 months, had AGEs-sAF levels of 3.09±0.65 AU (elevated in 13 [87%] patients), grip strength levels of 26.2±9.2 kg (11 [42%] patients with dynapenia), gait speed of 1.04±0.3 m/s (abnormal in 14 [58%] patients) and "timed-up-and-go test" (TUG) of 10.5±2.2s (abnormal in 7 [26%] patients). Correlations between AGEs-sAF levels and femoral rectus elastography (R=-0.74; p=0.02), anterior-tibialis elastography (R= -0.68; p=0.04) and CAC (R=0.64; p=0.04) were detected. Cumulative glucose load correlated with femoral rectal elastography (R=-0.6; p=0.02), and serum glycated hemoglobin concentrations correlated with psoas muscle density (R= -0.58; p=0.04) and CAC correlated with psoas muscle density (R=0.57; p=0.01) and lumbar square muscle density (R=-0.63; p=0.005). Conclusions: The study revealed associations between AGEs accumulation and lower muscle stiffness/density. Associations that linked muscle degeneration parameters with vascular calcification were observed.

Resumo Histórico: Pacientes com doença renal crônica (DRC) são afetados pela dinapenia, sarcopenia e calcificação vascular. Produtos finais da glicação avançada (AGEs) podem se acumular em pacientes em diálise peritoneal (DP) e favorecer a sarcopenia por meio de alterações em ligações cruzadas do colágeno, quebra da proteína muscular e calcificação das células do músculo liso arterial por meio da ativação da p38-MAPK. O objetivo deste estudo é explorar as relações entre AGEs, degeneração muscular e calcificação da artéria coronária. Métodos: Este foi um estudo clínico observacional em pacientes com DRC submetidos à DP, no qual foram medidos os AGEs séricos e teciduais (AGEs-sAF), a carga cumulativa de glicose, a força muscular e testes funcionais, ultrassonografias musculares com elastografia, quantificação do cálcio da artéria coronária (CAC), e a densidade muscular por tomografia computadorizada multislice. Resultados: 27 pacientes com idade entre 48±16 anos, tempo de diálise entre 27±17 meses, tinham níveis de AGEs-sAF de 3,09±0,65 UA (elevado em 13 [87%] pacientes), níveis de força de preensão de 26,2±9,2 kg (11 [42%] pacientes com dinapenia), velocidade de marcha de 1,04±0,3 m/s (anormal em 14 [58%] pacientes) e teste "timed-up-and-go" (TUG) de 10,5±2,2s (anormal em 7 [26%] pacientes). Foram detectadas correlações entre os níveis AGEs-sAF e a elastografia do reto femoral (R=-0,74; p=0,02), a elastografia tibial anterior (R= -0,68; p=0,04) e a CAC (R=0,64; p=0,04). A carga cumulativa de glicose se correlacionou com a elastografia do reto femoral (R=-0,6; p=0,02), as concentrações séricas de hemoglobina glicada se correlacionaram com a densidade muscular do psoas (R= -0,58; p=0,04) e o CAC se correlacionou com a densidade do músculo psoas (R=-0,57; p=0,01) e a densidade do músculo quadrado lombar (R=-0,63; p=0,005). Conclusões: O estudo revelou associações entre o acúmulo de AGEs e menor rigidez/densidade muscular. Foram observadas associações que ligavam parâmetros de degeneração muscular com a calcificação vascular.

Muscle fat content is strongly associated with NASH: A longitudinal study in patients with morbid obesity.

BACKGROUND & AIMS: Studies exploring the relationship between muscle fat content and non-alcoholic fatty liver disease (NAFLD) are scarce. Herein, we aimed to evaluate the association of muscle mass and fatty infiltration with biopsy-assessed NAFLD in patients with obesity. METHODS: At inclusion (n = 184) and 12 months after a dietary intervention (n = 15) or bariatric surgery (n = 24), we evaluated NAFLD by liver biopsy, and skeletal muscle mass index (SMI) by CT (CT-SMI) or bioelectrical impedance analysis (BIA-SMI). We developed an index to evaluate absolute fat content in muscle (skeletal muscle fat index [SMFI]) from CT-based psoas muscle density (SMFIPsoas). RESULTS: Muscle mass was higher in patients with NAFLD than in those without (CT-SMI 56.8 ± 9.9 vs. 47.4 ± 6.5 cm2/m2, p <0.0001). There was no association between sarcopenia and non-alcoholic steatohepatitis (NASH). SMFIPsoas was higher in NASH ≥F2 and early NASH F0-1 than in NAFL (78.5 ± 23.6 and 73.1 ± 15.6 vs. 61.2 ± 12.6, p <0.001). A 1-point change in the score for any of the individual cardinal NASH features (i.e. steatosis, inflammation or ballooning) was associated with an increase in SMFIPsoas (all p <0.05). The association between SMFIPsoas and NASH was highly significant even after adjustment for multiple confounders (all p <0.025). After intervention (n = 39), NASH improvement, defined by NAFLD activity score <3 or a 2-point score reduction, was achieved in more than 75% of patients (n = 25 or n = 27, respectively) that had pre-established NASH at inclusion (n = 32) and was associated with a significant decrease in SMFIPsoas (p <0.001). Strikingly, all patients who had ≥11% reduction in SMFIPsoas achieved NASH improvement (14/14, p <0.05). CONCLUSIONS: Muscle fat content, but not muscle mass, is strongly and independently associated with NASH. All individuals who achieved a ≥11% decrease in SMFIPsoas after intervention improved their NASH. These data indicate that muscle fatty infiltration could be a potential marker for (and perhaps a pathophysiological contributor to) NASH. LAY SUMMARY: The fat content in skeletal muscles is highly reflective of the severity of non-alcoholic fatty liver disease (NAFLD) in patients with morbid obesity. In particular, muscle fat content is strongly associated with non-alcoholic steatohepatitis (NASH) and decreases upon NASH improvement. These data indicate that muscle fatty infiltration could be a marker and possible pathophysiological contributor to NASH.

Acute application of photobiomodulation does not bring important gains for the muscular performance and functionality of diabetic individuals.

Photobiomodulation therapy (PBMT) has been used to improve the physical performance of individuals with advanced age; however, there are no studies in the literature that support the application of light-emitting diode (LED) therapy for the muscular performance of individuals with diabetes mellitus who show a decline in functionality. The aim of the study was to analyze the acute effects of PBMT on strength and functional performance in type 2 diabetic individuals. Sixty-three volunteers were recruited and randomized into five groups: control (C), sham (S), red LED (R), infrared LED (IR), and red LED + infrared LED (R + IR). On the first day, the volunteers were evaluated using the time up and go (TUG), the 6-min walk test (6MWT), and isokinetic dynamometer of the ankle. In the following 3 days, groups R, IR, R + IR, and S returned for application of PBMT bilaterally, with 180 J of energy on each leg. On the fifth day, a reassessment was performed. There was no statistical difference between groups for the variables of the isokinetic dynamometer, TUG, and 6MWT. Analysis of the size of the clinical effect for the isokinetic variables showed that there was no pattern among the effects observed. There is a moderate effect in favor of R, IR, and R + IR in relation to C for the TUG and a moderate effect of R + IR in relation to C for the 6MWT. The PBMT applied for a short period does not bring important gains for the muscular performance and functionality of diabetic individuals.

Muscle Quality Is Associated with History of Falls in Octogenarians.

OBJECTIVES: The aim of this study was to compare muscle quality (MQ) between octogenarians classified as non-fallers, fallers and recurrent fallers and identify confounding intrinsic and extrensic factors that impact likelihood for falls. DESIGN: This observational, descriptive, cross-sectional study included older adults (N=220) aged 80 years or older. MEASUREMENTS: The Short Physical Performance Battery (SPPB) was used to evaluate physical function and MQ was calculated using the ratio of grip strength to arm muscle mass (in kilograms) quantified by DXA. Variables related to sociodemographic, clinical, cognitive function, and falls were evaluated using a questionnaire and symptoms of depression were evaluated by the Geriatric Depression Scale (GDS). A Kruskal-Wallis H test was used to verify differences between groups. Binomial logistic regression was performed to determine the impact of age, depression, polypharmacy, balance, MQ, and sex on participants having more than four falls in their history. RESULTS: Increasing MQ was associated with reduced likelihood of more than four falls in their history. Non-fallers were statistically younger (p = 0.012) and took more medications (p = 0.023) than recurrent fallers. Recurrent fallers had lower MQ when compared with fallers (p = 0.007) and non-fallers (p = 0.001) and had a lower GDS score when compared with fallers (p = 0.022). Finally, fallers presented lower scores for balance when compared to non-fallers (p = 0.013). CONCLUSION: A higher MQ is associated with a reduction in the likelihood falls in octogenarians. Therefore, it may be advantageous for clinicians to evaluate MQ when the screening of the risk of falls in older adults.

Association of Lower-Extremity Muscle Performance and Physical Activity Level and Intensity in Middle-Aged and Older Adults: A Doubly Labeled Water and Accelerometer Study.

OBJECTIVES: The purpose of this study was to examine if there is a relationship between lower-extremity muscle performance (LEMP) and physical activity, especially the physical activity level (PAL) value, in community-dwelling middle-aged and older adults. DESIGN: Cross-sectional study. SETTING: Community-based. PARTICIPANTS: Participants were 54 community-dwelling and independent middle-aged and older individuals (aged 54-89 years). MEASUREMENTS: Physical activity level was calculated from the total energy expenditure of each participant obtained using the doubly labeled water method (PALDLW) and estimated basal metabolic rate. Daily step count and intensity of physical activity was monitored with a triaxial accelerometer, and LEMP was assessed using the five-repetition sit-to-stand test (STS-5) and vertical jumping (VJ). RESULTS: The results of STS-5 nearly negatively correlated with those of PALDLW when analysing the middle-aged and older man and woman, separately. VJ positively correlated with PALDLW when analysing the middle-aged and older men and woman, separately. The relationship between LEMP (e.g. STS-5 and VJ) and PAL were maintained, regardless of sex and body composition. PALDLW was significantly positively correlated with LPA, MVPA, and steps, and significantly negatively correlated with sedentary time. The relationship PALDLW and steps was described as following equation: PALDLW = 0.0000392 × steps +1.531. CONCLUSIONS: These findings suggest that PALDLW is a key contributor to increasing LEMP among middle-aged and older adults. Maintaining high PALDLW may be beneficial to independent living, and participation in recreational and social activities in middle-aged and older adults.

Impact of alignment and kinematic variation on resistive moment and dislocation propensity for THA with lipped and neutral liners.

Instability and dislocation remain leading indications for revision of total hip arthroplasty (THA). Many studies have addressed the links between implant design and dislocation; however, an understanding of the impact of alignment and kinematic variability on constraint of modern THA constructs to provide joint stability is needed. The objective of this study is to provide objective data to be considered in the treatment algorithm to protect against joint instability. Joint contact and muscle forces were evaluated using musculoskeletal models of THA patients performing activities consistent with posterior and anterior dislocation. Position and joint loads were transferred to a finite element simulation with an experimentally calibrated hip capsule representation, where they were kinematically extrapolated until impingement and eventual dislocation. Cup anteversion and inclination were varied according to clinical measurements, and variation in imposed kinematics was included. The resistive moment provided by the contact force and joint capsule, and overall dislocation rate (dislocations/total simulations) were determined with neutral and lipped acetabular liners. Use of a lipped liner did increase the resistive moment in posterior dislocation, by an average of 5.2 Nm, and the flexion angle at dislocation by 1.4° compared to a neutral liner. There was a reduction in similar magnitude in resistance to anterior dislocation. Increased cup anteversion and inclination, hip abduction and internal rotation all reduced the occurrence of posterior dislocation but increased anterior dislocation. A quantitative understanding of tradeoffs in the dislocation risk inherent to THA construct options is valuable in supporting surgical decision making.

Targeting reactive oxygen species (ROS) to combat the age-related loss of muscle mass and function.

The loss of muscle mass and function with age, termed sarcopenia, is an inevitable process, which has a significant impact on quality of life. During ageing we observe a progressive loss of total muscle fibres and a reduction in cross-sectional area of the remaining fibres, resulting in a significant reduction in force output. The mechanisms which underpin sarcopenia are complex and poorly understood, ranging from inflammation, dysregulation of protein metabolism and denervation. However, there is significant evidence to demonstrate that modified ROS generation, redox dis-homeostasis and mitochondrial dysfunction may have an important role to play. Based on this, significant interest and research has interrogated potential ROS-targeted therapies, ranging from nutritional-based interventions such as vitamin E/C, polyphenols (resveratrol) and targeted pharmacological compounds, using molecules such as SS-31 and MitoQ. In this review we evaluate these approaches to target aberrant age-related ROS generation and the impact on muscle mass and function.

Investigation of the Diet-Gut-Muscle Axis in the Osteoporotic Fractures in Men Study.

OBJECTIVES: To investigate the association between dietary fiber density (grams of fiber consumed per 100 kcal) with the gut-muscle axis in older adult men. DESIGN: Cross-sectional study. SETTING: Osteoporotic Fractures in Men (MrOS) cohort participants at Visit 4 (2014-16). PARTICIPANTS: Older adult men (average age, 85y) from the MrOS study. MEASUREMENTS: Men who were in the highest tertiles for dietary fiber density and the percentage of whole body lean mass were defined as T3T3 (n=42), whereas men who were in the lowest and intermediate tertiles for these variables were defined as T1T1 (n=32), T1T3 (n=24), and T3T1 (n=13), respectively. Additionally, measures of physical function, including the short physical performance battery (SPPB) score and grip strength were higher in T3T3 when compared with T1T1. Gut bacterial abundance was quantified with use of 16S v4 rRNA sequencing, and the bacterial functional potential was derived from the 16S data with PICRUSt. Chao1, ACE, Shannon, Simpson, and Fisher indices were used as measures of α-diversity. Weighted and unweighted Unifrac, and Bray-Curtis were used as measures of ß-diversity. Age, physical activity score, smoking, and number of medications-adjusted DESeq2 models were used to identify bacteria and functions that were different when comparing T3T3 with T1T1, but that were not also different when comparing T3T3 with T1T3 or T3T1. RESULTS: α-diversity was not different, but significant differences for ß-diversity (unweighted UniFrac, Bray-Curtis) were identified when comparing T3T3 with T1T1. Known butyrate-producing bacteria, including Ruminococcus, Lachnospira, and Clostridia, and gene counts for butyrate production (KEGG IDs: K01034, K01035) were higher in T3T3, when compared with T1T1. CONCLUSION: These data suggest that a high-fiber diet may positively impact butyrate-producing genera and gene counts, which collectively may be involved in mechanisms related to the percentage of whole body lean mass and physical functioning in older adult men. Future studies aimed at testing the causative role of this hypothesis are of interest.

Real-time shear wave ultrasound elastography: a new tool for the evaluation of diaphragm and limb muscle stiffness in critically ill patients.

BACKGROUND: Muscle weakness following critical illness is the consequence of loss of muscle mass and alteration of muscle quality. It is associated with long-term disability. Ultrasonography is a reliable tool to quantify muscle mass, but studies that evaluate muscle quality at the critically ill bedside are lacking. Shear wave ultrasound elastography (SWE) provides spatial representation of soft tissue stiffness and measures of muscle quality. The reliability and reproducibility of SWE in critically ill patients has never been evaluated. METHODS: Two operators tested in healthy controls and in critically ill patients the intra- and inter-operator reliability of the SWE using transversal and longitudinal views of the diaphragm and limb muscles. Reliability was calculated using the intra-class correlation coefficient and a bootstrap sampling method assessed their consistency. RESULTS: We collected 560 images. Longitudinal views of the diaphragm (ICC 0.83 [0.50-0.94]), the biceps brachii (ICC 0.88 [0.67-0.96]) and the rectus femoris (ICC 0.76 [0.34-0.91]) were the most reliable views in a training set of healthy controls. Intra-class correlation coefficient for inter-operator reproducibility and intra-operator reliability was above 0.9 for all muscles in a validation set of healthy controls. In critically ill patients, inter-operator reproducibility and intra-operator 1 and 2 reliability ICCs were respectively 0.92 [0.71-0.98], 0.93 [0.82-0.98] and 0.92 [0.81-0.98] for the diaphragm; 0.96 [0.86-0.99], 0.98 [0.94-0.99] and 0.99 [0.96-1] for the biceps brachii and 0.91 [0.51-0.98], 0.97 [0.93-0.99] and 0.99 [0.97-1] for the rectus femoris. The probability to reach intra-class correlation coefficient greater than 0.8 in a 10,000 bootstrap sampling for inter-operator reproducibility was respectively 81%, 84% and 78% for the diaphragm, the biceps brachii and the rectus femoris respectively. CONCLUSIONS: SWE is a reliable technique to evaluate limb muscles and the diaphragm in both healthy controls and in critically ill patients. TRIAL REGISTRATION: The study was registered (ClinicalTrial NCT03550222).

Quantity and quality of muscle in patients recently diagnosed with colorectal cancer: a comparison with cancer-free controls.

This cross-sectional study compares the muscle mass, core strength and physical fragility of patients recently diagnosed with colorectal cancer (pRD-CRC) with those of healthy subjects and identifies variables to be considered when designing pre-treatment physical interventions for such patients. Body composition, anthropometric variables, the muscle architecture of the lumbopelvic region, physical fitness and frailty were assessed in 32 pRD-CRC and 29 healthy control subjects. The patients showed a reduction in muscle mass (F = 10.059; P = 0.003), in the width of the lumbar multifidus (F = 21.869; P < 0.001), in the transverse abdominal muscle (U = 323.00; P = 0.042) and in the abdominal strength resistance (F = 12.264; P = 0.001). They were also frailer (P = 0.002) than the controls. These results suggest that pRD-CRC are affected by reduced strength and myopenia, leading to frailty. The early incorporation of these patients into strength-enhancing programs may be advisable.

The Use of Proton Pump Inhibitors May Increase Symptoms of Muscle Function Loss in Patients with Chronic Illnesses.

Long-term use of proton pump inhibitors (PPIs) is common in patients with muscle wasting-related chronic diseases. We explored the hypothesis that the use of PPIs may contribute to a reduction in muscle mass and function in these patients. Literature indicates that a PPI-induced reduction in acidity of the gastrointestinal tract can decrease the absorption of, amongst others, magnesium. Low levels of magnesium are associated with impaired muscle function. This unwanted side-effect of PPIs on muscle function has been described in different disease backgrounds. Furthermore, magnesium is necessary for activation of vitamin D. Low vitamin D and magnesium levels together can lead to increased inflammation involved in muscle wasting. In addition, PPI use has been described to alter the microbiota's composition in the gut, which might lead to increased inflammation. However, PPIs are often provided together with nonsteroidal anti-inflammatory drugs (NSAIDs), which are anti-inflammatory. In the presence of obesity, additional mechanisms could further contribute to muscle alterations. In conclusion, use of PPIs has been reported to contribute to muscle function loss. Whether this will add to the risk factor for development of muscle function loss in patients with chronic disease needs further investigation.

Forward lunge before and after anterior cruciate ligament reconstruction: Faster movement but unchanged knee joint biomechanics.

The forward lunge (FL) may be a promising movement to assess functional outcome after ACL reconstruction. Thus, we aimed to investigate the FL movement pattern before and after ACL reconstruction with a comparison to healthy controls to determine if differences were present. Twenty-eight ACL injured participants and 28 matched healthy controls were included. They performed FL movements while sagittal plane biomechanics of the knee and electromyography (EMG) of nine leg muscles was assessed. The ACL injured group was tested before and 10 months after surgery. The perceived knee function and activity level was assessed by questionnaires. The ACL injured group performed the FL significantly slower than the controls before surgery (mean difference: 0.41 s [95%CI: 0.04-0.79 s; p<0.05]) while they performed the FL as fast as the controls after surgery (~28% movement time reduction post-surgery). Perceived knee function and activity level improved significantly post-surgery. The knee joint flexion angle, extensor moment, power, angular velocity in the ACL injured group did not differ from pre to post-surgery. For the ACL injured group, the peak knee extensor moment observed both pre and post-surgery was significantly lower when compared to the controls. The EMG results showed minimal differences. In conclusion, at 10 months post-surgery, the FL was performed significantly faster and the movement time was comparable to that of the controls. While the perceived knee function and activity level improved post-surgery, the knee joint biomechanics were unchanged. This may reflect that knee joint function was not fully restored.

Muscle Weakness in Adults: Evaluation and Differential Diagnosis.

Although the prevalence of muscle weakness in the general population is uncertain, it occurs in about 5% of U.S. adults 60 years and older. Determining the cause of muscle weakness can be challenging. True muscle weakness must first be differentiated from subjective fatigue or pain-related motor impairment with normal motor strength. Muscle weakness should then be graded objectively using a formal tool such as the Medical Research Council Manual Muscle Testing scale. The differential diagnosis of true muscle weakness is extensive, including neurologic, rheumatologic, endocrine, genetic, medication- or toxin-related, and infectious etiologies. A stepwise approach to narrowing this differential diagnosis relies on the history and physical examination combined with knowledge of the potential etiologies. Frailty and sarcopenia are clinical syndromes occurring in older people that can present with generalized weakness. Asymmetric weakness is more common in neurologic conditions, whereas pain is more common in neuropathies or radiculopathies. Identifying abnormal findings, such as Chvostek sign, Babinski reflex, hoarse voice, and muscle atrophy, will narrow the possible diagnoses. Laboratory testing, including electrolyte, thyroid-stimulating hormone, and creatine kinase measurements, may also be helpful. Magnetic resonance imaging is indicated if there is concern for acute neurologic conditions, such as stroke or cauda equina syndrome, and may also guide muscle biopsy. Electromyography is indicated when certain diagnoses are being considered, such as amyotrophic lateral sclerosis, myasthenia gravis, neuropathy, and radiculopathy, and may also guide biopsy. If the etiology remains unclear, specialist consultation or muscle biopsy may be necessary to reach a diagnosis.