Mustn1 ablation in skeletal muscle results in functional alterations.

Mustn1, a gene expressed exclusively in the musculoskeletal system, was shown in previous in vitro studies to be a key regulator of myogenic differentiation and myofusion. Other studies also showed Mustn1 expression associated with skeletal muscle development and hypertrophy. However, its specific role in skeletal muscle function remains unclear. This study sought to investigate the effects of Mustn1 in a conditional knockout (KO) mouse model in Pax7 positive skeletal muscle satellite cells. Specifically, we investigated the potential effects of Mustn1 on myogenic gene expression, grip strength, alterations in gait, ex vivo investigations of isolated skeletal muscle isometric contractions, and potential changes in the composition of muscle fiber types. Results indicate that Mustn1 KO mice did not present any substantial phenotypic changes or significant variations in genes related to myogenic differentiation and fusion. However, an approximately 10% decrease in overall grip strength was observed in the 2-month-old KO mice in comparison to the control wild type (WT), but this decrease was not significant when normalized by weight. KO mice also generated approximately 8% higher vertical force than WT at 4 months in the hindlimb. Ex vivo experiments revealed decreases in about 20 to 50% in skeletal muscle contractions and about 10%-20% fatigue in soleus of both 2- and 4-month-old KO mice, respectively. Lastly, immunofluorescent analyses showed a persistent increase of Type IIb fibers up to 15-fold in the KO mice while Type I fibers decreased about 20% and 30% at both 2 and 4 months, respectively. These findings suggest a potential adaptive or compensatory mechanism following Mustn1 loss, as well as hinting at an association between Mustn1 and muscle fiber typing. Collectively, Mustn1's complex roles in skeletal muscle physiology requires further research, particularly in terms of understanding the potential role of Mustn1 in muscle repair and regeneration, as well as with influence of exercise. Collectively, these will offer valuable insights into Mustn1's key biological functions and regulatory pathways.

Gait Pathology in Subjects with Patellofemoral Instability: A Systematic Review.

Identifying potential gait deviations in patellofemoral instability (PI) can help with the development of effective rehabilitation strategies. The purpose of this systematic review was to examine whether there are specific gait alterations in subjects with PI. The present review followed the PRISMA guidelines and was initially registered at PROSPERO (CRD42021236765). The literature search was carried out in the databases of PubMed, the Cochrane library, Web of Science, ClinicalTrials.gov, and Medline. The search strategy resulted in the identification of seven relevant publications. Subjects with PI show decreased walking speed, stride length, and cadence. Some studies reported changes not only in knee kinematics and kinetics but also in hip and ankle kinematics and kinetics. There is evidence that most subjects with PI walk with a quadriceps avoidance gait and show increased genu valgum posture, but there is still great variability in the coping responses within individuals with PI. The discrepancy among the study results might underpin the fact that PI is a multifactorial problem, and subjects cope with the different underlying morphological as well as functional deficits using a variety of gait strategies, which makes the interpretation and understanding of the gait of subjects with PI a clinically challenging task.

Optimization of backpack loads using gait parameters in school boys.

BACKGROUND: Backpacks are an efficient way of manual carriage used by people of all ages, and is commonly used by schoolchildren. Carrying heavy backpacks may result in cumulative trauma later in life due to biomechanical adaptations during gait. Gait parameters are known to be sensitive to force vectors, which can be altered by load carrying. This study attempts to find the most favorable backpack weight using gait changes as an indicator. METHODS: This was an observational study conducted on twenty typically developing boys aged between 9 and 14 years. Gait analysis was done using standard recommendations, with increasing backpack loads with respect to their body weights. Gait cycles were captured using video cameras and analyzed using Kinovea0.8.25 motion analyzing software. RESULTS: As the backpack load increased, significant kinematic changes were noted in the child's ankle, knee, and hip joints. These changes were evident when the backpack load increased beyond 15% of their body weight. CONCLUSIONS: This study concludes that the optimum weight that can be carried without having an impact on dynamic posture will be less than 15% of the body weight.

A mobile app to transparently distinguish single- from dual-task walking for the ecological monitoring of age-related changes in daily-life gait.

BACKGROUND: Early detection of gait impairments in older adults allows the early uncovering of fall risk and/or cognitive deficits, resulting in timely interventions. Dual-task paradigms have been shown to be more sensitive than single-task conditions for the detection of subtle yet relevant gait impairments. RESEARCH QUESTION: Can a system - encompassing a pair of instrumented insoles and a customized mobile app - transparently and accurately study ecological walking activities in single- and dual-task conditions, with the aim of detecting early and subtle age-related alterations of gait? METHODS: The system was tested on 19 older adults during outdoor walking (two identical single-task trials and two motor-cognitive dual-task trials with the user engaged in a simple phone call and in a cognitive-demanding phone call). A single-task cognitive trial was included. Relative reliability of the gait parameters provided by the insoles during single-task walking was investigated (Intraclass Correlation Coefficient). The effect of dual tasking on both motor (Friedman test) and cognitive (Wilcoxon signed-rank test) domains was studied. To study usability, the system was tested on 5 older adults in real-life environment over 3 months. RESULTS: Most of the parameters showed excellent reliability. Independently from the cognitive demand, walking while talking resulted in increased gait cycle and step time, with a prolonged stance phase due to an augmented double-support. Variability of gait cycle and stance phase increased only during the most demanding dual-task. Dual tasking resulted in a reduced cognitive score. Usability feedback were excellent, with users reporting to understand the usefulness of the devised system and to feel at ease when using the system and the insoles. SIGNIFICANCE: This work paves the way toward fruitful applications of the devised system to achieve accurate and ecological monitoring of daily-life walking activities, with the final aim of detecting early and subtle alterations of gait.

A review of gait disorders in the elderly and neurological patients for robot-assisted training.

Purpose: Ambulation is an important objective for people with pathological gaits. Exoskeleton robots can assist these people to complete their activities of daily living. There are exoskeletons that have been presented in literature to assist the elderly and other pathological gait users. This article presents a review of the degree of support required in the elderly and neurological gait disorders found in the human population. This will help to advance the design of robot-assisted devices based on the needs of the end users.Methods: The articles included in this review are collected from different databases including Science Direct, Springer Link, Web of Science, Medline and PubMed and with the purpose to investigate the gait parameters of elderly and neurological patients. Studies were included after considering the full texts and only those which focus on spatiotemporal, kinematic and kinetic gait parameters were selected as they are most relevant to the scope of this review. A systematic review and meta-analysis were conducted.Results: The meta-analysis report on the spatiotemporal, kinematic and kinetic gait parameters of elderly and neurological patients revealed a significant difference based on the type and level of impairment. Healthy elderly population showed deviations in the gait parameters due to age, however, significant difference is observed in the gait parameters of the neurological patients.Conclusion: A level of agreement was observed in most of the studies however the review also noticed some controversies among different studies in the same group. The review on the spatiotemporal, kinematics and kinetic gait parameters will provide a summary of the fundamental needs of the users for the future design and development of robotic assistive devices.Implications for rehabilitationThe support requirements provide the foundation for designing assistive devices.The findings will be crucial in defining the design criteria for robot assistive devices.

Adjusting gait step-by-step: Brain activation during split-belt treadmill walking.

When walking on a split-belt treadmill, where each leg is driven at a different speed, a temporary change is made to the typical steady-state walking pattern. The exact ways in which the brain controls these temporary changes to walking are still unknown. Ten young adults (23±3y) walked on a split-belt treadmill for 30 min on 2 separate occasions: tied-belt control with both belts at comfortable walking speed, and continuous adjustment where speed ratio between belts changed every 15 seconds. 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET) imaging measured whole brain glucose metabolism distribution, or activation, during each treadmill walking condition. The continuous adjustment condition, compared to the tied-belt control, was associated with increased activity of supplementary motor areas (SMA), posterior parietal cortex (PPC), anterior cingulate cortex and anterior lateral cerebellum, and decreased activity of posterior cingulate and medial prefrontal cortex. In addition, peak activation of the PPC, SMA and PFC were correlated with cadence and temporal gait variability. We propose that a "fine-tuning" network for human locomotion exists which includes brain areas for sensorimotor integration, motor planning and goal directed attention. These findings suggest that distinct regions govern the inherent flexibility of the human locomotor plan to maintain a successful and adjustable walking pattern.

Hyponatremia, falls and bone fractures: A systematic review and meta-analysis.

OBJECTIVE: To perform a meta-analysis based on published studies that compared falls and bone fractures between patients with and without hyponatremia. CONTEXT: There is evidence suggesting that hyponatremia is associated with an increased risk of falls and bone fractures. DESIGN: An extensive Medline, Embase and Cochrane search was performed to retrieve all studies published up to, 30 April 2017, using the following words: "hyponatremia" or "hyponatraemia" AND "falls" and "bone fractures." A meta-analysis was performed including all studies comparing falls and bone fractures in subjects with or without hyponatremia. PATIENTS AND RESULTS: Of 216 retrieved articles, 15 studies satisfied inclusion criteria encompassing a total of 51 879 patients, of whom 2329 were hyponatremic. Across all studies, hyponatremia was associated with a significantly increased risk of falls (MH-OR = 2.14[1.71; 2.67]. This result was confirmed when only hospitalized patients were considered (MH-OR = 2.44 [1.97; 3.02]). A meta-regression analysis showed that the hyponatremia-related risk of falls was higher in those studies considering a lower serum [Na+ ] cut-off to define hyponatremia. Interestingly, the estimated risk of falls related to hyponatremia was already significantly higher when a serum [Na+ ] cut-off of 135 mmol/L was considered (MH-OR = 1.26[1.23;1.29]). The presence of hyponatremia was also associated with a higher risk of fractures, particularly hip fractures (MH-OR = 2.00[1.43;2.81]). CONCLUSIONS: This study confirms that hyponatremia is associated with an increased risk of falls and bone fractures. The clinical, social and economic relevance of such association is strengthened by the increased incidence of hyponatremia in older people.

Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve injury.

Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing hNF-L(E397K), which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we challenged wild type, hNF-L and hNF-L(E397K) mice with crush injury to the sciatic nerve. We analyzed functional recovery by measuring toe spread and analyzed gait using the Catwalk system. hNF-L(E397K) mice demonstrated reduced recovery from nerve injury consistent with increased susceptibility to neuropathy observed in CMT patients. In addition, hNF-L(E397K) developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-L(E397K). Exacerbation of neuropathy after injury and identification of gait alterations in combination with previously described pathology suggests that hNF-L(E397K) mice recapitulate many of clinical signs associated with CMT2. Therefore, hNF-L(E397K) mice provide a model for determining the efficacy of novel therapies.