Misfits Meet Art and Technology: Cripping Transmethodologies.

This article thinks with disability theory and artistic praxis to explore how disabled artists repurpose and invent technologies in artistic processes designed to enact care and access, extend embodiment, satiate the senses, and create crip culture. Drawing on four examples, we claim that disabled artists are creative technologists whose non-normative culture-making practices approach accessibility as a transmethodological process that requires and generates new forms of interconnected technology and artfulness. Disabled artists, as "creative users," change the uses and outcomes of technology, dis-using technologies in ways that lead to a more dynamic understanding of access and with it, of crip cultures as processual, artful, and political.

PASSIVE BICYCLE TRAINING STIMULATES EPIPHYSEAL BONE FORMATION AND RESTORES BONE INTEGRITY INDEPENDENT OF LOCOMOTOR RECOVERY IN A RAT SPINAL CORD INJURY MODEL.

It is unknown whether activity-based physical therapy (ABPT) modalities that mobilize the paralyzed limbs improve bone integrity at the highly fracture-prone epiphyseal regions of the distal femur and proximal tibia following severe spinal cord injury (SCI). In this study, four-months-old skeletally-mature littermate-matched male Sprague-Dawley rats received SHAM surgery or severe contusion SCI. At 1-week post-surgery, SCI rats were stratified to undergo no-ABPT or two 20-minute bouts/day of quadrupedal bodyweight-supported treadmill training (qBWSTT) or hindlimb passive-isokinetic bicycle (Cycle) training, 5-days/week for another 3-weeks. We assessed locomotor recovery and plantar flexor muscle mass, tracked cancellous and cortical bone microstructure at the distal femoral and proximal tibial epiphyses using in vivo microCT, and evaluated bone turnover at the tibial epiphysis with histomorphometry. All SCI animals displayed persistent hindlimb paralysis and pervasive muscle atrophy. Over the initial 2-weeks, which included 1-week of no exercise and 1-week of ABPT acclimation, a similar magnitude of bone loss developed in all SCI groups. Thereafter, cancellous bone loss and cortical bone decrements increased in the SCI no-ABPT group. qBWSTT attenuated this trabecular bone loss but did not prevent the ongoing cortical bone deficits. In comparison, twice-daily Cycle training increased the number and activity of osteoblasts vs other SCI groups and restored all bone microstructural parameters to SHAM levels at both epiphyseal sites. These data indicate that a novel passive-isokinetic Cycle training regimen reversed cancellous and cortical bone deterioration at key epiphyseal sites after experimental SCI, via osteoblast-mediated bone anabolic mechanisms, independent of locomotor recovery or increased muscle mass.

Hindlimb immobilization induces insulin resistance and elevates mitochondrial ROS production in the hippocampus of female rats.

Alzheimer's Disease (AD) is the 5th leading cause of death in older adults and treatment options are severely lacking. Recent findings demonstrate a strong relationship between skeletal muscle and cognitive function, with evidence supporting that muscle quality and cognitive function are positively correlated in older adults. Conversely, decreased muscle function is associated with a 3-fold increased risk of cognitive decline. Based on these observations, the purpose of this study was to investigate the negative effects of muscle disuse (via a model of hindlimb immobilization (HLI)) on hippocampal insulin sensitivity and mitochondrial function and identify the potential mechanisms involved. HLI for 10 days in 4-month-old female Wistar rats resulted in the following novel findings: 1) hippocampal insulin resistance and deficits in whole body glucose homeostasis, 2) dramatically increased mitochondrial reactive oxygen species (ROS) production in the hippocampus, 3) elevated markers for amyloidogenic cleavage of APP and tau protein in the hippocampus, 4) and reduced BDNF expression. These findings were associated with global changes in iron homeostasis, with muscle disuse producing muscle iron accumulation in association with decreased serum and whole brain iron levels. We report the novel finding that muscle disuse alters brain iron homeostasis and reveal a strong negative correlation between muscle and brain iron content. Overall, HLI-induced muscle disuse has robust negative effects on hippocampal insulin sensitivity and ROS production in association with altered brain iron homeostasis. This work provides potential novel mechanisms that may help explain how loss of muscle function contributes to cognitive decline and AD risk.

Sex similarities and divergences in systemic and muscle iron metabolism adaptations to extreme physical inactivity in rats.

BACKGROUND: Previous data in humans suggest that extreme physical inactivity (EPI) affects iron metabolism differently between sexes. Our objective was to deepen the underlying mechanisms by studying rats of both sexes exposed to hindlimb unloading (HU), the reference experimental model mimicking EPI. METHODS: Eight-week-old male and female Wistar rats were assigned to control (CTL) or hindlimb unloading (HU) conditions (n = 12/group). After 7 days of HU, serum, liver, spleen, and soleus muscle were removed. Iron parameters were measured in serum samples, and ICP-MS was used to quantify iron in tissues. Iron metabolism genes and proteins were analysed by RT-qPCR and Western blot. RESULTS: Compared with control males, control females exhibited higher iron concentrations in serum (+43.3%, p < 0.001), liver (LIC; +198%, P < 0.001), spleen (SIC; +76.1%, P < 0.001), and transferrin saturation (TS) in serum (+53.3%, P < 0.001), contrasting with previous observations in humans. HU rat males, but not females, exhibited an increase of LIC (+54% P < 0.001) and SIC (+30.1%, P = 0.023), along with a rise of H-ferritin protein levels (+60.9% and +134%, respectively, in liver and spleen; P < 0.05) and a decrease of TFRC protein levels (-36%; -50%, respectively, P < 0.05). HU males also exhibited an increase of splenic HO-1 and NRF2 mRNA levels, (p < 0.001), as well as HU females (P < 0.001). Concomitantly to muscle atrophy observed in HU animals, the iron concentration increased in soleus in females (+26.7, P = 0.004) while only a trend is observed in males (+17.5%, P = 0.088). In addition, the H-ferritin and myoglobin protein levels in soleus were increased in males (+748%, P < 0.001, +22%, P = 0.011, respectively) and in females (+369%, P < 0.001, +21.9%, P = 0.007, respectively), whereas TFRC and ferroportin (FPN) protein levels were reduced in males (-68.9%, P < 0.001, -76.8%, P < 0.001, respectively) and females (-75.9%, P < 0.001, -62.9%, P < 0.001, respectively). Interestingly, in both sexes, heme exporter FLVCR1 mRNA increased in soleus, while protein levels decreased (-39.9% for males P = 0.010 and -49.1% for females P < 0.001). CONCLUSIONS: Taken together, these data support that, in rats (1) extreme physical inactivity differently impacts the distribution of iron in both sexes, (2) splenic erythrophagocytosis could play a role in this iron misdistribution. The higher iron concentrations in atrophied soleus from both sexes are associated with a decoupling between the increase in iron storage proteins (i.e., ferritin and myoglobin) and the decrease in levels of iron export proteins (i.e., FPN and FLVCR1), thus supporting an iron sequestration in skeletal muscle under extreme physical inactivity.

Type 2 diabetes mellitus related sarcopenia: a type of muscle loss distinct from sarcopenia and disuse muscle atrophy.

Muscle loss is a significant health concern, particularly with the increasing trend of population aging, and sarcopenia has emerged as a common pathological process of muscle loss in the elderly. Currently, there has been significant progress in the research on sarcopenia, including in-depth analysis of the mechanisms underlying sarcopenia caused by aging and the development of corresponding diagnostic criteria, forming a relatively complete system. However, as research on sarcopenia progresses, the concept of secondary sarcopenia has also been proposed. Due to the incomplete understanding of muscle loss caused by chronic diseases, there are various limitations in epidemiological, basic, and clinical research. As a result, a comprehensive concept and diagnostic system have not yet been established, which greatly hinders the prevention and treatment of the disease. This review focuses on Type 2 Diabetes Mellitus (T2DM)-related sarcopenia, comparing its similarities and differences with sarcopenia and disuse muscle atrophy. The review show significant differences between the three muscle-related issues in terms of pathological changes, epidemiology and clinical manifestations, etiology, and preventive and therapeutic strategies. Unlike sarcopenia, T2DM-related sarcopenia is characterized by a reduction in type I fibers, and it differs from disuse muscle atrophy as well. The mechanism involving insulin resistance, inflammatory status, and oxidative stress remains unclear. Therefore, future research should further explore the etiology, disease progression, and prognosis of T2DM-related sarcopenia, and develop targeted diagnostic criteria and effective preventive and therapeutic strategies to better address the muscle-related issues faced by T2DM patients and improve their quality of life and overall health.

Remobilization with whole-body vibration improves functionality, histomorphometric parameters, and AQP1 expression in the soleus muscle of Wistar rats.

Background: Whole-body vibration (WBV) is used to enhance physical performance in sports and rehabilitation. The present study analyzed the effects of remobilization with WBV on the soleus muscle of Wistar rats. Methods: Twenty-eight animals were separated into four experimental groups (n = 7): CON (control); IM (immobilized); FR (immobilization and free remobilization); and WBV (immobilization and remobilization with WBV). The immobilization of the pelvic limb was carried out according to the standard protocol using a plaster cast for 15 days. For remobilization with WBV, a Frequency of 60 Hz was applied for 10 min, five days a week, for two weeks. After the remobilization period, the animals were euthanized, and the right soleus muscle was dissected followed by processing for histomorphometric analysis and immunolocalization of Aquaporin 1 (AQP1). Results: We observed a reduced larger diameter in IM compared to CON, with restored values in WBV. For the estimation of connective tissue, a significant increase was observed in the immobilized groups, while a reduction was noted in the remobilized groups. AQP1 expression decreased significantly in IM and increased in WBV. Conclusion: Immobilization caused morphofunctional damage to the soleus muscle, and remobilization with WBV is efficient and offers advantages over free remobilization.

Changes in brain functional connectivity and muscle strength independent of elbow flexor atrophy following upper limb immobilization in young females.

Muscle disuse induces a decline in muscle strength that exceeds the rate and magnitude of muscle atrophy, suggesting that factors beyond the muscle contribute to strength loss. The purpose of this study was to characterize changes in the brain and neuromuscular system in addition to muscle size following upper limb immobilization in young females. Using a within-participant, unilateral design, 12 females (age: 20.6 ± 2.1 years) underwent 14 days of upper arm immobilization using an elbow brace and sling. Bilateral measures of muscle strength (isometric and isokinetic dynamometry), muscle size (magnetic resonance imaging), voluntary muscle activation capacity, corticospinal excitability, cortical thickness and resting-state functional connectivity were collected before and after immobilization. Immobilization induced a significant decline in isometric elbow flexion (-21.3 ± 19.2%, interaction: P = 0.0440) and extension (-19.9 ± 15.7%, interaction: P = 0.0317) strength in the immobilized arm only. There was no significant effect of immobilization on elbow flexor cross-sectional area (CSA) (-1.2 ± 2.4%, interaction: P = 0.466), whereas elbow extensor CSA decreased (-2.9 ± 2.9%, interaction: P = 0.0177) in the immobilized arm. Immobilization did not differentially alter voluntary activation capacity, corticospinal excitability, or cortical thickness (P > 0.05); however, there were significant changes in the functional connectivity of brain regions related to movement planning and error detection (P < 0.05). This study reveals that elbow flexor strength loss can occur in the absence of significant elbow flexor muscle atrophy, and that the brain represents a site of functional adaptation in response to upper limb immobilization in young females.

Skeletal muscle immobilisation-induced atrophy: mechanistic insights from human studies.

Periods of skeletal muscle disuse lead to rapid declines in muscle mass (atrophy), which is fundamentally underpinned by an imbalance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). The complex interplay of molecular mechanisms contributing to the altered regulation of muscle protein balance during disuse have been investigated but rarely synthesised in the context of humans. This narrative review discusses human models of muscle disuse and the ensuing inversely exponential rate of muscle atrophy. The molecular processes contributing to altered protein balance are explored, with a particular focus on growth and breakdown signalling pathways, mitochondrial adaptations and neuromuscular dysfunction. Finally, key research gaps within the disuse atrophy literature are highlighted providing future avenues to enhance our mechanistic understanding of human disuse atrophy.

Decreased and Improved Movement Abilities in a Case of Myotonic Dystrophy Type 1: Examining Longitudinal Characteristics Based on Repeated Evaluations.

Several large longitudinal studies on myotonic dystrophy type 1 (DM1) patients have revealed that proximal muscles show more gradual muscle weakness than distal muscles and that the progression of muscle weakness might differ between the sexes. However, these longitudinal studies were based on two follow-up time points. The present report aimed to verify the longitudinal characteristics of muscle strength and various movement abilities in a case of DM1 by examining the results of 44 repeated evaluations for approximately two years. A 40-year-old male patient with DM1 could walk independently without any aid. We recorded the longitudinal changes in his muscle strength and movement ability during outpatient rehabilitation. During follow-up, he had a fall and was diagnosed with a right ankle sprain. To evaluate the effects of the fall, we examined his recorded data. He had a significant decrease in right knee extensor muscle strength after the fall, suggesting muscle weakness due to disuse syndrome. Although his right knee extensor muscle strength and walking speed decreased, the timed up-and-go test score was improved, and walking endurance in the 2-minute walk test was maintained. In the present case, there were some motor tasks in which the movement ability was maintained or improved, likely due to the use of compensation by residual function, even when muscle weakness was present. Regular and repeated evaluations of patients with DM1 lead to reveal longitudinal characteristics of their dysfunction and movement ability.

A multimodal exercise countermeasure prevents the negative impact of head-down tilt bed rest on muscle volume and mitochondrial health in older adults.

Mitochondrial dysfunctions are thought to contribute to muscle atrophy and weakness that develop during ageing and mechanical unloading caused by immobilization, bed rest and microgravity. Older adults are at greater risk of developing muscle and mitochondrial dysfunctions in response to unloading. Although exercise is well known to promote muscle and mitochondrial health, its protective effect during mechanical unloading in older adults remains largely unexplored. Here, we investigated the impact of 14 days of head-down tilt bed rest (HDBR) with and without a multimodal exercise countermeasure in older men and women (55-65 years). Leg muscle volume was assessed using magnetic resonance imaging. Biopsies of the vastus lateralis were performed to assess markers of mitochondrial content, respiration, reactive oxygen species (ROS) production and calcium retention capacity (mCRC). Indices of mitochondrial quality control (MQC), including markers of fusion (MFN1 and 2), fission (Drp1), mitophagy (Parkin) and autophagy (p62 and LC3I and II) were measured using immunoblots. Muscle cross-sections were stained for neural cell adhesion molecule (NCAM, a marker of denervation). HDBR triggered muscle atrophy, decreased mitochondrial content and respiration and increased mitochondrial ROS production. HDBR had no impact on mCRC or MQC markers but increased markers of autophagy and denervation. Exercise prevented the deleterious effects of HDBR on leg muscle volume, mitochondrial ROS production and markers of autophagy and denervation. Exercise also increased mitochondrial content and respiration without altering mCRC and MQC markers. Collectively, our results indicate that an exercise countermeasure that can be performed in bed is effective in protecting muscle and mitochondrial health during HDBR in older adults. KEY POINTS: Conditions associated with muscle unloading, such as immobilization, bed rest or microgravity, result in muscle atrophy and weakness, particularly in older adults. Mitochondrial dysfunctions are thought to contribute to muscle atrophy caused by unloading and ageing. However, whether exercise can counteract the deleterious effects of unloading in older adults remains largely unexplored. Here, we report that older adults exposed to 14 days of head-down tilt bed rest (HDBR) displayed upper leg muscle atrophy, a decrease in mitochondrial content and respiration, an increase in H2O2 emission, and an increase in autophagy and denervation markers. No impact of HDBR on mitochondrial quality control was observed. A multimodal exercise countermeasure prevented the deleterious effects of HDBR on upper leg muscle volume, mitochondrial reactive oxygen species emission, and markers of autophagy and denervation and increased mitochondrial content and respiration. These findings highlight the effectiveness of exercise in promoting muscle and mitochondrial health in older adults undergoing bed rest.

Physiological comparison of conditioned and non-conditioned university horses following semester break.

Periods of limited activity during semester break may reduce performance during return to ridden work. This study evaluated fitness and muscling of horses when returning to work, following a 12-week period during which horses either continued (conditioned) or discontinued (non-conditioned) ridden work. It was hypothesized that non-conditioned horses would have a lower level of fitness, resulting in higher resting and peak heart rates and lower levels of muscling. Twelve mature, stock type horses aged 16 ± 5 years were assigned to either a conditioned group that maintained light-to-moderate riding or a non-conditioned group receiving no formal exercise. All horses had access to voluntary exercise for 12-24hr/d on grass pasture (1.5-2.5 hectares). Following the 12-week period, all horses were placed into a light-to-moderate intensity exercise program with resting heart rate, peak heart rate, body condition score, gaskin and forearm circumference, and topline muscle measurements performed on d 0, 14, and 28. Peak and resting heart rates were not different between groups (P > 0.05) but increased for both groups throughout the study (P = 0.04). Gaskin circumference of non-conditioned horses was larger (P = 0.04), although non-conditioned horses tended to be heavier (551.4 versus 491.4 ± 21.4 kg; P = 0.07). Conditioned horses had greater average topline muscling scores (P = 0.02). Horses that were conditioned over a 12-week break had greater muscling, but changes in fitness were not detected. Pasture access could contribute to maintenance of fitness during unridden periods.

Measurement of Knee Extensor Torque During Repetitive Peripheral Magnetic Stimulation: Comparison of the Forces Induced by Different Stimulators.

OBJECTIVE: To investigate the factors that induce strong contractions during repetitive peripheral magnetic stimulation (rPMS) and compare the muscle torque induced by two stimulators (Stim A and Stim B) with different coil properties. METHODS: rPMS was applied to the right vastus lateralis of 30 healthy young adults. Stim A contained a 10.1 cm2 rectangular iron core coil, while Stim B contained a 191 cm2 round coil. The knee extensor torque (KET) induced by rPMS at 30 Hz was measured isometrically and divided by the maximum voluntary contraction (MVC) to obtain a relative value of MVC (%MVC). KET at 100% intensity of Stim A (A100%, 1.08 T) was compared to those at 100% or 70% intensity of Stim B (B100%, 1.47 T vs. B70%, 1.07 T). Additionally, we conducted a comprehensive literature search for studies that measured the KET during rPMS. RESULTS: Both the mean values of %MVC using B100% and B70% were significantly greater than that using A100%. Furthermore, the KET induced by Stim B was found to be larger than that described in previous reports, unless booster units were used to directly stimulate the main trunk of the femoral nerve. CONCLUSION: Stim B induced a stronger muscle contraction force than Stim A did. This may be because the larger the coil area, the wider the area that can be stimulated. Additionally, a circular coil allows for deeper stimulation.

Transcriptomics reveals transient and dynamic muscle fibrosis and atrophy differences following spinal cord injury in rats.

BACKGROUND: The rate and magnitude of skeletal muscle wasting after severe spinal cord injury (SCI) exceeds most other disuse conditions. Assessing the time course of molecular changes can provide insight into the progression of muscle wasting post-SCI. The goals of this study were (1) to identify potential targets that may prevent the pathologic features of SCI in soleus muscles and (2) to establish therapeutic windows for treating these pathologic changes. METHODS: Four-month-old Sprague-Dawley male rats received T9 laminectomy (SHAM surgery) or severe contusion SCI. Hindlimb locomotor function was assessed weekly, with soleus muscles obtained 1 week, 2 weeks, 1 month and 3 months post-surgery (n = 6-7 per group per timepoint). RNA was extracted from muscles for bulk RNA-sequencing analysis (n = 3-5 per group per timepoint). Differentially expressed genes (DEGs) were evaluated between age-matched SHAM and SCI animals. Myofiber size, muscle fibre type and fibrosis were assessed on contralateral muscles. RESULTS: SCI produced immediate and persistent hindlimb paralysis, with Basso-Beattie-Bresnahan locomotor scores remaining below 7 throughout the study, contributing to a progressive 25-50% lower soleus mass and myofiber atrophy versus SHAM (P < 0.05 at all timepoints). Transcriptional comparisons of SCI versus SHAM resulted in 184 DEGs (1 week), 436 DEGs (2 weeks), 133 DEGs (1 month) and 1200 DEGs (3 months). Upregulated atrophy-related genes included those associated with cell senescence, nuclear factor kappa B, ubiquitin proteasome and unfolded protein response pathways, along with upregulated genes that negatively influence muscle growth through the transforming growth factor beta pathway and inhibition of insulin-like growth factor-I/Akt/mechanistic target of rapamycin and p38/mitogen-activated protein kinase signalling. Genes associated with extracellular matrix (ECM), including collagens, collagen crosslinkers, proteoglycans and those regulating ECM integrity, were enriched within upregulated DEGs at 1 week but subsequently downregulated at 2 weeks and 3 months and were accompanied by >50% higher ECM areas and hydroxyproline levels in SCI muscles (P < 0.05). Myofiber remodelling genes were enriched in upregulated DEGs at 2 weeks and 1 month and were downregulated at 3 months. Genes that regulate neuromuscular junction remodelling were evident in muscles post-SCI, along with slow-to-fast fibre-type shifts: 1 week and 2 weeks SCI muscles were composed of 90% myosin heavy chain (MHC) type I fibres, which decreased to only 16% at 3 months and were accompanied by 50% fibres containing MHC IIX (P < 0.05). Metabolism genes were enriched in upregulated DEGs at 1 month and were further enriched at 3 months. CONCLUSIONS: Our results substantiate many known pathologic features of SCI-induced wasting in rat skeletal muscle and identify a progressive and dynamic transcriptional landscape within the post-SCI soleus. Future studies are warranted to consider these therapeutic treatment windows when countering SCI muscle pathology.

Deciphering the Therapeutic Role of Lactate in Combating Disuse-Induced Muscle Atrophy: An NMR-Based Metabolomic Study in Mice.

Disuse muscle atrophy (DMA) is a significant healthcare challenge characterized by progressive loss of muscle mass and function resulting from prolonged inactivity. The development of effective strategies for muscle recovery is essential. In this study, we established a DMA mouse model through hindlimb suspension to evaluate the therapeutic potential of lactate in alleviating the detrimental effects on the gastrocnemius muscle. Using NMR-based metabolomic analysis, we investigated the metabolic changes in DMA-injured gastrocnemius muscles compared to controls and evaluated the beneficial effects of lactate treatment. Our results show that lactate significantly reduced muscle mass loss and improved muscle function by downregulating Murf1 expression, decreasing protein ubiquitination and hydrolysis, and increasing myosin heavy chain levels. Crucially, lactate corrected perturbations in four key metabolic pathways in the DMA gastrocnemius: the biosynthesis of phenylalanine, tyrosine, and tryptophan; phenylalanine metabolism; histidine metabolism; and arginine and proline metabolism. In addition to phenylalanine-related pathways, lactate also plays a role in regulating branched-chain amino acid metabolism and energy metabolism. Notably, lactate treatment normalized the levels of eight essential metabolites in DMA mice, underscoring its potential as a therapeutic agent against the consequences of prolonged inactivity and muscle wasting. This study not only advances our understanding of the therapeutic benefits of lactate but also provides a foundation for novel treatment approaches aimed at metabolic restoration and muscle recovery in conditions of muscle wasting.

Navigating Post-Traumatic Osteoporosis: A Comprehensive Review of Epidemiology, Pathophysiology, Diagnosis, Treatment, and Future Directions.

Post-traumatic osteoporosis (PTO) presents a significant challenge in clinical practice, characterized by demineralization and decreased skeletal integrity following severe traumatic injuries. This literature review manuscript addresses the knowledge gaps surrounding PTO, encompassing its epidemiology, pathophysiology, risk factors, diagnosis, treatment, prognosis, and future directions. This review emphasizes the complexity of the etiology of PTO, highlighting the dysregulation of biomineralization processes, inflammatory cytokine involvement, hormonal imbalances, glucocorticoid effects, vitamin D deficiency, and disuse osteoporosis. Moreover, it underscores the importance of multidisciplinary approaches for risk mitigation and advocates for improved diagnostic strategies to differentiate PTO from other musculoskeletal pathologies. This manuscript discusses various treatment modalities, including pharmacotherapy, dietary management, and physical rehabilitation, while also acknowledging the limited evidence on their long-term effectiveness and outcomes in PTO patients. Future directions in research are outlined, emphasizing the need for a deeper understanding of the molecular mechanisms underlying PTO and the evaluation of treatment strategies' efficacy. Overall, this review provides a comprehensive overview of PTO and highlights avenues for future investigation to enhance clinical management and patient outcomes.

Optimal fibre length and maximum isometric force are the most influential parameters when modelling muscular adaptations to unloading using Hill-type muscle models.

Introduction: Spaceflight is associated with severe muscular adaptations with substantial inter-individual variability. A Hill-type muscle model is a common method to replicate muscle physiology in musculoskeletal simulations, but little is known about how the underlying parameters should be adjusted to model adaptations to unloading. The aim of this study was to determine how Hill-type muscle model parameters should be adjusted to model disuse muscular adaptations. Methods: Isokinetic dynamometer data were taken from a bed rest campaign and used to perform tracking simulations at two knee extension angular velocities (30°·s-1 and 180°·s-1). The activation and contraction dynamics were solved using an optimal control approach and direct collocation method. A Monte Carlo sampling technique was used to perturb muscle model parameters within physiological boundaries to create a range of theoretical and feasible parameters to model muscle adaptations. Results: Optimal fibre length could not be shortened by more than 67% and 61% for the knee flexors and non-knee muscles, respectively. Discussion: The Hill-type muscle model successfully replicated muscular adaptations due to unloading, and recreated salient features of muscle behaviour associated with spaceflight, such as altered force-length behaviour. Future researchers should carefully adjust the optimal fibre lengths of their muscle-models when trying to model adaptations to unloading, particularly muscles that primarily operate on the ascending and descending limbs of the force-length relationship.

Disuse-Induced Muscle Fatigue: Facts and Assumptions.

Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which include increased fatigue. The mechanisms of unloading-induced fatigue are far from complete understanding and cannot be explained by muscle atrophy only. In this review, we summarize the data concerning unloading-induced fatigue in different muscles and different unloading models and provide several potential mechanisms of unloading-induced fatigue based on recent experimental data. The unloading-induced changes leading to increased fatigue include both neurobiological and intramuscular processes. The development of intramuscular fatigue seems to be mainly contributed by the transformation of soleus muscle fibers from a fatigue-resistant, "oxidative" "slow" phenotype to a "fast" "glycolytic" one. This process includes slow-to-fast fiber-type shift and mitochondrial density decline, as well as the disruption of activating signaling interconnections between slow-type myosin expression and mitochondrial biogenesis. A vast pool of relevant literature suggests that these events are triggered by the inactivation of muscle fibers in the early stages of muscle unloading, leading to the accumulation of high-energy phosphates and calcium ions in the myoplasm, as well as NO decrease. Disturbance of these secondary messengers leads to structural changes in muscles that, in turn, cause increased fatigue.

Reduced osseointegration in disuse and denervation rat models results from impaired cellular responses to multiscale microstructured titanium surfaces.

Immobilization-induced skeletal unloading results in muscle atrophy and rapid bone loss, thereby increasing the risk of falling and the need for implant therapy in patients with extended bed rest or neuromuscular injuries. Skeletal unloading causes bone loss by altering bone growth and resorption, suggesting that implant performance might be affected. To test this, we focused on early events in implant osseointegration. We used the rat sciatic neurectomy-induced disuse model under two different settings. In Study 1, 16 Sprague Dawley rats (SD) were separated into control, sham operated+cast immobilization, and sciatic neurectomy+casting groups; titanium implants with multiscale microtextured topography and hydrophilic chemistry (modSLA) were inserted in the distal femoral metaphysis. Neurectomy surgeries and casting were performed at the same surgical setting as implant placement; rats were euthanized 4 weeks post-implantation. In Study 2, we established the unloaded condition before implantation. A total of 12 SD rats were divided into control and sciatic+femoral neurectomy groups. A total of 24 days after sciatic and femoral neurectomy surgery, rats received implants. Study 2 rats were euthanized at 4 weeks post-implantation. MicroCT and histomorphometry showed that trabecular bone and osseointegration were reduced when disuse was established before implantation. Osteoblasts isolated from Study 1 sciatic neurectomy tibial bones exhibited impaired differentiation on modSLA culture disks, revealing a possible mechanism responsible for the decreased osseointegration observed in the Study 2 rats. This study addressed the importance of considering the mechanical unloading and muscle function history before implant insertion and suggests that implant performance was reduced due to poor cellular ability to regenerate.

Combined action observation and mental imagery versus neuromuscular electrical stimulation as novel therapeutics during short-term knee immobilization.

Limb immobilization causes rapid declines in muscle strength and mass. Given the role of the nervous system in immobilization-induced weakness, targeted interventions may be able to preserve muscle strength, but not mass, and vice versa. The purpose of this study was to assess the effects of two distinct interventions during 1 week of knee joint immobilization on muscle strength (isometric and concentric isokinetic peak torque), mass (bioimpedance spectroscopy and ultrasonography), and neuromuscular function (transcranial magnetic stimulation and interpolated twitch technique). Thirty-nine healthy, college-aged adults (21 males, 18 females) were randomized into one of four groups: immobilization only (n = 9), immobilization + action observation/mental imagery (AOMI) (n = 10), immobilization + neuromuscular electrical stimulation (NMES) (n = 12), or control group (n = 8). The AOMI group performed daily video observation and mental imagery of knee extensions. The NMES group performed twice daily stimulation of the quadriceps femoris. Based on observed effect sizes, it appears that AOMI shows promise as a means of preserving voluntary strength, which may be modulated by neural adaptations. Strength increased from PRE to POST in the AOMI group, with +7.2% (Cohen's d = 1.018) increase in concentric isokinetic peak torque at 30°/s. However, NMES did not preserve muscle mass. Though preliminary, our findings highlight the specific nature of clinical interventions and suggest that muscle strength can be independently targeted during rehabilitation. This study was prospectively registered: ClinicalTrials.gov NCT05072652.

A conceptual framework for automation disengagements.

A better understanding of automation disengagements can lead to improved safety and efficiency of automated systems. This study investigates the factors contributing to automation disengagements initiated by human operators and the automation itself by analyzing semi-structured interviews with 103 users of Tesla's Autopilot and FSD Beta. The factors leading to automation disengagements are represented by categories. In total, we identified five main categories, and thirty-five subcategories. The main categories include human operator states (5), human operator's perception of the automation (17), human operator's perception of other humans (3), the automation's perception of the human operator (3), and the automation incapability in the environment (7). Human operators disengaged the automation when they anticipated failure, observed unnatural or unwanted automation behavior (e.g., erratic steering, running red lights), or believed the automation is not capable to operate safely in certain environments (e.g., inclement weather, non-standard roads). Negative experiences of human operators, such as frustration, unsafe feelings, and distrust represent some of the adverse human operate states leading to automation disengagements initiated by human operators. The automation, in turn, monitored human operators and disengaged itself if it detected insufficient vigilance or speed rule violations by human operators. Moreover, human operators can be influenced by the reactions of passengers and other road users, leading them to disengage the automation if they sensed discomfort, anger, or embarrassment due to the automation's actions. The results of the analysis are synthesized into a conceptual framework for automation disengagements, borrowing ideas from the human factor's literature and control theory. This research offers insights into the factors contributing to automation disengagements, and highlights not only the concerns of human operators but also the social aspects of this phenomenon. The findings provide information on potential edge cases of automated vehicle technology, which may help to enhance the safety and efficiency of such systems.