Understanding the impact of radical changes in diet and the gut microbiota on brain function and structure: rationale and design of the EMBRACE study.

BACKGROUND: Bariatric surgery leads to profound changes in gut microbiota and dietary patterns, both of which may interact to impact gut-brain communication. Though cognitive function improves postsurgery, there is a large variability in outcomes. How bariatric surgery-induced modifications in the gut microbiota and dietary patterns influence the variability in cognitive function is still unclear. OBJECTIVES: To elucidate the associations between bariatric surgery-induced changes in dietary and gut microbiota patterns with cognition and brain structure. SETTING: University hospital. METHODS: A total of 120 adult patients (≥30 years) scheduled to undergo a primary bariatric surgery along with 60 age-, sex-, and body mass index-matched patients on the surgery waitlist will undergo assessments 3-months presurgery and 6- and 12-month postsurgery (or an equivalent time for the waitlist group). Additionally, 60 age-and sex-matched nonbariatric surgery eligible individuals will complete the presurgical assessments only. Evaluations will include sociodemographic and health behavior questionnaires, physiological assessments (anthropometrics, blood-, urine-, and fecal-based measures), neuropsychological cognitive tests, and structural magnetic resonance imaging. Cluster analyses of the dietary and gut microbiota changes will define the various dietary patterns and microbiota profiles, then using repeated measures mixed models, their associations with global cognitive and structural brain alterations will be explored. RESULTS: The coordinating study site (Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, QC, Canada), provided the primary ethical approval (Research Ethics Board#: MP-32-2022-2412). CONCLUSIONS: The insights generated from this study can be used to develop individually-targeted neurodegenerative disease prevention strategies, as well as providing critical mechanistic information.

Regulatory Function of Sympathetic Innervation on the Endo/Lysosomal Trafficking of Acetylcholine Receptor.

Recent studies have demonstrated that neuromuscular junctions are co-innervated by sympathetic neurons. This co-innervation has been shown to be crucial for neuromuscular junction morphology and functional maintenance. To improve our understanding of how sympathetic innervation affects nerve-muscle synapse homeostasis, we here used in vivo imaging, proteomic, biochemical, and microscopic approaches to compare normal and sympathectomized mouse hindlimb muscles. Live confocal microscopy revealed reduced fiber diameters, enhanced acetylcholine receptor turnover, and increased amounts of endo/lysosomal acetylcholine-receptor-bearing vesicles. Proteomics analysis of sympathectomized skeletal muscles showed that besides massive changes in mitochondrial, sarcomeric, and ribosomal proteins, the relative abundance of vesicular trafficking markers was affected by sympathectomy. Immunofluorescence and Western blot approaches corroborated these findings and, in addition, suggested local upregulation and enrichment of endo/lysosomal progression and autophagy markers, Rab 7 and p62, at the sarcomeric regions of muscle fibers and neuromuscular junctions. In summary, these data give novel insights into the relevance of sympathetic innervation for the homeostasis of muscle and neuromuscular junctions. They are consistent with an upregulation of endocytic and autophagic trafficking at the whole muscle level and at the neuromuscular junction.

A Web-Based Physical Activity Portal for Individuals Living With a Spinal Cord Injury: Qualitative Study.

BACKGROUND: The population with a spinal cord injury (SCI) largely remains inactive following discharge from rehabilitation despite evidence on the benefits of physical activity. These individuals need to develop skills to self-manage their condition in order to prevent secondary comorbidities and rehospitalization. A Web-based physical activity portal can address this need. Few Web-based interventions incorporate theoretical frameworks, behavior change techniques, and modes of delivery into their design. OBJECTIVE: This study aimed to identify the preferred features of a Web-based self-management physical activity portal through stakeholder engagement with individuals with a spinal cord injury and health care professionals (HCPs). METHODS: An interpretative phenomenology methodology and participatory design, along with an integrated knowledge translation approach, were used to conduct this study. Convenience sampling was used to recruit individuals with an SCI living in the community, who were either interested or already engaging in physical activity, and HCPs working with individuals with an SCI, from three city-based rehabilitation sites. Individual 1-hour sessions involving navigation of an existing website and a semistructured interview were conducted with all participants. Individuals with an SCI completed a demographics questionnaire prior to the individual sessions, while demographic information of the HCPs was collected during their interviews. Additionally, all participants were asked a question on their intention to use or recommend a portal. An in-depth thematic analysis was used to derive themes from participants' responses. RESULTS: Thirteen individuals with an SCI and nine HCPs participated in the study. Five core themes emerged: (1) knowledge: guidance and barrier management; (2) possibility of achievement: the risks and benefits of physical activity and modelling; (3) self-regulation strategies: action planning, goal setting, tracking, rewards, and reminders; (4) interactivity: peers and professionals; and (5) format: appearance, language, and ease of use. The mean (median) ratings of the likelihood of promoting and using a Web-based portal tailored to individuals' needs were 9.00 (8.78) and 7.75 (7.88) for HCPs and individuals with an SCI, respectively. CONCLUSIONS: This study highlights features of an online self-management platform that can provide individuals with an SCI the motivation and volition to engage in physical activity. These findings will inform the design of a Web-based self-management physical activity portal to increase physical activity adherence and behavior change.

A Novel Optical Tissue Clearing Protocol for Mouse Skeletal Muscle to Visualize Endplates in Their Tissue Context.

Neuromuscular junctions (NMJs) mediate skeletal muscle contractions and play an important role in several neuromuscular disorders when their morphology and function are compromised. However, due to their small size and sparse distribution throughout the comparatively large, inherently opaque muscle tissue the analysis of NMJ morphology has been limited to teased fiber preparations, longitudinal muscle sections, and flat muscles. Consequently, whole mount analyses of NMJ morphology, numbers, their distribution, and assignment to a given muscle fiber have also been impossible to determine in muscle types that are frequently used in experimental paradigms. This impossibility is exacerbated by the lack of optical tissue clearing techniques that are compatible with clear and persistent NMJ stains. Here, we present MYOCLEAR, a novel and highly reproducible muscle tissue clearing protocol. Based on hydrogel-based tissue clearing methods, this protocol permits the labeling and detection of all NMJs in adult hindleg extensor digitorum longus muscles from wildtype and diseased mice. The method is also applicable to adult mouse diaphragm muscles and can be used for different staining agents, including toxins, lectins, antibodies, and nuclear dyes. It will be useful in understanding the distribution, morphological features, and muscle tissue context of NMJs in hindleg muscle whole mounts for biomedical and basic research.

Postnatal Development and Distribution of Sympathetic Innervation in Mouse Skeletal Muscle.

Vertebrate neuromuscular junctions (NMJs) have been conceived as tripartite synapses composed of motor neuron, Schwann cell, and muscle fiber. Recent work has shown the presence of sympathetic neurons in the immediate vicinity of NMJs and experimental and clinical findings suggest that this plays an eminent role in adult NMJ biology. The present study examined the postnatal development and distribution of sympathetic innervation in different muscles using immunofluorescence, confocal microscopy, and Western blot. This demonstrates the proximity of sympathetic neurons in diaphragm, extensor digitorum longus, tibialis anterior, soleus, and levator auris longus muscles. In extensor digitorum longus muscle, sympathetic innervation of NMJs was quantified from perinatal to adult stage and found to increase up to two months of age. In diaphragm muscle, an extensive network of sympathetic neurons was prominent along the characteristic central synapse band. In summary, these data demonstrate that an elaborate sympathetic innervation is present in several mouse skeletal muscles and that this is often next to NMJs. Although the presence of sympathetic neurons at the perisynaptic region of NMJs increased during postnatal development, many synapses were already close to sympathetic neurons at birth. Potential implications of these findings for treatment of neuromuscular diseases are discussed.

Optimal Combinations of Isometric Normalization Tests for the Production of Maximum Voluntary Activation of the Shoulder Muscles.

OBJECTIVE: To identify the smallest combinations of maximum voluntary isometric contraction (MVIC) tests that produce near-maximum voluntary activation (MVA) for a large proportion of participants for the shoulder girdle muscles. DESIGN: Cross-sectional study. SETTING: Research center. PARTICIPANTS: Healthy participants (N=38). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The electromyography of 12 shoulder muscles was recorded while participants performed 15 MVIC tests. The smallest combinations of MVIC tests that met our acceptance criterion (ie, produce 90% of MVA for 90% of participants) were identified. Optimal combinations were identified for each of the 12 muscles individually and for the 12 muscles simultaneously. Electromyographic activation levels of the 95th highest percentile obtained with our optimal combinations and with the Four Normalization Tests previously recommended were compared using paired t tests. RESULTS: Between 2 and 6 MVIC tests were required for each of the 12 muscles, and 12 MVIC tests were required for the 12 muscles to meet the acceptance criterion. These optimal combinations produced electromyographic activation levels of the 95th highest percentile comprised between 97% and 100% of MVA. These electromyographic activation levels were significantly higher than the electromyographic activation levels obtained with the Four Normalization Tests. CONCLUSIONS: Although the number of MVIC tests to normalize 12 shoulder muscles was increased compared with previous recommendations, the proposed method ensures that near-MVA (>90%) was obtained for a large proportion of participants (>90%). Moreover, because electromyographic activation levels of the 95th highest percentile were at least 97% of MVA, the identified combinations could reduce the interparticipant variability. The proposed combinations could help to improve electromyographic normalization and therefore reduce the misinterpretations regarding shoulder muscle activation levels.

Elucidating the scapulo-humeral rhythm calculation: 3D joint contribution method.

The scapulo-humeral rhythm quantifies shoulder joint coordination during arm elevation. The common method calculates a ratio of gleno-humeral (GH) elevation to scapulo-thoracic upward rotation angles. However the other rotations also contribute to arm elevation. The objective is to propose a 3D dynamic scapulo-humeral rhythm calculation method including all rotations of the shoulder joints and compare with the common method. Twenty-nine skin markers were placed on the trunk and dominant arm of 14 healthy males to measure shoulder kinematics. Two-way repeated measures ANOVAs were applied to compare the two methods of calculation of joint contributions and scapulo-humeral rhythm during arm elevation. Significant main effects (p < 0.05) were observed between methods in joint contribution angles and scapulo-humeral rhythms. A systematic overestimation of the GH contribution was observed when only using the GH elevation angle because the scapula is moved outside a vertical plane. Hence, the proposed 3D method to calculate the scapulo-humeral rhythm allows an improved functional shoulder evaluation.