SAFETY AND TOLERABILITY OF STRENGTH TRAINING IN SPINAL AND BULBAR MUSCULAR ATROPHY: A CASE REPORT.

Objective: Spinal and bulbar muscular atrophy is characterized by slow-progressive muscle weakness, decreased functional performance and falls. Research into the use of exercise in spinal and bulbar muscular atrophy has shown equivocal to negative results, although authors suggest that patients with spinal and bulbar muscular atrophy may benefit from both increased exercise intensity and shorter bout duration. The aim of this case report is to explore the safety of a moderate intensity strength training programme coupled with dynamic balance and function-specific training in a patient with spinal and bulbar muscular atrophy. Case report: A 56-year-old man with spinal and bulbar muscular atrophy presented with multiple falls and declining performance in physical, vocational, and recreational activities. Examination revealed several musculoskeletal impairments that were sub-clinical to mild compared with an SBMA natural history cohort. Intervention and outcome: A 15-week moderate intensity exercise programme combining weight-lifting and functional exercises was performed under clinical supervision. Exercise volume, frequency and intensity were adjusted based on patient-reported outcomes and muscle damage blood markers. Performance-based and self-reported functional improvements occurred that exceeded the minimal clinically important difference. The intervention was well tolerated and the patient nearly doubled his baseline 10-repetition maximums for weight-lifting exercises. Conclusion: Exercise therapy combining weight-lifting and upright functional training led to meaningful performance improvements in this case of a patient with spinal and bulbar muscular atrophy and relatively low disease burden.

Validation of Body-Worn Sensors for Gait Analysis During a 2-min Walk Test in Children.

Introduction: Instrumented gait mat systems have been regarded as one of the gold standard methods for measuring spatiotemporal gait parameters. However, their portable walkways confine walking to a restricted area and limit the number of gait cycles collected. Wearable inertial sensors are a potential alternative that allow more natural walking behavior and have fewer space restrictions. The objective of this pilot study was to establish the concurrent validity of body-worn sensors against the portable walkway system in older children. Methods: Twenty-one participants (10 males) 7-17 years old performed 2-min walk tests at a self-selected and fast pace in a 25-m-long hallway, while wearing three inertial sensors. Data collection were synchronized between devices and the portions of the walk when subjects passed on the walkway were used to compare gait speed, stride length, gait cycle duration, cadence, and double support time. Regression models and Bland-Altman analysis were completed to determine agreement between systems for the selected gait parameters. Results: Gait speed, cadence, gait cycle duration, and stride length as measured by inertial sensors demonstrated strong agreement overall. Double support time was found to have lower validity due to a combined bias of age, height, weight, and walking pace. Conclusion: These results support the validity of wearable inertial sensors in measuring gait speed, cadence, gait cycle duration, and stride length in children 7 years old and above during a 2-min walking test. Future studies are warranted with a broader age range to thoroughly represent the pediatric population.

Dynamic Balance in Spinal and Bulbar Muscular Atrophy: Relationship between Strength and Performance of Forward Lunge, Step Up and Over, and Step Quick Turn.

INTRODUCTION: Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder that leads to progressive weakness of bulbar and extremity muscles. Dynamic balance during functional tasks has not been reported in people with SBMA. OBJECTIVES: (1) To evaluate the ability to safely complete a forward lunge (FL), step quick turn (SQT), and step up and over (SUO), (2) to determine the presence and severity of dynamic balance impairments by comparing performance to normative data, and (3) to investigate the relationship between lower extremity strength and ability to complete each task. DESIGN: Cross-sectional analysis. Participants. Fifty-three people with SBMA were included in a cross-sectional analysis. Normative datasets provided by the NeuroCom manufacturer and isometric strength literature facilitated patient comparisons. Outcome Measures. Force plate-based dynamic balance measures included FL (distance, impact index, contact time, and force impulse), SQT (turn time and turn sway), and SUO (lift up index, movement time, and impact index). Maximal isometric contractions of knee extensors, ankle dorsiflexors, ankle plantar flexors, and hip extensors were measured with fixed frame dynamometry. RESULTS: The most difficult test, per completion rate, was SUO (52%), followed by FL (57%) and SQT (65%). t-tests revealed significant abnormalities in eight of nine balance variables (p < 0.05) accompanied by large Cohen's D effect sizes ≥ 0.8. Receiver operating characteristics analysis showed knee extensor (SUO 95% CI =0.78-1.00, SQT 95% CI =0.64-0.92) and ankle plantar flexor strength (SUO 95%CI = 0.75-0.99, SQT 95%CI = 0.64 - 0.92) significantly discriminated the ability to perform SUO and SQT tests with acceptable to excellent areas under the curve. CONCLUSIONS: Considerable dynamic balance abnormalities were observed. Lower extremity strength helps explain low test completion rates. Patients modified task movement patterns, enabling safe task performance. Study results can help direct patient care and future protocol design for people with SBMA.

A Comparative Study of Social Impacts of the COVID-19 Pandemic on Republic of Korea, Japan, and Taiwan.

OBJECTIVE: The frequency of various disasters has become a 21st century global crisis. The biological-disaster of the coronavirus disease of 2019 (COVID-19) gave rise to a multi-dimensional global impact. The 25 items of Societal Influences Survey Questionnaire (SISQ) was developed to assess various categories of social influence during the pandemic. This study compares the SISQ scores of Taiwan, Republic of Korea (Korea) and Japan. METHODS: Persons living in Korea, Japan, and Taiwan were recruited and evaluated through an SISQ online survey. The SISQ is composed of 25 items each with a 4-point Likert scale. The SISQ assesses the following six factors: self-restraint, social impact, government policy, social cost, concern of infection, and awareness of information. A principal factor analysis and reliability (Cronbach's alpha) were performed to validate the SISQ. The analysis of variance (ANOVA) and post-hoc analysis was conducted to explore the differences between groups. RESULTS: The SISQ had acceptable reliabilities, and accounted for 58.86% of the variance. The significance for ANOVA with post-hoc analysis showed that scores of self-restraints ranked highest in Japan followed by Taiwan and Korea. Taiwanese scored lower than other nations regarding the concern of infection. Koreans scored higher in awareness of information than the other two nations. The effect of age and marital status were also estimated. CONCLUSION: The SISQ comprehensively evaluate multiple domains of social influence, and it manifests the divergence of social impacts across the three nations.

Development and validation of the Lo's Healthy and Happy Lifestyle Scale (LHHLS): The resilience in general population facing COVID-19 in Taiwan.

BACKGROUND: This article explores the effectiveness of development of the Lo's Healthy and Happy Lifestyle Scale (LHHLS), which is an evaluative tool that monitors the resilience of the Taiwan population in times of such COVID-19 epidemic. Also, to verify factors of resilience, namely the reliability and validity of self-efficacy and positive thinking, and establishment of a prospective norm analysis. METHOD: The study mainly applied Explorative Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) to develop LHHLS and establish the reliability and validity of the tool's structure, verify norm analysis and the reliability of data from each question using Cronbach's alpha. RESULTS: According to statistics, LHHLS has a good factorial effectiveness and relatively high reliability, with factor reliability analyses where Cronbach's alpha lies between 0.83 to 0.94. The 14 questions in the LHHLS has a total variance of 67.04%. The tool includes two sub-assessments that are theoretically and statistically appropriate: mental health/self-efficacy and positive thinking. CONCLUSION: The tool LHHLS can be applied to populations affected by COVID-19. With participants' self-awareness of mental health state and state of happy living, this tool is valid and reliable in assessing and evaluating the resilience of such participants against times of COVID-19. This study can become future use for epidemic prevention communities in monitoring residents' healthy living and changes in their resilience. Also, can become a reference standard for interventions to reduce the impacts populations' happy and healthy living, in times of biological disasters.

Development and Implementation of Societal Influences Survey Questionnaire (SISQ) for Peoples during COVID-19 Pandemic: A Validity and Reliability Analysis.

The emergence of Coronavirus disease 2019 (COVID-19) had rapidly spread since FEB/MAR 2020. Policy to prevent transmission of COVDI-19 resulted in multi-dimensional impact on social interaction. We aimed to develop a beneficial survey tool with favorable quality and availability, the Societal Influences Survey Questionnaire (SISQ), to evaluate social influences on people during this pandemic. The SISQ was developed with 15 items and 4-point Likert scales consisting of five factors. These include social distance, social anxiety, social desirability, social information, and social adaptation. Construct validity and reliability were performed to verify the SISQ. A total of 1912 Taiwanese were recruited. The results demonstrated that the SISQ has acceptable reliability, with Cronbach's alphas ranging between 0.57 and 0.76. The SISQ accounted for 58.86% and satisfied the requirement of Kaiser-Mayer-Olkinvalues (0.78) and significant Bartlett's Test of sphericity. Moreover, the confirmatory factor analysis fit indices also indicated the adequacy of the model. As for multiple comparison, females scored higher than males in factor of social distance. Unemployed participants and those without partners scored higher in several domains of factors. The survey method and survey instrument prove reliable and valuable, also providing different categories of assessment results regarding social influences and their impacts. Further studies are warranted to extend the applicability of SISQ.

Cryptic Species Account for the Seemingly Idiosyncratic Secondary Metabolism of Sarcophyton glaucum Specimens Collected in Palau.

Sarcophyton glaucum is one of the most abundant and chemically studied soft corals with over 100 natural products reported in the literature, primarily cembrane diterpenoids. Yet, wide variation in the chemistry observed from S. glaucum over the past 50 years has led to its reputation as a capricious producer of bioactive metabolites. Recent molecular phylogenetic analysis revealed that S. glaucum is not a single species but a complex of at least seven genetically distinct species not distinguishable using traditional taxonomic criteria. We hypothesized that perceived intraspecific chemical variation observed in S. glaucum was actually due to differences between cryptic species (interspecific variation). To test this hypothesis, we collected Sarcophyton samples in Palau, performed molecular phylogenetic analysis, and prepared chemical profiles of sample extracts using gas chromatography-flame ionization detection. Both unsupervised (principal component analysis) and supervised (linear discriminant analysis) statistical analyses of these profiles revealed a strong relationship between cryptic species membership and chemical profiles. Liquid chromatography with tandem mass spectrometry-based analysis using feature-based molecular networking permitted identification of the chemical drivers of this difference between clades, including cembranoid diterpenes (2R,11R,12R)-isosarcophytoxide (5), (2S,11R,12R)-isosarcophytoxide (6), and isosarcophine (7). Our results suggest that early chemical studies of Sarcophyton may have unknowingly conflated different cryptic species of S. glaucum, leading to apparently idiosyncratic chemical variation.

Exercise Intervention Leads to Functional Improvement in a Patient with Spinal and Bulbar Muscular Atrophy.

INTRODUCTION: Spinal and bulbar muscular atrophy is a progressive neuromuscular disease that leads to muscle weakness and reduced physical function. Benefits of physical therapy for people with spinal and bulbar muscular atrophy have not been reported in the literature. CASE REPORT: A 62-year-old male patient with spinal and bulbar muscular atrophy reported falling, difficulty walking and completing upright tasks, and showed clinical signs of low baseline function on examination. Transportation challenges made it difficult for this patient to attend frequent one-on-one physical therapy sessions. INTERVENTIONS AND OUTCOMES: A minimally supervised home-based exercise intervention was chosen with the goal of safely improving his functional capacity. The 5-visit clinical intervention, spread over 10 months, provided 3 exercise modules: seated-to-standing postural alignment and core muscle activation; upright functional and endurance training; and balance training and rhythmic walking. Post-intervention the patient had increased lower extremity muscle strength, improved balance, and reduced self-reported fatigue. CONCLUSION: Home-based exercises were well tolerated with no increase in creatine kinase. Multiple clinical measures of strength and function improved, possibly related to the patients' excellent motivation and compliance with the programme. Promising utilization of a minimally supervised home-based programme is described here.

Body-Worn Sensors Are a Valid Alternative to Forceplates for Measuring Balance in Children.

Aims: Clinical evaluation of balance has relied on forceplate systems as the gold standard for postural sway measures. Recently, systems based on wireless inertial sensors have been explored, mostly in the adult population, as an alternative given their practicality and lower cost. Our goal was to validate body-worn sensors against forceplate balance measures in typically developing children during tests of quiet stance. Methods: 18 participants (8 males) 7 to 17 years old performed a quiet stance test standing on a forceplate while wearing 3 inertial sensors. Three 30-second trials were performed under 4 conditions: firm surface with eyes open and closed, and foam surface with eyes open and closed. Sway area, path length, and sway velocity were calculated. Results: We found 20 significant and 8 non-significant correlations. Variables found to be significant were represented across all conditions, except for the foam eyes closed condition. Conclusions: These results support the validity of wearable sensors in measuring postural sway in children. Inertial sensors may represent a viable alternative to the gold standard forceplate to test static balance in children.

Rate of psychiatric disorders and associations with quality of life among community members following the Kaohsiung gas explosion: an 18-month cross-sectional follow-up study.

OBJECTIVE: To conduct a follow-up on the rate and related risk factors of probable disaster-related psychiatric disorders such as depressive disorder (major depressive episode, MDE), stress disorders, post-traumatic (posttraumatic stress disorder, PTSD), and the quality of life of the survivors of a fossil gas explosion in Taiwan 18 months after the event. METHODS: A community-based survey of residents of a community that experienced a petrochemical gas explosion with cross-sectional assessments was conducted 18 months after the event. Two screening tools, including the Disaster-Related Psychological Screening Test (DRPST) and Short Form 12v2 (SF-12v2), were used to survey a representative sample of 388 participants. RESULTS: The average age of 388 participants is 43.27 ± 15.98 years (males: 203, average age: 41.44 ± 15.74 years; females: 185; average age: 45.27 ± 16.03 years). Probable PTSD, probable MDE, probable PTSD and MDE, and non-PTSD or non-MDE (non-P or -M) were present in 34 (8.8%), 14 (3.6%), 9 (2.3%), and 331 (85.3%) participants, respectively. The significant associated factor for probable PTSD or MDE among those who experienced disaster was financial problems. The associated factors on different quality of life subscales were old age, physical injury, employment, educational level, financial problems, probable PTSD and probable MDE. CONCLUSION: While participants' psychiatric status improved after 18 months, their quality of life continued to be affected, especially the quality of life of those with probable PTSD combined with MDE. Postdisaster treatment and follow-up should be addressed to a greater degree, especially for victims with mental illness, physical injuries and financial problems.

Tctex-1 controls ciliary resorption by regulating branched actin polymerization and endocytosis.

The primary cilium is a plasma membrane-protruding sensory organelle that undergoes regulated assembly and resorption. While the assembly process has been studied extensively, the cellular machinery that governs ciliary resorption is less well understood. Previous studies showed that the ciliary pocket membrane is an actin-rich, endocytosis-active periciliary subdomain. Furthermore, Tctex-1, originally identified as a cytoplasmic dynein light chain, has a dynein-independent role in ciliary resorption upon phosphorylation at Thr94. Here, we show that the remodeling and endocytosis of the ciliary pocket membrane are accelerated during ciliary resorption. This process depends on phospho(T94)Tctex-1, actin, and dynamin. Mechanistically, Tctex-1 physically and functionally interacts with the actin dynamics regulators annexin A2, Arp2/3 complex, and Cdc42. Phospho(T94)Tctex-1 is required for Cdc42 activation before the onset of ciliary resorption. Moreover, inhibiting clathrin-dependent endocytosis or suppressing Rab5GTPase on early endosomes effectively abrogates ciliary resorption. Taken together with the epistasis functional assays, our results support a model in which phospho(T94)Tctex-1-regulated actin polymerization and periciliary endocytosis play an active role in orchestrating the initial phase of ciliary resorption.

CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking.

Chloride intracellular channel 4 (CLIC4) is a mammalian homologue of EXC-4 whose mutation is associated with cystic excretory canals in nematodes. Here we show that CLIC4-null mouse embryos exhibit impaired renal tubulogenesis. In both developing and developed kidneys, CLIC4 is specifically enriched in the proximal tubule epithelial cells, in which CLIC4 is important for luminal delivery, microvillus morphogenesis, and endolysosomal biogenesis. Adult CLIC4-null proximal tubules display aberrant dilation. In MDCK 3D cultures, CLIC4 is expressed on early endosome, recycling endosome and apical transport carriers before reaching its steady-state apical membrane localization in mature lumen. CLIC4 suppression causes impaired apical vesicle coalescence and central lumen formation, a phenotype that can be rescued by Rab8 and Cdc42. Furthermore, we show that retromer- and branched actin-mediated trafficking on early endosome regulates apical delivery during early luminogenesis. CLIC4 selectively modulates retromer-mediated apical transport by negatively regulating the formation of branched actin on early endosomes.