Effect of Robotic Delivery of Physical Activity and Fall Prevention Exercise in Older Adults: A Pilot Cohort Study

Introduction: The high prevalence of falls, lack of stability and balance, and general physical deconditioning are concerning issues for longevity and quality of life for adults aged 65 years and older. Although supervised delivery of the Otago Exercise Program (OEP) has demonstrated evidence of effectiveness in reducing fall risk of older adults, opportunities for ongoing unsupervised exercise performance are warranted. An option to facilitate exercise and performance of health behaviors may be via a social robot. The purpose of this study was to examine feasibility and initial outcomes of a robot-delivered fall prevention exercise program for community-dwelling older adults. Methods: Five participants aged 65 years and older were recruited to receive robot-delivered modified OEP and walking program three times per week for four weeks. Outcomes of demographics, self-reported performance measures (Modified Falls Self-Efficacy Scale, Activities-specific Balance Confidence, and Almere Model assessing various constructs of acceptance of use of robotic technology), and physical performance measures (Timed Up and Go Test, Short Physical Performance Battery, Balance Tracking System [BTrackS] center of pressure sway) were collected. Data were analyzed descriptively and examined for trends in change. Measures of central tendency and distribution were used according to the distribution of the data. Results: The mean age of the participants was 75 years (range: 66-83 years; four females and one male). The range of participant exercise session completion was 7-12 (mode=11, n=3). Constructs on the Almere Model that started and remained positive were Attitudes Toward Technology and Perceived Enjoyment with the robot. Anxiety improved from 3.80 to 4.68, while Social Presence of the robot improved from 2.80 to 3.56. The construct of Trust was somewhat negative among participants upon commencing the program and did not substantially change over time. Two participants improved their confidence on the Activities-specific Balance Confidence scale by more than 10%, while all participants showed some improvement in confidence in their balance. Mixed results were found with the Modified Falls Self-Efficacy Scale. Mean gait speed for the participants improved by 0.76 seconds over 3 meters. Improvement was also demonstrated for the Short Physical Performance Battery, with two participants improving scores by 2-3 points out of 12. No appreciable changes were found with the Timed Up and Go test and the BTrackS assessment. Conclusion: Using a robot-led exercise program is an accessible and feasible way to deliver exercise to community-dwelling older adults in the home, but some technical constraints remain. Outcomes suggest that a four-week program is sufficient to elicit some positive trends in health outcomes and has the potential to reduce fall risk

A Randomized-Trial Evaluation of the Effect of Whose Future Is It Anyway? on Self-Determination

Promoting student involvement in planning has become best practice in the field of transition. Research documents the positive impact of such efforts on greater student involvement. Research also suggests that promoting student involvement results in greater student self-determination, but a causal link has not been established. This study used a randomized- trial, placebo control group design to study the impact of intervention with the Whose Future Is It Anyway? process on self-determination. The authors also examined the impact of intervention on transition knowledge and skills. Results indicated that instruction using the Whose Future Is It Anyway? process resulted in significant, positive differences in self- determination when compared with a placebo-control group and that students who received instruction gained transition knowledge and skills.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Specific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomas

Studies in pediatric high-grade astrocytomas (HGA) by our group and others have uncovered recurrent somatic mutations affecting highly conserved residues in histone 3 (H3) variants. One of these mutations leads to analogous p.Lys27Met (K27M) mutations in both H3.3 and H3.1 variants, is associated with rapid fatal outcome, and occurs specifically in HGA of the midline in children and young adults. This includes diffuse intrinsic pontine gliomas (80 %) and thalamic or spinal HGA (>90 %), which are surgically challenging locations with often limited tumor material available and critical need for specific histopathological markers. Here, we analyzed formalin-fixed paraffin-embedded tissues from 143 pediatric HGA and 297 other primary brain tumors or normal brain. Immunohistochemical staining for H3K27M was compared to tumor genotype, and also compared to H3 tri-methylated lysine 27 (H3K27me3) staining, previously shown to be drastically decreased in samples carrying this mutation. There was a 100 % concordance between genotype and immunohistochemical analysis of H3K27M in tumor samples. Mutant H3K27M was expressed in the majority of tumor cells, indicating limited intra-tumor heterogeneity for this specific mutation within the limits of our dataset. Both H3.1 and H3.3K27M mutants were recognized by this antibody while non-neoplastic elements, such as endothelial and vascular smooth muscle cells or lymphocytes, did not stain. H3K27me3 immunoreactivity was largely mutually exclusive with H3K27M positivity. These results demonstrate that mutant H3K27M can be specifically identified with high specificity and sensitivity using an H3K27M antibody and immunohistochemistry. Use of this antibody in the clinical setting will prove very useful for diagnosis, especially in the context of small biopsies in challenging midline tumors and will help orient care in the context of the extremely poor prognosis associated with this mutation. Electronic supplementary material The online version of this article (doi:10.1007/s00401-014-1337-4) contains supplementary material, which is available to authorized users

Alternative Splicing and Gene Duplication in the Evolution of the FoxP Gene Subfamily

The FoxP gene subfamily of transcription factors is defined by its characteristic 110 amino acid long DNA-binding forkhead domain and plays essential roles in vertebrate biology. Its four members, FoxP1–P4, have been extensively characterized functionally. FoxP1, FoxP2, and FoxP4 are involved in lung, heart, gut, and central nervous system (CNS) development. FoxP3 is necessary and sufficient for the specification of regulatory T cells (Tregs) of the adaptive immune system

Interaction of microtubules and actin during the post-fusion phase of exocytosis

Exocytosis is the intracellular trafficking step where a secretory vesicle fuses with the plasma membrane to release vesicle content. Actin and microtubules both play a role in exocytosis; however, their interplay is not understood. Here we study the interaction of actin and microtubules during exocytosis in lung alveolar type II (ATII) cells that secrete surfactant from large secretory vesicles. Surfactant extrusion is facilitated by an actin coat that forms on the vesicle shortly after fusion pore opening. Actin coat compression allows hydrophobic surfactant to be released from the vesicle. We show that microtubules are localized close to actin coats and stay close to the coats during their compression. Inhibition of microtubule polymerization by colchicine and nocodazole affected the kinetics of actin coat formation and the extent of actin polymerisation on fused vesicles. In addition, microtubule and actin cross-linking protein IQGAP1 localized to fused secretory vesicles and IQGAP1 silencing influenced actin polymerisation after vesicle fusion. This study demonstrates that microtubules can influence actin coat formation and actin polymerization on secretory vesicles during exocytosis

Functional Neuromuscular Junctions Formed by Embryonic Stem Cell-Derived Motor Neurons

A key objective of stem cell biology is to create physiologically relevant cells suitable for modeling disease pathologies in vitro. Much progress towards this goal has been made in the area of motor neuron (MN) disease through the development of methods to direct spinal MN formation from both embryonic and induced pluripotent stem cells. Previous studies have characterized these neurons with respect to their molecular and intrinsic functional properties. However, the synaptic activity of stem cell-derived MNs remains less well defined. In this study, we report the development of low-density co-culture conditions that encourage the formation of active neuromuscular synapses between stem cell-derived MNs and muscle cells in vitro. Fluorescence microscopy reveals the expression of numerous synaptic proteins at these contacts, while dual patch clamp recording detects both spontaneous and multi-quantal evoked synaptic responses similar to those observed in vivo. Together, these findings demonstrate that stem cell-derived MNs innervate muscle cells in a functionally relevant manner. This dual recording approach further offers a sensitive and quantitative assay platform to probe disorders of synaptic dysfunction associated with MN disease

Violence against primary school children with disabilities in Uganda: a cross-sectional study.

BACKGROUND: 150 million children live with disabilities globally, and a recent systematic review found 3 to 4 times the levels of violence versus non-disabled children in high income countries. However, almost nothing is known about violence against disabled children in lower income countries. We aim to explore the prevalence, patterns and risk factors for physical, sexual and emotional violence among disabled children attending primary school in Luwero District, Uganda. METHODS: We performed a secondary analysis of data from the baseline survey of the Good Schools Study. 3706 children and young adolescents aged 11-14 were randomly sampled from 42 primary schools. Descriptive statistics were computed and logistic regression models fitted. RESULTS: 8.8% of boys and 7.6% of girls reported a disability. Levels of violence against both disabled and non-disabled children were extremely high. Disabled girls report slightly more physical (99.1% vs 94.6%, p = 0.010) and considerably more sexual violence (23.6% vs 12.3%, p = 0.002) than non-disabled girls; for disabled and non-disabled boys, levels are not statistically different. The school environment is one of the main venues at which violence is occurring, but patterns differ by sex. Risk factors for violence are similar between disabled and non-disabled students. CONCLUSIONS: In Uganda, disabled girls are at particular risk of violence, notably sexual violence. Schools may be a promising venue for intervention delivery. Further research on the epidemiology and prevention of violence against disabled and non-disabled children in low income countries is urgently needed