Participation in Special Olympics reduces the rate for developing diabetes in adults with intellectual and developmental disabilities.

AIM: Adults with intellectual and developmental disabilities (IDD) have a significantly higher prevalence of Type 2 diabetes than the general population. Evidence that lifestyle and/or behavioural interventions, such as participation in Special Olympics, decreases the risk of developing diabetes in adults with IDD could help minimize health disparities and promote overall health in this population. METHODS: This was a 20-year retrospective cohort study of adults with IDD (30-39 years) in the province of Ontario, Canada, that compared hazard rates of diabetes among Special Olympics participants (n = 4145) to non-participants (n = 31,009) using administrative health databases housed at ICES. Using cox proportional hazard models, crude and adjusted hazard ratios were calculated for the association between the primary independent variable (Special Olympics participation status) and the dependent variable (incident diabetes cases). RESULTS: After controlling for other variables, the hazard ratio comparing rates for developing diabetes between Special Olympics participants and non-participants was 0.85. This represents a 15% reduction in the hazard among Special Olympics participants when followed for up to 20 years. This result was statistically significant and represents a small effect size. CONCLUSIONS: Special Olympics could be considered a complex intervention that promotes physical activity engagement through sport participation, health screenings, and the promotion of healthy eating habits through educational initiatives. This study provides evidence that Special Olympics participation decreases the rate for developing diabetes.

Clinical validation of a multi-protein, serum-based assay for disease activity assessments in multiple sclerosis.

An 18-protein multiple sclerosis (MS) disease activity (DA) test was validated based on associations between algorithm scores and clinical/radiographic assessments (N = 614 serum samples; Train [n = 426; algorithm development] and Test [n = 188; evaluation] subsets). The multi-protein model was trained based on presence/absence of gadolinium-positive (Gd+) lesions and was also strongly associated with new/enlarging T2 lesions, and active versus stable disease (composite of radiographic and clinical evidence of DA) with improved performance (p < 0.05) compared to the neurofilament light single protein model. The odds of having ≥1 Gd+ lesions with a moderate/high DA score were 4.49 times that of a low DA score, and the odds of having ≥2 Gd+ lesions with a high DA score were 20.99 times that of a low/moderate DA score. The MSDA Test was clinically validated with improved performance compared to the top-performing single-protein model and can serve as a quantitative tool to enhance the care of MS patients.

Serum neurofilament light levels in natalizumab-treated patients with multiple sclerosis who switch to extended interval dosing from every-4-week dosing in real-world clinical practice.

BACKGROUND: Serum levels of neurofilament light chain (sNfL) are a potentially useful biomarker for assessing the efficacy of multiple sclerosis (MS) treatments. OBJECTIVE: To compare levels of sNfL in patients with MS who switched from natalizumab every 4 weeks (Q4W) to extended interval dosing (EID) and patients who remained on Q4W dosing in real-world clinical practice. METHODS: This was a retrospective analysis of samples from patients treated with natalizumab from 2010 to 2015 at a single center in the United States. Levels of sNfL were compared in patients who stayed on Q4W dosing or who switched to EID (parallel-arm analyses) and during Q4W and EID periods in patients who switched to EID (pre- and post-switch analyses). RESULTS: The analysis included 139 patients (Q4W: n = 79; EID: n = 60). After adjustment, levels of sNfL did not significantly differ between patients who remained on Q4W dosing and those who switched to EID in parallel-arm analyses (adjusted Q4W-EID difference = 0.51 pg/mL; p = 0.60) or pre- and post-switch analyses (adjusted difference = 0.96 pg/mL; p = 0.10). CONCLUSION: These sNfL biomarker results suggest that the effectiveness of natalizumab is maintained in patients who switch from Q4W dosing to EID.

Young adults with intellectual and developmental disabilities who participate in Special Olympics are less likely to be diagnosed with depression.

PURPOSE: People with intellectual and developmental disabilities (IDD) experience high rates of depression. Evidence indicates that physical activity, or participation in a sports club, in a supportive social environment has mental and physical health benefits. Adults with IDD, on average, engage in low levels of physical activity. The purpose of this study was to compare the rates of depression among young adult Special Olympics participants with IDD compared to non-participants with IDD. METHODS: This was a 20-year retrospective cohort study of young adults (19-29 years) with IDD in the province of Ontario, Canada that compared rates of depression among Special Olympics participants (n = 8710) to non-participants (n = 42,393) using administrative health databases housed at ICES (formerly the Institute for Clinical Evaluative Sciences). Using cox proportional hazard models, the crude hazard ratios were calculated for the association between each independent variable and the dependent variable. RESULTS: After controlling for other variables, the hazard rate for depression among Special Olympics participants compared to the hazard rate for depression among non-participants generated an adjusted hazard ratio of 0.51. Over the 20-year follow-up, the participants were 0.51 times as likely to develop depression as non-participants; this represents a 49% reduction in risk among Special Olympics participants. This result was statistically significant and represents a medium effect size. CONCLUSION: Future research is needed on how much of this risk reduction is related to a physiological response to physical activity/exercise, and how much is related to the social connectedness of being part of a group participating in Special Olympics.

Comprehensive school health: teachers' perceptions and implementation of classroom physical activity breaks in US schools.

Modifications to the social-ecological model, such as Whole School, Whole Community, Whole Child (WSCC) frameworks, have been utilized in comprehensive school health interventions. Classroom physical activity breaks are used when implementing whole-of-school approaches. However, the onus to implement classroom physical activity breaks is on school stakeholders. This study aimed to explore teacher and principal perceptions and implementation of physical activity breaks in elementary schools. Further, this study investigated how theoretical factors representative of the social-ecological model and their interactions affect teacher and principal perceptions and utilization of classroom physical activity breaks. Interviews were conducted to understand teacher and principal perceptions and implementation. A total of 12 classroom teachers and five principals participated in semi-structured interviews which were analyzed using constant comparison and deductive analysis to identify relationships and themes coded across the social-ecological and WSCC models. To ensure fidelity individuals that led the professional development (n = 2) were also interviewed. Three main themes emerged as part of the data analysis: (i) The Connection Between Intrapersonal Knowledge and Interpersonal Professional Development, (ii) Resources, Sharing Means Caring and (iii) The Policy Level Creates Time. Teachers and principals valued knowledge and resources and felt that policy facilitated implementation. Results suggest that classroom physical activity breaks are influenced by multiple factors across varied levels of the social-ecological model. Understanding this relationship can inform future professional development to increase the provision of classroom physical activity breaks among teachers.

Global health statistics suggest that youth health is deteriorating. In response, international and national health organizations have called for school settings to adopt comprehensive school health approaches that provide youth with ample opportunities, such as physical activity across the school day, to improve their health behaviors and instill lifelong healthy habits. This study used the social­ecological model, which considers the interactions between an individual, their community, and the physical, social and political environments, to frame the exploration of how teachers and principals perceive and utilize physical activity breaks in elementary schools. Findings indicate that to foster school health, a comprehensive approach that supports teachers and their interactions while providing resources and policies is needed. Adoption of classroom physical activity breaks begins with teacher knowledge which fosters teacher interaction where best practices are built. Structural supports, including access to resources and the presence of policy, are also critical to sustained implementation because they can reinforce and support teachers' individual and shared use of health-based learning practices across the school day.

Visually directed action.

When people throw or walk to targets in front of them without visual feedback, they often respond short. With feedback, responses rapidly become approximately accurate. To understand this, an experiment is performed with four stages. 1) The errors in blind walking and blind throwing are measured in a virtual environment in light and dark cue conditions. 2) Error feedback is introduced and the resulting learning measured. 3) Transfer to the other response is then measured. 4) Finally, responses to the perceived distances of the targets are measured. There is large initial under-responding. Feedback rapidly makes responses almost accurate. Throw training transfers completely to walking. Walk training produces a small effect on throwing. Under instructions to respond to perceived distances, under-responding recurs. The phenomena are well described by a model in which the relation between target distance and response distance is determined by a sequence of a perceptual, a cognitive, and a motor transform. Walk learning is primarily motor; throw learning is cognitive.

Physical activity promotion and adults with intellectual disabilities: A neglected area.

BACKGROUND: The objective was to review physical activity (PA) promotion interventions among individuals with intellectual disability and provide recommendations for increasing PA. METHODS: A systematic mapping review was conducted in which physical activity intervention studies for adults with a disability were identified, selected, and appraised. Data were extracted regarding the study design, results, and authors' recommendations. Data were analyzed using a social-ecological framework. RESULTS: A comprehensive search of the peer reviewed literature yielded 5 studies (3 quantitative, 1 mixed methods, and 1 pre-post delayed). Studies used physical activity promotion strategies at the intrapersonal, interpersonal, organizational, community, and policy levels have been used to date. CONCLUSIONS: Recommendations are presented for researchers and practitioners seeking to increase the level of PA of adults with intellectual disability.

Estrogen modulates mesenchyme-epidermis interactions in the adult nipple.

Maintenance of specialized epidermis requires signals from the underlying mesenchyme; however, the specific pathways involved remain to be identified. By recombining cells from the ventral skin of the K14-PTHrP transgenic mice [which overexpress parathyroid hormone-related protein (PTHrP) in their developing epidermis and mammary glands] with those from wild type, we show that transgenic stroma is sufficient to reprogram wild-type keratinocytes into nipple-like epidermis. To identify candidate nipple-specific signaling factors, we compared gene expression signatures of sorted Pdgfrα-positive ventral K14-PTHrP and wild-type fibroblasts, identifying differentially expressed transcripts that are involved in WNT, HGF, TGFß, IGF, BMP, FGF and estrogen signaling. Considering that some of the growth factor pathways are targets for estrogen regulation, we examined the upstream role of this hormone in maintaining the nipple. Ablation of estrogen signaling through ovariectomy produced nipples with abnormally thin epidermis, and we identified TGFß as a negatively regulated target of estrogen signaling. Estrogen treatment represses Tgfß1 at the transcript and protein levels in K14-PTHrP fibroblasts in vitro, while ovariectomy increases Tgfb1 levels in K14-PTHrP ventral skin. Moreover, ectopic delivery of Tgfß1 protein into nipple connective tissue reduced epidermal proliferation. Taken together, these results show that specialized nipple epidermis is maintained by estrogen-induced repression of TGFß signaling in the local fibroblasts.

Gunshot damage to monoplace hyperbaric chamber acrylic.

Introduction: Health care workers are vulnerable to workplace violence, including active shooter incidents. Little is known about how firearms could damage monoplace chamber acrylic and whether a breached pressurized chamber presents additional threat to the patient or bystanders. Methods: In a remote area where firearm discharge is permitted, we tested the durability of sections of monoplace hyperbaric chamber acrylic under various firearm discharges. Firearms were discharged at acrylic sections from a distance of 17 feet at 45 degrees and 10 degrees from perpendicular while wearing protective gear. Firearm calibers ranged from .22 caliber handgun to 5.56 mm AR-15 rifle. We also conducted similar testing on a monoplace hyperbaric chamber pressurized with >99% oxygen to a differential pressure of 14.7 psig (2.0 atmospheres absolute at sea level). Handguns were remotely fired at a distance of 12 feet from the chamber (30 degrees from perpendicular), while the rifles were fired at a distance of 60 feet from the chamber. Result: Higher-caliber handguns penetrated or fractured the acrylic sections only after multiple shots. The tested rifles caused full-thickness penetration and fracture with a single shot. However, the pressurized monoplace hyperbaric chamber required two shots from the AR-15 rifle, separated by approximately 60 mm, to penetrate the acrylic, resulting in rapid depressurization. The chamber otherwise remained intact, with no explosion or conflagration observed. Conclusion: An intact or pressurized chamber performs differently than stand-alone acrylic sections under firearms testing. In a worst-case active shooter scenario, the pressurized monoplace chamber tested posed no additional threat to bystanders beyond the significant risk of ricochet.

Endurance training slows breast tumor growth in mice by suppressing Treg cells recruitment to tumors.

BACKGROUND: Aerobic exercise has been shown to slow tumor progression in rodents and humans, but the mechanisms behind this effect are still unclear. Here we show that aerobic exercise in the form of chronic endurance training suppresses tumor recruitment of FoxP3+ Treg cells thus enhancing antitumor immune efficiency. METHODS: Adult wild-type and athymic BALB/c female mice were endurance-trained for 8 weeks. Circulating leukocytes as well as muscle and liver mtDNA copy number were compared to aged-matched concurrent sedentary controls to establish systemic effects. 4 T1 murine mammary tumor cells were injected subcutaneously to the 4th mammary pad at the end of the training period. Tumor growth and survival rates were compared, together with antitumor immune response. RESULTS: Exercised wild-type had 17% slower growth rate, 24% longer survival, and 2-fold tumor-CD+ 8/FoxP3+ ratio than sedentary controls. Exercised athymic BALB/c females showed no difference in tumor growth or survival rates when compared to sedentary controls. CONCLUSIONS: Cytotoxic T cells are a significant factor in endurance exercise-induced suppression of tumor growth. Endurance exercise enhances antitumor immune efficacy by increasing intratumoral CD8+/FoxP3+ ratio.

Lateral effects in pattern vision.

There is a large literature on lateral effects in pattern vision but no consensus about them or comprehensive model of them. This paper reviews the literature with a focus on the effects of parallel context in the central fovea. It describes seven experiments that measure detection and discrimination thresholds in annular and Gabor-pattern contexts at different separations. It presents a model of these effects, which is an elaboration of Foley's (1994) model. The model describes the results well, and it shows that lateral context affects the response to the target by both multiplicative excitation and additive inhibition. Both lateral effects extend for several wavelengths beyond the target. They vary in relative strength, producing near suppression and far enhancement of the response to the target. The model describes the detection and discrimination results well, and it also describes the results of experiments on lateral effects on perceived contrast. The model is consistent with the physiology of V1 cells.

Anti-JCV serology during natalizumab treatment: Review and meta-analysis of 17 independent patient cohorts analyzing anti-John Cunningham polyoma virus sero-conversion rates under natalizumab treatment and differences between technical and biological sero-converters.

BACKGROUND: Anti-John Cunningham virus (JCV) serology has been studied with varying results concerning longitudinal changes. OBJECTIVES AND METHODS: Results from 17 published natalizumab-treated multiple sclerosis (MS) patient cohorts were analyzed with common parameters and subsequently verified in two large independent cohorts with 722 and 499 patients from Germany and the United States. RESULTS: Published studies and the verification showed (1) a mean of 10.80% sero-negative patients presented with sero-status change to positivity per year; (2) patients, who sero-convert to index values <0.9, convert from near the threshold and have a high probability of reverting with time; (3) patients, who convert to index values >0.9, start with low index values; (4) while JCV sero-positive patients with low index values sometimes revert to sero-negativity, patients with high index values almost never revert; and (5) the conversion rate of natalizumab-treated patients is three to four times higher than the biological conversion by age. CONCLUSION: JCV sero-conversion was comparable using standardized parameters and indicates influence of natalizumab on JCV immune control. Converters to low index values are probably consistently infected with JCV with varying low levels of activity, in line with their low risk to develop progressive multifocal leukoencephalopathy (PML). Patients with high index values rarely revert back to sero-negativity.

Psychometric Properties of the Test of Gross Motor Development-3 for Children With Visual Impairments.

Results of the Test of Gross Motor Development-2 (TGMD-2) consistently show acceptable validity and reliability for children/adolescents who are sighted and those who have visual impairments. Results of the Test of Gross Motor Development-3 (TGMD-3) are often valid and reliable for children who are sighted, but its psychometric properties are unknown for children with visual impairments. Participants (N = 66; Mage = 12.93, SD = 2.40) with visual impairments completed the TGMD-2 and TGMD-3. The TGMD-3 results from this sample revealed high internal consistency (ω = .89-.95), strong interrater reliability (ICC = .91-.92), convergence with the TGMD-2 (r = .96), and good model fit, χ2(63) = 80.10, p = .072, χ2/df ratio = 1.27, RMSEA = .06, CFI = .97. Researchers and practitioners can use the TGMD-3 to assess the motor skill performance for children/adolescents with visual impairments and most likely produce results that are valid and reliable.

Body mass index and waist circumference of Latin American adult athletes with intellectual disability.

OBJECTIVES: To examine both body mass index (BMI) status and waist circunference (WC) in a large international sample of adult Special Olympics participants from Latin America. It also explored the association of age and sex with obesity in this population. MATERIALS AND METHODS: BMI and WC records from a total of 4174 (2683 male and 1491 female) participant records from the Special Olympics International Health Promotion database were examined. RESULTS: The prevalence of overweight and obesity was quite high (i.e. > 40%), but generally lower than studies involving adults with intellectual disabilities from Europe and the USA. Chi-square analyses revealed that both increasing age and being female significantly predicted levels of overweight, obesity, and WC. CONCLUSIONS: These results suggest that efforts need to be made to prevent and reduce rates of overweight and obesity among Latin American Special Olympics participants, particularly women.

Baseline EEG abnormalities in mild traumatic brain injury from the BIMA study.

The Brain Injury and Mechanisms of Action of HBO2 for Persistent Post-Concussive Symptoms after Mild Traumatic Brain Injury (BIMA), sponsored by the Department of Defense, is a randomized, double-blind, sham-controlled trial of hyperbaric oxygen (HBO2) in service members with persistent post-concussive symptoms following mild TBI, undergoing comprehensive assessments. The clinical EEG was assessed by neurologists for slow wave activity, ictal/interictal epileptiform abnormalities, and background periodic discharges. There is scant literature about EEG findings in this population, so we report baseline clinical EEG results and explore associations with other evaluations, including demographics, medication, neurological assessments, and clinical MRI outcomes. Seventy-one participants were enrolled: median age 32 years, 99% male, 49% comorbid PTSD, 28% with mTBI in the previous year, 32% blast injuries only, and 73% multiple injuries. All participants reported medication use (mean medications = 8, SD = 5). Slowing was present in 39%: generalized 37%, localized 8%, both 6%. No other abnormalities were identified. Slowing was not significantly associated with demographics, medication or neurological evaluation. Participants without EEG abnormalities paradoxically had significantly higher number of white matter hyperintensities as identified on MRI (p = 0.003). EEG slowing is present in more than one-third of participants in this study without evidence of associations with demographics, medications or neurological findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01611194; https://clinicaltrials.gov/show/NCT01611194.

Latin American Physical Educators' Intention to Teach Individuals With Disabilities.

PURPOSE: To analyze Latin American physical education (PE) teachers' intentions toward teaching students with disabilities. PARTICIPANTS: 474 in-service PE teachers from 5 different Latin American countries. METHOD: Descriptive survey. Data were collected using a modified version of the Physical Educators' Intention Toward Teaching Individuals With Disabilities Survey. Multiple-regression analysis showed significant differences in the attitudes of teachers by gender, the number of adapted-PE courses taken, and years of experience working with individuals with disabilities. RESULTS: The predictor variables had a significant impact on the participants' intentions toward teaching children with disabilities; however, the effects of these predictor variables differed between countries.

Selectivity in the Use of Gi/o Proteins Is Determined by the DRF Motif in CXCR6 and Is Cell-Type Specific.

CXCR6, the receptor for CXCL16, is expressed on multiple cell types and can be a coreceptor for human immunodeficiency virus 1. Except for CXCR6, all human chemokine receptors contain the D(3.49)R(3.50)Y(3.51) sequence, and all but two contain A(3.53) at the cytoplasmic terminus of the third transmembrane helix (H3C), a region within class A G protein-coupled receptors that contacts G proteins. In CXCR6, H3C contains D(3.49)R(3.50)F(3.51)I(3.52)V(3.53) at positions 126-130. We investigated the importance and interdependence of the canonical D126 and the noncanonical F128 and V130 in CXCR6 by mutating D126 to Y, F128 to Y, and V130 to A singly and in combination. For comparison, we mutated the analogous positions D142, Y144, and A146 to Y, F, and V, respectively, in CCR6, a related receptor containing the canonical sequences. Mutants were analyzed in both human embryonic kidney 293T and Jurkat E6-1 cells. Our data show that for CXCR6 and/or CCR6, mutations in H3C can affect both receptor signaling and chemokine binding; noncanonical H3C sequences are functionally linked, with dual changes mitigating the effects of single mutations; mutations in H3C that compromise receptor activity show selective defects in the use of individual Gi/o proteins; and the effects of mutations in H3C on receptor function and selectivity in Gi/o protein use can be cell-type specific. Our findings indicate that the ability of CXCR6 to make promiscuous use of the available Gi/o proteins is exquisitely dependent on sequences within the H3C and suggest that the native sequence allows for preservation of this function across different cellular environments.

Cross-generational impact of a male murine pheromone 2-sec-butyl-4,5- dihydrothiazole in female mice.

The current understanding of the activity of mammalian pheromones is that endocrine and behavioural effects are limited to the exposed individuals. Here, we demonstrate that the nasal exposure of female mice to a male murine pheromone stimulates expansion of mammary glands, leading to prolonged nursing of pups. Subsequent behavioural testing of the pups from pheromone-exposed dams exhibited enhanced learning. Sialic acid components in the milk are known to be involved in brain development. We hypothesized that the offspring might have received more of this key nutrient that promotes brain development. The mRNA for polysialyltransferase, which produces polysialylated neural cell adhesion molecules related to brain development,was increased in the brain of offspring of pheromone-exposed dams at post-natal day 10, while it was not different at embryonic stages, indicating possible differential brain development during early post-natal life.

The chicken frizzle feather is due to an α-keratin (KRT75) mutation that causes a defective rachis.

Feathers have complex forms and are an excellent model to study the development and evolution of morphologies. Existing chicken feather mutants are especially useful for identifying genetic determinants of feather formation. This study focused on the gene F, underlying the frizzle feather trait that has a characteristic curled feather rachis and barbs in domestic chickens. Our developmental biology studies identified defects in feather medulla formation, and physical studies revealed that the frizzle feather curls in a stepwise manner. The frizzle gene is transmitted in an autosomal incomplete dominant mode. A whole-genome linkage scan of five pedigrees with 2678 SNPs revealed association of the frizzle locus with a keratin gene-enriched region within the linkage group E22C19W28_E50C23. Sequence analyses of the keratin gene cluster identified a 69 bp in-frame deletion in a conserved region of KRT75, an α-keratin gene. Retroviral-mediated expression of the mutated F cDNA in the wild-type rectrix qualitatively changed the bending of the rachis with some features of frizzle feathers including irregular kinks, severe bending near their distal ends, and substantially higher variations among samples in comparison to normal feathers. These results confirmed KRT75 as the F gene. This study demonstrates the potential of our approach for identifying genetic determinants of feather forms.

Homozygous truncating PTPRF mutation causes athelia.

Athelia is a very rare entity that is defined by the absence of the nipple-areola complex. It can affect either sex and is mostly part of syndromes including other congenital or ectodermal anomalies, such as limb-mammary syndrome, scalp-ear-nipple syndrome, or ectodermal dysplasias. Here, we report on three children from two branches of an extended consanguineous Israeli Arab family, a girl and two boys, who presented with a spectrum of nipple anomalies ranging from unilateral hypothelia to bilateral athelia but no other consistently associated anomalies except a characteristic eyebrow shape. Using homozygosity mapping after single nucleotide polymorphism (SNP) array genotyping and candidate gene sequencing we identified a homozygous frameshift mutation in PTPRF as the likely cause of nipple anomalies in this family. PTPRF encodes a receptor-type protein phosphatase that localizes to adherens junctions and may be involved in the regulation of epithelial cell-cell contacts, peptide growth factor signaling, and the canonical Wnt pathway. Together with previous reports on female mutant Ptprf mice, which have a lactation defect, and disruption of one allele of PTPRF by a balanced translocation in a woman with amastia, our results indicate a key role for PTPRF in the development of the nipple-areola region.