Special Article: Physical Activity, Physical Fitness, and Cardiovascular Risk Factors in Childhood

In adults, physical activity and exercise training are associated with reduced cardiovascular morbidity and mortality, a reduced likelihood of developing adverse cardiovascular risk factors, and improved insulin sensitivity. In childhood, participation in appropriate physical activity may prevent the development of cardiovascular risk factors in the future and complement treatment of existing cardiovascular risk factors, including hypertension, dyslipidemia, and overweight. Exercise in children can also significantly improve insulin sensitivity independent of weight loss. These e fects are mediated in overweight children by increases in lean body mass relative to fat mass and associated improvements in inflammatory mediators, endothelial function, and the associated adverse hormonal milieu

Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

Vitamin D in the general population of young adults with autism in the Faroe Islands

Vitamin D deficiency has been proposed as a possible risk factor for developing autism spectrum disorder (ASD). 25-Hydroxyvitamin D3 (25(OH)D3) levels were examined in a cross-sectional population-based study in the Faroe Islands. The case group consisting of a total population cohort of 40 individuals with ASD (aged 15–24 years) had significantly lower 25(OH)D3 than their 62 typically-developing siblings and their 77 parents, and also significantly lower than 40 healthy age and gender matched comparisons. There was a trend for males having lower 25(OH)D3 than females. Effects of age, month/season of birth, IQ, various subcategories of ASD and Autism Diagnostic Observation Schedule score were also investigated, however, no association was found. The very low 25(OH)D3 in the ASD group suggests some underlying pathogenic mechanism

No straight lines – young women’s perceptions of their mental health and wellbeing during and after pregnancy: a systematic review and meta-ethnography

Background: Young mothers face mental health challenges during and after pregnancy including increased rates of depression compared to older mothers. While the prevention of teenage pregnancy in countries such as the United States and the United Kingdom has been a focus for policy and research in recent decades, the need to understand young women’s own experiences has been highlighted. The aim of this meta-ethnography was to examine young women’s perceptions of their mental health and wellbeing during and after pregnancy to provide new understandings of those experiences. Methods: A systematic review and meta-ethnographic synthesis of qualitative research was conducted. Seven databases were systematically searched and forward and backward searching conducted. Papers were included if they were from Organisation for Economic Co-operation and Development countries and explored mental health and wellbeing experiences of young mothers (age under 20 in pregnancy; under 25 at time of research) as a primary research question – or where evidence about mental health and wellbeing from participants was foregrounded. Nineteen papers were identified and the Critical Appraisal Skills Programme checklist for qualitative research used to appraise the evidence. Following the seven-step process of meta-ethnography, key constructs were examined within each study and then translated into one another. Results: Seven translated themes were identified forming a new line of argument wherein mental health and wellbeing was analysed as relating to individual bodily experiences; tied into past and present relationships; underpinned by economic insecurity and entangled with feelings of societal surveillance. There were ‘no straight lines’ in young women’s experiences, which were more complex than dominant narratives around overcoming adversity suggest. Conclusions: The synthesis concludes that health and social care professionals need to reflect on the operation of power and stigma in young women’s lives and its impact on wellbeing. It adds to understanding of young women’s mental health and wellbeing during and after pregnancy as located in physical and structural factors rather than individual capacities alone

How Do Bone Marrow Lesions Cause Osteoarthritis Pain? a Structural and Functional Tissue-Based Study

Background/Purpose: Susceptibility to ankylosing spondylitis (AS) is primarily genetic; thus far 113 susceptibility variants for AS have been identified. However, most of the AS associated SNPs do not directly affect protein-coding genes. Studies of disease- and trait-associated SNPs suggest they may act by affecting gene regulatory regions in specific cell types or tissues. Therefore, identifying the AS relevant cell types is crucial for further mechanistic studies. Methods: We applied several bioinformatics methods to utilize epigenetic, gene and protein expression information to identify the primary relevant cell types through which genetic variants associated with AS operate. In total, there are 113 AS associated loci; 39 of them show genome-wide significance in AS-only analyses, whereas the remainder are genome-wide significant in analyses leveraging pleiotrophy with other related diseases (Crohn’s disease (CD), psoriasis, primary sclerosing cholangitis (PSC) and ulcerative colitis (UC))1. Results: AS-associated SNPs are disproportionately found in regions bearing epigenetic marks indicating transcriptional activity found in immune cell types including monocytes, CD4+ and CD8+ T cells, NK cells, regulatory T cells, and B cells. Gene expression studies showed enrichment of AS associated loci in genes specifically expressed in monocytes and NK cells while protein expression study shows protein products of AS associated loci were significantly enriched in CD8+ T cells. Epigenetic analyses also showed evidence that AS-associated signals operate in gut cell types including in mucosa from the small intestine, sigmoid colon and rectum. These findings particularly relate to pleiotropic loci also associated with IBD, psoriasis, and PSC. Conclusion: These findings highlight the role of key immune cell types in the mechanism by which genetic associations with AS drive the disease, as well as providing further evidence for the involvement of the gut in the pathogenesis of AS. 1Ellinghaus D. at al, Nature Genetics 201

The what and where of adding channel noise to the Hodgkin-Huxley equations

One of the most celebrated successes in computational biology is the Hodgkin-Huxley framework for modeling electrically active cells. This framework, expressed through a set of differential equations, synthesizes the impact of ionic currents on a cell's voltage -- and the highly nonlinear impact of that voltage back on the currents themselves -- into the rapid push and pull of the action potential. Latter studies confirmed that these cellular dynamics are orchestrated by individual ion channels, whose conformational changes regulate the conductance of each ionic current. Thus, kinetic equations familiar from physical chemistry are the natural setting for describing conductances; for small-to-moderate numbers of channels, these will predict fluctuations in conductances and stochasticity in the resulting action potentials. At first glance, the kinetic equations provide a far more complex (and higher-dimensional) description than the original Hodgkin-Huxley equations. This has prompted more than a decade of efforts to capture channel fluctuations with noise terms added to the Hodgkin-Huxley equations. Many of these approaches, while intuitively appealing, produce quantitative errors when compared to kinetic equations; others, as only very recently demonstrated, are both accurate and relatively simple. We review what works, what doesn't, and why, seeking to build a bridge to well-established results for the deterministic Hodgkin-Huxley equations. As such, we hope that this review will speed emerging studies of how channel noise modulates electrophysiological dynamics and function. We supply user-friendly Matlab simulation code of these stochastic versions of the Hodgkin-Huxley equations on the ModelDB website (accession number 138950) and http://www.amath.washington.edu/~etsb/tutorials.html.Comment: 14 pages, 3 figures, review articl

Sharing Data for Public Health Research by Members of an International Online Diabetes Social Network

Background: Surveillance and response to diabetes may be accelerated through engaging online diabetes social networks (SNs) in consented research. We tested the willingness of an online diabetes community to share data for public health research by providing members with a privacy-preserving social networking software application for rapid temporal-geographic surveillance of glycemic control. Methods and Findings: SN-mediated collection of cross-sectional, member-reported data from an international online diabetes SN entered into a software applicaction we made available in a “Facebook-like” environment to enable reporting, charting and optional sharing of recent hemoglobin A1c values through a geographic display. Self-enrollment by 17% (n = 1,136) of n = 6,500 active members representing 32 countries and 50 US states. Data were current with 83.1% of most recent A1c values reported obtained within the past 90 days. Sharing was high with 81.4% of users permitting data donation to the community display. 34.1% of users also displayed their A1cs on their SN profile page. Users selecting the most permissive sharing options had a lower average A1c (6.8%) than users not sharing with the community (7.1%, p = .038). 95% of users permitted re-contact. Unadjusted aggregate A1c reported by US users closely resembled aggregate 2007–2008 NHANES estimates (respectively, 6.9% and 6.9%, p = 0.85). Conclusions: Success within an early adopter community demonstrates that online SNs may comprise efficient platforms for bidirectional communication with and data acquisition from disease populations. Advancing this model for cohort and translational science and for use as a complementary surveillance approach will require understanding of inherent selection and publication (sharing) biases in the data and a technology model that supports autonomy, anonymity and privacy.Centers for Disease Control and Prevention (U.S.) (P01HK000088-01)Centers for Disease Control and Prevention (U.S.) (P01HK000016 )National Institute of Alcohol Abuse and Alcoholism (U.S.) (R21 AA016638-01A1)National Center for Research Resources (U.S.) (1U54RR025224-01)Children's Hospital (Boston, Mass.) (Program for Patient Safety and Quality

US public opinion regarding proposed limits on resident physician work hours

<p>Abstract</p> <p>Background</p> <p>In both Europe and the US, resident physician work hour reduction has been a source of controversy within academic medicine. In 2008, the Institute of Medicine (IOM) recommended a reduction in resident physician work hours. We sought to assess the American public perspective on this issue.</p> <p>Methods</p> <p>We conducted a national survey of 1,200 representative members of the public via random digit telephone dialing in order to describe US public opinion on resident physician work hour regulation, particularly with reference to the IOM recommendations.</p> <p>Results</p> <p>Respondents estimated that resident physicians currently work 12.9-h shifts (95% CI 12.5 to 13.3 h) and 58.3-h work weeks (95% CI 57.3 to 59.3 h). They believed the maximum shift duration should be 10.9 h (95% CI 10.6 to 11.3 h) and the maximum work week should be 50 h (95% CI 49.4 to 50.8 h), with 1% approving of shifts lasting >24 h (95% CI 0.6% to 2%). A total of 81% (95% CI 79% to 84%) believed reducing resident physician work hours would be very or somewhat effective in reducing medical errors, and 68% (95% CI 65% to 71%) favored the IOM proposal that resident physicians not work more than 16 h over an alternative IOM proposal permitting 30-h shifts with ≥5 h protected sleep time. In all, 81% believed patients should be informed if a treating resident physician had been working for >24 h and 80% (95% CI 78% to 83%) would then want a different doctor.</p> <p>Conclusions</p> <p>The American public overwhelmingly favors discontinuation of the 30-h shifts without protected sleep routinely worked by US resident physicians and strongly supports implementation of restrictions on resident physician work hours that are as strict, or stricter, than those proposed by the IOM. Strong support exists to restrict resident physicians' work to 16 or fewer consecutive hours, similar to current limits in New Zealand, the UK and the rest of Europe.</p

Living with foot and ankle disorders in rheumatic and musculoskeletal diseases: A systematic review of qualitative studies to inform the work of the OMERACT Foot and Ankle Working Group

Objectives This study aimed to determine outcome domains of importance to patients living with foot and ankle disorders in rheumatic and musculoskeletal diseases (RMDs), by exploring the symptoms and impact of these disorders reported in existing qualitative studies. Methods Six databases were searched from inception to March 2022. Studies were included if they used qualitative interview or focus group methods, were published in English, and involved participants living with RMDs (inflammatory arthritis, osteoarthritis, crystal arthropathies, connective tissue diseases, and musculoskeletal conditions in the absence of systemic disease) who had experienced foot and ankle problems. Quality was assessed using the Critical Appraisal Skills Programme qualitative tool and confidence in the findings was assessed using the Grading of Recommendations Assessment, Development and Evaluation Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) approach. All data from the results section of included studies were extracted, coded and synthesised to develop themes. Results Of 1,443 records screened, 34 studies were included, with a total of 503 participants. Studies included participants with rheumatoid arthritis (n = 18), osteoarthritis (n = 5), gout (n = 3), psoriatic arthritis (n = 1), lupus (n = 1), posterior tibial tendon dysfunction (n = 1), plantar heel pain (n = 1), Achilles tendonitis (n = 1), and a mixed population (n = 3), who live with foot and ankle disorders. Seven descriptive themes were generated from the thematic synthesis: pain, change in appearance, activity limitations, social isolation, work disruption, financial burden and emotional impact. Descriptive themes were inductively analysed further to construct analytical themes relating to potential outcome domains of importance to patients. Foot or ankle pain was the predominant symptom experienced by patients across all RMDs explored in this review. Based on grading of the evidence, we had moderate confidence that most of the review findings represented the experiences of patients with foot and ankle disorders in RMDs. Conclusions Findings indicate that foot and ankle disorders impact on multiple areas of patients’ lives, and patients’ experiences are similar regardless of the RMD. This study will inform the development of a core domain set for future foot and ankle research and are also useful for clinicians, helping to focus clinical appointments and measurement of outcomes within clinical practice

A multi-dimensional investigation of self-regulated learning in a blended classroom context : a case study on eLDa MOOC

Online systems such as massive open online courses (MOOCs) are new innovative learning technology in education. With the proliferation of MOOC systems, little has been mentioned about blended MOOC system and how it enhances students’ performance. Blended classroom is a form of learning taking place between two different activities of which one is online and the other is traditional teaching method using bricks and mortal classroom settings. This study reveals the effectiveness of blended classroom teaching for an undergraduate course. The module was embedded in an eLDa MOOC platform, which is a platform for delivery computing concepts, and Python programme course. This research aims to investigate students’ perceptions of self-regulated learning (SRL) habits. A multi-dimensional survey was designed to evaluate each aspect of SRL skills, motivation and attaining better grades within the course. This research analysis explores (a) cognitive process of students improving their self-regulated learning skills (b) potential of students’ preparedness and motivation to engage with the course content in a blended context (c) potential difference in addressing the relation among the methods of engagement and achievement in their weekly assessment results. The research applied an online self-regulated learning questionnaire (OSLQ) as the instrument for measuring the self-regulated learning skills of the students in the learning platform environment. In relation to developing a revised OSLQ to address the use of the instrument to measure self-regulated learning in an online blended classroom context. Data collection process was conducted on a sample of first year undergraduate students who took a seminar module via a blended course format. The results indicate the level of self-regulated learning explored from the measure of the self-regulation in the blended learning environment in this study