An intervention with dance and yoga for girls with functional abdominal pain disorders (Just in TIME): Protocol for a randomized controlled trial

©Anna Philipson, Stefan Särnblad, Lars Ekstav, Mats Eriksson, Ulrika L Fagerberg, Margareta Möller, Evalotte Mörelius, Anna Duberg. Background: Functional abdominal pain disorders (FAPDs) affect many children worldwide, predominantly girls, and cause considerable long-term negative consequences for individuals and society. Evidence-based and cost-effective treatments are therefore strongly needed. Physical activity has shown promising effects in the practical management of FAPDs. Dance and yoga are both popular activities that have been shown to provide significant psychological and pain-related benefits with minimal risk. The activities complement each other, in that dance involves dynamic, rhythmic physical activity, while yoga enhances relaxation and focus. Objective: This study aims to evaluate the effects of a dance and yoga intervention among girls aged 9 to 13 years with FAPDs. Methods: The study is a prospective randomized controlled trial among girls aged 9 to 13 years with functional abdominal pain, irritable bowel syndrome, or both. The target sample size was 150 girls randomized into 2 arms: an intervention arm that receives dance and yoga sessions twice weekly for 8 months and a control arm that receives standard care. Outcomes will be measured at baseline and after 4, 8, 12, and 24 months, and long-term follow-up will be conducted 5 years from baseline. Questionnaires, interviews, and biomarker measures, such as cortisol in saliva and fecal microbiota, will be used. The primary outcome is the proportion of girls in each group with reduced pain, as measured by the faces pain scale-revised in a pain diary, immediately after the intervention. Secondary outcomes are gastrointestinal symptoms, general health, mental health, stress, and physical activity. The study also includes qualitative evaluations and health economic analyses. This study was approved by the Regional Ethical Review Board in Uppsala (No. 2016/082 1-2). Results: Data collection began in October 2016. The intervention has been performed in 3 periods from 2016 through 2019. The final 5-year follow-up is anticipated to be completed by fall 2023. Conclusions: Cost-effective and easily accessible interventions are warranted to reduce the negative consequences arising from FAPDs in young girls. Physical activity is an effective strategy, but intervention studies are needed to better understand what types of activities facilitate regular participation in this target group. The Just in TIME (Try, Identify, Move, and Enjoy) study will provide insights regarding the effectiveness of dance and yoga and is anticipated to contribute to the challenging work of reducing the burden of FAPDs for young girls

joineRML: a joint model and software package for time-to-event and multivariate longitudinal outcomes

Background: Joint modelling of longitudinal and time-to-event outcomes has received considerable attention over recent years. Commensurate with this has been a rise in statistical software options for fitting these models. However, these tools have generally been limited to a single longitudinal outcome. Here, we describe the classical joint model to the case of multiple longitudinal outcomes, propose a practical algorithm for fitting the models, and demonstrate how to fit the models using a new package for the statistical software platform R, joineRML. Results: A multivariate linear mixed sub-model is specified for the longitudinal outcomes, and a Cox proportional hazards regression model with time-varying covariates is specified for the event time sub-model. The association between models is captured through a zero-mean multivariate latent Gaussian process. The models are fitted using a Monte Carlo Expectation-Maximisation algorithm, and inferences are based on approximate standard errors from the empirical profile information matrix, which are contrasted to an alternative bootstrap estimation approach. We illustrate the model and software on a real data example for patients with primary biliary cirrhosis with three repeatedly measured biomarkers. Conclusions: An open-source software package capable of fitting multivariate joint models is available. The underlying algorithm and source code makes use of several methods to increase computational speed

The C-terminal cysteine annulus participates in auto-chaperone function for Salmonella phage P22 tailspike folding and assembly

Elongated trimeric adhesins are a distinct class of proteins employed by phages and viruses to recognize and bind to their host cells, and by bacteria to bind to their target cells and tissues. The tailspikes of E. coli phage K1F and Bacillus phage Ø29 exhibit auto-chaperone activity in their trimeric C-terminal domains. The P22 tailspike is structurally homologous to those adhesins. Though there are no disulfide bonds or reactive cysteines in the native P22 tailspikes, a set of C-terminal cysteines are very reactive in partially folded intermediates, implying an unusual local conformation in the domain. This is likely to be involved in the auto-chaperone function. We examined the unusual reactivity of C-terminal tailspike cysteines during folding and assembly as a potential reporter of auto-chaperone function. Reaction with IAA blocked productive refolding in vitro, but not off-pathway aggregation. Two-dimensional PAGE revealed that the predominant intermediate exhibiting reactive cysteine side chains was a partially folded monomer. Treatment with reducing reagent promoted native trimer formation from these species, consistent with transient disulfide bonds in the auto-chaperone domain. Limited enzymatic digestion and mass spectrometry of folding and assembly intermediates indicated that the C-terminal domain was compact in the protrimer species. These results indicate that the C-terminal domain of the P22 tailspike folds itself and associates prior to formation of the protrimer intermediate, and not after, as previously proposed. The C-terminal cysteines and triple β-helix domains apparently provide the staging for the correct auto-chaperone domain formation, needed for alignment of P22 tailspike native trimer

MAES Service Case: Wetland ecosystem condition mapping (v.1.0)

SWOS Technical publicationThe MAES working group is preparing the workshop on “ecosystem condition mapping” to streamline the efforts done so far with regards to the mapping and assessment of the condition of Europe’s ecosystems. The MAES WG has requested directly to SWOS partners a specific document to support the mapping and assessing wetland ecosystem condition for this workshop. This document shall highlight the different elements to take into account for the mapping and assessment of wetland ecosystems with the aim of supporting Member States and the European Commission in their efforts to better describe the situation of wetland ecosystems in Europe. This document represents the major output of the MAES Service case that shall show how SWOS outputs are useful to support the MAES WG with regards to wetland ecosystem mapping and assessment

Femininity, Childhood and the Non-Making of a Sporting Celebrity: The Beth Tweddle Case

Gymnastics is regularly classified as a feminine-appropriate sport, embodying grace and elegance and is an Olympic sport which has regularly produced female sporting celebrities. Beth Tweddle is the most successful British gymnast of all time and the first to achieve international success, culminating in a medal at London 2012, yet she has received relatively little media coverage and few corporate endorsements. Employing a 'negative case' methodology, this athlete's relative lack of celebrity is investigated. The article suggests that it can be explained by (a) contradictions underpinning the gender-designation of gymnastics, and (b) the social invisibility of a core audience for the sport: young girls. An implication is that the achievement of celebrity within 'feminine' sport may be increasingly unattainable, especially for female athletes. The article uses mixed methods, including primary analysis of print and social media and secondary analysis of a national survey of young people in the UK

Tooth Discoloration in Patients With Neonatal Diabetes After Transfer Onto Glibenclamide: A previously unreported side effect

PublishedJournal ArticleMulticenter StudyResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tOBJECTIVE To assess if tooth discoloration is a novel side effect of sulfonylurea therapy in patients with permanent neonatal diabetes due to mutations in KCNJ11. RESEARCH DESIGN AND METHODS A total of 67 patients with a known KCNJ11 mutation who had been successfully transferred from insulin injections onto oral sulfonylureas were contacted and asked about the development of tooth discoloration after transfer. RESULTS Altered tooth appearance was identified in 5 of the 67 patients. This was variable in severity, ranging from mild discoloration/staining (n = 4) to loss of enamel (n = 1) and was only seen in patients taking glibenclamide (glyburide). CONCLUSIONS These previously unreported side effects may relate to the developing tooth and/or to the high local concentrations in the children who frequently chewed glibenclamide tablets or took it as a concentrated solution. Given the multiple benefits of sulfonylurea treatment for patients with activating KCNJ11 mutations, this association warrants further investigation but should not preclude such treatment.This work was funded by the Welcome Trust (grant 067463/Z/2/Z), National Institutes of Health Grants DK-44752 and DK-20595, and a gift from the Kovler Family Foundation. S.E.F. is the Sir Graham Wilkins, Peninsula Medical School Research Fellow. A.T.H. is a Welcome Trust Research Leave Fellow. O.R.-C. was supported by an “Ayuda para contratos post-Formacio´n Sanitaria Especializada” from the “Instituto de Salud Carlos III” (FIS CM06/00013

Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic β cells

Insulin resistance, hyperinsulinemia, and hyperproinsulinemia occur early in the pathogenesis of type 2 diabetes (T2D). Elevated levels of proinsulin and proinsulin intermediates are markers of β-cell dysfunction and are strongly associated with development of T2D in humans. However, the mechanism(s) underlying β-cell dysfunction leading to hyperproinsulinemia is poorly understood. Here, we show that disruption of insulin receptor (IR) expression in β cells has a direct impact on the expression of the convertase enzyme carboxypeptidase E (CPE) by inhibition of the eukaryotic translation initiation factor 4 gamma 1 translation initiation complex scaffolding protein that is mediated by the key transcription factors pancreatic and duodenal homeobox 1 and sterol regulatory element-binding protein 1, together leading to poor proinsulin processing. Reexpression of IR or restoring CPE expression each independently reverses the phenotype. Our results reveal the identity of key players that establish a previously unknown link between insulin signaling, translation initiation, and proinsulin processing, and provide previously unidentified mechanistic insight into the development of hyperproinsulinemia in insulin-resistant states