Identifying app components that promote physical activity: a group concept mapping study.

Background: Digital interventions are a promising avenue to promote physical activity in healthy adults. Current practices recommend to include end-users early on in the development process. This study focuses on the wishes and needs of users regarding an a mobile health (mHealth) application that promotes physical activity in healthy adults, and on the differences between participants who do or do not meet the World Health Organization's recommendation of an equivalent of 150 minutes of moderate intensity physical activity. Methods: We used a mixed-method design called Group Concept Mapping. In a first phase, we collected statements completing the prompt "In an app that helps me move more, I would like to see/ do/ learn the following…" during four brainstorming sessions with physically inactive individuals (n = 19). The resulting 90 statements were then sorted and rated by a new group of participants (n = 46). Sorting data was aggregated, and (dis)similarity matrices were created using multidimensional scaling. Hierarchical clustering was applied using Ward's method. Analyses were carried out for the entire group, a subgroup of active participants and a subgroup of inactive participants. Explorative analyses further investigated ratings of the clusters as a function of activity level, gender, age and education. Results: Six clusters of statements were identified, namely 'Ease-of-use and Self-monitoring', 'Technical Aspects and Advertisement', 'Personalised Information and Support', 'Motivational Aspects', 'Goal setting, goal review and rewards', and 'Social Features'. The cluster 'Ease-of-use and Self-monitoring' was rated highest in the overall group and the active subgroup, whereas the cluster 'Technical Aspects and Advertisement' was scored as most relevant in the inactive subgroup. For all groups, the cluster 'Social Features' was scored the lowest. Explorative analysis revealed minor between-group differences. Discussion: The present study identified priorities of users for an mHealth application that promotes physical activity. First, the application should be user-friendly and accessible. Second, the application should provide personalized support and information. Third, users should be able to monitor their behaviour and compare their current activity to their past performance. Fourth, users should be provided autonomy within the app, such as over which and how many notifications they would like to receive, and whether or not they want to engage with social features. These priorities can serve as guiding principles for developing mHealth applications to promote physical activity in the general population.

Hyperhidrosis and Hypermobility Spectrum Disorders Among Adolescents.

This cross-sectional study assesses the prevalence and risk of excessive sweating and joint hypermobility in Israeli adolescents aged 16 to 19 years.

The relationship of affective and bodily states with goals and plans to increase physical activity: An 8-day study in students.

Planning is an important tool to translate intentions into physical activity (PA) behavior. Affective and bodily states are known to influence how much PA individuals perform, but their impact on to formulation of PA plans is not yet known. The aim of the current study is to explore the effect of within- and between-subject variations in affective and bodily states on the content of PA goals and plans. Over eight consecutive days, 362 students created action and coping plans to achieve their daily PA goals. They also reported their affective and bodily states. Generalized linear mixed effect models were used to analyze the associations between these states and the content of the goals and plans. The results showed that both between- and within-subject variations in affective and bodily states were associated with goals formulated in terms of minutes, the intensity and context of planned activities, and anticipated barriers, though more effects were found for within-subject differences. Affective and bodily states impact daily PA goals and plans, highlighting the dynamic nature of planning. Our findings can be a first step toward personalized suggestions for goals, action plans, and coping strategies that are based on individual affective and bodily states.

Building on Existing Classifications of Behavior Change Techniques to Classify Planned Coping Strategies: Physical Activity Diary Study.

BACKGROUND: When trying to be more physically active, preparing for possible barriers by considering potential coping strategies increases the likelihood of plan enactment. Digital interventions can support this process by providing personalized recommendations for coping strategies, but this requires that possible coping strategies are identified and classified. Existing classification systems of behavior change, such as the compendium of self-enactable techniques, may be reused to classify coping strategies in the context of physical activity (PA) coping planning. OBJECTIVE: This study investigated whether coping strategies created by a student population to overcome barriers to be physically active can be mapped onto the compendium of self-enactable techniques and which adaptations or additions to the frameworks are needed. METHODS: In total, 359 Flemish university students created action and coping plans for PA for 8 consecutive days in 2020, resulting in 5252 coping plans. A codebook was developed iteratively using the compendium of self-enactable techniques as a starting point to code coping strategies. Additional codes were added to the codebook iteratively. Interrater reliability was calculated, and descriptive statistics were provided for the coping strategies. RESULTS: Interrater reliability was moderate (Cohen κ=0.72) for the coded coping strategies. Existing self-enactable techniques covered 64.6% (3393/5252) of the coded coping strategies, and added coping strategies covered 28.52% (n=1498). The remaining coping strategies could not be coded as entries were too vague or contained no coping strategy. The added classes covered multiple ways of adapting the original action plan, managing one's time, ensuring the availability of required material, and doing the activity with someone else. When exploring the data further, we found that almost half (n=2371, 45.1%) of the coping strategies coded focused on contextual factors. CONCLUSIONS: The study's objective was to categorize PA coping strategies. The compendium of self-enactable techniques addressed almost two-thirds (3393/5252, 64.6%) of these strategies, serving as valuable starting points for classification. In total, 9 additional strategies were integrated into the self-enactable techniques, which are largely absent in other existing classification systems. These new techniques can be seen as further refinements of "problem-solving" or "coping planning." Due to data constraints stemming from the COVID-19 pandemic and the study's focus on a healthy Flemish student population, it is anticipated that more coping strategies would apply under normal conditions, in the general population, and among clinical groups. Future research should expand to diverse populations and establish connections between coping strategies and PA barriers, with ontologies recommended for this purpose. This study is a first step in classifying the content of coping strategies for PA. We believe this is an important and necessary step toward digital health interventions that incorporate personalized suggestions for PA coping plans.

Body mass index and migraine in adolescence: A nationwide study.

BACKGROUND: The association between body mass index (BMI) and migraine in adults has been well established. However, studies in children and adolescents are inconclusive. We aimed to study the association between BMI and migraine using a national dataset that comprises the electronic medical records of more than two million adolescents. METHODS: This study included all Israeli adolescents (57.7% males, 42.3% females; mean age 17 years) who were medically assessed before mandatory military service during 1990-2020. As part of the pre-recruitment medical assessment, all the adolescents were screened for migraine and their height and weight were measured. Diagnoses of migraine were confirmed by board-certified neurologists. Prevalences and odds ratios (ORs) for migraine were computed across BMI subgroups. Spline models were applied. RESULTS: A total of 2,094,862 adolescents were included, of whom 57,385 (2.8%) had active migraine. Among males, the adjusted ORs for migraine were 1.11 (95% confidence interval, 1.06-1.16), 1.13 (1.08-1.17), and 1.24 (1.19-1.30), for the underweight, overweight, and obesity subgroups, respectively, compared to the reference group of low-normal BMI (5th-49th percentile). Among females, the respective adjusted ORs were 1.12 (1.05-1.19), 1.23 (1.19-1.28), and 1.38 (1.31-1.46). Results persisted in sensitivity analyses accounting for other medical and psychiatric comorbidities and parental history of migraine. Spline models demonstrated a J-shaped relation between BMI and migraine. CONCLUSIONS: Both adolescent obesity and underweight were associated with migraine in a sex-dependent manner. This association peaked in female adolescents with overweight and obesity.

Hypermobility spectrum disorders and irritable bowel syndrome: A nationwide study of 1.6 million adolescents.

BACKGROUND AND AIM: The association between hypermobility spectrum disorders/hypermobile type Ehlers-Danlos syndrome (HDS/hEDS) and irritable bowel syndrome (IBS) is yet to be clarified. We aimed to assess this association in a national sample of adolescents. METHODS: A population-based cross-sectional study included 1 627 345 Israeli adolescents (58% male; mean age 17 years) who were medically assessed before compulsory military service during 1998-2020. Diagnoses of HSD/hEDS and IBS were confirmed by board-certified specialists. The prevalence and odds ratios (ORs) for IBS in adolescents with and without HSD/hEDS were computed. RESULTS: A total of 4686 adolescents (2553 male) with HSD/hEDS were identified, of whom 71 were diagnosed with IBS (prevalence = 1.5%). Of the 1 621 721 adolescents in the control group, 8751 were diagnosed with IBS (prevalence = 0.5%). Unadjusted logistic regression revealed a significant association between HSD/hEDS and IBS (OR = 2.16 [95% confidence interval, CI, 1.90-2.45]), which persisted in multivariable adjusted models (OR = 2.58 [95% CI, 2.02-3.24]), and in several sensitivity analyses. The association was evident in both male and female adolescents with ORs of 2.60 (95% CI, 1.87-3.49), and 2.46 (95% CI, 1.66-3.49), respectively. The association was accentuated in a sensitivity analysis accounting for other medical and psychiatric comorbidities. CONCLUSIONS: We found a significant association between HSD/hEDS and IBS in both male and female adolescents. Clinical awareness of the association can promote early diagnosis of IBS and appropriate multidisciplinary treatment. Further research is required to identify the common pathological pathways of the conditions and to develop new IBS treatment strategies for people with HSD/hEDS.

Hypermobility spectrum disorders and active migraine in Israeli adolescents: A nationwide study.

OBJECTIVE: To assess the association between hypermobility spectrum disorders/hypermobile type Ehlers Danlos Syndrome (HSD/hEDS) and migraine in a national sample of adolescents in Israel. BACKGROUND: The association between HSD/hEDS and migraine is unclear, even more so in pediatric populations. METHODS: This population-based, cross-sectional study included 1,627,345 Israeli adolescents (945,519/1,626,407 [58%] males; mean age 17 ± 0.5 years) who were medically assessed before mandatory military service during 1998-2020. Diagnoses of migraine with at least one attack per month (active migraine) and HSD/hEDS were confirmed by certified specialists. The prevalences of active migraine in adolescents with and without HSD/hEDS were computed and the association between HSD/hEDS and active migraine was examined. RESULTS: Active migraine was significantly more prevalent in adolescents with HSD/hEDS (307/4686 [6.5%]) compared to those without HSD/hEDS (51,931/1,621,721 [3.2%]) (OR = 2.16, 95% CI 1.90-2.45). The association between HSD/hEDS and active migraine persisted in a multivariable analysis (OR = 2.08, 95% CI 1.85-2.34) and in several sensitivity analyses. CONCLUSIONS: We found a significant association between HSD/hEDS and active migraine in both male and female adolescents. Clinical awareness of the association can promote early diagnosis and treatment of migraine. Further research is required to identify appropriate pharmacologic and nonpharmacologic migraine treatment strategies for individuals with HSD/hEDS.

Content and quality of physical activity ontologies: a systematic review.

INTRODUCTION: Ontologies are a formal way to represent knowledge in a particular field and have the potential to transform the field of health promotion and digital interventions. However, few researchers in physical activity (PA) are familiar with ontologies, and the field can be difficult to navigate. This systematic review aims to (1) identify ontologies in the field of PA, (2) assess their content and (3) assess their quality. METHODS: Databases were searched for ontologies on PA. Ontologies were included if they described PA or sedentary behavior, and were available in English language. We coded whether ontologies covered the user profile, activity, or context domain. For the assessment of quality, we used 12 criteria informed by the Open Biological and Biomedical Ontology (OBO) Foundry principles of good ontology practice. RESULTS: Twenty-eight ontologies met the inclusion criteria. All ontologies covered PA, and 19 included information on the user profile. Context was covered by 17 ontologies (physical context, n = 12; temporal context, n = 14; social context: n = 5). Ontologies met an average of 4.3 out of 12 quality criteria. No ontology met all quality criteria. DISCUSSION: This review did not identify a single comprehensive ontology of PA that allowed reuse. Nonetheless, several ontologies may serve as a good starting point for the promotion of PA. We provide several recommendations about the identification, evaluation, and adaptation of ontologies for their further development and use.

A deep look into the storm: Israeli multi-center experience of coronavirus disease 2019 (COVID-19) in patients with autoimmune inflammatory rheumatic diseases before and after vaccinations.

Objective: We aimed to characterize the course of COVID-19 in autoimmune inflammatory rheumatic disease (AIIRD) patients in Israel, taking into consideration several remarkable aspects, including the outcomes of the different outbreaks, the effect of vaccination campaigns, and AIIRD activity post-recovery. Methods: We established a national registry of AIIRD patients diagnosed with COVID-19, including demographic data, AIIRD diagnosis, duration and systemic involvement, comorbidities, date of COVID-19 diagnosis, clinical course, and dates of vaccinations. COVID-19 was diagnosed by a positive SARS-CoV-2 polymerase chain reaction. Results: Israel experienced 4 outbreaks of COVID-19 until 30.11.2021. The first three outbreaks (1.3.2020 - 30.4.2021) comprised 298 AIIRD patients. 64.9% had a mild disease and 24.2% had a severe course; 161 (53.3%) patients were hospitalized, 27 (8.9%) died. The 4th outbreak (delta variant), starting 6 months after the beginning of the vaccination campaign comprised 110 patients. Despite similar demographic and clinical characteristics, a smaller proportion of AIIRD patients had negative outcomes as compared to the first 3 outbreaks, with regards to severity (16 patients,14.5%), hospitalization (29 patients, 26.4%) and death (7 patients, 6.4%). COVID-19 did not seem to influence the AIIRD activity 1-3 months post-recovery. Conclusions: COVID-19 is more severe and has an increased mortality in active AIIRD patients with systemic involvement, older age and comorbidities. Vaccination with 3 doses of the mRNA vaccine against SARS-CoV-2 protected from severe COVID-19, hospitalization and death during the 4th outbreak. The pattern of spread of COVID-19 in AIIRD patients was similar to the general population.

Transcriptome changes in DM1 patients' tissues are governed by the RNA interference pathway.

Myotonic dystrophy type 1 (DM1) is a multisystemic disease caused by pathogenic expansions of CTG repeats. The expanded repeats are transcribed to long RNA and induce cellular toxicity. Recent studies suggest that the CUG repeats are processed by the RNA interference (RNAi) pathway to generate small interfering repeated RNA (siRNA). However, the effects of the CTG repeat-derived siRNAs remain unclear. We hypothesize that the RNAi machinery in DM1 patients generates distinct gene expression patterns that determine the disease phenotype in the individual patient. The abundance of genes with complementary repeats that are targeted by siRNAs in each tissue determines the way that the tissue is affected in DM1. We integrated and analyzed published transcriptome data from muscle, heart, and brain biopsies of DM1 patients, and revealed shared, characteristic changes that correlated with disease phenotype. These signatures are overrepresented by genes and transcription factors bearing endogenous CTG/CAG repeats and are governed by aberrant activity of the RNAi machinery, miRNAs, and a specific gain-of-function of the CTG repeats. Computational analysis of the DM1 transcriptome enhances our understanding of the complex pathophysiology of the disease and may reveal a path for cure.

Asymmetric inheritance of RNA toxicity in C. elegans expressing CTG repeats.

Nucleotide repeat expansions are a hallmark of over 40 neurodegenerative diseases and cause RNA toxicity and multisystemic symptoms that worsen with age. Through an unclear mechanism, RNA toxicity can trigger severe disease manifestation in infants if the repeats are inherited from their mother. Here we use Caenorhabditis elegans bearing expanded CUG repeats to show that this asymmetric intergenerational inheritance of toxicity contributes to disease pathogenesis. In addition, we show that this mechanism is dependent on small RNA pathways with maternal repeat-derived small RNAs causing transcriptomic changes in the offspring, reduced motility, and shortened lifespan. We rescued the toxicity phenotypes in the offspring by perturbing the RNAi machinery in the affected hermaphrodites. This points to a novel mechanism linking maternal bias and the RNAi machinery and suggests that toxic RNA is transmitted to offspring, causing disease phenotypes through intergenerational epigenetic inheritance.

The Hereditary Nature of Adolescent Spinal Deformities: A Study of Over 600,000 Adolescents.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: We designed this study to investigate the risk for spinal deformity among individuals whose parents had a spinal deformity. SUMMARY OF BACKGROUND DATA: Adolescent idiopathic scoliosis and Scheuermann kyphosis (SK) are common adolescent spinal deformities (ASD) with a significant impact on public health. Timely treatment with bracing is effective in halting or slowing the progression of these deformities. However, screening healthy adolescents for spinal deformities remains debatable. While the leading medical organizations endorse contradictory positions regarding the screening of the general population, there is a consensus that screening of targeted population should be considered. Due to their genetic predisposition, adolescents whose parents suffer from a spinal deformity may be candidates for targeted screening. METHODS: We conducted a nationwide, population-based study of 611,689 Israeli adolescents, aged 16 to 19 years old, who were screened for spinal deformities between the years 2000 and 2019. The data for this study were derived from a central database containing medical records of all adolescents who were examined preliminary to mandatory military service. In our study, ASD were strictly defined by plain x-ray. RESULTS: Compared with adolescents of whose parents did not have a spinal deformity, the odds ratios (OR) for ASD among adolescents whose father, mother, or both parents had spinal deformity were 1.46, 1.74, and 2.58, respectively. These ratios were consistent in multivariate models. CONCLUSION: We have found a considerable increased risk for adolescent spinal deformities among adolescents whose parents suffered from spinal deformities. We believe that our findings should serve the leading medical organizations when considering the screening of targeted populations. LEVEL OF EVIDENCE: 4.

Aurintricarboxylic Acid Decreases RNA Toxicity in a C. elegans Model of Repeat Expansions.

Pathologic expansions of DNA nucleotide tandem repeats may generate toxic RNA that triggers disease phenotypes. RNA toxicity is the hallmark of multiple expansion repeat disorders, including myotonic dystrophy type 1 (DM1). To date, there are no available disease-modifying therapies for DM1. Our aim was to use drug repositioning to ameliorate the phenotype of affected individuals in a nematode model of DM1. As the RNA interference pathway plays a key role in mediating RNA toxicity, we investigated the effect of aurintricarboxylic acid. We demonstrated that by perturbing the RNA interference machinery using aurintricarboxylic acid, we could annihilate the RNA toxicity and ameliorate the phenotype. As our approach targets a universal disease mechanism, it is potentially relevant for more expansion repeat disorders.

Disease activity and humoral response in patients with inflammatory rheumatic diseases after two doses of the Pfizer mRNA vaccine against SARS-CoV-2.

BACKGROUND: The registration trials of messenger RNA (mRNA) vaccines against SARS-CoV-2 did not address patients with inflammatory rheumatic diseases (IRD). OBJECTIVE: To assess the humoral response after two doses of mRNA vaccine against SARS-CoV-2, in patients with IRD treated with immunomodulating drugs and the impact on IRD activity. METHODS: Consecutive patients treated at the rheumatology institute, who received their first SARS-CoV-2 (Pfizer) vaccine, were recruited to the study, at their routine visit. They were reassessed 4-6 weeks after receiving the second dose of vaccine, and blood samples were obtained for serology. IRD activity assessment and the vaccine side effects were documented during both visits. IgG antibodies (Abs) against SARS-CoV-2 were detected using the SARS-CoV-2 IgG II Quant (Abbott) assay. RESULTS: Two hundred and sixty-four patients with stable disease, (mean(SD) age 57.6 (13.18) years, disease duration 11.06 (7.42) years), were recruited. The immunomodulatory therapy was not modified before or after the vaccination. After the second vaccination, 227 patients (86%) mounted IgG Ab against SARS-CoV-2 (mean (SD) 5830.8 (8937) AU/mL) and 37 patients (14%) did not, 22/37 were treated with B cell-depleting agents. The reported side effects of the vaccine were minor. The rheumatic disease remained stable in all patients. CONCLUSIONS: The vast majority of patients with IRD developed a significant humoral response following the administration of the second dose of the Pfizer mRNA vaccine against SARS-CoV-2 virus. Only minor side effects were reported and no apparent impact on IRD activity was noted.

A Pictorial Dot Probe Task to Assess Food-Related Attentional Bias in Youth With and Without Obesity: Overview of Indices and Evaluation of Their Reliability.

Several versions of the dot probe detection task are frequently used to assess maladaptive attentional processes associated with a broad range of psychopathology and health behavior, including eating behavior and weight. However, there are serious concerns about the reliability of the indices derived from the paradigm as measurement of attentional bias toward or away from salient stimuli. The present paper gives an overview of different attentional bias indices used in psychopathology research and scrutinizes three types of indices (the traditional attentional bias score, the dynamic trial-level base scores, and the probability index) calculated from a pictorial version of the dot probe task to assess food-related attentional biases in children and youngsters with and without obesity. Correlational analyses reveal that dynamic scores (but not the traditional and probability indices) are dependent on general response speed. Reliability estimates are low for the traditional and probability indices. The higher reliability for the dynamic indices is at least partially explained by general response speed. No significant group differences between youth with and without obesity are found, and correlations with weight are also non-significant. Taken together, results cast doubt on the applicability of this specific task for both experimental and individual differences research on food-related attentional biases in youth. However, researchers are encouraged to make and test adaptations to the procedure or computational algorithm in an effort to increase psychometric quality of the task and to report psychometric characteristics of their version of the task for their specific sample.

ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spillover infection in December 2019 has caused an unprecedented pandemic. SARS-CoV-2, as other coronaviruses, binds its target cells through the angiotensin-converting enzyme 2 (ACE2) receptor. Accordingly, this makes ACE2 research essential for understanding the zoonotic nature of coronaviruses and identifying novel drugs. Here we present a systematic analysis of the ACE2 conservation and co-evolution protein network across 1,671 eukaryotes, revealing an unexpected conservation pattern in specific metazoans, plants, fungi, and protists. We identified the co-evolved protein network and pinpointed a list of drugs that target this network by using data integration from different sources. Our computational analysis found widely used drugs such as nonsteroidal anti-inflammatory drugs and vasodilators. These drugs are expected to perturb the ACE2 network affecting infectivity as well as the pathophysiology of the disease.

Titanium Tackles the Endoplasmic Reticulum: A First Genomic Study on a Titanium Anticancer Metallodrug.

PhenolaTi is an advanced non-toxic anticancer chemotherapy; this inert bis(phenolato)bis(alkoxo) Ti(IV) complex demonstrates the intriguing combination of high and wide efficacy with no detected toxicity in animals. Here we unravel the cellular pathways involved in its mechanism of action by a first genome study on Ti(IV)-treated cells, using an attuned RNA sequencing-based available technology. First, phenolaTi induced apoptosis and cell-cycle arrest at the G2/M phase in MCF7 cells. Second, the transcriptome of the treated cells was analyzed, identifying alterations in pathways relating to protein translation, DNA damage, and mitochondrial eruption. Unlike for common metallodrugs, electrophoresis assay showed no inhibition of DNA polymerase activity. Reduced in vitro cytotoxicity with added endoplasmic reticulum (ER) stress inhibitor supported the ER as a putative cellular target. Altogether, this paper reveals a distinct ER-related mechanism by the Ti(IV) anticancer coordination complex, paving the way for wider applicability of related techniques in mechanistic analyses of metallodrugs.

Systemic Sclerosis Sine Scleroderma With Pulmonary Arterial Hypertension in a 3-Year-Old Girl.

Systemic sclerosis sine scleroderma (ssSSc) is a rare variant of systemic sclerosis, with only one pediatric case reported in the medical literature to date. Pulmonary arterial hypertension as the presenting feature of ssSSc is extremely rare, even in adults, and so far has never been reported in children. We report, for the first time, a case of pediatric ssSSc in a 3-year-old girl, who presented with interstitial lung disease and pulmonary hypertension. The patient was prescribed early aggressive pulmonary vasodilators combined with anti-inflammatory medications. The clinical response was good, and her current condition at 12 years of age is remarkable, considering the high mortality rates reported in adults. We underscore the importance of early aggressive treatment in future cases of similar presentation.

Expanded CUG Repeats Trigger Disease Phenotype and Expression Changes through the RNAi Machinery in C. elegans.

Myotonic dystrophy type 1 is an autosomal-dominant inherited disorder caused by the expansion of CTG repeats in the 3' untranslated region of the DMPK gene. The RNAs bearing these expanded repeats have a range of toxic effects. Here we provide evidence from a Caenorhabditis elegans myotonic dystrophy type 1 model that the RNA interference (RNAi) machinery plays a key role in causing RNA toxicity and disease phenotypes. We show that the expanded repeats systematically affect a range of endogenous genes bearing short non-pathogenic repeats and that this mechanism is dependent on the small RNA pathway. Conversely, by perturbating the RNA interference machinery, we reversed the RNA toxicity effect and reduced the disease pathogenesis. Our results unveil a role for RNA repeats as templates (based on sequence homology) for moderate but constant gene silencing. Such a silencing effect affects the cell steady state over time, with diverse impacts depending on tissue, developmental stage, and the type of repeat. Importantly, such a mechanism may be common among repeats and similar in human cells with different expanded repeat diseases.