Review of eating disorders and oxytocin receptor polymorphisms.

BACKGROUND AND AIMS: Oxytocin, a nine amino acid peptide synthesised in the hypothalamus, has been widely recognised for its role in anxiolysis, bonding, sociality, and appetite. It binds to the oxytocin receptor (OXTR)-a G-protein coupled receptor-that is stimulated by the actions of oestrogen both peripherally and centrally. Studies have implicated OXTR genotypes in conferring either a risk or protective effect in autism, schizophrenia, and eating disorders (ED). There are numerous DNA variations of this receptor, with the most common DNA variation being in the form of the single nucleotide polymorphisms (SNPs). Two OXTR SNPs have been most studied in relation to ED: rs53576 and rs2254298. Each SNP has the same allelic variant that produces genotypes AA, AG, and GG. In this critical review we will evaluate the putative role of rs53576 and rs2254298 SNPs in ED. Additionally, this narrative review will consider the role of gene-environment interactions in the development of ED pathology. FINDINGS: The OXTR SNPs rs53576 and rs2254298 show independent associations between the A allele and restrictive eating behaviours. Conversely, the G allele of the OXTR rs53576 SNP is associated with binging behaviours, findings that were also evident in neuroanatomy. One study found the A allele of both OXTR SNPs to confer risk for more severe ED symptomatology while the G allele conferred some protective effect. An interaction between poor maternal care and rs2254298 AG/AA genotype conferred increased risk for binge eating and purging in women. CONCLUSIONS: Individual OXTR SNP are unlikely in themselves to explain complex eating disorders but may affect the expression of and/or effectiveness of the OXTR. A growing body of G x E work is indicating that rs53576G homozygosity becomes disadvantageous for later mental health under early adverse conditions but further research to extend these findings to eating pathology is needed. The GWAS approach would benefit this area of knowledge

The impact of COVID-19-related living restrictions on eating behaviours in children and adolescents: a systematic review

The COVID-19 pandemic prompted the imposition of physical and social distancing measures worldwide. Emerging data suggest that younger age groups may be particularly vulnerable to the adverse mental health impacts of the pandemic. Since the start of the COVID-19 pandemic, there has been an unprecedented increase in demand for child and adolescent eating disorder services. The aim of this review was to systematically review and appraise the current literature on the impact of COVID-19-related living restrictions on the eating behaviours of children and adolescents. Searches of eight electronic databases were conducted in March 2021 and December 2021 for published and grey literature on eating behaviours of population samples of children and adolescents (aged 18 months to 18 years old) who were exposed to COVID-19-related living restrictions. Of 3165 retrieved references, sixteen studies were included in this review, comprising data from 125, 286 participants. There was a pattern towards healthier eating behaviours among children and adolescents during the COVID-19 lockdown. However, young people from lower socioeconomic groups showed a tendency towards more unhealthy eating behaviours, and there was an association between mood difficulties and greater changes in eating; this suggests that such groups may be more vulnerable to the adverse health consequences of lockdowns

RA-specific expression profiles and new candidate genes

Objective: To identify rheumatoid arthritis- (RA)-specific profiles of differentially expressed genes. Methods: Synovial tissues from RA and osteoarthritis (OA) patients and from normal joints were selected according to their disease-characteristic histology. Gene expression was analyzed using DNA microarrays (GeneChip; Unigene-array) and representational difference analysis (RDA). Data were validated on larger cohorts of patients by RT-PCR. Results: Nine hundred and eighty genes were significantly regulated in RA synovial tissue as compared with non-RA. Specialized cluster analysis identified a set of 312 genes as sufficient of unequivocally discriminating RA from non-RA patterns (class discovery). Genes of highest regulation were associated with leukocyte activation (chemokines, chemokine receptors, B- and T-cell genes), endothelial and angiogenic activation, tissue destruction and remodelling [MMP-3, BMP-4, TIMPs]. Interestingly, a large set of genes was down-regulated in RA (TGF-β superfamily, apoptosis-related genes, transcription factors). Osteopontin-like genes (n=46) — up-regulated in RA — and glutathione peroxidase-3-like genes (n=85) — down-regulated in RA — yielded the highest correlation coefficients (>0.94). Megakaryocyte stimulating factor (MSF), down-regulated in a subset of RA, may hold the key to subclassification: a loss-of-function mutation in the MSF-encoding gene leads to synovial hyperplasia in camptodactyly–arthropathy–coxa vara–pericarditis syndrome, and, as in RA, also to pericardial involvement. A further candidate, vitamin-D3-up-regulated protein-1 (VDUP-1), is regulated like MSF and predisposes to premature coronary artery disease when mutated, again a feature of a subset of RA. Conclusion: RA specific gene profiles were identified and are useful to improve diagnostics of the disease. Novel gene candidates not yet in the focus of RA pathogenesis have been identified that are likely to further the understanding of RA

Mindcraft, a mobile mental health monitoring platform for children and young people: development and acceptability pilot study

BACKGROUND: Children and young people's mental health is a growing public health concern, which is further exacerbated by the COVID-19 pandemic. Mobile health apps, particularly those using passive smartphone sensor data, present an opportunity to address this issue and support mental well-being. OBJECTIVE: This study aimed to develop and evaluate a mobile mental health platform for children and young people, Mindcraft, which integrates passive sensor data monitoring with active self-reported updates through an engaging user interface to monitor their well-being. METHODS: A user-centered design approach was used to develop Mindcraft, incorporating feedback from potential users. User acceptance testing was conducted with a group of 8 young people aged 15-17 years, followed by a pilot test with 39 secondary school students aged 14-18 years, which was conducted for a 2-week period. RESULTS: Mindcraft showed encouraging user engagement and retention. Users reported that they found the app to be a friendly tool helping them to increase their emotional awareness and gain a better understanding of themselves. Over 90% of users (36/39, 92.5%) answered all active data questions on the days they used the app. Passive data collection facilitated the gathering of a broader range of well-being metrics over time, with minimal user intervention. CONCLUSIONS: The Mindcraft app has shown promising results in monitoring mental health symptoms and promoting user engagement among children and young people during its development and initial testing. The app's user-centered design, the focus on privacy and transparency, and a combination of active and passive data collection strategies have all contributed to its efficacy and receptiveness among the target demographic. By continuing to refine and expand the app, the Mindcraft platform has the potential to contribute meaningfully to the field of mental health care for young people

Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials

Introduction: This integrated analysis describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, at 15 and 30 mg once daily for up to 3 years of exposure in patients with active psoriatic arthritis (PsA) who had a prior inadequate response or intolerance to ≥ 1 non-biologic or biologic disease-modifying antirheumatic drug. Methods: Safety data were pooled and analyzed from two randomized, placebo-controlled phase 3 trials. Both trials evaluated upadacitinib 15 mg and 30 mg once daily, and one trial also evaluated adalimumab 40 mg every other week. Treatment-emergent adverse events (TEAEs) and laboratory data were summarized for four groups: pooled placebo, pooled upadacitinib 15 mg, pooled upadacitinib 30 mg, and adalimumab. TEAEs were reported as exposure-adjusted event rates (events per 100 patient-years [E/100 PY]) up to a data cut-off of June 29, 2020. Results: A total of 2257 patients received ≥ 1 dose of upadacitinib 15 mg (N = 907) or 30 mg (N = 921) for 2504.6 PY of exposure or adalimumab (N = 429) for 549.7 PY of exposure. Upper respiratory tract infection, nasopharyngitis, and increased creatine phosphokinase (CPK) were the most common TEAEs with upadacitinib. Rates of malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs), and deaths were similar across treatment groups. Rates of herpes zoster (HZ) and opportunistic infections (OI; excluding tuberculosis, HZ, and oral candidiasis) were higher with upadacitinib versus adalimumab. Serious infection, anemia, and CPK elevations were most frequent with upadacitinib 30 mg. Potentially clinically significant laboratory abnormalities were uncommon. Conclusions: Upadacitinib 15 mg and adalimumab had similar safety profiles with the exception of HZ and OIs, consistent with what was observed in rheumatoid arthritis. Rates of malignancies, MACEs, VTEs, and deaths were comparable among patients receiving upadacitinib and adalimumab. No new safety risks emerged with longer-term exposure to upadacitinib. Trial Registration Numbers: SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374

Dynamic Group Diffie-Hellman Key Exchange under Standard Assumptions

Authenticated Diffie-Hellman key exchange allows two principals communicating over a public network, and each holding public /private keys, to agree on a shared secret value. In this paper we study the natural extension of this cryptographic problem to a group of principals. We begin from existing formal security models and refine them to incorporate major missing details (e.g., strong-corruption and concurrent sessions). Within this model we define the execution of a protocol for authenticated dynamic group Diffie-Hellman and show that it is provably secure under the decisional Diffie-Hellman assumption. Our security result holds in the standard model and thus provides better security guarantees than previously published results in the random oracle model

Skeletal Muscle–Derived Cell Implantation for the Treatment of Fecal Incontinence: A Randomized, Placebo-Controlled Study

Background and Aims: Fecal incontinence (FI) improvement following injection of autologous skeletal muscle–derived cells has been previously suggested. This study aimed to test the efficacy and safety of said cells through a multicenter, placebo-controlled study, to determine an appropriate cell dose, and to delineate the target patient population that can most benefit from cell therapy. Methods: Patients experiencing FI for at least 6 months were randomized to receive a cell-free medium or low or high dose of cells. All patients received pelvic floor electrical stimulation before and after treatment. Incontinence episode frequency (IEF), FI quality of life, FI burden assessed on a visual analog scale, Wexner score, and parameters reflecting anorectal physiological function were all assessed for up to 12 months. Results: Cell therapy improved IEF, FI quality of life, and FI burden, reaching a preset level of statistical significance in IEF change compared with the control treatment. Post hoc exploratory analyses indicated that patients with limited FI duration and high IEF at baseline are most responsive to cells. Effects prevailed or increased in the high cell count group from 6 to 12 months but plateaued or diminished in the low cell count and control groups. Most physiological parameters remained unaltered. No unexpected adverse events were observed. Conclusions: Injection of a high dose of autologous skeletal muscle–derived cells followed by electrical stimulation significantly improved FI, particularly in patients with limited FI duration and high IEF at baseline, and could become a valuable tool for treatment of FI, subject to confirmatory phase 3 trial(s). (ClinicalTrialRegister.eu; EudraCT Number: 2010-021463-32)