Online peer support training to promote adolescents’ emotional support skills, mental health and agency during COVID-19: Randomised controlled trial and qualitative evaluation

Adolescents often look to their peers for emotional support, so it is critical that they are prepared to take on a supportive role, especially during a health crisis. Using a randomised controlled trial (ISRCTN99248812, 28/05/2020), we tested the short-term efficacy of an online training programme to equip young people with skills to support to their peers’ mental wellbeing during the COVID-19 pandemic. In June 2020, one-hundred UK adolescents (aged 16–18) recruited through social media were randomly allocated (1:1) to immediate 5-day peer support training or a wait-list, via an independently generated allocation sequence. Primary outcomes were indicators of ability to help others (motivation, perceived skills, frequency of help provided, compassion to others and connectedness to peers). Secondary outcomes included emotional symptoms, mental wellbeing, and indicators of agency (civic engagement and self-efficacy). We also collected qualitative reports of participants’ experience. Assessments were completed at baseline and 1 week post randomisation (primary endpoint), and up to 4 weeks post randomisation (training group only). The training increased support-giving skills, frequency of providing support, compassion and peer connectedness (medium–large-effect sizes), but not motivation to provide support, 1 week post randomisation, compared to controls. Gains in the training group were maintained 4 weeks post randomisation. Training also improved adolescents’ mental health and agency, and qualitative reports revealed further positive outcomes including increased self-care and empowerment. Leveraging digital platforms that are familiar to young people, peer support training has the potential to enable adolescents to support their own and their peers’ mental wellbeing during a health crisis

Assessment of Atherosclerosis in Chronic Granulomatous Disease

BACKGROUND: Patients with Chronic Granulomatous Disease (CGD) suffer immunodeficiency due to defects in the phagocyte NADPH oxidase (NOX2) and concomitant reduction in reactive oxygen intermediates. This may result in a reduction in atherosclerotic injury. METHODS AND RESULTS: We prospectively assessed the prevalence of cardiovascular risk factors, biomarkers of inflammation and neutrophil activation, and the presence of MRI and CT quantified subclinical atherosclerosis in the carotid and coronary arteries of 41 CGD patients and 25 healthy controls in the same age range. Uni- and multivariable associations between risk factors, inflammatory markers and atherosclerosis burden were assessed. CGD patients had significant elevations in traditional risk factors and inflammatory markers compared with controls, including; hypertension, hsCRP, oxidized LDL, and low HDL. Despite this, CGD patients had a 22% lower internal carotid artery wall volume compared with controls (361.3 ± 76.4 mm(3) vs. 463.5 ± 104.7 mm(3), p<0.001). This difference was comparable in p47(phox) and gp91(phox) deficient subtypes of CGD, and independent of risk factors in multivariate regression analysis. In contrast, prevalence of coronary arterial calcification was similar between CGD patients and controls (14.6%, CGD, and 6.3%, controls, p=0.39). CONCLUSIONS: The observation by MRI of reduced carotid but not coronary artery atherosclerosis in CGD patients despite the high prevalence of traditional risk factors raises questions about the role of NOX2 in the pathogenesis of clinically significant atherosclerosis. Additional high-resolution studies in multiple vascular beds are required to address the therapeutic potential of NOX-inhibition in cardiovascular diseases. CLINICAL TRIAL REGISTRATION INFORMATION: clinicaltrials.gov. Identifier: NCT01063309

Emotional experiences and psychological well-being in 51 countries during the COVID-19 pandemic.

The COVID-19 pandemic presents challenges to psychological well-being, but how can we predict when people suffer or cope during sustained stress? Here, we test the prediction that specific types of momentary emotional experiences are differently linked to psychological well-being during the pandemic. Study 1 used survey data collected from 24,221 participants in 51 countries during the COVID-19 outbreak. We show that, across countries, well-being is linked to individuals' recent emotional experiences, including calm, hope, anxiety, loneliness, and sadness. Consistent results are found in two age, sex, and ethnicity-representative samples in the United Kingdom (n = 971) and the United States (n = 961) with preregistered analyses (Study 2). A prospective 30-day daily diary study conducted in the United Kingdom (n = 110) confirms the key role of these five emotions and demonstrates that emotional experiences precede changes in well-being (Study 3). Our findings highlight differential relationships between specific types of momentary emotional experiences and well-being and point to the cultivation of calm and hope as candidate routes for well-being interventions during periods of sustained stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Heterozygous variants in MYBPC1 are associated with an expanded neuromuscular phenotype beyond arthrogryposis

Encoding the slow skeletal muscle isoform of myosin binding protein-C, MYBPC1 is associated with autosomal dominant and recessive forms of arthrogryposis. The authors describe a novel association for MYBPC1 in four patients from three independent families with skeletal muscle weakness, myogenic tremors, and hypotonia with gradual clinical improvement. The patients carried one of two de novo heterozygous variants in MYBPC1, with the p.Leu263Arg variant seen in three individuals and the p.Leu259Pro variant in one individual. Both variants are absent from controls, well conserved across vertebrate species, predicted to be damaging, and located in the M-motif. Protein modeling studies suggested that the p.Leu263Arg variant affects the stability of the M-motif, whereas the p.Leu259Pro variant alters its structure. In vitro biochemical and kinetic studies demonstrated that the p.Leu263Arg variant results in decreased binding of the M-motif to myosin, which likely impairs the formation of actomyosin cross-bridges during muscle contraction. Collectively, our data substantiate that damaging variants in MYBPC1 are associated with a new form of an early-onset myopathy with tremor, which is a defining and consistent characteristic in all affected individuals, with no contractures. Recognition of this expanded myopathic phenotype can enable identification of individuals with MYBPC1 variants without arthrogryposis

De Novo Pathogenic Variants in N-cadherin Cause a Syndromic Neurodevelopmental Disorder with Corpus Collosum, Axon, Cardiac, Ocular, and Genital Defects

Cadherins constitute a family of transmembrane proteins that mediate calcium-dependent cell-cell adhesion. The extracellular domain of cadherins consists of extracellular cadherin (EC) domains, separated by calcium binding sites. The EC interacts with other cadherin molecules in cis and in trans to mechanically hold apposing cell surfaces together. CDH2 encodes N-cadherin, whose essential roles in neural development include neuronal migration and axon pathfinding. However, CDH2 has not yet been linked to a Mendelian neurodevelopmental disorder. Here, we report de novo heterozygous pathogenic variants (seven missense, two frameshift) in CDH2 in nine individuals with a syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, variable axon pathfinding defects (corpus callosum agenesis or hypoplasia, mirror movements, Duane anomaly), and ocular, cardiac, and genital anomalies. All seven missense variants (c.1057G&gt;A [p.Asp353Asn]; c.1789G&gt;A [p.Asp597Asn]; c.1789G&gt;T [p.Asp597Tyr]; c.1802A&gt;C [p.Asn601Thr]; c.1839C&gt;G [p.Cys613Trp]; c.1880A&gt;G [p.Asp627Gly]; c.2027A&gt;G [p.Tyr676Cys]) result in substitution of highly conserved residues, and six of seven cluster within EC domains 4 and 5. Four of the substitutions affect the calcium-binding site in the EC4-EC5 interdomain. We show that cells expressing these variants in the EC4-EC5 domains have a defect in cell-cell adhesion; this defect includes impaired binding in trans with N-cadherin-WT expressed on apposing cells. The two frameshift variants (c.2563_2564delCT [p.Leu855Valfs∗4]; c.2564_2567dupTGTT [p.Leu856Phefs∗5]) are predicted to lead to a truncated cytoplasmic domain. Our study demonstrates that de novo heterozygous variants in CDH2 impair the adhesive activity of N-cadherin, resulting in a multisystemic developmental disorder, that could be named ACOG syndrome (agenesis of corpus callosum, axon pathfinding, cardiac, ocular, and genital defects)

Early warning signs of a mental health tsunami: a coordinated response to gather initial data insights from multiple digital services providers

Introduction: The immediate impact of COVID-19 on morbidity and mortality has raised the need for accurate and real time data monitoring and communication. The aim of this study is to document initial observations from multiple digital services providers during the COVID-19 crisis, especially those related to mental health and wellbeing. Methods: We used email and social media to announce an urgent call for support. Digital mental health services providers (N=46), financial services providers (N=4) and other relevant digital data source providers (N=3) responded with quantitative and/or qualitative data insights. People with lived experience of distress, as service users/consumers, and carers are included as co-authors. Results: This study provides proof-of-concept of the viability for researchers and private companies to work collaboratively towards a common good. Digital services providers reported a diverse range of mental health concerns. A recurring observation is that demand for digital mental health support has risen, and that the nature of this demand has also changed since COVID-19, with an apparent increased presentation of anxiety and loneliness. Conclusion: Following this study, we will continue to work with providers in more in-depth ways to capture follow-up insights at regular time points. We will also onboard new providers to address data representativeness. Looking ahead, we anticipate the need for a rigorous process to interpret insights from an even wider variety of sources in order to monitor and respond to mental health needs

Clinical application of a scale to assess genomic healthcare empowerment (GEmS): Process and illustrative case examples

The Genome Empowerment Scale (GEmS), developed as a research tool, assesses perspectives of parents of children with undiagnosed disorders about to undergo exome or genome sequencing related to the process of empowerment. We defined genomic healthcare empowerment as follows: perceived ability to understand and seek new information related to the genomic sequencing, manage emotions related to the diagnostic process and outcomes, and utilize genomic sequencing information to the betterment of the individual/child and family. The GEmS consists of four scales, two are primarily emotion-focused (Meaning of a Diagnosis, and Emotional Management of the Process) and two are action-oriented (Seeking Information and Support, and Implications and Planning). The purpose of this research was to provide a strategy for interpreting results from the GEmS and present illustrative cases. These illustrations should serve to facilitate use of the GEmS in the clinical and research arena, particularly with respect to guiding genetic counseling processes for parents of children with undiagnosed conditions