Online compassion-based self-help for depression in people with skin conditions: a feasibility study.

BACKGROUND: There is a need to develop psychological interventions for depression in people with skin conditions. This study aimed to investigate the acceptability, feasibility, and effects of an online compassion-based self-help intervention for depression in people with skin conditions. METHODS: Adult participants (n = 34) with skin conditions and mild-moderate depressive symptoms were invited to undertake a six-week, compassion-based online intervention for depression with email support. Engagement with the intervention was monitored, along with time spent facilitating the intervention, and participant feedback was collected each week and post-intervention. Pre-post changes in depression, self-compassion and dermatological quality of life were also assessed. RESULTS: The intervention was started by 25 participants and completed by 13. Feedback scores indicated that the website was evaluated positively and that the sessions had positive impacts on participants. Participants appreciated the skin-specific aspects of the intervention but varied as to which of the compassion-based exercises they found helpful. The online intervention was feasible to provide and facilitate, and treatment completers showed improvements in depression, quality of life and self-compassion. CONCLUSIONS: The online compassion-based intervention holds promise as a treatment for depression in people with skin conditions. Recommendations are made for future research and further development of the intervention. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on 21 October 2019, NCT04132973.

Burden of Disease and Treatment Patterns Amongst Patients With Vitiligo: Findings From a National, Longitudinal Retrospective Study in the United Kingdom.

This retrospective study, using UK Clinical Practice Research Datalink and Hospital Episode Statistics databases, analysed 17,239 incident patients with vitiligo. Mean incidence of vitiligo was 0.16 (2010-2021) per 1000 person-years (range: 0.10 [2010-COVID] to 0.19 [2013/2018]); prevalence increased from 0.21% (2010) to 0.38% (2021). The most common comorbidities recorded after vitiligo diagnosis were diabetes (19.4%), eczema (8.9%), thyroid disease (7.5%), and rheumatoid arthritis (6.9%). Mental health diagnoses recorded at any time were most commonly depression and/or anxiety (24.6%), depression (18.5%), anxiety (16.0%), and sleep disturbance (12.7%); recorded after vitiligo diagnosis in 6.4%, 4.4%, 5.5%, and 3.9%, respectively. Mental health comorbidities were more common among White patients (eg, depression and/or anxiety, 29.0%) than Black (18.8%), Asian (16.1%), and other ethnicities (21.4%). In adolescents, depression and/or anxiety was most commonly diagnosed after vitiligo diagnosis (7.4% vs before, 1.8%). Healthcare resources were used most frequently in the first year after vitiligo diagnosis (incident cohort), typically dermatology-related outpatient appointments (101.9/100 person-years) and general practitioner consultations (97.9/100 person-years). In the year after diagnosis, 60.8% of incident patients did not receive vitiligo-related treatments (ie, topical corticosteroids, topical calcineurin inhibitors, oral corticosteroids, phototherapy), increasing to 82.0% the next year; median (95% CI) time from diagnosis to first treatment was 34.0 (31.6-36.4) months. Antidepressants and/or anxiolytics were recorded for 16.7% of incident patients in the year after diagnosis. In 2019, 85.0% of prevalent patients did not receive vitiligo-related treatments; 16.6% had a record of antidepressant and/or anxiolytic treatments. Most patients were not on vitiligo-related treatments within a year of diagnosis, with time to first treatment >2 years, suggesting that vitiligo may be dismissed as unimportant and not treated early, in part due to limited effectiveness of available treatments. New effective treatments, early initiation, and psychological intervention and support are needed to reduce vitiligo burden on patients.

How healthcare systems are experienced by autistic adults in the United Kingdom: A meta-ethnography.

LAY ABSTRACT: Autistic adults are more likely to experience mental and physical health difficulties, and yet can find it difficult to get the support that they need. A meta-ethnographic approach was used to review the existing research on autistic adults' experiences of accessing healthcare. Four databases were searched for qualitative and mixed-method studies which looked at the experiences of autistic adults who did not also have a learning disability when using healthcare services in the United Kingdom. Fifteen papers met the criteria to be included, and seven steps were used to analyse the information and develop new themes. Three main themes were identified: Professionals' lack of knowledge can be damaging, Need to reduce processing demands and Adaptation to improve engagement. This review highlights how damaging misdiagnosis, inappropriate treatment, overwhelming environments and systems that are difficult to access can have on the well-being of autistic adults. Limited knowledge and understanding about autism knowledge among healthcare professionals along with autistic adult's own communication and sensory differences indicate that there is a need for improved training developed with autistic adults and adaptations.

A comparison of two learning approach inventories and their utility in predicting examination performance and study habits.

The revised two-factor Study Process Questionnaire and the Approaches and Study Skills Inventory for Students are two instruments commonly used to measure student learning approach. Although they are designed to measure similar constructs, it is unclear whether the metrics they provide differ in terms of their real-world classification of learning approach. The purpose of this study is to compare outcomes of these two inventories in a study population from an undergraduate (baccalaureate) human anatomy course. The three central goals of this study are to compare the inventories in terms of 1) how students are classified, 2) the relationship between examination performance, time spent studying, and learning approach, and 3) instrument reliability. Results demonstrate that student classifications of corresponding scales of each inventory are significantly correlated, suggesting they measure similar constructs. Although the inventories had similar reliability, neither was consistently strong in predicting examination performance or study habits. Overall, these results suggest that the two inventories are comparable in terms of how they measure learning approach, but the lack of correspondence between learning approach scores and measurement outcomes questions their validity as tools that can be used universally in classrooms.NEW & NOTEWORTHY Although learning approach inventories have been used extensively in education research, there has been no direct comparison of how student classification differs between instruments or how classification influences the interpretation of how learning approach impacts student performance. This is especially relevant in light of recent research questioning the validity of the Study Process Questionnaire (LoGiudice AB, Norman GR, Manzoor S, Monteiro S. Adv Health Sci Educ Theory Pract 28: 47-63, 2023; Johnson SN, Gallagher ED, Vagnozzi AM. PLoS One 16: e0250600, 2021).

A qualitative feasibility and acceptability study of an acceptance and commitment-based bibliotherapy intervention for people with cancer.

Self-directed bibliotherapy interventions can be effective means of psychological support for individuals with cancer, yet mixed findings as to the efficacy of these interventions indicate the need for further research. We investigated the experience of individuals with cancer after using a new self-help book, based on Acceptance and Commitment Therapy (ACT). Ten participants with cancer (nine females and one male, 40-89 years old) were given access to a bibliotherapy self-help ACT-based book and participated in post-intervention semi-structured interviews. Five themes were generated from reflexive thematic analysis: (1) The value of bibliotherapy (2) Timing is important (3) Resonating with cancer experiences (4) Tools of the book (5) ACT in action. The book was found to be acceptable (self-directed, accessible, understandable content, good responsiveness to exercises) and feasible (easy to use, ACT-consistent). Although not explicitly evaluated, participants' reports indicated defusion, present moment awareness, and consideration of values, as the ACT processes that contributed to adjustment, via helping them to regain control over their lives and become more present within the moment. Findings also indicate that the intervention may be best accessed following completion of initial medical treatment.

Anchovy boom and bust linked to trophic shifts in larval diet.

Although massive biomass fluctuations of coastal-pelagic fishes are an iconic example of the impacts of climate variability on marine ecosystems, the mechanisms governing these dynamics are often elusive. We construct a 45-year record of nitrogen stable isotopes measured in larvae of Northern Anchovy (Engraulis mordax) in the California Current Ecosystem to assess patterns in food chain length. Larval trophic efficiency associated with a shortened food chain increased larval survival and produced boom periods of high adult biomass. In contrast, when larval food chain length increased, and energy transfer efficiency decreased, the population crashed. We propose the Trophic Efficiency in Early Life (TEEL) hypothesis, which states that larval fishes must consume prey that confer sufficient energy for survival, to help explain natural boom-bust dynamics of coastal pelagic fishes. Our findings illustrate a potential for trophic indicators to generally inform larval survival and adult population dynamics of coastal-pelagic fishes.

'I'm not just being difficult . . . I'm finding it difficult': A qualitative approach to understanding experiences of autistic parents when interacting with statutory services regarding their autistic child.

LAY ABSTRACT: Becoming a parent is an important part of adult life for many people, including autistic people. Many parents of autistic children can find getting the right support for their children difficult. Knowledge is currently poor about how this is experienced by parents who are also autistic themselves. The main researcher is also an autistic parent to an autistic child and other experts by experience were consulted in the development of the study. Ten autistic mothers with autistic children in mainstream education were interviewed about their experiences of seeking support for their autistic children from services such as healthcare and education. Participants talked about finding the overall system being the main problem, rather than the individuals working in it, and about needing to fight to get the right support for their children. These are points that non-autistic parents have also raised before. Participants also talked about feeling judged and stigmatised for being autistic, and about struggling to manage sensory and communication difficulties, which is something that has not been talked about by non-autistic parents. Improving services to offer better support to autistic families is important and can be achieved through better training. This training should be developed and run by autistic adults and focus on positive aspects of autism, rather than negative.

Drug discovery for heart failure targeting myosin-binding protein C.

Cardiac MyBP-C (cMyBP-C) interacts with actin and myosin to fine-tune cardiac muscle contractility. Phosphorylation of cMyBP-C, which reduces the binding of cMyBP-C to actin and myosin, is often decreased in patients with heart failure (HF) and is cardioprotective in model systems of HF. Therefore, cMyBP-C is a potential target for HF drugs that mimic its phosphorylation and/or perturb its interactions with actin or myosin. We labeled actin with fluorescein-5-maleimide (FMAL) and the C0-C2 fragment of cMyBP-C (cC0-C2) with tetramethylrhodamine (TMR). We performed two complementary high-throughput screens (HTS) on an FDA-approved drug library, to discover small molecules that specifically bind to cMyBP-C and affect its interactions with actin or myosin, using fluorescence lifetime (FLT) detection. We first excited FMAL and detected its FLT, to measure changes in fluorescence resonance energy transfer (FRET) from FMAL (donor) to TMR (acceptor), indicating binding. Using the same samples, we then excited TMR directly, using a longer wavelength laser, to detect the effects of compounds on the environmentally sensitive FLT of TMR, to identify compounds that bind directly to cC0-C2. Secondary assays, performed on selected modulators with the most promising effects in the primary HTS assays, characterized the specificity of these compounds for phosphorylated versus unphosphorylated cC0-C2 and for cC0-C2 versus C1-C2 of fast skeletal muscle (fC1-C2). A subset of identified compounds modulated ATPase activity in cardiac and/or skeletal myofibrils. These assays establish the feasibility of the discovery of small-molecule modulators of the cMyBP-C-actin/myosin interaction, with the ultimate goal of developing therapies for HF.

An ACT self-help intervention for adults with a visible difference in appearance: A pilot feasibility and acceptability randomized controlled study.

Individuals living with a visible difference in appearance experience high levels of social anxiety, yet self-help interventions for this heterogeneous population are not available. We conducted a pilot trial of a novel Acceptance and Commitment Therapy (ACT) based self-help intervention.Individuals with anxiety about having a visible difference in appearance (n = 284) were randomized to an ACT-based four-week intervention (n = 145) or a waitlist control condition (n = 139). We collected pre and follow-up (four-weeks after the completion of the intervention) data. Primary outcomes included social anxiety and impairments in functioning. Psychological flexibility (PF) was also examined. ANCOVAs, controlling for pre scores, indicated significant improvements in functioning by the intervention group. No significant differences were observed for anxiety and PF between conditions at follow-up. Drop out was 68% for the intervention and 41% for the control group, with no differences in the groups in age, origin, gender, or type of visible difference. Participants in the intervention group found the intervention almost equally, useful (77%) and helpful (73%). An ACT-based self-help intervention can alleviate distress related to visible difference in appearance. More sophisticated designs are needed now, to collect idiographic and longitudinal data and examine personalized changes across time in this population.

Development of an Orthopedic Surgery Anatomy Curricular Model for Fourth Year Medical Students Using a Modified Delphi Method.

OBJECTIVE: The purpose of this study was to develop anatomy-focused learning outcomes that can be used to design a fourth-year elective for students matriculating into orthopedic surgery residencies. DESIGN: A series of proposed learning outcomes (N=72) was developed using the ACGME Orthopedic Milestones 2.0 as a framework. In 2021, these were converted into a survey asking participants to rate the importance of each outcome on a 5-point Likert scale. The modified Delphi Method was used to refine the list of outcomes until group consensus was achieved. The consensus was defined using a conservative 3-tier approach. SETTING: Eighteen academic centers with an associated orthopedic surgery residency. PARTICIPANTS: Twenty-six orthopedic surgeons (ranging from 1 to 42 years in practice). RESULTS: Of the 72 learning outcomes from the first-round survey, 25 met consensus criteria. Of the 62 learning outcomes from the second-round survey, 45 met consensus criteria. All learning outcomes that met consensus criteria after the second-round survey were stratified into low-yield (n = 8), intermediate-yield (n = 34), and high-yield (n = 28) categories. CONCLUSION: Using a modified Delphi Method, this study elicited feedback from experts in the field of orthopedic surgery to develop a framework for a fourth-year elective focused on anatomical concepts important for students applying to residencies in orthopedic surgery. The product of this process affords a great deal of flexibility when utilizing the results of this study in institution-specific curricular development.

A systematic review of psychological interventions in adults with pulmonary hypertension: Is the evidence-base disproportionate to the problem?

INTRODUCTION: Our understanding of the psychological impact of living with pulmonary hypertension (PH) is growing, particularly for how anxiety and depression present in this group. There is evidence for the use of psychological interventions in other chronic lung conditions; however, trials focusing on adults with PH have yet to be subject to a systematic review. METHODS: We systematically searched four databases for evidence examining the effectiveness of psychological interventions for adults with PH. A narrative approach has been used to present findings. RESULTS: Overall, 186 unique articles were identified of which four were suitable. Data was gathered from 143 individuals. Cognitive behavioural therapy (CBT), metacognitive therapy (MCT) or counselling were investigated. All three studies reported a significant reduction in anxiety and depression, and some secondary outcomes were also associated with change. DISCUSSION: The evidence supporting the use of psychological therapies for adults with PH is promising, although limited. There is an urgent need for more research in this area to better understand how we can support this clinical group.

The effectiveness of mindfulness-based cognitive therapy for social anxiety symptoms in people living with alopecia areata: a single-group case-series design.

BACKGROUND: Alopecia areata (AA) is an immunological disorder characterised by hair loss. Individuals with AA report high levels of social anxiety. One intervention that holds potential for reducing social anxiety in individuals with AA is mindfulness-based cognitive therapy (MBCT). AIMS: Our key aim was to investigate whether MBCT reduces social anxiety in individuals with AA. The study also investigated whether MBCT reduces depression, general anxiety, and increases quality of life and increases trait mindfulness in individuals with AA. METHOD: Five participants with AA took part in an 8-session in-person MBCT intervention. A multiple-baseline single-group case series design was adopted. Idiographic measures of social anxiety were measured each day from baseline, through intervention, to follow-up. Standardised questionnaires of trait mindfulness, social anxiety, depression, anxiety, and quality of life were completed at baseline, post-intervention, and at 4-week follow-up. RESULTS: All participants completed the MBCT course, but one participant was excluded from the idiographic analysis due to a high amount of missing data. The remaining four participants demonstrated reductions in idiographic measures of social anxiety from baseline to follow-up. These effects were larger between baseline and follow-up, than between baseline and post-intervention. Two participants demonstrated significant improvement in standardised measures of wellbeing from baseline to follow-up - they also practised mindfulness most regularly at home between sessions. CONCLUSION: MBCT may be effective in reducing social anxiety and improving wellbeing in individuals with AA, although this might be dependent on the extent to which participants regularly practise mindfulness exercises.

Fluorescence lifetime FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators.

We have used FRET-based biosensors in live cells, in a robust high-throughput screening (HTS) platform, to identify small-molecules that alter the structure and activity of the cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA2a). Our primary aim is to discover drug-like small-molecule activators that improve SERCA's function for the treatment of heart failure. We have previously demonstrated the use of an intramolecular FRET biosensor, based on human SERCA2a, by screening two different small validation libraries using novel microplate readers that detect the fluorescence lifetime or emission spectrum with high speed, precision, and resolution. Here we report results from FRET-HTS of 50,000 compounds using the same biosensor, with hit compounds functionally evaluated using assays for Ca2+-ATPase activity and Ca2+-transport. We focused on 18 hit compounds, from which we identified eight structurally unique scaffolds and four scaffold classes as SERCA modulators, approximately half of which are activators and half are inhibitors. Five of these compounds were identified as promising SERCA activators, one of which activates Ca2+-transport even more than Ca2+-ATPase activity thus improving SERCA efficiency. While both activators and inhibitors have therapeutic potential, the activators establish the basis for future testing in heart disease models and lead development, toward pharmaceutical therapy for heart failure.

Perceived Stigmatization among Dermatological Outpatients Compared with Controls: An Observational Multicentre Study in 17 European Countries.

Perceived stigmatization places a large psychosocial burden on patients with some skin conditions. Little is known about the experience of stigmatization across a wide range of skin diseases. This observational cross-sectional study aimed to quantify perceived stigmatization and identify its predictors among patients with a broad spectrum of skin diseases across 17 European countries. Self-report questionnaires assessing perceived stigmatization and its potential predictors were completed by 5,487 dermatology outpatients and 2,808 skin-healthy controls. Dermatological diagnosis, severity, and comorbidity were clinician-assessed. Patients experienced higher levels of perceived stigmatization than controls (p < 0.001, d = 0.26); patients with psoriasis, atopic dermatitis, alopecia, and bullous disorders were particularly affected. Multivariate regression analyses showed that perceived stigmatization was related to sociodemographic (lower age, male sex, being single), general health-related (higher body mass index, lower overall health), disease-related (higher clinician-assessed disease severity, presence of itch, longer disease duration), and psychological (greater distress, presence of suicidal ideation, greater body dysmorphic concerns, lower appearance satisfaction) variables. To conclude, perceived stigmatization is common in patients with skin diseases. Factors have been identified that will help clinicians and policymakers to target vulnerable patient groups, offer adequate patient management, and to ultimately develop evidence-based interventions.

A network analysis of psychological flexibility, coping, and stigma in dermatology patients.

Introduction: Despite the negative effects of stigma in individuals with skin conditions, interventions to address its effects are rare. This might be in part due to a continued lack of understanding as to how individuals respond to stigma. Methods: In this study, we employed a step-case analytic method, using traditional regression, moderation, and network analyses, to examine the role of psychological flexibility (PF) with stigmatized experiences, and stigma-related outcomes. We run a cross-sectional study (n = 105 individuals with various skin conditions) and analyzed stigma-related variables. We included variables examining perceived stigmatization (PSQ), anxiety (GAD-7), depression (PHQ-9), well-being (EQ5D5L), and variables stemming from the PF model (CompACT), presented as three coping with stigma responses, namely "open," "aware," and "active.". Results: Using network analysis, the most influential or central variables that contributed to stigma were generalized anxiety, perceived stigmatization, and valued actions. In relation to PF, being open to the experience of stigma (as opposed to avoidance), keeping a distance from stigmatized thoughts (as opposed to self-stigmatizing), and bringing attention to value-based committed actions (as opposed to passivity) were all found to contribute to less stigmatized experiences. Discussion: The results indicate that two of the three skills of the PF model ("open" and "active") may be important targets for interventions targeting stigma in people living with skin conditions.

Allosteric coupling asymmetry mediates paradoxical activation of BRAF by type II inhibitors.

The type II class of RAF inhibitors currently in clinical trials paradoxically activate BRAF at subsaturating concentrations. Activation is mediated by induction of BRAF dimers, but why activation rather than inhibition occurs remains unclear. Using biophysical methods tracking BRAF dimerization and conformation we built an allosteric model of inhibitor-induced dimerization that resolves the allosteric contributions of inhibitor binding to the two active sites of the dimer, revealing key differences between type I and type II RAF inhibitors. For type II inhibitors the allosteric coupling between inhibitor binding and BRAF dimerization is distributed asymmetrically across the two dimer binding sites, with binding to the first site dominating the allostery. This asymmetry results in efficient and selective induction of dimers with one inhibited and one catalytically active subunit. Our allosteric models quantitatively account for paradoxical activation data measured for 11 RAF inhibitors. Unlike type II inhibitors, type I inhibitors lack allosteric asymmetry and do not activate BRAF homodimers. Finally, NMR data reveal that BRAF homodimers are dynamically asymmetric with only one of the subunits locked in the active αC-in state. This provides a structural mechanism for how binding of only a single αC-in inhibitor molecule can induce potent BRAF dimerization and activation.

Drug discovery for heart failure targeting myosin-binding protein C.

Cardiac MyBP-C (cMyBP-C) interacts with actin-myosin to fine-tune cardiac muscle contractility. Phosphorylation of cMyBP-C, which reduces binding of cMyBP-C to actin or myosin, is often decreased in heart failure (HF) patients, and is cardioprotective in model systems for HF. Therefore, cMyBP-C is a potential target for HF drugs that mimic phosphorylation and/or perturb its interactions with actin or myosin. We labeled actin with fluorescein-5-maleimide (FMAL), and the C0-C2 fragment of cMyBP-C (cC0-C2) with tetramethyl rhodamine (TMR). We performed two complementary high-throughput screens (HTS) on an FDA-approved drug library, to discover small molecules that specifically bind to cMyBP-C and affect its interactions with actin or myosin, using fluorescence lifetime (FLT) detection. We first excited FMAL and detected its FLT, to measure changes in fluorescence resonance energy transfer (FRET) from FMAL (donor) to TMR (acceptor), indicating binding and/or structural changes in the protein complex. Using the same samples, we then excited TMR directly, using a longer wavelength laser, to detect the effects of compounds on the environmentally sensitive FLT of TMR, to identify compounds that bind directly to cC0-C2. Secondary assays, performed on selected modulators with the most promising effects in the primary HTS assays, characterized specificity of these compounds for phosphorylated versus unphosphorylated cC0-C2 and for cC0-C2 versus C1-C2 of fast skeletal muscle (fskC1-C2). A subset of identified compounds modulated ATPase activity in cardiac and/or skeletal myofibrils. These assays establish feasibility for discovery of small-molecule modulators of the cMyBP-C-actin/myosin interaction, with the ultimate goal of developing therapies for HF.

FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators.

We have used FRET-based biosensors in live cells, in a robust high-throughput screening (HTS) platform, to identify small-molecules that alter the structure and activity of the cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA2a). Our primary aim is to discover drug-like small-molecule activators that improve SERCA’s function for the treatment of heart failure. We have previously demonstrated the use of an intramolecular FRET biosensor, based on human SERCA2a, by screening a small validation library using novel microplate readers that can detect the fluorescence lifetime or emission spectrum with high speed, precision, and resolution. Here we report results from a 50,000-compound screen using the same biosensor, with hit compounds functionally evaluated using Ca 2+ -ATPase and Ca 2+ -transport assays. We focused on 18 hit compounds, from which we identified eight structurally unique compounds and four compound classes as SERCA modulators, approximately half of which are activators and half are inhibitors. While both activators and inhibitors have therapeutic potential, the activators establish the basis for future testing in heart disease models and lead development, toward pharmaceutical therapy for heart failure.