USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism.

Interferon-induced ubiquitin (Ub)-like modifier ISG15 covalently modifies host and viral proteins to restrict viral infections. Its function is counteracted by the canonical deISGylase USP18 or Ub-specific protease 18. Notwithstanding indications for the existence of other ISG15 cross-reactive proteases, these remain to be identified. Here, we identify deubiquitinase USP16 as an ISG15 cross-reactive protease by means of ISG15 activity-based profiling. Recombinant USP16 cleaved pro-ISG15 and ISG15 isopeptide-linked model substrates in vitro, as well as ISGylated substrates from cell lysates. Moreover, interferon-induced stimulation of ISGylation was increased by depletion of USP16. The USP16-dependent ISG15 interactome indicated that the deISGylating function of USP16 may regulate metabolic pathways. Targeted enzymes include malate dehydrogenase, cytoplasmic superoxide dismutase 1, fructose-bisphosphate aldolase A, and cytoplasmic glutamic-oxaloacetic transaminase 1. USP16 may thus contribute to the regulation of a subset of metabolism-related proteins during type-I interferon responses.

Tripolar concentric ring electrodes for capturing localised electroencephalography signals during sleep.

By design, tripolar concentric ring electrodes (TCRE) provide more focal brain activity signals than conventional electroencephalography (EEG) electrodes placed further apart. This study compared spectral characteristics and rates of data loss to noisy epochs with TCRE versus conventional EEG signals recorded during sleep. A total of 20 healthy sleepers (12 females; mean [standard deviation] age 27.8 [9.6] years) underwent a 9-h sleep study. Participants were set up for polysomnography recording with TCRE to assess brain activity from 18 sites and conventional electrodes for EEG, eyes, and muscle movement. A fast Fourier transform using multitaper-based estimation was applied in 5-s epochs to scored sleep. Odds ratios with Bonferroni-adjusted 95% confidence intervals were calculated to determine the proportional differences in the number of noisy epochs between electrode types. Relative power was compared in frequency bands throughout sleep. Linear mixed models showed significant main effects of signal type (p < 0.001) and sleep stage (p < 0.001) on relative spectral power in each power band, with lower relative spectral power across all stages in TCRE versus EEG in alpha, beta, sigma, and theta activity, and greater delta power in all stages. Scalp topography plots showed distinct beta activation in the right parietal lobe with TCRE versus EEG. EEG showed higher rates of noisy epochs compared to TCRE (1.3% versus 0.8%, p < 0.001). TCRE signals showed marked differences in brain activity compared to EEG, consistent with more focal measurements and region-specific differences during sleep. TCRE may be useful for evaluating regional differences in brain activity with reduced muscle artefact compared to conventional EEG.

Estimating vigilance from the pre-work shift sleep using an under-mattress sleep sensor.

Predicting vigilance impairment in high-risk shift work occupations is critical to help to reduce workplace errors and accidents. Current methods rely on multi-night, often manually entered, sleep data. This study developed a machine learning model for predicting vigilance errors based on a single prior sleep period, derived from an under-mattress sensor. Twenty-four healthy volunteers (mean [SD] age = 27.6 [9.5] years, 12 male) attended the laboratory on two separate occasions, 1 month apart, to compare wake performance and sleep under two different lighting conditions. Each condition occurred over an 8 day protocol comprising a baseline sleep opportunity from 10 p.m. to 7 a.m., a 27 h wake period, then daytime sleep opportunities from 10 a.m. to 7 p.m. on days 3-7. From 12 a.m. to 8 a.m. on each of days 4-7, participants completed simulated night shifts that included six 10 min psychomotor vigilance task (PVT) trials per shift. Sleep was assessed using an under-mattress sensor. Using extra-trees machine learning models, PVT performance (reaction times <500 ms, reaction, and lapses) during each night shift was predicted based on the preceding daytime sleep. The final extra-trees model demonstrated moderate accuracy for predicting PVT performance, with standard errors (RMSE) of 19.9 ms (reaction time, 359 [41.6]ms), 0.42 reactions/s (reaction speed, 2.5 [0.6] reactions/s), and 7.2 (lapses, 10.5 [12.3]). The model also correctly classified 84% of trials containing ≥5 lapses (Matthews correlation coefficient = 0.59, F1 = 0.83). Model performance is comparable to current fatigue prediction models that rely upon self-report or manually entered data. This efficient approach may help to manage fatigue and safety in non-standard work schedules.

Sleep-wake state discrepancy does not impair the efficacy of cognitive behavioural therapy for insomnia: Findings from a large clinic sample.

The current study determined the extent to which sleep-wake state discrepancy impairs the efficacy of cognitive behavioural therapy for insomnia in a real-world clinical sample. Sleep-wake state discrepancy occurs when there is an inconsistency between a person's subjective and objective sleep, and is a common phenomenon amongst patients with insomnia. Limited information is available on the effectiveness of cognitive behavioural therapy for insomnia in treating patients who experience significant sleep-wake state discrepancy in "real-world" samples. In the present study, all patients with insomnia received cognitive behavioural therapy for insomnia through an outpatient insomnia program (N = 386; mean age = 51.96 years, SD = 15.62; 65.97% [N = 254] female). Prior to treatment, participants completed a polysomnography sleep study and sleep diary, which was used to calculate sleep-wake state discrepancy. At pre-treatment, post-treatment and 3-month follow-up, participants completed the Insomnia Severity Index and other questionnaires, and 1 week of sleep diaries from which sleep-onset latency, wake after sleep onset and other sleep variables were calculated. There were no differences in self-reported sleep-onset latency, wake after sleep onset or Insomnia Severity Index scores at post-treatment or 3-month follow-up between quintiles of sleep-wake state discrepancy. These results indicate that sleep-wake state discrepancy at pre-treatment does not predict treatment response to cognitive behavioural therapy for insomnia. Future research could examine multi-night assessments of sleep-wake state discrepancy to determine whether variations in discrepancy may relate to pre-treatment insomnia severity and cognitive behavioural therapy for insomnia outcomes.

Cognitive testing of the Children's Palliative Outcome Scale (C-POS) with children, young people and their parents/carers.

BACKGROUND: The Children's Palliative Outcome Scale (C-POS) is being developed using best methodological guidance on outcome measure development, This recommends cognitive testing, an established method of item improvement, prior to psychometric testing. AIM: To cognitively test C-POS within the target population to establish comprehensibility, comprehensiveness, relevance and acceptability. DESIGN: Cross-sectional cognitive interview study following COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology and Rothrock guidance on outcome measure development. Cognitive interviews were conducted using 'think aloud' and verbal probing techniques. SETTING/PARTICIPANTS: Children 5-⩽17 years old with life-limiting conditions and parents/carers of children with life-limiting conditions were recruited from 14 UK sites. RESULTS: Forty-eight individuals participated (36 parents; 12 children) in cognitively testing the five versions of C-POS over two to seven rounds. Content and length were acceptable, and all questions were considered important. Refinements were made to parent/carer versions to be inclusive of non-verbal children such as changing 'share' to 'express' feelings; and 'being able to ask questions' to 'having the appropriate information'. Changes to improve comprehensibility of items such as 'living life to the fullest' were also made. Parents reported that completing an outcome measure can be distressing but this is anticipated and that being asked is important. CONCLUSION: Cognitive interviewing has facilitated refinement of the C-POS, especially for non-verbal children who represent a large proportion of those with a life-limiting condition. This study has enhanced the face and content validity of the measure and provided preliminary evidence for acceptability for use in routine practice.

'My life is a mess but I cope': An analysis of the language children and young people use to describe their own life-limiting or life-threatening condition.

BACKGROUND: Children and young people with life-limiting and life-threatening conditions have multidimensional needs and heterogenous cognitive and communicative abilities. There is limited evidence to support clinicians to tailor their communication to each individual child. AIM: To explore the language children and young people use to describe their own condition, to inform strategies for discussing needs and priorities. DESIGN: Positioned within a social constructivist paradigm, a secondary discourse analysis of semi-structured interview data was conducted incorporating the discourse dynamics approach for figurative language. SETTING/PARTICIPANTS: A total of 26 children and young people aged 5-17 years with life-limiting or life-threatening conditions (6 cancer; 20 non-cancer) were recruited from nine clinical services (six hospitals and three hospices) across two UK nations. RESULTS: The language children and young people use positions them as 'experts in their condition'. They combine medical terminology with their preferred terms for their body to describe symptoms and treatments, and use comparatives and superlatives to communicate their health status. Their language depicts their condition as a 'series of (functional and social) losses', which single them out from their peers as 'the sick one'. Older children and young people also incorporate figurative language to expand their descriptions. CONCLUSION/DISCUSSION: Children and young people can provide rich descriptions of their condition. Paying attention to their lexical choices, and converging one's language towards theirs, may enable more child-centred discussions. Expanding discussions about 'what matters most' with consideration of the losses and differences they have experienced may facilitate a fuller assessment of their concerns, preferences and priorities.

What are the anticipated benefits, risks, barriers and facilitators to implementing person-centred outcome measures into routine care for children and young people with life-limiting and life-threatening conditions? A qualitative interview study with key stakeholders.

BACKGROUND: There is a growing evidence-base underpinning implementation of person-centred outcome measures into adult palliative care. However evidence on how best to achieve this with children facing life-threatening and life-limiting conditions is limited. AIM: To identify the anticipated benefits, risks, barriers and facilitators to implementing person-centred outcome measures for children with life-limiting and life-threatening conditions. DESIGN: Cross-sectional qualitative semi-structured interview study with key stakeholders analysed using Framework analysis informed by the adapted-Consolidated Framework for Implementation Research. SETTING/PARTICIPANTS: A total of n = 26 children with life-limiting or life-threatening conditions, n = 40 parents/carers, n = 13 siblings and n = 15 health and social care professionals recruited from six hospitals and three children's hospices and n = 12 Commissioners of health services. RESULTS: All participants were supportive of future implementation of person-centred outcome measures into care. Anticipated benefits included: better understanding of patient and family priorities, improved communication and collaborative working between professionals and families and standardisation in data collection and reporting. Anticipated risks included increased workload for staff and measures not being used as intended. Implementation barriers included: acceptability and usability of outcome measures by children; burden and capacity of parents/carers regarding completion; privacy concerns; and language barriers. Implementation facilitators included designing measures using language that is meaningful to children and families, ensuring potential benefits of person-centred outcome measures are communicated to encourage 'buy-in' and administering measures with known and trusted professional. CONCLUSIONS: Implementation of person-centred outcome measures offer potential benefits for children with life-limiting and life-threatening conditions. Eight recommendations are made to maximise benefits and minimise risks in implementation.

Multicentre, England-wide randomised controlled trial of the 'Foundations' smartphone application in improving mental health and well-being in a healthcare worker population.

BACKGROUND: Healthcare workers (HCWs) have faced considerable pressures during the COVID-19 pandemic. For some, this has resulted in mental health distress and disorder. Although interventions have sought to support HCWs, few have been evaluated. AIMS: We aimed to determine the effectiveness of the 'Foundations' application (app) on general (non-psychotic) psychiatric morbidity. METHOD: We conducted a multicentre randomised controlled trial of HCWs at 16 NHS trusts (trial registration number: EudraCT: 2021-001279-18). Participants were randomly assigned to the app or wait-list control group. Measures were assessed at baseline, after 4 and 8 weeks. The primary outcome was general psychiatric morbidity (using the General Health Questionnaire). Secondary outcomes included: well-being; presenteeism; anxiety; depression and insomnia. The primary analysis used mixed-effects multivariable regression, presented as adjusted mean differences (aMD). RESULTS: Between 22 March and 3 June 2021, 1002 participants were randomised (500:502), and 894 (89.2%) followed-up. The sample was predominately women (754/894, 84.3%), with a mean age of 44⋅3 years (interquartile range (IQR) 34-53). Participants randomised to the app had a reduction in psychiatric morbidity symptoms (aMD = -1.39, 95% CI -2.05 to -0.74), improvement in well-being (aMD = 0⋅54, 95% CI 0⋅20 to 0⋅89) and reduction in insomnia (adjusted odds ratio (aOR) = 0⋅36, 95% CI 0⋅21 to 0⋅60). No other significant findings were found, or adverse events reported. CONCLUSIONS: The app had an effect in reducing psychiatric morbidity symptoms in a sample of HCWs. Given it is scalable with no adverse effects, the app may be used as part of an organisation's tiered staff support package. Further evidence is needed on long-term effectiveness and cost-effectiveness.

The efficacy of intensive sleep retraining for insomnia: A systematic review and research agenda.

Intensive sleep retraining (ISR) is a brief behavioural treatment for sleep onset insomnia, administered in just a single overnight treatment session. This systematic review evaluates existing trials about the efficacy of intensive sleep retraining for treating insomnia, to inform whether there is enough evidence to recommend its use for clinical practice. A systematic literature search was conducted across three databases, yielding 108 results. Of these studies, three were deemed suitable for inclusion in this review. The included studies consistently reported significant reductions in insomnia symptoms following intensive sleep retraining, particularly decreases in sleep diary-derived sleep latency and increases in total sleep time. Based on these inconclusive but promising findings, a research agenda is proffered to test intensive sleep retraining as a treatment for insomnia. Large randomised controlled trials are needed to elucidate the potential benefits of intensive sleep retraining for different populations with insomnia, as are mechanistic trials to test which components underlie its seemingly therapeutic effects. Since more practical modalities of intensive sleep retraining administration have been developed, such trials are more feasible to conduct now than ever before.

Comparative short-term safety and efficacy of hypnotics: A quantitative risk-benefit analysis.

Several professional societies have provided recommendations for prescribing medications for insomnia. None has provided an integrative analysis that concurrently quantifies safety and efficacy (e.g., risk-benefit ratios). This represents an important gap for informing clinician decision-making. Accordingly, the aim of the present review is to provide such an analysis for five classes of sleep-promoting medications. Adverse event data values were extracted from the most recent FDA-approved package inserts and converted to an integer before being placebo-adjusted and standardized as a rate per 1000 (AEr). Efficacy data, pre-to-post self-reported data for active and placebo conditions were acquired from pivotal trials identified in "white papers" and systematic reviews/meta-analyses. Weighted effect sizes were calculated for subjective sleep latency, wake time after sleep onset and total sleep time, and then were averaged by medication class for each sleep continuity variable. Overall efficacy was represented by a single variable, SWT (sleep latency + wake time after sleep onset + total sleep time). Risk-benefit was represented using a simple ratio value. For safety, it was found that melatonin receptor agonists had the lowest adverse event rate (AEr = 43.1), and non-benzodiazepine benzodiazepine receptor agonists had the highest rate (AEr = 255.0). For efficacy, it was found that the pre-to-post placebo adjusted effect sizes were largest for benzodiazepines (effect size = 1.94) and smallest for melatonin receptor agonists (effect size = 0.109). For risk-benefit, histamine antagonist had the most favourable profile (risk-benefit = 69.5), while melatonin receptor agonist had the least favourable profile (risk-benefit = 395.7). Overall, the combined metric for risk-benefit suggests that treatment with a histamine antagonist is optimal and potentially represents the best first-line therapy for the medical management of insomnia.

The Good Sleeper Scale-15 items: a questionnaire for the standardised assessment of good sleepers.

Research with 'good sleepers' is ubiquitous, yet there are no standardised criteria to identify a 'good sleeper'. The present study aimed to create and validate a questionnaire for identifying good sleepers for use in research studies known as the Good Sleeper Scale-15 items (GSS-15). Data were derived from a population-based survey of Australian adults (n = 2,044). A total of 23 items were chosen for possible inclusion. An exploratory factor analysis (EFA) was conducted on ~10% of the survey dataset (n = 191) for factor identification and item reduction. A confirmatory factor analysis (CFA) was conducted on the remaining data (n = 1,853) to test model fit. Receiver operating characteristic curves and correlations were conducted to derive cut-off scores and test associations with sleep, daytime functioning, health, and quality-of-life. The EFA identified six factors: 'Sleep Difficulties', 'Timing', 'Duration', 'Regularity', 'Adequacy', and 'Perceived Sleep Problem'. The CFA showed that model fit was high and comparable to other sleep instruments, χ2 (63) = 378.22, p < 0.001, root mean square error of approximation = 0.05, with acceptable internal consistency (α = 0.76). Strong correlations were consistently found between GSS-15 global scores and outcomes, including 'a good night's sleep' (r = 0.7), 'feeling un-refreshed' (r = -0.59), and 'experienced sleepiness' (r = -0.51), p < 0.001. Cut-off scores were derived to categorise individuals likely to be a good sleeper (GSS-15 score ≥40) and those very likely to be a good sleeper (GSS-15 score ≥45). The GSS-15 is a freely available, robust questionnaire that will assist in identifying good sleepers for the purpose of sleep research. Future work will test relationships with other sleep measures in community and clinical samples.

Implementation of child-centred outcome measures in routine paediatric healthcare practice: a systematic review.

BACKGROUND: Person-centred outcome measures (PCOMs) are commonly used in routine adult healthcare to measure and improve outcomes, but less attention has been paid to PCOMs in children's services. The aim of this systematic review is to identify and synthesise existing evidence of the determinants, strategies, and mechanisms that influence the implementation of PCOMs into paediatric healthcare practice. METHODS: The review was conducted and reported in accordance with PRISMA guidelines. Databased searched included CINAHL, Embase, Medline, and PsycInfo. Google scholar was also searched for grey literature on 25th March 2022. Studies were included if the setting was a children's healthcare service, investigating the implementation or use of an outcome measure or screening tool in healthcare practice, and reported outcomes relating to use of a measure. Data were tabulated and thematically analysed through deductive coding to the constructs of the adapted-Consolidated Framework for Implementation Research (CFIR). Results were presented as a narrative synthesis, and a logic model developed. RESULTS: We retained 69 studies, conducted across primary (n = 14), secondary (n = 13), tertiary (n = 37), and community (n = 8) healthcare settings, including both child self-report (n = 46) and parent-proxy (n = 47) measures. The most frequently reported barriers to measure implementation included staff lack of knowledge about how the measure may improve care and outcomes; the complexity of using and implementing the measure; and a lack of resources to support implementation and its continued use including funding and staff. The most frequently reported facilitators of implementation and continued use include educating and training staff and families on: how to implement and use the measure; the advantages of using PCOMs over current practice; and the benefit their use has on patient care and outcomes. The resulting logic model presents the mechanisms through which strategies can reduce the barriers to implementation and support the use of PCOMs in practice. CONCLUSIONS: These findings can be used to support the development of context-specific implementation plans through a combination of existing strategies. This will enable the implementation of PCOMs into routine paediatric healthcare practice to empower settings to better identify and improve child-centred outcomes. TRIAL REGISTRATION: Prospero CRD 42022330013.

Spiritual, religious, and existential concerns of children and young people with life-limiting and life-threatening conditions: A qualitative interview study.

BACKGROUND: Despite being a core domain of palliative care, primary data on spiritual and existential concerns has rarely been collected among children with life-limiting and life-threatening conditions and their families. Existing evidence has tended to focus on the religious aspects among children with cancer. AIM: To identify the spiritual needs of children with life-limiting and life-threatening conditions. DESIGN: Cross-sectional semi-structured, qualitative interview study with children, families and health and social care professionals. Verbatim transcripts were analysed using Framework analysis. SETTING/PARTICIPANTS: Purposively sampled children with life-limiting and life-threatening conditions, their parents and siblings, health and social care professionals recruited from six hospitals and three children's hospices in the UK, and commissioners of paediatric palliative care services recruited through networks and a national charity. RESULTS: One hundred six participants were interviewed: 26 children (5-17 years), 53 family members (parents/carers of children 0-17 years and siblings (5-17 years)), 27 professionals (health and social care professionals and commissioners of paediatric palliative care). Themes included: living life to the fullest, meaning of life and leaving a legacy, uncertainty about the future, determination to survive, accepting or fighting the future and role of religion. Children as young as 5 years old identified needs or concerns in the spiritual domain of care. CONCLUSIONS: Addressing spiritual concerns is essential to providing child- and family-centred palliative care. Eliciting spiritual concerns may enable health and social care professionals to identify the things that can support and enhance a meaningful life and legacy for children and their families.

Achieving consensus on priority items for paediatric palliative care outcome measurement: Results from a modified Delphi survey, engagement with a children's research involvement group and expert item generation.

BACKGROUND: There is no validated outcome measure for use in children's palliative care outside sub-Saharan Africa. Stakeholders must be involved in the development of such measures to ensure face and content validity. AIM: To gain expert stakeholder consensus on items for inclusion in a paediatric palliative care outcome measure to establish face and content validity. DESIGN: This study was conducted in two phases following Rothrock and COSMIN guidance on patient-reported outcome measure development. Phase 1: Three-round modified Delphi survey to establish consensus on priority items. Phase 2: Item generation meeting with key stakeholders to develop initial measure versions. A young person's advisory group was also consulted on priority outcomes. SETTING AND PARTICIPANTS: Delphi survey: Parents and professionals with experience of caring for a child with a life-limiting condition. Young person's advisory group: young people age 10-20 years. Item generation meeting: bereaved parents, academics and clinicians. RESULTS: Phase 1: Delphi survey (n = 82). Agreement increased from Kendall's W = 0.17 to W = 0.61, indicating movement towards consensus. Agreement between professional and parent ranking was poor (Cohen's kappa 0.13). Professionals prioritised physical symptoms, whereas parents prioritised psychosocial and practical concerns. Advisory group: Children (n = 22) prioritised items related to living a 'normal life' in addition to items prioritised by adult participants. Phase 2: Five age/developmental stage appropriate child and proxy-reported versions of C-POS, containing 13 items, were drafted. CONCLUSIONS: This study highlights the importance and feasibility of involving key stakeholders in PROM item generation, as important differences were found in the priority outcomes identified by children, parents and professionals.

Multinight Prevalence, Variability, and Diagnostic Misclassification of Obstructive Sleep Apnea.

Rationale: Recent studies suggest that obstructive sleep apnea (OSA) severity can vary markedly from night to night, which may have important implications for diagnosis and management. Objectives: This study aimed to assess OSA prevalence from multinight in-home recordings and the impact of night-to-night variability in OSA severity on diagnostic classification in a large, global, nonrandomly selected community sample from a consumer database of people that purchased a novel, validated, under-mattress sleep analyzer. Methods: A total of 67,278 individuals aged between 18 and 90 years underwent in-home nightly monitoring over an average of approximately 170 nights per participant between July 2020 and March 2021. OSA was defined as a nightly mean apnea-hypopnea index (AHI) of more than 15 events/h. Outcomes were multinight global prevalence and likelihood of OSA misclassification from a single night's AHI value. Measurements and Main Results: More than 11.6 million nights of data were collected and analyzed. OSA global prevalence was 22.6% (95% confidence interval, 20.9-24.3%). The likelihood of misdiagnosis in people with OSA based on a single night ranged between approximately 20% and 50%. Misdiagnosis error rates decreased with increased monitoring nights (e.g., 1-night F1-score = 0.77 vs. 0.94 for 14 nights) and remained stable after 14 nights of monitoring. Conclusions: Multinight in-home monitoring using novel, noninvasive under-mattress sensor technology indicates a global prevalence of moderate to severe OSA of approximately 20%, and that approximately 20% of people diagnosed with a single-night study may be misclassified. These findings highlight the need to consider night-to-night variation in OSA diagnosis and management.

A realist interview study of a participatory public mental health project "#KindnessByPost".

BACKGROUND: #KindnessByPost (KbP) is a participatory public health initiative in which people anonymously send and receive cards containing messages of goodwill with others also taking part in the programme. Quantitative evaluations of KbP consistently find evidence of improvements to people's mental wellbeing and feelings of loneliness after participation and three months later. Our aim in the present study is to develop a programme theory of KbP, which describes for whom the KbP intervention improves mental wellbeing, other reported impacts, in which contexts it has these effects, and the mechanisms by which it works. METHODS: We use a realist interviewing methodology to develop the programme theory. We conducted a focus group with the KbP executive team, and 20 one-to-one interviews with KbP participants. During analysis, a co-production working group iteratively developed a Theory of Change model comprising context-mechanism-outcome statements [CMOs] to map out the mechanisms present in KbP. RESULTS: We developed 145 CMO statements, which we condensed and categorized into 32 overarching CMOs across nine thematic topics: access to scheme; pathways to involvement; resources; culture; giving post; receiving post; content of received post; community; long term impact. These CMOs set out pathways through which KbP benefited participants, including from doing something kind for someone else, of receiving post and appreciating the effort that went into it, and from the creative process of creating post and writing the messages inside them. Effects were sustained in part through people keeping the cards and through the social media communities that emerged around KbP. DISCUSSION: Both giving and receiving post and the sense of community benefited participants and improved their mood and feelings of connectedness with others. Connection with a stranger, rather than friends or family, was also an important feature of the initiative for participants. Our wide range of CMO pathways by which KbP produced positive outcomes may mean that the intervention is applicable or adaptable across many communities and settings. Taken together with evidence from the quantitative evaluations, KbP is potentially an effective, low-cost, and highly scalable public health intervention for reducing loneliness and improving wellbeing.

Associations between systemic melatonin and human myopia: A systematic review.

PURPOSE: Experimental models have implicated the role of melatonin circadian rhythm disruption in refractive error development. Recent studies have examined melatonin concentration and its diurnal patterns on refractive error with equivocal results. This systematic review aimed to summarise the literature on melatonin circadian rhythms in myopia. RECENT FINDINGS: PubMed, EMBASE, Web of Science, Scopus, ProQuest Central, LILACS, Cochrane and Medline databases were searched for papers between January 2010 and December 2022 using defined search terms. Seven studies measured melatonin and circadian rhythms in three biological fluids (blood serum, saliva and urine) in both myopes and non-myopes. Morning melatonin concentrations derived from blood serum varied significantly between studies in individuals aged 10-30 years, with a maximum of 89.45 pg/mL and a minimum of 5.43 pg/mL using liquid chromatography and mass spectrometry. The diurnal variation of salivary melatonin was not significantly different between myopes and emmetropes when measured every 4 h for 24 h and quantified with enzyme-linked immunosorbent assay. Significantly elevated salivary melatonin concentrations were reported in myopes compared with emmetropes, aged 18-30 years when measured hourly from evening until their habitual bedtime using liquid chromatography. However, the relationship between dim light melatonin onset and refractive group was inconsistent between studies. The 6-sulphatoxymelatonin concentration derived from overnight urine volume, measured using a double antibody radioimmunoassay, was found to be significantly lower in myopes (29.17 pg/mL) than emmetropes (42.51 pg/mL). SUMMARY: The role of melatonin concentration and rhythm in myopia has not been studied extensively. This systematic review confirms conflicting findings across studies, with potential relationships existing. Future studies with uniform methodological approaches are required to ascertain the causal relationship between melatonin dysregulation and myopia in humans.

Targeted Mass Spectrometry Reveals Interferon-Dependent Eicosanoid and Fatty Acid Alterations in Chronic Myeloid Leukaemia.

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, the detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography-dynamic multiple reaction monitoring-targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of chronic myeloid leukaemia (CML), we found that the levels of intra- and extracellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), extracellular Prostaglandin F2α (PGF2α), extracellular 5-Hydroxyeicosatetraenoic acid (5-HETE), extracellular Palmitic acid (PA, C16:0) and extracellular Stearic acid (SA, C18:0), were altered in response to immunomodulation by type I interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism, with potential relevance in the context of cancer inflammation and CML.

Is Irritability a Top Problem in Youth Mental Health Care? A Multi-informant, Multi-method Investigation.

Irritability is often described as a common problem affecting youth referred for mental health services; however, little is known about the prevalence and nature of irritability as a focus of treatment. We examined assessment data from a diverse sample of youths (N = 206; ages 7-15; 52% male, 48% female; 33% White, 27% Black, 25% Latinx) referred for outpatient treatment of emotional and behavioral concerns. Caregivers and youths completed nomothetic (standardized checklist) and idiographic (free response) measures at intake. Irritability was identified as a top problem (TP) in 58% of cases, commonly reported by caregivers (38%), youths (42%), or both (23%)-rates that were significantly greater than those of other TP domains (depression, anxiety, ADHD, conduct, and defiance). Further analyses identified clinical correlates of irritability TPs, with results supporting the incremental utility of multiple informants and methods. Findings suggest that irritability is among the most common problems for which families seek youth treatment.

Language Problems and ADHD Behaviors: Unique and Interactive Associations with School Readiness in a Socioeconomically Disadvantaged Preschool Sample.

This study examined the unique and interactive effects of receptive language ability and ADHD behaviors on six school readiness outcomes, over and above the effects of socioeconomic status, in 49 preschoolers (Mage = 3.98, SDage = .58; 53.06% female) recruited from Head Start-affiliated classrooms. Hierarchical regression analyses revealed unique positive associations between receptive language ability and cognitive and mathematics readiness, and unique negative associations between ADHD behaviors and social-emotional, physical, cognitive, and literacy readiness. Moderation analyses indicated that at higher, but not lower, levels of ADHD behaviors, lower receptive language ability was associated with lower social-emotional readiness. Results highlight that, when considered together, children's receptive language ability and ADHD behaviors vary in how they predict school readiness. Further, results provide preliminary evidence for ADHD behaviors as a risk factor in the association between receptive language deficits and social-emotional school readiness. Educational and clinical practice implications are discussed.