A qualitative study exploring the benefits of involving young people in mental health research.

INTRODUCTION: It is increasingly accepted that young people need to be centrally involved in research on issues that affect them. The aim of this study was to explore young people's perceptions of the benefits for them of being involved in mental health research and the processes that enabled these benefits. METHODS: Qualitative interviews were conducted by co-researchers (young people with lived experience and/or interest in mental health) with 13 young people (aged 13-24 years) who had experience of being involved in mental health research when they were between 11 and 16 years of age. Reflective thematic analysis was used to identify important aspects of young people's experiences. RESULTS: Four main themes were identified: (1) opportunity to have a meaningful impact, (2) opportunity to be part of a supportive community, (3) opportunity to learn and grow and (4) increasing opportunities for young people. CONCLUSION: This study highlights young people's experiences of being involved in mental health research and identifies ways in which researchers can ensure that involvement opportunities bring benefits to both the young people and the research. PATIENT OR PUBLIC CONTRIBUTION: This research was a response to issues raised by young people involved in research. The project was supported by co-researchers throughout, including design, data collection, analysis and write-up.

Factor structure and measurement invariance of the Mood and Feelings Questionnaire: a cross-cultural study among Thai and British adolescents.

The Mood and Feelings Questionnaire-child self-report (MFQ-C) is a widely used measure of child and adolescent depression. This study evaluated possible factor solutions and examined the measurement invariance of the MFQ-C as a prerequisite for its use in cross-cultural comparisons between Thai (N = 1272) and British samples (N = 1817) by using multigroup confirmatory factor analysis (MGCFA). The latent means of Thai and British samples were also examined. A five-factor structure of the MFQ-C was confirmed through confirmatory factor analysis. A partial scalar invariant model was supported, and thus latent means were compared, with British adolescents reporting significantly higher mean MFQ-C scores than Thai adolescents on four of the five factors (Vegetative Symptoms, Suicidality, Cognitive Symptoms, Agitated Distress). There was no difference for the Core Symptoms factor. The findings also suggest that the MFQ-C is a valid measure to assess depression in Thai and British adolescents and maybe useful in cross-cultural comparisons of adolescent depression.

The representation and plasticity of body emotion expression.

Emotions are expressed by the face, the voice and the whole body. Research on the face and the voice has not only demonstrated that emotions are perceived categorically, but that this perception can be manipulated. The purpose of this study was to investigate, via two separate experiments using adaptation and multisensory techniques, whether the perception of body emotion expressions also shows categorical effects and plasticity. We used an approach developed for studies investigating both face and voice emotion perception and created novel morphed affective body stimuli, which varied in small incremental steps between emotions. Participants were instructed to perform an emotion categorisation of these morphed bodies after adaptation to bodies conveying different expressions (Experiment 1), or while simultaneously hearing affective voices (Experiment 2). We show that not only is body expression perceived categorically, but that both adaptation to affective body expressions and concurrent presentation of vocal affective information can shift the categorical boundary between body expressions, specifically for the angry body expressions. Overall, our findings provide significant new insights into emotional body categorisation, which may prove important in gaining a deeper understanding of body expression perception in everyday social situations.

Understanding anhedonia: a qualitative study exploring loss of interest and pleasure in adolescent depression.

Anhedonia (or loss of interest and pleasure) is a core symptom of depression and may predict poor treatment outcome. However, little is known about the subjective experience of anhedonia, and it is rarely targeted in psychological treatment for depression. The aim of this study is to examine how young people experience anhedonia in the context of depression. Semi-structured interviews were conducted with 34 adolescents with a primary diagnosis of depression (N = 12) or elevated depressive symptoms (N = 22). Thematic analysis was used to identify important aspects of adolescents' experiences. Four main themes were identified: (1) experiencing a loss of joy and a flattening of emotion; (2) struggling with motivation and active engagement; (3) losing a sense of connection and belonging; and (4) questioning sense of self, purpose, and the bigger picture. The results challenge the framing of anhedonia as simply the loss of interest and pleasure. Adolescents reported a range of experiences that mapped closely onto the cluster of negative symptoms associated with schizophrenia and were similar to the sense of 'apathy' characteristic in Parkinson's disease. This highlights the potential benefit of taking a trans-diagnostic approach to understanding and treating reward deficits associated with mental health problems.

Beyond olefins: new metathesis directions for synthesis.

The olefin-olefin metathesis reaction has emerged as one of the most important carbon-carbon bond-forming reactions, as illustrated by its wide use in the synthesis of complex molecules, natural products and pharmaceuticals. The corresponding metathesis reaction between carbonyls and olefins or alkynes similarly allows for the formation of carbon-carbon bonds. Although these variants are far less developed and utilized in organic synthesis, they possess attractive qualities that have prompted chemists to incorporate and explore these modes of reactivity in complex molecule synthesis. This review highlights selected examples of carbonyl-olefin and carbonyl-alkyne metathesis reactions in organic synthesis, in particular in the total synthesis of natural products and complex molecules, and provides an overview of current advantages and limitations.

Sex differences in leucocyte telomere length in a free-living mammal.

Mounting evidence suggests that average telomere length reflects previous stress and predicts subsequent survival across vertebrate species. In humans, leucocyte telomere length (LTL) is consistently shorter during adulthood in males than in females, although the causes of this sex difference and its generality to other mammals remain unknown. Here, we measured LTL in a cross-sectional sample of free-living Soay sheep and found shorter telomeres in males than in females in later adulthood (>3 years of age), but not in early life. This observation was not related to sex differences in growth or parasite burden, but we did find evidence for reduced LTL associated with increased horn growth in early life in males. Variation in LTL was independent of variation in the proportions of different leucocyte cell types, which are known to differ in telomere length. Our results provide the first evidence of sex differences in LTL from a wild mammal, but longitudinal studies are now required to determine whether telomere attrition rates or selective disappearance are responsible for these observed differences.

The Glasgow Voice Memory Test: Assessing the ability to memorize and recognize unfamiliar voices.

One thousand one hundred and twenty subjects as well as a developmental phonagnosic subject (KH) along with age-matched controls performed the Glasgow Voice Memory Test, which assesses the ability to encode and immediately recognize, through an old/new judgment, both unfamiliar voices (delivered as vowels, making language requirements minimal) and bell sounds. The inclusion of non-vocal stimuli allows the detection of significant dissociations between the two categories (vocal vs. non-vocal stimuli). The distributions of accuracy and sensitivity scores (d') reflected a wide range of individual differences in voice recognition performance in the population. As expected, KH showed a dissociation between the recognition of voices and bell sounds, her performance being significantly poorer than matched controls for voices but not for bells. By providing normative data of a large sample and by testing a developmental phonagnosic subject, we demonstrated that the Glasgow Voice Memory Test, available online and accessible from all over the world, can be a valid screening tool (~5 min) for a preliminary detection of potential cases of phonagnosia and of "super recognizers" for voices.

Crossmodal adaptation in right posterior superior temporal sulcus during face-voice emotional integration.

The integration of emotional information from the face and voice of other persons is known to be mediated by a number of "multisensory" cerebral regions, such as the right posterior superior temporal sulcus (pSTS). However, whether multimodal integration in these regions is attributable to interleaved populations of unisensory neurons responding to face or voice or rather by multimodal neurons receiving input from the two modalities is not fully clear. Here, we examine this question using functional magnetic resonance adaptation and dynamic audiovisual stimuli in which emotional information was manipulated parametrically and independently in the face and voice via morphing between angry and happy expressions. Healthy human adult subjects were scanned while performing a happy/angry emotion categorization task on a series of such stimuli included in a fast event-related, continuous carryover design. Subjects integrated both face and voice information when categorizing emotion-although there was a greater weighting of face information-and showed behavioral adaptation effects both within and across modality. Adaptation also occurred at the neural level: in addition to modality-specific adaptation in visual and auditory cortices, we observed for the first time a crossmodal adaptation effect. Specifically, fMRI signal in the right pSTS was reduced in response to a stimulus in which facial emotion was similar to the vocal emotion of the preceding stimulus. These results suggest that the integration of emotional information from face and voice in the pSTS involves a detectable proportion of bimodal neurons that combine inputs from visual and auditory cortices.

The human voice areas: Spatial organization and inter-individual variability in temporal and extra-temporal cortices.

fMRI studies increasingly examine functions and properties of non-primary areas of human auditory cortex. However there is currently no standardized localization procedure to reliably identify specific areas across individuals such as the standard 'localizers' available in the visual domain. Here we present an fMRI 'voice localizer' scan allowing rapid and reliable localization of the voice-sensitive 'temporal voice areas' (TVA) of human auditory cortex. We describe results obtained using this standardized localizer scan in a large cohort of normal adult subjects. Most participants (94%) showed bilateral patches of significantly greater response to vocal than non-vocal sounds along the superior temporal sulcus/gyrus (STS/STG). Individual activation patterns, although reproducible, showed high inter-individual variability in precise anatomical location. Cluster analysis of individual peaks from the large cohort highlighted three bilateral clusters of voice-sensitivity, or "voice patches" along posterior (TVAp), mid (TVAm) and anterior (TVAa) STS/STG, respectively. A series of extra-temporal areas including bilateral inferior prefrontal cortex and amygdalae showed small, but reliable voice-sensitivity as part of a large-scale cerebral voice network. Stimuli for the voice localizer scan and probabilistic maps in MNI space are available for download.

Temperature-Dependence of Lipid A Acyl Structure in Psychrobacter cryohalolentis and Arctic Isolates of Colwellia hornerae and Colwellia piezophila.

Lipid A is a fundamental Gram-negative outer membrane component and the essential element of lipopolysaccharide (endotoxin), a potent immunostimulatory molecule. This work describes the metabolic adaptation of the lipid A acyl structure by Psychrobacter cryohalolentis at various temperatures in its facultative psychrophilic growth range, as characterized by MALDI-TOF MS and FAME GC-MS. It also presents the first elucidation of lipid A structure from the Colwellia genus, describing lipid A from strains of Colwellia hornerae and Colwellia piezophila, which were isolated as primary cultures from Arctic fast sea ice and identified by 16S rDNA sequencing. The Colwellia strains are obligate psychrophiles, with a growth range restricted to 15 °C or less. As such, these organisms have less need for fluidity adaptation in the acyl moiety of the outer membrane, and they do not display alterations in lipid A based on growth temperature. Both Psychrobacter and Colwellia make use of extensive single-methylene variation in the size of their lipid A molecules. Such single-carbon variations in acyl size were thought to be restricted to psychrotolerant (facultative) species, but its presence in these Colwellia species shows that odd-chain acyl units and a single-carbon variation in lipid A structure are present in obligate psychrophiles, as well.

Quantifying the clinical and economic burden of desquamating dermatological conditions: Implications for a supraregional burns centre.

INTRODUCTION: This study aimed to identify the spectrum of desquamating skin diseases referred for tertiary burns care and quantify the care requirements and expenses associated with caring for these patients within the burns service. METHODS: Patient records were identified with nonburn-induced skin loss between 2016 and 2022. Data was extracted from inpatient records, operative notes, and dressing clinic records. A cost analysis was conducted using figures from the National Schedule of National Health Service Costs and our own unit-specific costs. RESULTS: Twenty patients were identified, with a median age of 46.5 and a median total body surface area of 30%. The mean length of stay was 21.2 days, with 8/20 patients requiring intensive care. Overall mortality was 30%, rising to 50% if patients required intensive treatment unit (ITU) admission. Patients had a mean of 1.5 procedures under general anaesthesia and a mean operative time of 169 min per patient. Postoperatively, a mean of 8.3 dressing changes was required per patient (range 1-21). Of 75% of patients referred as suspected toxic epidermal necrolysis syndrome (TENS), only 32% of patients histologically had TENS (32%), with linear IgA disease, pemphigus vulgaris and bullous lupus comprising the other diagnoses. Cost analysis predicted a total cost to the unit of £1,422,106. CONCLUSION: Desquamating dermatological diseases are life-threatening conditions with exhaustive care requirements. Our experiences highlight the importance of awareness of the range of desquamating skin conditions beyond TENS to enable optimum management and the need to ensure adequate financial provisions to accommodate the care requirements mandated by these patients.

Synthetic Approaches to the New Drugs Approved During 2022.

In 2022, 23 new small molecule chemical entities were approved as drugs by the United States FDA, European Union EMA, Japan PMDA, and China NMPA. This review describes the synthetic approach demonstrated on largest scale for each new drug based on patent or primary literature. The synthetic routes highlight practical methods to construct molecules, sometimes on the manufacturing scale, to access the new drugs. Ten additional drugs approved in 2021 and one approved in 2020 are included that were not covered in the previous year's review.

Object discrimination and reversal learning in infant and juvenile non-human primates in a non-clinical laboratory.

BACKGROUND: Biopharmaceutical development necessitates use of non-human primates in toxicology, leading to adoption of non-traditional methods including cognitive function assessment. METHODS: A two-object discrimination and reversal test in cynomolgus monkeys (Macaca fascicularis) was performed using a Wisconsin General Testing Apparatus (WGTA). Non-clinical study design and regulatory considerations dictate that infants are raised by their biological mothers until weaning at 6 months. Thirty-four animals (6-21 months of age) were trained to discriminate between two randomly selected stimulus objects to retrieve a reward. Following training, days to first reversal after interchanging the reward were measured. RESULTS: Both sexes acquired visual discrimination skills at similar rates. Trends in learning and reversals completed were uniform across age groups. Completing training early in some subjects had no impact on subsequent testing phases. CONCLUSIONS: Weaned cynomolgus monkey infants can be successfully tested for cognitive abilities using the WGTA in a non-clinical laboratory setting.

Development of a versatile enzyme immunoassay for non-invasive assessment of glucocorticoid metabolites in a diversity of taxonomic species.

Endocrinology is a useful tool for conservation biologists and animal managers, and measuring glucocorticoids can help understand biological mechanisms associated with species decline and animal welfare. The current study describes the development and optimization of a glucocorticoid enzyme immunoassay (EIA) to non-invasively assess adrenal activity in a variety of taxa. The antiserum (CJM006) was raised in rabbits to a corticosterone-3-CMO-BSA immunogen and used in a standard competitive EIA system. However, the EIA initially produced results with unacceptably high inter-assay variation, attributed to consistent patterns observed within the optical density of developing plates. To determine the cause of this variability, a number of factors were examined using synthetic corticosterone standard and endogenous faecal extract, including: plate type (Nunc MaxiSorp® II versus Immulon IB plates); the use of non-specific secondary antibody; type (artificial versus natural) and presence (light versus dark) of light during incubation; plate loading temperature (4°C versus room temperature); and substrate reagent temperature (4°C versus room temperature). Results indicated that variability was associated with plate location effects, which were not initially detected because control samples were always run in the same positions across plates. Light and temperature were the two major factors that affected EIA reliability. For this assay, the standard protocol required slight modification, with the optimal protocol using Nunc MaxiSorp® plates, room temperature substrate reagents and dark incubation conditions. Following optimization, this EIA was then validated biochemically for 38 species, through parallel displacement curves and interference assessment tests of faecal and urine samples. Additionally, biological validation was performed opportunistically in a subset of species, with use of this EIA demonstrating significant elevations in faecal glucocorticoid metabolites following potentially challenging events. In summary, this glucocorticoid EIA cross-reacts with excreted glucocorticoid metabolites across a wide range of taxa, including ungulates, primates, felids, birds, rodents and amphibians. We conclude that when used with optimal reagent and incubation conditions, this EIA will be useful for non-invasive monitoring of adrenal activity in a wide range of wildlife species.

Challenging stigma and attitudes towards ECT via an educational video.

While electroconvulsive therapy (ECT) is an effective therapeutic modality for the treatment of mental illness, negative attitudes and stigma exist about ECT in the general community and even within health services. Investigating interventions that improve the attitudes of health professionals towards ECT is beneficial as this reduces stigma and increases the acceptability of ECT for consumers. The primary aim of this study was to evaluate the change in attitude of nursing graduates and medical students towards ECT by watching an educational video. The secondary aim was to compare health professional attitudes to those of the general community. An educational video was co-designed with consumers and members of the mental health Lived Experience (Peer) Workforce Team about ECT outlining the procedure, side effects, treatment considerations and lived experiences. Nursing graduates and medical students completed the ECT Attitude Questionnaire (EAQ) prior to and after watching the video. Descriptive statistics, paired samples t-tests and one sample t-tests were completed. One hundred and twenty-four participants completed pre- and post- questionnaires. Attitudes towards ECT significantly improved after watching the video. Positive responses towards ECT increased from 67.09% to 75.72%. Participants in this study reported higher positive attitudes towards ECT than members of the general public before and after watching the intervention. Results indicated that the video educational intervention was effective in improving attitudes towards ECT for nursing graduates and medical students. While the video is promising as an educational tool, further research is required to explore the use of the video in reducing stigma for consumers and carers.

Mifepristone induced liver injury in a patient with Cushing syndrome: a case report and review of the literature.

BACKGROUND: Mifepristone, also known as RU-486, is an anti-progestational steroid with similar chemical structure to anabolic steroids. Given as a single dose in conjunction with misoprostol, mifepristone is used to induce medical abortion. Mifepristone administered chronically at a higher dose is also approved for the management of hypercortisolism. There have been only 2 reported cases of mifepristone associated liver injury, in both cases, in the setting of Cushing syndrome. We report a third patient with Cushing syndrome with mifepristone induced liver injury with unique histological findings that provide insight to the pathophysiology of liver injury in mifepristone and anabolic steroids. CASE PRESENTATION: Patient is a 63-year-old Caucasian female Cushing disease with no prior history of liver disease. She was started on mifepristone and semaglutide. Ninety days after initiating mifepristone, she developed deep jaundice, severe pruritus, fatigue, and nausea. Liver tests revealed a mixed hepatocellular/cholestatic pattern. Viral and autoimmune serologies were negative and there was no biliary dilatation on imaging. Liver biopsy showed severe cholestasis but no bile duct injury. Focal endothelialitis was present within a central venule. Cholestatic symptoms persisted for one month after presentation before slowly subsiding. Four months after stopping mifepristone, the patient's symptoms completely resolved, and liver tests became normal. Compilation of Roussell Uclaf Causality Assessment Method score indicated probable causality. CONCLUSIONS: Mifepristone shares a similar chemical structure as synthetic anabolic/androgenic steroids and there are many similarities in the clinical presentation of liver injury. This case and the 2 other reported cases share similar clinical characteristics. The observation of endothelialitis in our patient may provide a mechanistic link between mifepristone, or anabolic steroids in general, and the development of vascular complications such as peliosis.

Synthetic Approaches to the New Drugs Approved During 2021.

Each year, new drugs are introduced to the market, representing structures that have affinity for biological targets implicated in human diseases and conditions. These new chemical entities (NCEs), particularly small molecules and antibody-drug conjugates, provide insight into molecular recognition and serve as potential leads for the design of future medicines. This annual review is part of a continuing series highlighting the most likely process-scale synthetic approaches to 35 NCEs that were first approved anywhere in the world during 2021.

Developmental and reproductive outcomes in humans and animals after glyphosate exposure: a critical analysis.

Glyphosate is the active ingredient of several widely used herbicide formulations. Glyphosate targets the shikimate metabolic pathway, which is found in plants but not in animals. Despite the relative safety of glyphosate, various adverse developmental and reproductive problems have been alleged as a result of exposure in humans and animals. To assess the developmental and reproductive safety of glyphosate, an analysis of the available literature was conducted. Epidemiological and animal reports, as well as studies on mechanisms of action related to possible developmental and reproductive effects of glyphosate, were reviewed. An evaluation of this database found no consistent effects of glyphosate exposure on reproductive health or the developing offspring. Furthermore, no plausible mechanisms of action for such effects were elucidated. Although toxicity was observed in studies that used glyphosate-based formulations, the data strongly suggest that such effects were due to surfactants present in the formulations and not the direct result of glyphosate exposure. To estimate potential human exposure concentrations to glyphosate as a result of working directly with the herbicide, available biomonitoring data were examined. These data demonstrated extremely low human exposures as a result of normal application practices. Furthermore, the estimated exposure concentrations in humans are >500-fold less than the oral reference dose for glyphosate of 2 mg/kg/d set by the U.S. Environmental Protection Agency (U.S. EPA 1993). In conclusion, the available literature shows no solid evidence linking glyphosate exposure to adverse developmental or reproductive effects at environmentally realistic exposure concentrations.

Barriers and facilitators to physical activity participation for child, adolescent, and young adult cancer survivors: a systematic review.

PURPOSE: The aim of this systematic review is to explore and describe the barriers and facilitators to physical activity (PA) participation for child, adolescent, and young adult cancer survivors. METHODS: MEDLINE, Embase, AMED, CINAHL, Cochrane, and Web of Science were searched for manuscripts published between January 2000 and February 2021. To be included in this review, studies had to report qualitative or quantitative data on barriers and facilitators to PA participation in child (4 to < 10 years), adolescent (10 to 19 years), and young adult (> 19 to < 40 years) cancer survivors. Six independent reviewers assessed methodological quality using the Mixed Methods Appraisal Tool (MMAT-version 18) in duplicate. RESULTS: Fifteen studies were included in this systematic review. Fatigue and psychological factors were the most prevalent barriers shared between children, adolescents, and young adults. Support from others was a shared facilitator between age groups. CONCLUSION: Psychological barriers and social support are important to address in younger cancer survivors. Clinicians can use these findings to create exercise interventions to facilitate and overcome barriers to PA participation. IMPLICATIONS FOR CANCER SURVIVORS: While PA is beneficial for cancer survivors of all ages, different barriers and facilitators to PA participation exist depending on a survivors age and life stage. Survivors should discuss PA with their healthcare team at all timepoints in the cancer treatment trajectory in order to gain the associated benefits during and after treatment.