The Lived Experience of Play and How It Relates to Psychological Wellbeing: An Interpretive Phenomenological Analysis (IPA) Study Amongst Undergraduate Students from Medicine, Nursing, and Allied Health Professions' Programmes in the United Kingdom.

Current literature acknowledges that undergraduate students undertaking programmes in medicine, nursing, and allied health professions experience occupational stress which presents as a detriment to mental health, psychological wellbeing (PWB), and burnout. Strategies to improve the wellbeing of students have been slow to embed and have had limited impact, indeed the issue of declining wellbeing amongst this group is escalating. Studies from the business literature suggest that organisations that foster a playful environment reap benefits in terms of employee wellbeing. This interpretive phenomenological analysis (IPA) study explored the lived experiences of play amongst undergraduate students from medicine, nursing, and allied health professions' programmes in the clinical practice setting. The resultant findings offer some unique empirical insights into the types of play that the students engaged in, ranging from informal banter with peers and patients to artful, sophisticated, cocreated play. The study also revealed insights about the factors which facilitate play, notably the "big personalities" on the ward. The factors which limited play are related to the tension between being a health professional and the enactment of play as well as hierarchical factors. Crucially, the study found that the practice of play induced key hedonic and eudaimonic PWB benefits to the students, ranging from positive affect to improved relationships, a sense of meaning, and a positive learning environment, offering original empirical insights. These findings have not been observed previously and shine a conceptual light on a previously unknown phenomenon.

Morphological profiling in human neural progenitor cells classifies hits in a pilot drug screen for Alzheimer's disease.

Alzheimer's disease accounts for 60-70% of dementia cases. Current treatments are inadequate and there is a need to develop new approaches to drug discovery. Recently, in cancer, morphological profiling has been used in combination with high-throughput screening of small-molecule libraries in human cells in vitro. To test feasibility of this approach for Alzheimer's disease, we developed a cell morphology-based drug screen centred on the risk gene, SORL1 (which encodes the protein SORLA). Increased Alzheimer's disease risk has been repeatedly linked to variants in SORL1, particularly those conferring loss or decreased expression of SORLA, and lower SORL1 levels are observed in post-mortem brain samples from individuals with Alzheimer's disease. Consistent with its role in the endolysosomal pathway, SORL1 deletion is associated with enlarged endosomes in neural progenitor cells and neurons. We, therefore, hypothesized that multi-parametric, image-based cell phenotyping would identify features characteristic of SORL1 deletion. An automated morphological profiling method (Cell Painting) was adapted to neural progenitor cells and used to determine the phenotypic response of SORL1-/- neural progenitor cells to treatment with compounds from a small internationally approved drug library (TargetMol, 330 compounds). We detected distinct phenotypic signatures for SORL1-/- neural progenitor cells compared to isogenic wild-type controls. Furthermore, we identified 16 compounds (representing 14 drugs) that reversed the mutant morphological signatures in neural progenitor cells derived from three SORL1-/- induced pluripotent stem cell sub-clones. Network pharmacology analysis revealed the 16 compounds belonged to five mechanistic groups: 20S proteasome, aldehyde dehydrogenase, topoisomerase I and II, and DNA synthesis inhibitors. Enrichment analysis identified DNA synthesis/damage/repair, proteases/proteasome and metabolism as key pathways/biological processes. Prediction of novel targets revealed enrichment in pathways associated with neural cell function and Alzheimer's disease. Overall, this work suggests that (i) a quantitative phenotypic metric can distinguish induced pluripotent stem cell-derived SORL1-/- neural progenitor cells from isogenic wild-type controls and (ii) phenotypic screening combined with multi-parametric high-content image analysis is a viable option for drug repurposing and discovery in this human neural cell model of Alzheimer's disease.

A cautionary note on the use of N-acetylcysteine as a reactive oxygen species antagonist to assess copper mediated cell death.

A new form of cell death has recently been proposed involving copper-induced cell death, termed cuproptosis. This new form of cell death has been widely studied in relation to a novel class of copper ionophores, including elesclomol and disulfiram. However, the exact mechanism leading to cell death remains contentious. The oldest and most widely accepted biological mechanism is that the accumulated intracellular copper leads to excessive build-up of reactive oxygen species and that this is what ultimately leads to cell death. Most of this evidence is largely based on studies using N-acetylcysteine (NAC), an antioxidant, to relieve the oxidative stress and prevent cell death. However, here we have demonstrated using inductively coupled mass-spectrometry, that NAC pretreatment significantly reduces intracellular copper uptake triggered by the ionophores, elesclomol and disulfiram, suggesting that reduction in copper uptake, rather than the antioxidant activity of NAC, is responsible for the diminished cell death. We present further data showing that key mediators of reactive oxygen species are not upregulated in response to elesclomol treatment, and further that sensitivity of cancer cell lines to reactive oxygen species does not correlate with sensitivity to these copper ionophores. Our findings are in line with several recent studies proposing the mechanism of cuproptosis is instead via copper mediated aggregation of proteins, resulting in proteotoxic stress leading to cell death. Overall, it is vital to disseminate this key piece of information regarding NAC's activity on copper uptake since new research attributing the effect of NAC on copper ionophore activity to quenching of reactive oxygen species is being published regularly and our studies suggest their conclusions may be misleading.

The causative factors of psychological distress and mental ill-health among ICU nurses during the pandemic.

The coronavirus disease (COVID-19) pandemic had a global impact on health systems and health professionals. Nurses, particularly those working in intensive care units (ICUs), held a central critical role in the care of COVID-19 patients, facing numerous challenges in the delivery of care, leading to significant psychological and mental health issues. This article reports on findings from a qualitative narrative review of the literature related to psychological ill-being and mental health of ICU nurses' during the pandemic. Four key themes emerged: (1) isolation (2) workload (3) clinical preparedness and lack of protocols and (4) fear.

Assessing Sustainability Priorities of U.S. Food Hub Managers: Results from a National Survey.

Food hubs have emerged as innovative alternatives to the conventional United States food system. As aggregators of small local farms, food hubs hold the potential to transform food production, distribution, and consumption, while fostering environmental sustainability and social equity. However, assessing their contributions to environmental sustainability and social equity is challenging due to the diverse structures and practices of U.S. food hubs. This study presents the findings of a national survey of food hub managers conducted in 2022 to assess the sustainability objectives and practices of food hubs across the United States. Our survey questions were designed based on a comprehensive framework of social and environmental sustainability criteria. Our results reveal that food hubs make valuable contributions in supporting small producers and providing healthy local food options. However, there is room for improvement in their environmental sustainability practices, as they only meet 47% of the defined environmental sustainability goals. Addressing food insecurity is a high priority for food hubs, although not their top priority, and many offer fresh food access to low-income households. Food hubs also contribute to environmental sustainability by reducing food transportation, promoting healthy food production methods, and minimizing waste. While food hubs meet 67% of the defined social sustainability goals, there are opportunities for improvement in reaching important institutional stakeholders and enhancing consumer education on healthy nutrition and lifestyles. Expanding technical assistance for farmers is also critical. By addressing these opportunities for improvement, food hubs can drive progress towards a more resilient and equitable food system in the United States.

What to Look for in Relationships: Development, inter-rater reliability, and initial validity estimates for a young child-caregiver relationship assessment.

Introduction: Observational assessments are important for understanding a range of behaviors and emotions in the young child-caregiver relationship. This paper provides initial data on a multidimensional assessment for professionals who work with young children and their caregivers, the What to Look for in Relationships (WLR). The WLR was designed to assist providers in evaluating strengths and areas for improvement in five areas of young child-caregiver relationship dimensions. This paper reports on the development, interrater reliability, initial convergent and discriminant validity, and incremental utility of the scales. Methods: Data were collected from caregiver-child dyads, who participated in a semi-structured observational caregiver-child interaction session as part of a clinic evaluation for relationship-based therapeutic services for young children in child protection. Recorded interactions were coded using the WLR scales with 146 interactions coded by at least two independent observers for interrater reliability analyses. Results: The scales showed adequate internal consistency, good inter-rater reliability, strong convergent associations with a single dimension measure (i.e., the Parent-Infant Relationship Global Assessment Scale; PIR-GAS) and discriminated those in the clinical range from those with adaptive functioning on the PIR-GAS. Discussion: This study provides initial support for the usefulness of the WLR scales for assessing dimensions of caregiver-child relationships during early childhood that may be useful targets of intervention.

Undergraduate nursing students' experiences of online education: A cross-sectional survey.

During the coronavirus pandemic, UK Academics were required to adjust their learning and teaching environment and pedagogical approaches, with little guidance or time. Feelings of frustration and uncertainty around student engagement were commonplace across Higher Education Institutions. This was heightened in professionally regulated courses, such as nursing. The shift to online learning created a situation where academics were frequently faced with a 'sea of black screens' and unable to ascertain student engagement. This study investigated undergraduate nursing students' experience of online education during the COVID-19 pandemic. An anonymous survey was distributed to each year of the undergraduate nursing programme and data subsequently analysed. Responses from 54 students revealed that engagement varied between different year groups. There were significant differences between those with pre-COVID (traditional face-to-face) teaching experience (years 2 and 3) and those without (year 1) in regard to self-reported engagement with online learning. The findings from this study revealed some powerful and emotional insights into the experience of online learning amongst UK students undertaking an undergraduate nursing programme during the COVID-19 pandemic.

Perceptions of Resilience and Physical Health Symptom Improvement Following Post Disaster Integrated Health Services.

OBJECTIVE: Theorists and researchers have linked resilience with a host of positive psychological and physical health outcomes. This paper examines perceptions of resilience and physical health symptoms in a sample of individuals exposed to multiple community disasters following involvement in integrated mental health services. METHODS: A multiwave naturalistic design was used to follow 762 adult clinic patients (72% female; 28% minority status), ages 18-92 years (mean age=40 years), who were evaluated for resilience and physical health symptoms prior to receiving services and at 1, 3, and 6 months' follow-up. RESULTS: Data indicated increases in perceptions of resilience and decreased physical health symptoms reported over time. Results also indicated that resilience predicted physical health symptoms, such that resilience and physical health symptoms were negatively associated (ie, improved resilience was associated with decreases in physical health symptoms). These effects were primarily observed for those individuals with previous exposure to natural disasters. CONCLUSIONS: Findings provide correlational evidence for behavioral health treatment provided as part of a stepped-care, collaborative model in reducing physical health symptoms and increasing resilience post-disaster. Controlled trials are warranted. (Disaster Med Public Health Preparedness. 2019;13:223-229).

CAMKK2 Promotes Prostate Cancer Independently of AMPK via Increased Lipogenesis.

: New targets are required for treating prostate cancer, particularly castrate-resistant disease. Previous studies reported that calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) expression is increased in human prostate cancer. Here, we show that Camkk2 deletion or pharmacologic inhibition protects against prostate cancer development in a preclinical mouse model that lacks expression of prostate-specific Pten. In contrast, deletion of AMP-activated protein kinase (Ampk) ß1 resulted in earlier onset of adenocarcinoma development. These findings suggest for the first time that Camkk2 and Ampk have opposing effects in prostate cancer progression. Loss of CAMKK2 in vivo or in human prostate cancer cells reduced the expression of two key lipogenic enzymes, acetyl-CoA carboxylase and fatty acid synthase. This reduction was mediated via a posttranscriptional mechanism, potentially involving a decrease in protein translation. Moreover, either deletion of CAMKK2 or activation of AMPK reduced cell growth in human prostate cancer cells by inhibiting de novo lipogenesis. Activation of AMPK in a panel of human prostate cancer cells inhibited cell proliferation, migration, and invasion as well as androgen-receptor signaling. These findings demonstrate that CAMKK2 and AMPK have opposing effects on lipogenesis, providing a potential mechanism for their contrasting effects on prostate cancer progression in vivo. They also suggest that inhibition of CAMKK2 combined with activation of AMPK would offer an efficacious therapeutic strategy in treatment of prostate cancer. SIGNIFICANCE: These findings show that CAMKK2 and its downstream target AMPK have opposing effects on prostate cancer development and raise the possibility of a new combined therapeutic approach that inhibits CAMKK2 and activates AMPK.

Comparative familial aggregation of bipolar disorder in patients with bipolar I and bipolar II disorders.

OBJECTIVE: We sought to quantify the prevalence and differential prevalence of a bipolar disorder among family members of patients with a bipolar I or II disorder. METHODS: The sample comprised 1165 bipolar and 1041 unipolar patients, with the former then sub-typed as having either a bipolar I or II condition. Family history data was obtained via an online self-report tool. RESULTS: Prevalence of a family member having a bipolar disorder (of either sub-type) was distinctive (36.8%). Patients with a bipolar I disorder reported a slightly higher family history (41.2%) compared to patients with a bipolar II disorder (36.3%), and with both significantly higher than the rate of bipolar disorder in family members of unipolar depressed patients (18.5%). CONCLUSIONS: Findings support the view that bipolar disorder is heritable. The comparable rates in the two bipolar sub-types support the positioning of bipolar II disorder as a valid condition with strong genetic underpinnings.

Is 'subthreshold' bipolar II disorder more difficult to differentiate from borderline personality disorder than formal bipolar II disorder?

Recent research indicates that borderline personality disorder (BPD) can be diagnostically differentiated from the bipolar disorders. However, no studies have attempted to differentiate participants with sub-threshold bipolar disorder or SubT BP (where hypomanic episodes last less than 4 days) from those with a BPD. In this study, participants were assigned a SubT BP, bipolar II disorder (BP II) or BPD diagnosis based on clinical assessment and DSM-IV criteria. Participants completed self-report measures and undertook a clinical interview which collected socio-demographic information, a mood history, family history, developmental history, treatment information, and assessed cognitive, emotional and behavioural functioning. Both bipolar groups, whether SubT BP or BP II, differed to the BPD group on a number of key variables (i.e. developmental trauma, depression correlates, borderline personality scores, self-harm and suicide attempts), and compared to each other, returned similar scores on nearly all key variables. Borderline risk scores resulted in comparable classification rates of 0.74 (for BPD vs BP II) and 0.82 (for BPD vs sub-threshold BP II). Study findings indicate that both SubT BP and BP II disorder can be differentiated from BPD on a set of refined clinical variables with comparable accuracy.

Is there consensus across international evidence-based guidelines for the psychotropic drug management of bipolar disorder during the perinatal period?

BACKGROUND: Clinicians treating a patient with bipolar disorder who is pregnant or breastfeeding may seek advice from bipolar management guidelines that provide recommendations for perinatal treatment. We examine the consistency of such recommendations across several evidence-based guidelines. METHODS: A literature search in the National Guideline Clearinghouse, the Cochrane Database of Systematic Reviews, PsycInfo and PubMed was undertaken using the search terms "bipolar disorder" and "guidelines," which generated 11 sets of evidence-based guidelines published by professional organizations during the 2005-2015 period. Information relevant to management during the perinatal period was reviewed by two independent reviewers, with key themes qualitatively analysed. RESULTS: There was a moderate level of agreement across guidelines regarding the potential teratogenic effects of lithium, sodium valproate and carbamazepine, with most highlighting caution in using these medications during the perinatal period. There was less agreement regarding the safety risks associated with lamotrigine, antipsychotics, and antidepressants, and little agreement regarding the risks and recommendations of medications during breastfeeding. LIMITATIONS: Some differences in recommendations are likely due to varying publication dates, with recent guidelines having more up-to-date evidence available to use when formulating recommendations. Further, due to ethical issues surrounding pregnancy and infant research, the evidence used to formulate perinatal recommendations is largely based on retrospective reports and/or case studies. It is therefore unrealistic to expect such recommendations to be entirely consistent and based on rigorous evidence. CONCLUSIONS: While there was some consistency across guidelines on key recommendations, there were also substantial inconsistencies, with the latter risking compromising clinical management.

Relationship between photoperiod and hospital admissions for mania in New South Wales, Australia.

BACKGROUND: Causes for a seasonal impact on admissions for mania remain to be clarified. We examined the impact of photoperiod, rate of change of photoperiod and hours of sunshine on admissions over an extended period. METHODS: Monthly admission data to NSW psychiatric hospitals for more than twenty thousand patients admitted for mania over a fifteen-year period were correlated with photoperiod and sunshine changes. RESULTS: While the peak in admissions occurred in spring, the shift in admissions being under-represented to being precipitously over-represented corresponded with the photoperiod commencing to increase in winter (i.e. July). Analyses identified rate of change in photoperiod as somewhat more influential than change in photoperiod and with hours of sunshine not making a distinctive contribution. Immediate and delayed impacts of rate of change as well as change in photoperiod across the whole year accounted for a distinctive 20% of the variance in hospital admissions. LIMITATIONS: Validity of mania diagnoses cannot be established from the data set, admission data were obtained from across the state while meteorological data were obtained from the capital city, lag periods between onset of a mania and hospitalization (while identified) would impact on associations, social factors were not included and study associations do not imply causality. CONCLUSIONS: The lack of a strong year-long correlation may reflect photoperiod changes being only a weak causal factor or that its influence may be through a strong impact phase after the winter solstice and with the spring peaking of admissions reflecting secondary photoperiod or other influences.

Identifying trajectories of change to improve understanding of integrated health care outcomes on PTSD symptoms post disaster.

INTRODUCTION: Addressing life stressors is an important function for integrated care, especially for health care homes located in disaster prone environments. This study evaluated trajectories of change for patients with postdisaster posttraumatic stress disorder (PTSD) who were seen in integrated care. In addition to describing the results, this article provides the methods of subgroup analyses as this may be useful for others working in real-world practice. METHOD: Patients (N = 340) receiving services at 5 rural health clinics self-reported PTSD symptoms as part of an ongoing evaluation to study the effectiveness of integrated health. Analysis of variance was used to assess differences overtime and trajectories were identified with cluster analyses. Disaster and trauma related factors associated with these trajectories were assessed using logistic regression. RESULTS: Significant overall decreases in PTSD symptoms overtime were found; individual trajectories were identified and include stable low, steep declines, stable high symptoms, and increasing symptoms. Stress related to disaster and the number of other traumas patients experienced correctly classified trajectory membership. DISCUSSION: Trajectories indicate that patients have differing treatment needs and cluster analysis as an evaluation technique may be useful in identifying what treatment works and for whom. The present study addresses a major concern for health care providers serving disaster prone communities and emphasizes the importance of identifying pre incident and disaster related risk vulnerabilities that contribute to mental health outcomes. Subgroup analyses are a useful tool for developing more targeted treatment within integrated care and may be an accessible research strategy for others working in such settings. (PsycINFO Database Record

Trends in the diagnosis of bipolar disorder: Has the story changed?

OBJECTIVE: A recent study reported an 8% increase in bipolar diagnoses in public and community mental health services in New South Wales from 2003 to 2014, an increase interpreted by the authors as reflecting increasing diagnostic boundaries of bipolar disorder, and bipolar II in particular. If valid, we would expect an increase in hospital admissions for hypomania as well as for mania and so analysed a relevant dataset to test that hypothesis. METHODS: Data were examined for 27,255 individuals hospitalised in NSW psychiatric hospitals over a 14-year period (2000-2014) for ICD-10 diagnosed mania or hypomania and with analyses examining rates of hospitalisation/per year for both mania and for hypomania. RESULTS: While overall admissions for mania and hypomania increased over the study period by 16.4%, admissions for mania increased by 31.0% and admissions for hypomania actually decreased by 32.1%. CONCLUSION: The increased rate in admissions of those with a bipolar disorder appears to reflect a trend over more than four decades. The hypothesis that any increase in the diagnostic boundaries of bipolar II disorder would be associated with an increase in hospitalisation rates was rejected, with the converse trend being identified.

Parenting Behaviors, Parent Heart Rate Variability, and Their Associations with Adolescent Heart Rate Variability.

Adolescence is a potentially important time in the development of emotion regulation and parenting behaviors may play a role. We examined associations among parenting behaviors, parent resting heart rate variability, adolescent resting heart rate variability and parenting behaviors as moderators of the association between parent and adolescent resting heart rate variability. Ninety-seven youth (11-17 years; 49.5 % female; 34 % African American, 37.1 % Euro-American, 22.6 % other/mixed ethnic background, and 7.2 % Hispanic) and their parents (n = 81) completed a physiological assessment and questionnaires assessing parenting behaviors. Inconsistent discipline and corporal punishment were negatively associated with adolescent resting heart rate variability, while positive parenting and parental involvement were positively associated. Inconsistent discipline and parental involvement moderated the relationship between parent and adolescent resting heart rate variability. The findings provide evidence for a role of parenting behaviors in shaping the development of adolescent resting heart rate variability with inconsistent discipline and parental involvement potentially influencing the entrainment of resting heart rate variability in parents and their children.

Examining for any impact of climate change on the association between seasonality and hospitalization for mania.

BACKGROUND: Studies have established higher rates of hospitalization for mania in spring and summer and posit various explanatory climatic variables. As the earth's climate is changing, we pursue whether this is reflected in the yearly seasonal variation in hospitalizations for mania. This would be indicated by the presence of secular changes in both the hospitalization seasonal pattern and climatic variables, and associations between both variable sets. METHODS: Data were obtained for 21,882 individuals hospitalized to psychiatric hospitals in the Australian state of New South Wales (NSW) over a 14-year period (2000-2014) with ICD-diagnosed mania - and with NSW population figures and salient climatic variables collected for the same period. Regression analyses were conducted to examine the predictive value of climate variables on hospital admissions. RESULTS: Data quantified a peak for manic admissions in spring of the southern hemisphere, in the months of October and November. There was a significant linear increase in manic admissions (0.5%/year) over the 14-year time period, with significant variation across years. In terms of climatic variables, there was a significant linear trend over the interval for solar radiation, although the trend indicated a decrease rather than an increase. Seasonal variation in admissions was most closely associated with two climate variables - evaporation in the current month and temperature in the previous month. LIMITATIONS: Hospitalization rates do not necessarily provide an accurate estimate of the onset of manic episodes and findings may be limited to the southern hemisphere, or New South Wales. CONCLUSIONS: While overall findings do not support the hypothesis that climate change is leading to a higher seasonal impact for manic hospital admissions in the southern hemisphere, analyses identified two climate/weather variables - evaporation and temperature - that may account for the yearly spring excess.

Vitamin D and depression.

OBJECTIVE: To examine whether vitamin D deficiency or insufficiency is associated with depression and whether vitamin D supplementation is an effective treatment for depression. METHOD: Empirical papers published in recent years were identified using three search engines and online databases - PubMed, Google Scholar and Cochrane Database. Specific search terms used were 'vitamin D', 'depression' and 'treatment' and articles were selected that examined the association between vitamin D deficiency/insufficiency and depression, vitamin D supplementation and Vitamin D as a treatment for depression. Our review weighted more recent studies (from 2011), although also considered earlier publications. RESULTS: Empirical studies appear to provide increasing evidence for an association between vitamin D insufficiency and depression, and for vitamin D supplementation and augmentation in those with clinical depression who are vitamin D deficient. Methodological limitations associated with many of the studies are detailed. LIMITATIONS: Articles were restricted to those in the English language while publication bias may have weighted studies with positive findings. CONCLUSIONS: There remains a need for empirical studies to move beyond cross-sectional designs to undertake more randomised controlled longitudinal trials so as to clarify the role of vitamin D in the pathogenesis of depression and its management, as well as to establish whether currently suggested associations are clinically significant and distinctive.

Clinical Characteristics Associated With Treatment-Resistant Bipolar Disorder.

There has been limited consideration and empirical studies on treatment-resistant bipolar disorder (TRBD). This exploratory study was designed to identify factors contributing to TRBD in patients with a bipolar (I or II) disorder. Patients were categorized with "low," "medium," or "high" levels of treatment resistance based on a) the total number of psychiatric medications received and, for a second analysis, b) the number of mood stabilizer medications received. The study identified a number of factors associated with TRBD, such as being female and older and having an older age at illness onset, a higher incidences of family depression, less likelihood of being in paid employment, a higher number of lifetime stressors, medical conditions and comorbid anxiety disorders, a different personality and temperament profile, and more regular use of benzodiazepines. There were few factors associated with TRBD when defined by number of mood stabilizers trialed. Potential explanations for these findings were explored.