Analysis of Learning Outcomes in LGBTQ+ Medical School Curriculum

Introduction. Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) youth are at increased risk for negative health outcomes and experience increased barriers to health care.https://scholarworks.uvm.edu/comphp_gallery/1088/thumbnail.jp

Interactive video games to reduce paediatric procedural pain and anxiety: a systematic review and meta-analysis

Background: Procedural pain and anxiety in children can be poorly controlled, leading to significant short- and long-term sequelae, such as longer procedure times or future healthcare avoidance. Caregiver anxiety can exacerbate these effects. We aimed to evaluate the effect of interactive video game interventions on children's procedural pain and anxiety, including the effect of different types of video games on those outcomes. Methods: We conducted a systematic review and meta-analysis of the effectiveness of interactive video games compared with standard care in children (0–18 yr) undergoing painful procedures. We searched the databases MEDLINE, Embase, and PsycINFO. We conducted random-effects meta-analysis using ‘R’ of children's procedural pain and anxiety and caregivers' anxiety. Results: Of 2185 studies screened, 36 were eligible (n=3406 patients). Studies commonly involved venous access (33%) or day surgery (31%). Thirty-four studies were eligible for meta-analyses. Interactive video games appear to reduce children's procedural pain (standardised mean difference [SMD]=–0.43; 95% confidence interval [CI]: –0.67 to –0.20), anxiety (SMD=0.61; 95% CI: –0.88 to –0.34), and caregivers' procedural anxiety (SMD=–0.31; 95% CI: –0.58 to –0.04). We observed no difference between preparatory and distracting games, or between virtual reality and non-virtual reality games. We also observed no difference between interactive video games compared with standard care for most medical outcomes (e.g. procedure length), except a reduced need for restraint. Studies reported minimal adverse effects and typically had high intervention acceptability and satisfaction. Conclusions: Our findings support introducing easily available video games, such as distraction-based conventional video games, into routine practice to minimise paediatric procedural pain and child/caregiver anxiety

Chronic Stress Induces Maladaptive Behaviors by Activating Corticotropin-Releasing Hormone Signaling in the Mouse Oval Bed Nucleus of the Stria Terminalis

The bed nucleus of the stria terminalis (BNST) is a forebrain region highly responsive to stress that expresses corticotropin-releasing hormone (CRH) and is implicated in mood disorders, such as anxiety. However, the exact mechanism by which chronic stress induces CRH-mediated dysfunction in BNST and maladaptive behaviors remains unclear. Here, we first confirmed that selective acute optogenetic activation of the oval nucleus BNST (ovBNST) increases maladaptive avoidance behaviors in male mice. Next, we found that a 6 week chronic variable mild stress (CVMS) paradigm resulted in maladaptive behaviors and increased cellular excitability of ovBNST CRH neurons by potentiating mEPSC amplitude, altering the resting membrane potential, and diminishing M-currents (a voltage-gated K+ current that stabilizes membrane potential) in ex vivo slices. CVMS also increased c-fos+ cells in ovBNST following handling. We next investigated potential molecular mechanism underlying the electrophysiological effects and observed that CVMS increased CRH+ and pituitary adenylate cyclase-activating polypeptide+ (PACAP; a CRH upstream regulator) cells but decreased striatal-enriched protein tyrosine phosphatase+ (a STEP CRH inhibitor) cells in ovBNST. Interestingly, the electrophysiological effects of CVMS were reversed by CRHR1-selective antagonist R121919 application. CVMS also activated protein kinase A (PKA) in BNST, and chronic infusion of the PKA-selective antagonist H89 into ovBNST reversed the effects of CVMS. Coadministration of the PKA agonist forskolin prevented the beneficial effects of R121919. Finally, CVMS induced an increase in surface expression of phosphorylated GluR1 (S845) in BNST. Collectively, these findings highlight a novel and indispensable stress-induced role for PKA-dependent CRHR1 signaling in activating BNST CRH neurons and mediating maladaptive behaviors

Transcriptional targets of the schizophrenia risk gene MIR137

Genome-wide association studies (GWAS) have strongly implicated MIR137 (the gene encoding the microRNA miR-137) in schizophrenia. A parsimonious hypothesis is that a pathway regulated by miR-137 is important in the etiology of schizophrenia. Full evaluation of this hypothesis requires more definitive knowledge about biological targets of miR-137, which is currently lacking. Our goals were to expand knowledge of the biology of miR-137 by identifying its empirical targets, and to test whether the resulting lists of direct and indirect targets were enriched for genes and pathways involved in risk for schizophrenia. We overexpressed miR-137 in a human neural stem cell line and analyzed gene expression changes at 24 and 48 h using RNA sequencing. Following miR-137 overexpression, 202 and 428 genes were differentially expressed after 24 and 48 h. Genes differentially expressed at 24 h were enriched for transcription factors and cell cycle genes, and differential expression at 48 h affected a wider variety of pathways. Pathways implicated in schizophrenia were upregulated in the 48 h findings (major histocompatibility complex, synapses, FMRP interacting RNAs and calcium channels). Critically, differentially expressed genes at 48 h were enriched for smaller association P-values in the largest published schizophrenia GWAS. This work provides empirical support for a role of miR-137 in the etiology of schizophrenia

Psychological and somatic symptoms among breast cancer patients in four European countries : A cross-lagged panel model

Psychological and physical health among women with breast cancer are linked. However, more research is needed to test the interrelations between psychological and somatic symptoms, over time and throughout the different phases of breast cancer treatment, to determine when and which interventions should be prioritized. Six hundred and eighty nine women from four countries (Finland, Israel, Italy and Portugal) completed questionnaires during their first clinical consultation following diagnosis with breast cancer, and again after 3 and 6 months. The questionnaires included self-reported measures of psychological symptoms (Hospital Anxiety and Depression Scale; the Positive and Negative Affect Schedule Short Form) and somatic symptoms [selected items from the International European Organization for Research and Treatment of Cancer (EORTC) questionnaires]. Psychological and somatic symptoms were relatively stable across the three time-points. Cross-lagged paths leading from somatic to psychological symptoms (beta coefficients of 0.08-0.10), as well as vice-versa (beta 0.11-0.12), were found to be significant. No evidence was found for cross-cultural differences in mutual effects of psychological and somatic symptoms. The findings of this study call for tailoring personal interventions for breast cancer patients-either from a somatic perspective or a psychological perspective-and adjust them to the specific experiences of the individual patient.Peer reviewe

Trajectories of Quality of Life among an International Sample of Women during the First Year after the Diagnosis of Early Breast Cancer: A Latent Growth Curve Analysis

The current study aimed to track the trajectory of quality of life (QoL) among subgroups of women with breast cancer in the first 12 months post-diagnosis. We also aimed to assess the number and portion of women classified into each distinct trajectory and the sociodemographic, clinical, and psychosocial factors associated with these trajectories. The international sample included 699 participants who were recruited soon after being diagnosed with breast cancer as part of the BOUNCE Project. QoL was assessed at baseline and after 3, 6, 9, and 12 months, and we used Latent Class Growth Analysis to identify trajectory subgroups. Sociodemographic, clinical, and psychosocial factors at baseline were used to predict latent class membership. Four distinct QoL trajectories were identified in the first 12 months after a breast cancer diagnosis: medium and stable (26% of participants); medium and improving (47%); high and improving (18%); and low and stable (9%). Thus, most women experienced improvements in QoL during the first year post-diagnosis. However, approximately one-third of women experienced consistently low-to-medium QoL. Cancer stage was the only variable which was related to the QoL trajectory in the multivariate analysis. Early interventions which specifically target women who are at risk of ongoing low QoL are needed

Genetic Analysis of Hematological Parameters in Incipient Lines of the Collaborative Cross

Hematological parameters, including red and white blood cell counts and hemoglobin concentration, are widely used clinical indicators of health and disease. These traits are tightly regulated in healthy individuals and are under genetic control. Mutations in key genes that affect hematological parameters have important phenotypic consequences, including multiple variants that affect susceptibility to malarial disease. However, most variation in hematological traits is continuous and is presumably influenced by multiple loci and variants with small phenotypic effects. We used a newly developed mouse resource population, the Collaborative Cross (CC), to identify genetic determinants of hematological parameters. We surveyed the eight founder strains of the CC and performed a mapping study using 131 incipient lines of the CC. Genome scans identified quantitative trait loci for several hematological parameters, including mean red cell volume (Chr 7 and Chr 14), white blood cell count (Chr 18), percent neutrophils/lymphocytes (Chr 11), and monocyte number (Chr 1). We used evolutionary principles and unique bioinformatics resources to reduce the size of candidate intervals and to view functional variation in the context of phylogeny. Many quantitative trait loci regions could be narrowed sufficiently to identify a small number of promising candidate genes. This approach not only expands our knowledge about hematological traits but also demonstrates the unique ability of the CC to elucidate the genetic architecture of complex traits

Identification of an ATP/P2X7/Mast Cell Pathway Mediating Ozone-Induced Bronchial Hyperresponsiveness

Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through P2X7 receptors on mast cells. Both mast cell-deficient and P2X7 receptor-deficient (P2X7-/-) mice demonstrated markedly attenuated BHR to ozone. Reconstitution of mast cell-deficient mice with WT mast cells and P2X7-/- mast cells restored ozone-induced BHR. Despite equal numbers of mast cells in reconstituted mouse lungs, mice reconstituted with P2X7-/- mast cells demonstrated significantly less robust BHR than mice reconstituted with WT mast cells. These results support a model where P2X7 on mast cells and other cell types contribute to ozone-induced BHR

Adolescents at risk of self-harm in Ghana: a qualitative interview study exploring the views and experiences of key adult informants

Background In Ghana, rates of self-harm in young people are as high as they are in high income countries. Self-reported interpersonal, familial and societal stressors form the most important background, and self-harm is seen by young people as a way of responding to that stress. In the present study, we obtained the views of key adult informants about self-harm among adolescents in Ghana – what they thought as possible reasons for self-harm in young people and what actions might be needed at an individual or population level to respond to the problem. Methods We interviewed face-to-face 11 adults, using a semi-structured interview guide. We used an experiential thematic analysis technique to analyse the transcribed interviews. Results The analysis identified five themes: “underestimating the prevalence of self-harm in adolescents”, “life on the streets makes self-harm less likely”, “self-harm in adolescents is socially and psychologically understandable”, “ambivalence about responding to adolescent self-harm”, and “few immediate opportunities for self-harm prevention in Ghana”. Adolescent self-harm was acknowledged but its scale was underestimated. The participants offered explanations for adolescent self-harm in social and psychological terms that are recognisable from accounts in high income countries. Low rates among street-connected young people were explained by their overarching orientation for survival. Participants agreed that identification was important, but they expressed a sense of inadequacy in identifying and supporting adolescents at risk of self-harm. Again, the participants agreed that self-harm in adolescents should be prevented, but they recognised that relevant policies were not in place or if there were policies they were not implemented – mental health and self-harm were not high on public or political priorities. Conclusions The adults we interviewed about young people who self-harm see themselves as having a role in identifying adolescents at risk of self-harm and see the organisations in which they work as having a role in responding to individual young people in need. These are encouraging findings that point to at least one strand of a policy in Ghana for addressing the problem of self-harm in young people