Exploring networks of complex developmental trauma symptomatology among children and adolescents involved in child welfare.

Background: Clinical presentations of child and adolescent psychopathology can vary systematically for boys and girls. While network analysis is increasingly being applied to explore psychopathology in adults, there is a dearth of network studies considering differences in symptoms for boys and girls, particularly in developmental trauma-related symptomatology. Methods: This study involves rural children (n = 375, 39.47% girls) and adolescents (n = 291, 51.20% girls) involved with child protection services in Ontario, Canada. Caregivers completed the Assessment Checklist for Children or Adolescents within the first 6 months of care. Psychometric network analyses were conducted using subscales for boys and girls. Differences were examined via network comparison permutation tests, moderated network models, and independent t-tests. Results: Attachment-related interpersonal difficulties were the most central nodes in the child and adolescent networks for both boys and girls. Emotional dysregulation also had high strength centrality for adolescents. While network comparison tests found the overall network structures and global network strength to be invariant between boys and girls for children and adolescents, moderated network models and independent t-tests revealed several differences with regards to the expression of specific symptoms. Among children, girls exhibited more indiscriminate and pseudomature interpersonal behaviors, whereas boys expressed significantly more non-reciprocal interpersonal behaviors and self-injury. Adolescent girls exhibited more behavioral dysregulation and suicide discourse in the moderated network model; t-tests also indicated higher levels of emotional dysregulation, negative self-image, and other items considered clinically important complex trauma symptoms (e.g., distrust of adults, confused belonging). Discussion: This study supports evidence of differences in the expression of complex trauma symptomatology for boys and girls. Additionally, girls exhibit more symptoms, in general. Consistent with the transdiagnostic conceptualization of the consequences of developmental trauma, findings demonstrate the primacy of attachment-specific difficulties and emotion dysregulation.

Comprehensive molecular analyses of cuproptosis-related genes with regard to prognosis, immune landscape, and response to immune checkpoint blockers in lung adenocarcinoma.

BACKGROUND: Recent studies have emphasized the importance of the biological processes of different forms of cell death in tumor heterogeneity and anti-tumor immunity. Nonetheless, the relationship between cuproptosis and lung adenocarcinoma (LUAD) remains largely unexplored. METHODS: Data for 793 LUAD samples and 59 normal lung tissues obtained from TCGA-LUAD cohort GEO datasets were used in this study. A total of 165 LUAD tissue samples and paired normal lung tissue samples obtained from our hospital were used to verify the prognostic value of dihydrolipoamide S-acetyltransferase (DLAT) and dihydrolipoamide branched chain transacylase E2 (DBT) for LUAD. The cuproptosis-related molecular patterns of LUAD were identified using consensus molecular clustering. Recursive feature elimination with random forest and a tenfold cross-validation method was applied to construct the cuproptosis score (CPS) for LUAD. RESULTS: Bioinformatic and immunohistochemistry (IHC) analyses revealed that 13 core genes of cuproptosis were all significantly elevated in LUAD tissues, among which DBT and DLAT were associated with poor prognosis (DLAT, HR = 6.103; DBT, HR = 4.985). Based on the expression pattern of the 13 genes, two distinct cuproptosis-related patterns have been observed in LUAD: cluster 2 which has a relatively higher level of cuproptosis was characterized by immunological ignorance; conversely, cluster 1 which has a relatively lower level of cuproptosis is characterized by TILs infiltration and anti-tumor response. Finally, a scoring scheme termed the CPS was established to quantify the cuproptosis-related pattern and predict the prognosis and the response to immune checkpoint blockers of each individual patient with LUAD. CONCLUSION: Cuproptosis was found to influence tumor microenvironment (TME) characteristics and heterogeneity in LUAD. Patients with a lower CPS had a relatively better prognosis, more abundant immune infiltration in the TME, and an enhanced response to immune checkpoint inhibitors.

Children's activities, parental concerns, and child care service utilization in the early stages of the COVID-19 pandemic.

Introduction: In the early stages of the COVID-19 pandemic, most Canadian provinces and territories enacted public health measures to reduce virus spread, leading most child care centers across the country to limit or halt in-person service delivery. While it is broadly known that the range of activities available to children and youth reduced drastically as a result, research has yet to explore if and how children's activities shifted in relation to changes in child care arrangements. Method: Children's activities during the early months of the pandemic were assessed based on parent-report data (n = 19,959). Activity patterns were extracted via latent profile analysis. Thereafter, differences in child-care related outcomes across profiles were compared via logistic regression models. Results: Latent profile analysis yielded three distinct activity patterns: Screenies (91.5%) were children who engaged in high amounts of screen use relative to all other activities; Analog children (3.1%) exhibited mostly off-screen activities (e.g., reading, physical exercise); and children in the Balanced group (5.4%) appeared to pursue a wide variety of activities. Children were more likely to fall into the Screenies or Balanced profiles when caregivers reported changes in child care arrangements. Moreover, parents of children with Balanced activity profiles were more likely to be planning to use child care when services reopened post-pandemic, compared to parents of children in the Analog group. Discussion: The present findings call attention to heterogeneity in children's activities during COVID-19, which should be considered in the context of pandemic-related child care closures. Implications for children, families, and child care services during and beyond COVID-19 are discussed.

Intravenous Reelin Treatment Rescues Atrophy of Spleen White Pulp and Correlates to Rescue of Forced Swim Test Immobility and Neurochemical Alterations Induced by Chronic Stress.

Reelin, an extracellular matrix protein with putative antidepressant-like properties, becomes dysregulated by chronic stress. Improvement in cognitive dysfunction and depression-like behavior induced by chronic stress has been reported with both intrahippocampal and intravenous Reelin treatment but the mechanisms responsible are not clear. To determine if treatment with Reelin modifies chronic stress-induced dysfunction in immune organs and whether this relates to behavioral and/or neurochemical outcomes, spleens were collected from both male (n = 62) and female (n = 53) rats treated with daily corticosterone injections for three weeks that received Reelin or vehicle. Reelin was intravenously administered once on the final day of chronic stress, or repeatedly, with weekly treatments throughout chronic stress. Behavior was assessed during the forced swim test and the object-in-place test. Chronic corticosterone caused significant atrophy of the spleen white pulp, but treatment with a single shot of Reelin restored white pulp in both males and females. Repeated Reelin injections also resolved atrophy in females. Correlations were observed between recovery of white pulp atrophy and recovery of behavioral deficits and expression of both Reelin and glutamate receptor 1 in the hippocampus, supporting a role of the peripheral immune system in the recovery of chronic stress-induced behaviors following treatment with Reelin. Our data adds to research indicating Reelin could be a valuable therapeutic target for chronic stress-related disorders including major depression.

Post-translational modifications of soluble α-synuclein regulate the amplification of pathological α-synuclein.

Cell-to-cell transmission and subsequent amplification of pathological proteins promote neurodegenerative disease progression. Most research on this has focused on pathological protein seeds, but how their normal counterparts, which are converted to pathological forms during transmission, regulate transmission is less understood. Here we show in cultured cells that phosphorylation of soluble, nonpathological α-synuclein (α-Syn) at previously identified sites dramatically affects the amplification of pathological α-Syn, which underlies Parkinson's disease and other α-synucleinopathies, in a conformation- and phosphorylation site-specific manner. We performed LC-MS/MS analyses on soluble α-Syn purified from Parkinson's disease and other α-synucleinopathies, identifying many new α-Syn post-translational modifications (PTMs). In addition to phosphorylation, acetylation of soluble α-Syn also modified pathological α-Syn transmission in a site- and conformation-specific manner. Moreover, phosphorylation of soluble α-Syn could modulate the seeding properties of pathological α-Syn. Our study represents the first systematic analysis how of soluble α-Syn PTMs affect the spreading and amplification of pathological α-Syn, which may affect disease progression.

Transcriptional coactivator MED1 in the interface of anti-estrogen and anti-HER2 therapeutic resistance.

Breast cancer is one of the most common cancer and leading causes of death in women in the United States and Worldwide. About 90% of breast cancers belong to ER+ or HER2+ subtypes and are driven by key breast cancer genes Estrogen Receptor and HER2, respectively. Despite the advances in anti-estrogen (endocrine) and anti-HER2 therapies for the treatment of these breast cancer subtypes, unwanted side effects, frequent recurrence and resistance to these treatments remain major clinical challenges. Recent studies have identified ER coactivator MED1 as a key mediator of ER functions and anti-estrogen treatment resistance. Interestingly, MED1 is also coamplified with HER2 and activated by the HER2 signaling cascade, and plays critical roles in HER2-mediated tumorigenesis and response to anti-HER2 treatment as well. Thus, MED1 represents a novel crosstalk point of the HER2 and ER pathways and a highly promising new therapeutic target for ER+ and HER2+ breast cancer treatment. In this review, we will discuss the recent progress on the role of this key ER/HER2 downstream effector MED1 in breast cancer therapy resistance and our development of an innovative RNA nanotechnology-based approach to target MED1 for potential future breast cancer therapy to overcome treatment resistance.

Gambling Features and Monetization in Video Games Create Challenges for Young People, Families, and Clinicians.

Video gaming (also known as computer gaming or electronic gaming) has stirred scientific interest since its widespread adoption as a recreational activity in the 1980s. Initial research focused on the negative consequences of violent content and the development of excessive or addictive use by players. Based on evidence showing that some players develop clinically significant addiction-like symptoms such as loss of control and impaired individual, social, and occupational functioning,1 Gaming Disorder has been recognized as an official diagnosis in the International Classification of Diseases, 11thedition (ICD-11).2 However, recent changes in video games have again produced qualitatively new problems.

Anxiety, depression and stress during the COVID-19 pandemic: Results from a cross-sectional survey.

BACKGROUND: Multiple survey studies have demonstrated a mental health (MH) burden of COVID-19 globally. However, few studies have examined relevant risk factors for pandemic-related MH issues. METHODS: A link to an online survey was posted from April 8th - June 11th, 2020 which included questions regarding COVID-19 experience, perceived impact of the pandemic on life domains (e.g., social communication, finances), behavioural alterations (e.g., online activities, substance use), and MH treatment history. Current psychiatric symptom severity and impairment were evaluated using the Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and the Perceived Stress Scale. RESULTS: Overall, 632 individuals (82% female, mean age:42.04 ± 16.56) in Canada and the United States completed the survey. While few reported contracting COVID-19 (0.5%), the impact of the pandemic was evident, with a vast majority reporting anxiety around COVID-19 infecting loved ones (88%). Almost half (43%) reported previous MH treatment and 31% met criteria for GAD, 29% for MDD and 63% reported significantly high levels of stress. Female sex, younger age and past MH treatment emerged as significant predictors of these issues(p < .01). Age-related differences in the impact of COVID-19 on life domains, substance use, and online activity were also noted. CONCLUSION: The findings from the current sample add to the growing literature suggesting negative effects of COVID-19 on MH, while highlighting specific risk factors. Age may be an important factor in predicting MH during this pandemic.

The role of cannabis in treating anxiety: an update.

PURPOSE OF REVIEW: Cannabis use for medical purposes has become increasingly common, including as treatment for mental health disorders such as anxiety. Unfortunately, the evidence examining its use in mental health has been slow to evolve, but is emerging. Given the widespread use of cannabis, it is important for both clinicians and those who suffer with anxiety to understand the effects of cannabis on symptoms of anxiety. In this review, we present recent, available evidence from animal models, clinical trials, and survey studies and evaluate the contribution of these studies to the current understanding of the role of cannabis in treating anxiety. RECENT FINDINGS: In reviewing recent evidence, we observed significant inconsistencies across findings from preclinical studies. Large-scale surveys suggest that cannabis may be effective in reducing anxiety, however, these results stand in contrast to equivocal findings from clinical trials. SUMMARY: The literature evaluating the efficacy of cannabis in anxiety disorders is in its infancy. The survey data is generally positive. Although, while some animal studies posit cannabis constituents to have anxiolytic effects, others suggest the opposite or null results. Few new clinical trials have been conducted recently, and the extant trials have significant flaws in methodology. Although anecdotal evidence from survey studies, and a small signal found in animal studies and single-dose clinical trials provide early support that cannabis may be effective for alleviating anxiety, ultimately, the current evidence is equivocal. More high-quality clinical trials must be published before sound conclusions regarding the efficacy of cannabis for treating anxiety can be drawn.

Body Mass Index and Mortality in a Very Large Cohort: Is It Really Healthier to Be Overweight?

CONTEXT: Controversy persists about optimal body weight. Many experts define "normal" (healthy) body mass index (BMI) as 18.5 to 24.9 kg/m2, 25 to 29.9 kg/m2 as overweight, and 30 kg/m2 or greater as obese. Obesity is subdivided into 30 to 34.9 kg/m2 (Grade 1), 35 to 39.9 kg/m2 (Grade 2), and 40 kg/m2 and above (Grade 3). Studies consistently show higher mortality for underweight and Grade 2 or 3 obesity, but results conflict for the overweight category and Grade 1 obesity. OBJECTIVE: To study 30-year risk of death related to baseline BMI. DESIGN: Retrospective cohort study in a multiracial population of 273,843 persons using logistic regression with 7 covariates (sex, age, race-ethnicity, education, marital status, smoking, alcohol intake). MAIN OUTCOME MEASURES: Mortality risk by baseline BMI. RESULTS: With average follow-up exceeding 30 years, there were 103,218 deaths: 41,215 attributed to cardiovascular causes and 62,003 to noncardiovascular causes. Odds ratios (and 95% confidence intervals) for all deaths in BMI categories, with a BMI of 18.5 to 24.9 kg/m2 as the referent, were BMI below 18.5 kg/m2 = 1.1 (1.0-2.0), BMI 25 to 29 kg/m2 = 1.1 (1.1-1.2), BMI 30 to 34 kg/m2 = 1.5 (1.4-1.5), BMI 35 to 39 kg/m2 = 2.1 (1.9-2.3), and BMI 40 kg/m2 or higher = 2.7 (2.4-3.0). Disparities existed regarding age, race/ethnicity, cause of death, and interval to death. CONCLUSION: Compared with persons with BMI defined as normal, persons who were underweight, overweight, and obese were at increased risk of death over 30 years.

Skin-mountable stretch sensor for wearable health monitoring.

This work presents a wrinkled Platinum (wPt) strain sensor with tunable strain sensitivity for applications in wearable health monitoring. These stretchable sensors show a dynamic range of up to 185% strain and gauge factor (GF) of 42. This is believed to be the highest reported GF of any metal thin film strain sensor over a physiologically relevant dynamic range to date. Importantly, sensitivity and dynamic range are tunable to the application by adjusting wPt film thickness. Performance is reliable over 1000 cycles with low hysteresis after sensor conditioning. The possibility of using such a sensor for real-time respiratory monitoring by measuring chest wall displacement and correlating with lung volume is demonstrated.