Longitudinal Neuropathological Consequences of Extracranial Radiation Therapy in Mice.

Cancer-related cognitive impairment (CRCI) is a consequence of chemotherapy and extracranial radiation therapy (ECRT). Our prior work demonstrated gliosis in the brain following ECRT in SKH1 mice. The signals that induce gliosis were unclear. Right hindlimb skin from SKH1 mice was treated with 20 Gy or 30 Gy to induce subclinical or clinical dermatitis, respectively. Mice were euthanized at 6 h, 24 h, 5 days, 12 days, and 25 days post irradiation, and the brain, thoracic spinal cord, and skin were collected. The brains were harvested for spatial proteomics, immunohistochemistry, Nanostring nCounter® glial profiling, and neuroinflammation gene panels. The thoracic spinal cords were evaluated by immunohistochemistry. Radiation injury to the skin was evaluated by histology. The genes associated with neurotransmission, glial cell activation, innate immune signaling, cell signal transduction, and cancer were differentially expressed in the brains from mice treated with ECRT compared to the controls. Dose-dependent increases in neuroinflammatory-associated and neurodegenerative-disease-associated proteins were measured in the brains from ECRT-treated mice. Histologic changes in the ECRT-treated mice included acute dermatitis within the irradiated skin of the hindlimb and astrocyte activation within the thoracic spinal cord. Collectively, these findings highlight indirect neuronal transmission and glial cell activation in the pathogenesis of ECRT-related CRCI, providing possible signaling pathways for mitigation strategies.

How much do adverse childhood experiences contribute to adolescent anxiety and depression symptoms? Evidence from the longitudinal study of Australian children.

This study aims to: (i) examine the association between adverse childhood experiences (ACEs) and elevated anxiety and depressive symptoms in adolescents; and (ii) estimate the burden of anxiety and depressive symptoms attributable to ACEs.Data were analyzed from 3089 children followed between Waves 1 (age 4-5 years) and 7 (16-17 years) of the Longitudinal Study of Australian Children. Logistic regression was used to estimate the associations between ACEs and child-reported elevated anxiety and depressive symptoms at age 16-17. Anxiety and depressive symptoms were measured using the Children's Anxiety Scale and Short Mood and Feelings Questionnaire, respectively. The punaf command available in STATA 14 was used to calculate the population attributable fraction (PAF).Before the age of 18 years, 68.8% of the children had experienced two or more ACEs. In the analysis adjusted for confounding factors, including co-occurring ACEs, both history and current exposure to bullying victimisation and parental psychological distress were associated with a statistically significant increased likelihood of elevated anxiety and depressive symptoms at age 16-17. Overall, 47% of anxiety symptoms (95% CI for PAF: 35-56) and 21% of depressive symptoms (95% CI: 12-29) were attributable to a history of bullying victimisation. Similarly, 17% (95% CI: 11-25%) of anxiety and 15% (95% CI: 4-25%) of depressive symptoms at age 16-17 years were attributable to parental psychological distress experienced between the ages of 4-15 years.The findings demonstrate that intervention to reduce ACEs, especially parental psychological distress and bullying victimisation, may reduce the substantial burden of mental disorders in the population.

Vascular dementia: From pathobiology to emerging perspectives.

Vascular dementia (VaD) is the second most common type of dementia. VaD is synonymous with ageing, and its symptoms place a significant burden on the health and wellbeing of older people. Despite the identification of a substantial number of risk factors for VaD, the pathological mechanisms underpinning this disease remain to be fully elucidated. Consequently, a biogerontological imperative exists to highlight the modifiable lifestyle factors which can mitigate against the risk of developing VaD. This review will critically examine some of the factors which have been revealed to modulate VaD risk. The survey commences by providing an overview of the putative mechanisms which are associated with the pathobiology of VaD. Next, the factors which influence the risk of developing VaD are examined. Finally, emerging treatment avenues including epigenetics, the gut microbiome, and pro-longevity pharmaceuticals are discussed. By drawing this key evidence together, it is our hope that it can be used to inform future experimental investigations in this field.

The Effects of Australia's First Residential Peer-Support Suicide Prevention and Recovery Centre (SPARC).

Aim: This paper reports preliminary evidence of the impacts of Australia's first residential peer-support service for people at risk of suicide. Methods: Psychological distress was measured preintervention, postintervention, and after 3 months and analyzed using paired t tests. Interviews were held postintervention and were analyzed using thematic analysis. Results: Psychological distress significantly improved from preintervention to postintervention (n = 16, d = 1.77) and at follow-up (n = 5, d = 1.12). Interviews (n = 10) indicated that participants experienced improvements in mental well-being and feelings of connectedness, respite, and confidence to engage with other services. The peer-support workers were key. Some participants felt that the location was too remote, too little information was given, and a longer stay would have been preferable. Limitations: The study did not include a control group, the sample was relatively small, and participants may have been subject to socially desirable answers. Conclusions: These findings indicate that residential peer-support services potentially offer a valuable alternative to conventional inpatient treatment for people at risk of suicide.

The Association of Speech/Language Risk With Phonological Awareness, Rapid Naming, and Reading Ability in Children With Cleft Lip and/or Palate.

Children with cleft lip and/or palate were assessed for speech, language, phonological awareness (PA), rapid naming (RN) and reading ability using standardized instruments at baseline (T1; N = 142, Mage = 6.14 years, 51% males) and 2-year follow-up (T2; 89% retention, Mage = 8.38). Children with no speech or language risk scored higher for T1 and T2 PA, RN, and reading than children with both speech and language risk [Adjusted Mean Difference (AMD) ranged from 11.79 to 21.25]; language risk (AMD 8.37 to 13.58); and speech risk (0.51 to 6.87). No significant differences by cleft type or child sex.

The hole in my heart is closing: Indigenous relative reunification identity verification.

OBJECTIVE: The current study explored the experience of reunification as place identity verification for Indigenous individuals who were fostered/adopted as youth. BACKGROUND: Research on reunification tends to focus on disproportionality in child welfare and the factors associated with reunification. Few studies focus on experiences of reunification among Indigenous individuals including their perceptions and comprehensions about the reunification experience. METHOD: Data from 70 fostered/adopted Indigenous individuals that reunified during adulthood were analyzed from the Experiences of Adopted and Fostered Individuals Project. Inductive thematic analysis was used to examine open-ended survey data about experience of reunification. RESULTS: Three themes inductively emerged including: (1) relative reunification, (2) perceptions about reunification, and (3) comprehensions about reunification. During relative reunification, participants reunified with parent(s), extended caregiver(s), grandparent(s), sibling(s), cousin(s), niece(s)/nephew(s), and tribe. Participant's perceptions about reunification included happiness, relief, anger, mourning, and anxiety/excitement. Participant's comprehensions about reunification related to belonging, sense of place, history/heritage, healing, and resemblance. All five functions of place identity verification were met in reunification according to the Indigenous participant's voices. CONCLUSIONS: This study explored the experience of relative reunification of Indigenous individuals who were separated from their families of origin during childhood by foster care and adoption.

Immunogenicity and Vaccine Shedding After 1 or 2 Doses of rVSVΔG-ZEBOV-GP Ebola Vaccine (ERVEBO®): Results From a Phase 2, Randomized, Placebo-controlled Trial in Children and Adults.

BACKGROUND: The rVSVΔG-ZEBOV-GP vaccine (ERVEBO®) is a single-dose, live-attenuated, recombinant vesicular stomatitis virus vaccine indicated for the prevention of Ebola virus disease (EVD) caused by Zaire ebolavirus in individuals 12 months of age and older. METHODS: The Partnership for Research on Ebola VACcination (PREVAC) is a multicenter, phase 2, randomized, double-blind, placebo-controlled trial of 3 vaccine strategies in healthy children (ages 1-17) and adults, with projected 5 years of follow-up (NCT02876328). Using validated assays (GP-ELISA and PRNT), we measured antibody responses after 1-dose rVSVΔG-ZEBOV-GP, 2-dose rVSVΔG-ZEBOV-GP (given on Day 0 and Day 56), or placebo. Furthermore, we quantified vaccine virus shedding in a subset of children's saliva using RT-PCR. RESULTS: In total, 819 children and 783 adults were randomized to receive rVSVΔG-ZEBOV-GP (1 or 2 doses) or placebo. A single dose of rVSVΔG-ZEBOV-GP increased antibody responses by Day 28 that were sustained through Month 12. A second dose of rVSVΔG-ZEBOV-GP given on Day 56 transiently boosted antibody concentrations. In vaccinated children, GP-ELISA titers were superior to placebo and non-inferior to vaccinated adults. Vaccine virus shedding was observed in 31.7% of children, peaking by Day 7, with no shedding observed after Day 28 post-dose 1 or any time post-dose 2. CONCLUSIONS: A single dose of rVSVΔG-ZEBOV-GP induced robust antibody responses in children that was non-inferior to the responses induced in vaccinated adults. Vaccine virus shedding in children was time-limited and only observed after the first dose. Overall, these data support the use of rVSVΔG-ZEBOV-GP for the prevention of EVD in at-risk children. Clinical Trials Registration. The study is registered at ClinicalTrials.gov (NCT02876328), the Pan African Clinical Trials Registry (PACTR201712002760250), and the European Clinical Trials Register (EudraCT number: 2017-001798-18).

A new mathematical model of folate homeostasis in E. coli highlights the potential importance of the folinic acid futile cycle in cell growth.

Folate (vitamin B9) plays a central role in one-carbon metabolism in prokaryotes and eukaryotes. This pathway mediates the transfer of one-carbon units, playing a crucial role in nucleotide synthesis, methylation, and amino acid homeostasis. The folinic acid futile cycle adds a layer of intrigue to this pathway, due to its associations with metabolism, cell growth, and dormancy. It also introduces additional complexity to folate metabolism. A logical way to deal with such complexity is to examine it by using mathematical modelling. This work describes the construction and analysis of a model of folate metabolism, which includes the folinic acid futile cycle. This model was tested under three in silico growth conditions. Model simulations revealed: 1) the folate cycle behaved as a stable biochemical system in three growth states (slow, standard, and rapid); 2) the initial concentration of serine had the greatest impact on metabolite concentrations; 3) 5-formyltetrahydrofolate cyclo-ligase (5-FCL) activity had a significant impact on the levels of the 7 products that carry the one-carbon donated from folates, and the redox couple NADP/NADPH; this was particularly evident in the rapid growth state; 4) 5-FCL may be vital to the survival of the cells by maintaining low levels of homocysteine, as high levels can induce toxicity; and 5) the antifolate therapeutic trimethoprim had a greater impact on folate metabolism with higher nutrient availability. These results highlight the important role of 5-FCL in intracellular folate homeostasis and mass generation under different metabolic scenarios.

Religiosity and spirituality in the prevention and management of depression and anxiety in young people: a systematic review and meta-analysis.

Historically, religion has had a central role in shaping the psychosocial and moral development of young people. While religiosity and spirituality have been linked to positive mental health outcomes in adults, their role during the developmental context of adolescence, and the mechanisms through which such beliefs might operate, is less well understood. Moreover, there is some evidence that negative aspects of religiosity are associated with poor mental health outcomes. Guided by lived experience consultants, we undertook a systematic review and quality appraisal of 45 longitudinal studies and 29 intervention studies identified from three electronic databases (Medline, PsycINFO and Scopus) exploring the role of religiosity and spiritual involvement (formal and informal) in prevention and management of depression and anxiety in young people aged 10 to 24 years. Most studies were from high-income countries and of low to moderate quality. Meta-analysis of high-quality longitudinal studies (assessed using Joanna Briggs Institute critical appraisal tools, n = 25) showed a trend towards association of negative religious coping (i.e., feeling abandoned by or blaming God) with greater depressive symptoms over time (Pearson's r = 0.09, 95% confidence interval (CI) -0.009, 0.188) whereas spiritual wellbeing was protective against depression (Pearson's r = -0.153, CI -0.187, -0.118). Personal importance of religion was not associated with depressive symptoms overall (Pearson's r = -0.024, CI-0.053, 0.004). Interventions that involved religious and spiritual practices for depression and anxiety in young people were mostly effective, although the study quality was typically low and the heterogeneity in study designs did not allow for a meta-analysis. The lived experience consultants described spirituality and religious involvement as central to their way of life and greatly valued feeling watched over during difficult times. While we require more evidence from low- and middle-income countries, in younger adolescents and for anxiety disorders, the review provides insight into how spirituality and religious involvement could be harnessed to design novel psychological interventions for depression and anxiety in young people.Review RegistrationThe systematic review was funded by Wellcome Trust Mental Health Priority Area 'Active Ingredients' 2021 commission and registered with PROSPERO 2021 (CRD42021281912).

Computationally Modelling Cholesterol Metabolism and Atherosclerosis.

Cardiovascular disease (CVD) is the leading cause of death globally. The underlying pathological driver of CVD is atherosclerosis. The primary risk factor for atherosclerosis is elevated low-density lipoprotein cholesterol (LDL-C). Dysregulation of cholesterol metabolism is synonymous with a rise in LDL-C. Due to the complexity of cholesterol metabolism and atherosclerosis mathematical models are routinely used to explore their non-trivial dynamics. Mathematical modelling has generated a wealth of useful biological insights, which have deepened our understanding of these processes. To date however, no model has been developed which fully captures how whole-body cholesterol metabolism intersects with atherosclerosis. The main reason for this is one of scale. Whole body cholesterol metabolism is defined by macroscale physiological processes, while atherosclerosis operates mainly at a microscale. This work describes how a model of cholesterol metabolism was combined with a model of atherosclerotic plaque formation. This new model is capable of reproducing the output from its parent models. Using the new model, we demonstrate how this system can be utilized to identify interventions that lower LDL-C and abrogate plaque formation.

Examining the quality of news media reporting of complex mental illness in relation to violent crime in Australia.

PURPOSE: News reporting on mental illness can perpetuate stigma. An understanding of the current picture of such reporting is important to identify areas for improvement. This study investigated the quality of Australian news media coverage of complex mental illness in the context of crime and violence over a 2-year period, prior to the release of new media guidelines. METHODS: This research utilised a systematic search of Australian news articles that were published between July 2018 and July 2020 and reported on mental illness in relation to violent crime. Researchers developed a Mental Illness and Crime Reporting Quality Framework to determine quality scores for news articles according to 11 relevant factors in media guidelines. An additional 11 characteristics of articles were extracted for further descriptive analysis. RESULTS: One-hundred and twenty-eight Australian news articles met inclusion criteria. The average quality score was 50 (SD = 13.91) out of a possible maximum score of 100 (range 11-78). Strengths and weaknesses were identified as some criteria were consistently met, and other criteria were met rarely or not at all. There were emerging trends between quality scores and article characteristics, including publication source, though these analyses were not statistically significant. CONCLUSION: The findings indicate that Australian news coverage of complex mental illness and violent crime met half of the criteria of reporting guidelines that minimises risk of perpetuating or reinforcing stigma. This demonstrates significant opportunity to improve the overall quality of media reporting on crime and mental illness. Future research should evaluate the impact of the guidelines on the quality of news reporting after their implementation by utilising a similar methodology, using these findings as a baseline measure.

Adolescent peer support for mental health problems: evaluation of the validity and reliability of the Mental Health Support Scale for Adolescents.

BACKGROUND: The Mental Health Support Scale for Adolescents (MHSSA) is a criterion-referenced measure of adolescents' supportive intentions towards peers with mental health problems, which was developed for use in evaluations of adolescent mental health interventions, such as the teen Mental Health First Aid (tMHFA) program. The present study aimed to examine the validity and reliability of the MHSSA. METHODS: A sample of 3092 school students (Mean ± SD: 15.9 ± 0.4 years old) and 65 tMHFA Instructors (the adult group with known expertise in tMHFA) completed the 12 items of the MHSSA. A sub-sample of 1201 students repeated the scale after a 3-4-week interval. Item concordance rates with the tMHFA Action Plan across helpful and harmful intentions scales were calculated. Scale reliabilities were assessed using agreement coefficients from a single test administration and test-retest reliability measured by intraclass correlation coefficients. The mean differences of MHSSA scores of students and Instructors were compared using independent samples t-tests, while convergent validity was tested via correlations of the scale with validated measures of confidence in providing help, social distance and personal stigma. RESULTS: The average score of Instructors was significantly higher than that of students. The scale was positively associated with confidence in providing help, whilst negatively associated with social distance and dimensions of personal stigma. All scales of MHSSA had high agreement coefficients (all > 0.80) and fair to good test-retest reliability over 3-4 weeks. CONCLUSIONS: The MHSSA shows evidence of validity and reliability for use among adolescents for evaluating the quality of intentions to help peers with mental health problems.

"Each week feels like a mountain": The impact of COVID-19 on mental health providers' wellbeing and clinical work.

The SARS-CoV-2 (COVID-19) pandemic has placed a tremendous strain on healthcare providers. Although there is a burgeoning body of literature on how COVID-19 has impacted frontline healthcare workers (i.e., providers treating COVID-19 patients), little attention has been dedicated to second-line workers (i.e., providers treating the mental health of people impacted by COVID-19). In this paper, we present findings from a thematic analysis of open text responses (n = 136) examining how COVID-19 shaped both the wellbeing of second-line workers, specifically mental health providers, as well as their clinical work in the early months of the COVID-19 pandemic in the United States. Results indicated that mental health providers were experiencing significant COVID-19-related burnout and poor physical and mental health outcomes. Participants described diminished negative effects on the quality of their clinical care from the burnout and trauma associated with COVID-19. Many also demonstrated resilience, identifying the duality of both negative (e.g., exhaustion) and positive (e.g., pride in helping others) meaning derived from their second-line work experiences. We conclude with recommendations for preventing and addressing burnout among mental health professionals in the era of COVID-19 and subsequent health emergencies.

Marital quality and depression as mediators linking childhood maltreatment to adult physical health.

BACKGROUND: Childhood maltreatment is known to influence adult physical health among midlife adults. Evidence suggests that depressive symptoms mediate the association. However, research has discounted the role of marital quality in understanding health outcomes among adults maltreated in childhood. OBJECTIVE: To advance this line of inquiry, we examined the relationship between marital quality and depressive symptoms in a sequential mediation model linking childhood maltreatment to adult physical health over ten years. PARTICIPANTS AND SETTING: Our sample consisted of midlife adults (n = 550) from three waves of the Midlife Development in the United States (MIDUS) study. The majority (n = 91.4 %) were white. At MIDUS 2, the mean age was 54.84 (SD = 10.78) and the mean age at MIDUS 3 was 63.96 (SD = 10.81). METHODS: Structural equation modeling was used to examine the degree to which marital quality and depressive symptoms mediated the relationship between childhood maltreatment and adult physical outcomes. Bootstrapping procedures were used to estimate the indirect effects. RESULTS: The serial mediation effects from maltreatment to adult physical health through marital quality and depressive symptoms were significant. Likewise, the simple indirect effects from maltreatment to subjective evaluations and the number of chronic health conditions through depressive symptoms were also significant. CONCLUSIONS: Childhood maltreatment is linked to adult physical health problems through marital quality and depressive symptoms, suggesting that the quality of adult marriages may play a critical role in health outcomes. Improving the quality of marriages may reduce risk factors, such as depression, that potentate future physical health problems.

Evaluation of the Conversations about Non-Suicidal Self-Injury Mental Health First Aid Course: Effects on Knowledge, Stigmatising Attitudes, Confidence and Helping Behaviour.

BACKGROUND: Non-suicidal self-injury (NSSI) is a common mental health problem, with a 19% lifetime prevalence in Australian adolescents and 12% in adults. Though rates of professional help-seeking for NSSI are low, disclosure to family and friends is more common, providing opportunities for them to encourage professional support. Mental Health First Aid® Australia's Conversations about Non-Suicidal Self-Injury course provides evidence-based training for the general public to support a person engaging in NSSI. METHODS: This uncontrolled trial evaluated the effects of the Conversations about Non-Suicidal Self-Injury course on participants' knowledge, confidence, stigmatising attitudes, and intended and actual helping behaviours. Surveys were administered pre- and post-course, and at a six-month follow-up. A linear mixed-model analysis determined mean change over time, and effect sizes were estimated using Cohen's d. Course satisfaction was assessed using descriptive statistics and summative content analysis of qualitative data. RESULTS: The pre-course survey was completed by 147 Australian participants (77.5% female, mean age 45.8 years), 137 (93.2%) at post-course and 72 (49%) at follow-up. Knowledge, confidence, quality of intended helping behaviours, and quality of actual helping behaviours increased significantly at both time points. Social distance decreased significantly at all time points and stigma decreased significantly at post-course. The course was perceived to be highly acceptable by participants. CONCLUSIONS: There is initial evidence that the Conversations about Non-Suicidal Self-Injury course is effective and acceptable for members of the public who may support a person engaging in NSSI.

Comparing mental health and well-being of US undergraduate and graduate students during the early stages of the COVID-19 pandemic.

Objective: This study explored how COVID-related mental health and well-being varied between undergraduate and graduate students. Relationships with physical health behaviors were also examined. Participants: Undergraduate (n = 897) and graduate (n = 314) students were recruited from three US universities between mid-April and late-May 2020. Methods: Participants in this cross-sectional survey self-reported perceived stress, financial stress, resilience, repetitive negative thinking, mood, anxiety, diet, sleep, and physical activity using validated instruments. Results: Undergraduate students reported more perceived stress, more repetitive negative thinking, less positive mood, and less support from professors than graduate students. Perceived stress, repetitive negative thinking, negative mood, and anxiety increased among all students (p < .05 for all). Correlations between mental health outcomes and physical health behaviors were weak to moderate (r = .08 to .49). Conclusions: College students, particularly undergraduates, perceived negative mental health impacts during COVID. Creative approaches for meeting student needs are necessary.

Development of the Mental Health Support Scale: A New Measure of Mental Health First Aid Behaviors.

Mental health first aid (MHFA) courses teach community members the knowledge and skills needed to recognize and respond to mental health problems until professional help is received or the crisis resolves. This study aimed to develop a reliable and valid measure of MHFA behaviors. A pool of actions that were recommended and not recommended were selected from MHFA guidelines and developed into two scales measuring either intended or provided support. Items were tested with a sample of 697 adults. Item response theory guided the selection of final items. The Mental Health Support Scale (MHSS) Intended version has 23 items across two subscales and the MHSS-Provided has 12 items across two subscales. These scales demonstrated convergent validity, discrimination between respondents with and without MHFA expertise, and acceptable measurement precision across a range of skill levels. Overall, findings suggest that the MHSS is a valid and useful measure of MHFA behaviors.

Young people's help-giving actions towards a peer with a mental health problem: A systematic review and narrative synthesis.

AIMS: Young people often seek help from their peers for mental health problems. However, little is known about young people's experiences of helping a peer with a mental health problem. The aim of this study was to systematically review the literature on young people's help-giving actions, highlight any gaps in the research and examine the evidence for interventions designed to increase and improve help-giving. The secondary aim was to compare findings between help-giving in face-to-face and online settings. METHODS: Embase, SCOPUS, PsycINFO and MEDLINE electronic databases were searched for English studies published from 2003 onwards. Studies focusing on the help-giving actions of young people (aged 12-25 years) towards a peer with a mental health problem were included. Risk of bias was assessed using the Joanna Briggs Institute quality appraisal tools. Data were synthesized using thematic and narrative analysis. RESULTS: Twenty-one studies (3440 participants) were included. The most frequently reported help-giving themes were encouraging professional and adult support and providing emotional support. Although limited studies reported on online help-giving, online settings allowed for immediate help to be provided despite time or location. Both positive and negative outcomes for helping were identified. Improvements in the quality of help-giving were found after training; however, help-giving for mental health crises was poor. CONCLUSIONS: Further research regarding the young people's help-giving actions to peers online is required. Training programs need to consider how to further improve the quality of help-giving among young people and to increase the trainees' confidence in helping, particularly in a mental health crisis.