The Effectiveness of an Online Interdisciplinary Intervention for Mental Health Promotion: A Randomized Controlled Trial

Background There is an urgent need for efficacious interventions to combat the global mental health crisis, and mental health promotion and primary prevention approaches are paramount. The aim of this study is to examine whether an online interdisciplinary intervention that incorporates evidence-based strategies from the disciplines of Lifestyle Medicine and Positive Psychology improves measures of mental health and emotional wellness. Methods A randomized controlled trial with a wait-list control (N = 425, aged 46.97 ± 14.5, 69.9% females) was conducted in Australia and New Zealand. The intervention group participated in a 10-week online interdisciplinary intervention. Primary outcome measures of mental health and emotional wellness were taken at baseline (Week 1), post-intervention (Week 12), and 12 weeks post-intervention (Week 24). The wait-list control completed the same assessments. Results General Linear Modelling analyses indicated that the intervention group experienced significantly greater improvements than the wait-list control group over time in all outcome measures: mental health (F(319) = 7.326, p = 0.007) and vitality (F(319) = 9.445, p = 0.002) subscales of the Short Form Survey (SF-36); depression (F(319) = 7.841, p = 0.005), anxiety (F(319) = 4.440, p = 0.36) and stress (F(319) = 12.494, p \u3c 0.001) scales of the Depression, Anxiety and Stress Scale (DASS-21); and life satisfaction (F(319) = 8.731, p = 0.003) as measured by the Satisfaction With Life Scale. Within the intervention group, significant improvements were observed from Week 1 to 12 in all outcome measures: mental health (10%, t(167) = − 6.423), p \u3c 0.001, dz = 0.50), vitality (22%, t(167) = − 7.043, p \u3c 0.001, dz = 0.54), depression (− 41%, t(167) = 6.189, p \u3c 0.001, dz = 0.48), anxiety (− 38%, t(167) = 5.030, p \u3c 0.001, dz = 0.39), stress (− 31%, t(167) = 6.702, p \u3c 0.001, dz = 0.52) and life satisfaction (8%, t(167) = − 6.199, p \u3c 0.001, dz = 0.48). Improvements in the outcome measures remained significant in the intervention group at 12 weeks post-intervention. Conclusion The online interdisciplinary intervention improved measures of mental health and emotional wellness suggesting that such interventions may be useful for mental health promotion and prevention

The Influence of Human Support on the Effectiveness of an Online Mental Wellbeing Intervention

Purpose: To compare the influence of three modes of human support on the outcomes of an online, lifestyle-focused mental health promotion intervention. Background: There is a need for efficacious lifestyle interventions to promote the mental wellbeing of both healthy and clinical cohorts. Evidence regarding the usefulness of adding human support (i.e. guidance) to improve the outcomes of online interventions for clinical populations is mixed,1-3 however little is known about healthy cohorts. Methods: A total of 458 participants self-selected to participate in a 10-week online, multimodal lifestyle intervention that addressed mental wellbeing. The participants were randomized into three groups, differentiated by support mode: standard - automated emails only (S); standard plus personalised SMS messages (S+pSMS); standard plus videoconference support (S+VCS). At pre- and post-intervention, the participants completed the following measures: the ‘mental health’ and ‘vitality’ sub-scales from the Short Form Health Survey (SF-36); Depression Anxiety and Stress Scales (DASS-21); Satisfaction With Life (SWL) scale; and Flourishing scale. Results: A total of 320 participants (S, n=103; S+pSMS, n=114; S+VCS, n=103) completed the study. Significant within-group changes were recorded from pre- to post-intervention in all groups for every outcome measure (PP=0.77), vitality (P=0.65), depression (P=0.93), anxiety (P=0.25), stress (P=0.57), SWL (P=0.65) or flourishing (P=0.99). Attendance at the weekly videoconference support sessions was poor, but those who attended seven or more of the ten sessions experienced significantly better outcomes in mental health (P=.006, d=0.71), vitality (P=.005, d=0.73), depression (P=.04, d=0.54), and SWL (P=.046, d=0.50), than those who attended less than seven. Conclusions: A lifestyle-focused, online mental health promotion intervention enhanced measures of mental wellbeing among a healthy cohort, irrespective of the human support provided. Supplementing a psychological intervention with videoconference support might improve outcomes, when attendance is optimised

The Effect of an Online Multimodal Lifestyle Intervention on Mental Health and Emotional Wellness: A Randomised Control Trial

PURPOSE: This study examined the effect of an online multimodal lifestyle intervention, which incorporated evidence-based strategies from Lifestyle Medicine and Positive Psychology, on the mental health and emotional wellness of adults throughout Australia and New Zealand. BACKGROUND: Common mental health disorders have reached epidemic proportions worldwide (1). In the US, one in five adults have a common mental health disorder (2), and in Australia, a similar number have experienced an affective disorder in the past twelve months (3). Antidepressants are ranked in the top three most commonly used therapeutic drug classes in the US (4), and are the most commonly used psychotropic medications in Australia (5). A new paradigm is needed focusing on primary prevention to address this burgeoning mental health problem. METHODS: 508 individuals self-selected to participate in the study and were randomized to an intervention or delay-controlled group. Both groups completed an online survey using validated instruments which assessed the participantsʼ emotional wellness at three intervals: baseline, and at 3 months and 6 months post-intervention. 425 individuals completed the baseline assessment and entered the study (intervention n=217, control group n=208), and 359 (84%) completed the post intervention questionnaire. The intervention group participated in a 10-week online multimodal lifestyle intervention, called “The Live More Project” also known as The Lift Project”(6). RESULTS: Overall, the cohort was in the ‘normal’ range at baseline for the domains of emotional wellness measured. At 3 months, significant reductions were observed in symptoms of ‘depression’ (-31%, p\u3c0.001), ‘anxiety’ (-43%, p\u3c0.001) and ‘stress’ (-22%, p\u3c0.001) in the intervention compared to the control group. Significant improvements were observed in ‘mental health’ (8%, p\u3c0.001), ‘vitality’ (18%, p\u3c0.001) and overall ‘life 2 satisfaction’ (8%, p\u3c0.001). Improvements in the measures of mental health and emotional wellness were generally sustained in the 6-month follow-up. CONCLUSIONS: This study supports the use of an online multimodal lifestyle intervention combining strategies from Lifestyle Medicine and Positive Psychology for the promotion of mental health and emotional wellness among normal populations (i.e. primary prevention). Further analyses will examine the impact of the intervention on subnormal populations to assess its potential role in secondary and tertiary prevention

The Effectiveness of the Complete Health Improvement Program (CHIP) in Australasia for Reducing Selected Chronic Disease Risk Factors: A Feasibility Study

Abstract Aim To examine the effectiveness within the Australasian context of the Complete Health Improvement Program (CHIP) lifestyle intervention, which has been shown to produce meaningful reductions in selected chronic disease risk factors in the United States. Methods Changes in body weight, blood pressure, blood lipid profile and fasting plasma glucose were assessed in 836 self-selected participants (age=55.9±12.7 yrs, 35% male/65% female) from 18 sites throughout New Zealand (N=731) and Australia (N=105). Results In the 30 days of the program, significant overall reductions (pConclusions Significant reductions in selected chronic disease risk factors were observed in 30 days using the CHIP intervention and the improvements were comparable to that observed in cohorts from the United States. The results of this feasibility study indicate that lifestyle interventions like CHIP may be useful for combating the burgeoning epidemic of chronic disease and further research is warranted

Factors Predicting the Mental Health of Adolescents Attending a Faith-based Australian School System: A Multi-group Structural Equation Analysis

Background: Adolescents attending Seventh-day Adventist schools (Adventist) in Australia tend to experience good health and exhibit better health behaviors than national norms, however few studies have investigated factors predicting their mental health. Aims: The aim of this study was to explore the complex network of factors that predict the mental health status (MHS) of adolescents attending Adventist schools in Australia. Methods: A survey instrument was used to collect data from 1527 secondary school students attending Adventist schools across Australia. Structural equation modeling was employed to examine concomitantly the direct and indirect effects of childhood experiences, present attitudes and selected health behaviors on MHS. Results: Childhood family dynamics had the strongest association with MHS (βtotal = 0.33) followed by a sense of meaning and purpose (βtotal = 0.27), perceived social misfit status (βtotal = –0.19), and school academic performance (βtotal = 0.18). Multi-group analysis found significant pathway differences in the model for gender with regards to the association of meaning and purpose, physical activity and sleep quantity with MHS. Conclusions: The outcomes of the study highlight the importance of early positive childhood family dynamics and the discovery of meaning and purpose during adolescence to promote positive mental health among adolescents

The role of microRNA-155/liver X receptor pathway in experimental and idiopathic pulmonary fibrosis

Background: Idiopathic Pulmonary Fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF therefore microRNAs may reveal novel pathogenic pathways. Objectives: To determine the regulatory role of microRNA(miR)-155 in the pro-fibrotic function of murine lung macrophages and fibroblasts, IPF lung fibroblasts and its contribution to experimental pulmonary fibrosis. Methods: Bleomycin-induced lung fibrosis in wild-type and miR-155-/- mice was analyzed by histology, collagen and pro-fibrotic gene expression. Mechanisms were identified by in silico and molecular approaches; validated in mouse lung fibroblasts and macrophages, and in IPF lung fibroblasts, using loss-and-gain of function assays, and in vivo using specific inhibitors. Results: miR-155-/- mice developed exacerbated lung fibrosis, increased collagen deposition, collagen 1 and 3 mRNA expression, TGFβ production, and activation of alternatively-activated macrophages, contributed by deregulation of the microRNA-155 target gene the liver X receptor (LXR)α in lung fibroblasts and macrophages. Inhibition of LXRα in experimental lung fibrosis and in IPF lung fibroblasts reduced the exacerbated fibrotic response. Similarly, enforced expression of miR-155 reduced the pro-fibrotic phenotype of IPF and miR-155-/- fibroblasts. Conclusion: We describe herein a molecular pathway comprising miR-155 and its epigenetic LXRα target that when deregulated enables pathogenic pulmonary fibrosis. Manipulation of the miR-155/LXR pathway may have therapeutic potential for IPF

Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening

The first crystal structure is reported of a glutaryl-CoA dehydrogenase in the apo state without flavin adenine dinucleotide cofactor bound. Additional structures with small molecules complexed in the catalytic active site were obtained by fragment-based screening

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription

Intellectual disability (ID) is a common condition with considerable genetic heterogeneity. Next-generation sequencing of large cohorts has identified an increasing number of genes implicated in ID, but their roles in neurodevelopment remain largely unexplored. Here we report an ID syndrome caused by de novo heterozygous missense, nonsense, and frameshift mutations in BCL11A, encoding a transcription factor that is a putative member of the BAF swi/snf chromatin-remodeling complex. Using a comprehensive integrated approach to ID disease modeling, involving human cellular analyses coupled to mouse behavioral, neuroanatomical, and molecular phenotyping, we provide multiple lines of functional evidence for phenotypic effects. The etiological missense variants cluster in the amino-terminal region of human BCL11A, and we demonstrate that they all disrupt its localization, dimerization, and transcriptional regulatory activity, consistent with a loss of function. We show that Bcl11a haploinsufficiency in mice causes impaired cognition, abnormal social behavior, and microcephaly in accordance with the human phenotype. Furthermore, we identify shared aberrant transcriptional profiles in the cortex and hippocampus of these mouse models. Thus, our work implicates BCL11A haploinsufficiency in neurodevelopmental disorders and defines additional targets regulated by this gene, with broad relevance for our understanding of ID and related syndromes.This article is available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.Wellcome Trust (grant number WT098051)Published (open access