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Background This feasibility pilot of the Parenting for Lifelong Health for Young Children program in Thailand aimed to: 1) explore the feasibility of study evaluation approaches; 2) assess the feasibility of delivering an adapted program; 3) report indicative effects on child maltreatment and related outcomes; and 4) examine intervention content associated with key mechanisms of change perceived by caregivers and facilitators. Method Sixty primary caregivers of children aged 2–9 years were recruited for an 8-week parenting program embedded within the local health system. Mixed-methods approaches included quantitative caregiver-report and observational data from standardized instruments, and qualitative data from individual and group interviews with caregivers and program facilitators. Analyses involved Wilcoxon signed-rank tests, paired t-tests, Friedman’s ANOVA, and thematic analysis. Results Participants reported that most (65%) were grandparents or great-grandparents. Study retention and response rates were high, and enrolled caregivers attended an average of 93% of sessions. Primary outcomes showed caregiver-reported pre-post reductions in overall child maltreatment ( d  = − 0.58, p  < 0.001), as well as reductions in physical ( d  = − 0.58, p  < 0.001) and emotional abuse ( d  = − 0.40, p  < 0.001). Combined caregiver report and observational assessments using the HOME Inventory showed reductions in abusive and harsh parenting ( d  = − 0.52, p  < 0.001). Secondary outcomes demonstrated decreases in child neglect; dysfunctional parenting; poor child monitoring and supervision; parental sense of inefficacy; child behavior problems; daily report on child problem behavior; parent overall depression, anxiety, and stress; and attitudes supporting physical punishment and harsh discipline. There were increases in overall positive parenting, daily positive parenting behavior, as well as HOME Inventory assessments on parent-child relationships. Thematic analyses from interviews and focus group data identified six key program themes associated with strengthened parent-child relationships, reduced child behavior problems, improved attitudes and strategies toward discipline, and improved management of parental stress. Conclusions This study represents one of few evaluations to test the feasibility of an evidence-based parenting program embedded within routine public health service delivery in a low- or middle-income country. Findings show preliminary effectiveness in reducing child maltreatment, improvements on 22 of 24 secondary outcomes, and perceived mechanisms of change that support quantitative findings. Prospects are promising for program scalability, pending randomized controlled trial results. Trial registration 11/01/2019, ClinicalTrials.gov, ID# NCT03539341 .

Background Depression contributes substantially to the burden of disease in South Africa. Little is known about how neighbourhoods affect the mental health of the people living in them. Methods Using nationally representative data ( N =11,955) from the South African National Income Dynamics Study and the South African Indices of Multiple Deprivation (SAIMD) modelled at small-area level, this study tested associations between neighbourhood-level deprivation and depression, after controlling for individual-level covariates. Results Results showed a significant positive association between neighbourhood-level deprivation and depression using the composite SAIMD ( β = 0.31 (0.15); p =0.04) as well as the separate deprivation domains. Living environment deprivation ( β =0.53 (0.16); p =0.001) and employment deprivation ( β = 0.38 (0.13); p =0.004), respectively, were the two most salient domains in predicting this relationship. Conclusions Findings supported the hypothesis that there is a positive association between living in a more deprived neighbourhood and depression, even after controlling for individual-level covariates. This study suggests that alleviating structural poverty could reduce the burden of depression in South Africa.

The purpose of this study was to estimate the economic burden of violence against children in South Africa. We assembled summative estimates of lifetime prevalence, calculated the magnitude of associations with negative outcomes, and thereby estimated the economic burden of violence against children. According to our calculations, 2.3 million and 84,287 disability-adjusted life-years (DALYs) lost in South Africa in 2015 were attributable to nonfatal and fatal violence against children, respectively. The estimated economic value of DALYs lost to violence against children (including both fatal and nonfatal) in South Africa in 2015 totalled ZAR173 billion (US$13.5 billion)—or 4.3% of South Africa’s gross domestic product (GDP) in 2015. In addition, the reduced earnings attributable to childhood physical violence and emotional violence in South Africa in 2015 were ZAR25.2 billion (US $ 2.0 billion) and ZAR9.6 billion (US$750 million), respectively. In addition, South Africa spent ZAR1.6 billion (US $ 124 million) on child care and protection in fiscal year 2015/2016, many of which costs are directly related to violence against children. This study confirms the importance of prioritising violence against children as a key social and economic concern for South Africa’s future.

We evaluated an intervention to increase positive parenting, reduce corporal punishment, and improve children's mental health community-wide. All Parenting for Lifelong Health programmes were available to all interested parents alongside an action media intervention designed to amplify positive parenting messages across the community. Three community-wide surveys of parents and of children aged 10+ were conducted at baseline and at 18-month intervals. Parent and child surveys assessed parenting and corporal punishment; parent surveys also addressed intimate partner violence (IPV), parent and child mental health, parent alcohol misuse, and parenting stress. 536 parent-child dyads were included in the surveys; 110 (20.5%) parents attended a parenting programme at least once. Positive parenting did not increase across the whole community; there was a trend towards reduction of corporal punishment. Parenting stress declined and children's mental health improved by the third survey, possibly through increased parent employment rather than the intervention. IPV, parent mental health, and parent alcohol misuse were unchanged, and were associated with less positive parenting and more children's mental health symptoms. The action media process may indeed have enabled diffusion of parenting information, but also appeared to be associated with small negative effects on positive parenting, parenting stress and children's internalising and externalising. Reduction in parenting stress, a trend towards a reduction in corporal punishment, and improvement in children's mental health, were observed by year three. Parents' mental health, substance abuse and IPV must be addressed alongside parenting interventions to improve both parenting and children's mental health.

Background Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress. Since only the mutants, but not the endogenous wild-type FUS, are associated with stress granules under most of the stress conditions reported to date, the relationship between FUS and stress granules represents a mutant-specific phenotype and thus may be of significance in mutant-induced pathogenesis. While the association of mutant-FUS with stress granules is well established, the effect of the mutant protein on stress granules has not been examined. Here we investigated the effect of mutant-FUS on stress granule formation and dynamics under conditions of oxidative stress. Results We found that expression of mutant-FUS delays the assembly of stress granules. However, once stress granules containing mutant-FUS are formed, they are more dynamic, larger and more abundant compared to stress granules lacking FUS. Once stress is removed, stress granules disassemble more rapidly in cells expressing mutant-FUS. These effects directly correlate with the degree of mutant-FUS cytoplasmic localization, which is induced by mutations in the nuclear localization signal of the protein. We also determine that the RGG domains within FUS play a key role in its association to stress granules. While there has been speculation that arginine methylation within these RGG domains modulates the incorporation of FUS into stress granules, our results demonstrate that this post-translational modification is not involved. Conclusions Our results indicate that mutant-FUS alters the dynamic properties of stress granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in stress granule assembly and cellular stress response.

Background This paper enumerates and characterizes latent classes of adverse childhood experiences and investigates how they relate to prenatal substance use (i.e., smoking, alcohol, and other drugs) and poor infant outcomes (i.e., infant prematurity and low birthweight) across eight low- and middle-income countries (LMICs). Methods A total of 1189 mother-infant dyads from the Evidence for Better Lives Study cohort were recruited. Latent class analysis using the Bolck, Croon, and Hagenaars (BCH) 3-step method with auxiliary multilevel logistic regressions was performed. Results Three high-risk classes and one low-risk class emerged: (1) highly maltreated (7%, n  = 89), (2 ) emotionally and physically abused with intra-familial violence exposure (13%, n  = 152), (3), emotionally abused (40%, n  = 474), and (4) low household dysfunction and abuse (40%, n  = 474). Pairwise comparisons between classes indicate higher probabilities of prenatal drug use in the highly maltreated and emotionally abused classes compared with the low household dysfunction and abuse class. Additionally, the emotionally and physically abused with intra-familial violence exposure class had higher probability of low birthweight than the three remaining classes. Conclusion Our results highlight the multifaceted nature of ACEs and underline the potential importance of exposure to childhood adversities on behaviors and outcomes in the perinatal period. This can inform the design of antenatal support to better address these challenges.

Background Heightened local inflammation due to muscle trauma or disease is associated with impaired bone regeneration. Methods We hypothesized that FK506, an FDA approved immunomodulatory compound with neurotrophic and osteogenic effects, will rescue the early phase of fracture healing which is impaired by concomitant muscle trauma in male (~4 months old) Lewis rats. FK506 (1 mg/kg; i.p.) or saline was administered systemically for 14 days after an endogenously healing tibia osteotomy was created and fixed with an intermedullary pin, and the overlying tibialis anterior (TA) muscle was either left uninjured or incurred volumetric muscle loss injury (6 mm full thickness biopsy from middle third of the muscle). Results The salient observations of this study were that 1) concomitant TA muscle trauma impaired recovery of tibia mechanical properties 28 days post-injury, 2) FK506 administration rescued the recovery of tibia mechanical properties in the presence of concomitant TA muscle trauma but did not augment mechanical recovery of an isolated osteotomy (no muscle trauma), 3) T lymphocytes and macrophage presence within the traumatized musculature were heightened by trauma and attenuated by FK506 3 days post-injury, and 4) T lymphocyte but not macrophage presence within the fracture callus were attenuated by FK506 at 14 days post-injury. FK506 did not improve TA muscle isometric torque production Conclusion Collectively, these findings support the administration of FK506 to ameliorate healing of fractures with severe muscle trauma comorbidity. The results suggest one potential mechanism of action is a reduction in local T lymphocytes within the injured musculoskeletal tissue, though other mechanisms to include direct osteogenic effects of FK506 require further investigation.

Background Childhood adversities, such as poor parental practices, exposure to violence, and risk behaviours strongly impact children’s future mental and behavioural problems. Adversities affect families living in disadvantaged environments and low- and middle-income countries (LMICs) to a greater extent than in high-income countries. Parenting programmes are an effective way to alleviate them, although their outreach and scalability is still limited in LMICs. Methods/design A multi-site randomised controlled trial will be conducted in North Macedonia, Republic of Moldova and Romania to test the efficacy and cost-effectiveness of an optimised version of the promising Parenting for Lifelong Health Programme for Young Children (PLH-YC, 5 sessions), against a standard lecture on parenting issues (control group, 1 session). At least 864 participants who report having children between 2 and 9 years old who display elevated levels of behavioural difficulties will be randomised on a 1:1 basis to the intervention and control groups. The primary outcome will consist of parent report of child oppositional aggressive behaviour. Post-test (four months) and follow-up (12 months) assessments will provide information on short- and longer-term effects of PLH-YC compared to the parenting lecture in the control group. Discussion This randomised trial will test the efficacy of PLH-YC in alleviating child behavioural problems and assess the cost-effectiveness, transportability across three different cultural contexts, and potential for scalability of the programme. Trial registration ClinicalTrials.gov ., Registration number: NCT04721730 ( https://clinicaltrials.gov/ct2/show/NCT04721730 ). Registered 13.01.2021

In the effort to address behavioural risk factors – which contribute significantly to the global burden of disease – there is a growing movement in public health towards the use of interventions informed by behavioural science. These interventions have the benefit of being amenable to testing in randomised controlled trials, are cost-effective and, when scaled up, can have significant public health benefits. A subset of these interventions attempts to change behaviour by shifting social norms perception (what I think everyone else does and thinks). We surveyed the work on social norms intervention and considered its applicability to issues of public health in South Africa. Social norms interventions have widespread and significant potential to address issues of public health in South Africa; policymakers should look to these interventions as cost-effective tools to address key issues. More broadly, we advocate for an expansion of the use of behavioural science in developing public policy in South Africa. Significance: • The application of behavioural science to issues of public health will contribute to evidence-based policy efforts in South Africa.