Parenting for Lifelong Health for Young Children in Montenegro: Preliminary Outcomes, Dissemination, and Broader Embedding of the Program.

The quality of parenting program implementation significantly affects the extent to which a program is delivered effectively as well as the likelihood of it becoming embedded in everyday services. The group based Parenting for Lifelong Health for Young Children (PLH-YC) program for parents of children aged 2-9 years was developed specifically for implementation in low- and middle-income contexts, has been tested in five randomized trials, and incorporates a number of strategies to encourage fidelity of delivery. This paper reports on the introduction of PLH-YC to Montenegro, including initial work to engage government agencies and service providers, adapt the program and, following initial evidence of effectiveness, implement strategies to promote effective delivery and embed the program. Following program adaptation and initial facilitator training, eight groups were run, supported with resources and supervision and independently evaluated. The successful pilot led to program training accreditation by national professional agencies and a series of steps to successfully further embed it into routine settings in Montenegro, including by recognizing the program in national policy documents. This led to further facilitator trainings, now numbering 97 facilitators and the certification of ten coaches and two trainers. By the end of 2023, 1278 parents, across 13 municipalities (half of all municipalities in Montenegro) and a range of service providers, have received the program. The paper describes the project phases and key fidelity components that underpinned the successful introduction and embedding of the program in Montenegro. The plan has resulted in Montenegro having its own domestic resources to continue to implement the program effectively and further plan for widespread dissemination.

Switching diets after 6-months does not result in renewed weight loss: a secondary analysis of a 12-month crossover randomized trial.

Weight change trajectory from diet and lifestyle interventions typically involves rapid weight loss followed by a weight plateau after approximately 6 months. Changing from one weight-loss diet to another at the time of the plateau could instigate renewed weight loss. Therefore, our secondary analysis aimed to assess trajectory of weight loss in a 12-month, randomized, cross-over study. Forty-two adults were randomized to eat a healthy low-fat or healthy low-carbohydrate diet for 6 months then switched to the opposite diet for an additional 6 months. Regardless of diet assignment, participants experienced rapid initial weight loss, which slowed between 3 to 6 months. After switching diets at 6 months, weight modestly decreased until 9 months, but at a rate slower than the initial 3 months and slower than the rate from 3 to 6 months. This suggests that the weight loss plateau typically seen at 6 months is physiological and cannot be overcome by simply switching to a different weight-loss diet.

FATP5 is indispensable for the growth of intrahepatic cholangiocarcinoma.

Altered lipid metabolism is a common hallmark of various cancers, including Intrahepatic Cholangiocarcinoma (ICC), a highly lethal carcinoma that lacks effective treatment options. To elucidate the lipid metabolism changes in ICC, we coupled the expression of the firefly luciferase gene (FFL) to AKT1 (AKT-FFL) via an IRES linker, and then hydrodynamically injected mice with AKT-FFL and Notch1 intracellular cytoplasmic domain (NICD) to establish a luciferase-positive ICC model. This model not only enabled us to monitor and quantify tumor growth by injecting the mice with luciferin, but also allowed us to assess the fatty acid uptake rate by injecting the mice with free fatty acid luciferin (FFA-Luc). The ICC model exhibited robust uptake of exogenous fatty acids compared with the HCC model induced by AKT-FFL/ neuroblastoma Ras (Ras). Lipidomics analysis showed a dramatically higher level of fatty acid in ICC, further supporting the increased fatty acids uptake. Mechanistic studies identified FATP5 as the predominant mediator of fatty acid uptake required for ICC growth using Fatp5 knockout mice and AAV-based shRNA silencing of Fatp5. Our study discovered a novel therapeutic target for the treatment of ICC and shed light on the contributions of lipid metabolism to ICC development. Implications: This study provides the first in vivo evidence that FATP5 is a potential therapeutic target for treating ICC.

Using Non-Violent Discipline Tools: Evidence Suggesting the Importance of Attunement.

Training in non-violent discipline is important to prevent violence against children and ensure that their caregivers remain a safe base for them. This paper aims to deepen understanding of non-violent discipline by exploring attunement as a mechanism in the effectiveness of non-violent discipline tools. Attunement describes the sensitive responsiveness of caregivers towards their children and has been found to be central to the formation of secure attachment bonds and development of self-regulation. It includes understanding or being "in tune with" the child's needs and signals, matching these with appropriate responses. The objective of this paper is to explore attunement in relation to non-violent discipline. Peer-reviewed systematic reviews previously included in a systematic overview of evidence on non-violent discipline options were screened for information relevant to attunement. All reviews were published in English between 1999 and 2018 and offered evidence on at least one non-violent discipline tool. Although no reviews explicitly addressed attunement, evidence was found suggesting its importance in the use and effectiveness of discipline methods. Research directly investigating attunement in discipline is needed.

Cardiometabolic Effects of Omnivorous vs Vegan Diets in Identical Twins: A Randomized Clinical Trial.

Importance: Increasing evidence suggests that, compared with an omnivorous diet, a vegan diet confers potential cardiovascular benefits from improved diet quality (ie, higher consumption of vegetables, legumes, fruits, whole grains, nuts, and seeds). Objective: To compare the effects of a healthy vegan vs healthy omnivorous diet on cardiometabolic measures during an 8-week intervention. Design, Setting, and Participants: This single-center, population-based randomized clinical trial of 22 pairs of twins (N = 44) randomized participants to a vegan or omnivorous diet (1 twin per diet). Participant enrollment began March 28, 2022, and continued through May 5, 2022. The date of final follow-up data collection was July 20, 2022. This 8-week, open-label, parallel, dietary randomized clinical trial compared the health impact of a vegan diet vs an omnivorous diet in identical twins. Primary analysis included all available data. Intervention: Twin pairs were randomized to follow a healthy vegan diet or a healthy omnivorous diet for 8 weeks. Diet-specific meals were provided via a meal delivery service from baseline through week 4, and from weeks 5 to 8 participants prepared their own diet-appropriate meals and snacks. Main Outcomes and Measures: The primary outcome was difference in low-density lipoprotein cholesterol concentration from baseline to end point (week 8). Secondary outcome measures were changes in cardiometabolic factors (plasma lipids, glucose, and insulin levels and serum trimethylamine N-oxide level), plasma vitamin B12 level, and body weight. Exploratory measures were adherence to study diets, ease or difficulty in following the diets, participant energy levels, and sense of well-being. Results: A total of 22 pairs (N = 44) of twins (34 [77.3%] female; mean [SD] age, 39.6 [12.7] years; mean [SD] body mass index, 25.9 [4.7]) were enrolled in the study. After 8 weeks, compared with twins randomized to an omnivorous diet, the twins randomized to the vegan diet experienced significant mean (SD) decreases in low-density lipoprotein cholesterol concentration (-13.9 [5.8] mg/dL; 95% CI, -25.3 to -2.4 mg/dL), fasting insulin level (-2.9 [1.3] µIU/mL; 95% CI, -5.3 to -0.4 µIU/mL), and body weight (-1.9 [0.7] kg; 95% CI, -3.3 to -0.6 kg). Conclusions and Relevance: In this randomized clinical trial of the cardiometabolic effects of omnivorous vs vegan diets in identical twins, the healthy vegan diet led to improved cardiometabolic outcomes compared with a healthy omnivorous diet. Clinicians can consider this dietary approach as a healthy alternative for their patients. Trial Registration: ClinicalTrials.gov Identifier: NCT05297825.

The Genomics Education Partnership: First findings on genomics research in community colleges.

The Genomics Education Partnership (GEP), a consortium of diverse colleges/universities, provides support for integrating genomics research into undergraduate curricula. To increase research opportunities for underrepresented students, GEP is expanding to more community colleges (CC). Genomics research, requiring only a computer with internet access, may be particularly accessible for 2-year institutions with limited research capacity and significant budget constraints. To understand how GEP supports student research at CCs, we analyzed student knowledge and self-reported outcomes. We found that CC student gains are comparable to non-CC student gains, with improvements in attitudes toward science and thriving in science. Our early findings suggest that the GEP model of centralized support with flexible CURE implementation benefits CC students and may help mitigate barriers to implementing research at CCs.

Co-Occurrence of Intimate Partner Violence Against Mothers and Maltreatment of Their Children With Behavioral Problems in Eastern Europe.

This study investigates the co-occurrence of intimate partner violence (IPV) against mothers and their risk of perpetrating child maltreatment (CM) in North Macedonia, the Republic of Moldova, and Romania. Risk factors for IPV, CM, and their co-occurrence were identified. Two samples (N1 = 112, N2 = 701) of mothers with children with behavioral problems were assessed. IPV was reported by 64% of mothers, CM by 96%, and their co-occurrence by 63%. Mothers exposed to emotional IPV reported more physical and emotional CM. Mothers exposed to physical IPV reported more physical CM. Mothers own history of CM and offspring's behavior problems were associated with IPV and CM co-occurrence.

Pre-post Mixed Methods Study of a Parent and Teen Support Intervention to Prevent Violence Against Adolescents in the Philippines.

PURPOSE: This study examines the feasibility of a culturally adapted parenting intervention (MaPa Teens) within the national cash transfer system to reduce violence against adolescents, the first such program in the Philippines. METHODS: Thirty caregiver-adolescent dyads who were beneficiaries of a government conditional cash transfer program participated in a pilot of a locally adapted version of the Parenting for Lifelong Health for Parents and Teens program. Primary outcomes of reducing child maltreatment and associated risk factors were evaluated using a single-group, pre-post design. Focus group discussions explored the perceptions of participants and facilitators regarding program acceptability and feasibility. RESULTS: Significant and moderate reductions were reported in overall child maltreatment and physical abuse (caregiver and adolescent reports) and in emotional abuse (adolescent report). There were significant reductions in neglect, attitudes supporting punishment, parenting stress, parental and adolescent depressive symptoms, parent-child relationship problems, and significant improvement in parental efficacy in managing child behavior. Adolescents reported reduced behavior problems, risk behavior, and witnessing of family violence. Participants valued learning skills using a collaborative approach, sustained their engagement between sessions through text messages and phone calls, and appreciated the close interaction with caring and skilled facilitators. Program areas of improvement included addressing barriers to attendance, increasing adolescent engagement, and revising the sexual health module. DISCUSSION: The study provides preliminary support for the effectiveness and feasibility of the program in reducing violence against Filipino adolescents. Findings suggest potential adaptations of the program, and that investment in more rigorous testing using a randomized controlled trial would be worthwhile.

Adaptations and staff experiences in delivering parenting programmes and other family support services in three community-based organisations in Cape Town, South Africa during the COVID pandemic.

We explore how organisations working on parenting programmes and other types of family support and violence prevention in low-resource settings experienced the pandemic. In August 2020-May 2021, we interviewed (1) staff from three community-based organisations delivering evidence-informed parenting interventions and other psychosocial services for families in Cape Town, South Africa, (2) staff from a parenting programme training organisation and (3) staff from two international organisations supporting psychosocial services in South Africa. Interviews (22) were thematically analysed, with findings in three areas. First, respondents noted changes in the context, including the job losses, food insecurity, and stress experienced by local communities, and reductions in organisational funding. Second, we found that in response to these context changes, the organisations shifted their focus to food provision and COVID prevention. Parenting and psychosocial programmes were adapted - e.g. by changing the physical delivery settings, reducing group sizes, and taking up digital and phone implementation. Participants reported improved perceptions of remote delivery as a feasible approach for working with families - but internet and phone access remained challenging. Third, the pandemic brought new responsibilities for staff, and both the challenges of working from home and the health risks of in-person work.

Measuring antenatal depressive symptoms across the world: A validation and cross-country invariance analysis of the Patient Health Questionnaire-9 (PHQ-9) in eight diverse low-resource settings.

Measures that produce valid and reliable antenatal depressive symptom scores in low-resource country contexts are important for efforts to illuminate risk factors, outcomes, and effective interventions in these contexts. Establishing the psychometric comparability of scores across countries also facilitates analyses of similarities and differences across contexts. To date, however, few studies have evaluated the psychometric properties and comparability of the most widely used antenatal depressive symptom measures across diverse cultural, political, and social contexts. To address this gap, we used data from the Evidence for Better Lives Study-Foundational Research (EBLS-FR) project to examine the internal consistency reliability, nomological network validity, and cross-country measurement invariance of the nine-item version of the Patient Health Questionnaire (PHQ-9) in antenatal samples across eight low-resource contexts. We found that the PHQ-9 scores had good internal consistency across all eight countries. Correlations between PHQ-9 scores and constructs conceptually associated with depression were generally consistent, with a few exceptions. In measurement invariance analyses, only partial metric invariance held and only across four of the countries. Our results suggest that the PHQ-9 yields internally consistent scores when administered in culturally diverse antenatal populations; however, the meaning of the scores may vary. Thus, interpretation of PHQ-9 scores should consider local meanings of symptoms of depression to ensure that context-specific conceptualizations and manifestations of antenatal depressive symptoms are adequately reflected. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

"What does that mean?": The content validity of the ISPCAN Child Abuse Screening Tool - Child version (ICAST-C) in Romania, South Africa, and the Philippines.

BACKGROUND: The International Society for Prevention of Child Abuse and Neglect (ISPCAN) Child Abuse Screening Tool (Children's Version), known as the ICAST-C Version 3, is used widely to assess violence against children, but there is limited psychometric evidence, especially on content validity. OBJECTIVE: This study aimed to assess the content validity of the ICAST-C with adolescents in Romania, South Africa, and the Philippines. METHODS: A purposive sample of adolescents (N = 53, 51 % female) were recruited from urban areas in Romania, the Eastern Cape Province of South Africa, and Metro Manila, Philippines. Semi-structured one-on-one in-depth cognitive interviews sought adolescent perspectives on the relevance, comprehensibility, and comprehensiveness of the ICAST-C. Data were analysed using template analysis. RESULTS: The ICAST-C was broadly perceived to be relevant and comprehensive in measuring violence against children in all study locations. However, there were issues with the comprehensibility of the measure, described at three levels: interpreting items, undertaking coherent elaborations of relevant behaviors and places, and generating a coherent response to the questions. CONCLUSIONS: Suggestions to revise the ICAST-C include, among others, adding a practice or how-to section on answering the survey, clarifying the intent of questions, especially on neglect and sexual abuse, emphasizing that questions cover all locations, and asking more positive questions. Pilot studies testing the content validity and cultural appropriateness are needed as a matter of practice in large self-report surveys.

Associations Between ADHD Symptoms and Maternal and Birth Outcomes: An Exploratory Analysis in a Multi-Country Cohort of Expectant Mothers.

OBJECTIVE: ADHD symptoms can adversely impact functioning in a range of domains relevant for maternal well-being and fetal development; however, there has been almost no research examining their impact during pregnancy. We aimed to address this gap. METHOD: We used data (n = 1,204) from a longitudinal birth cohort study spanning eight countries to address this gap. RESULTS: ADHD symptoms in the third trimester of pregnancy were associated with lower social support from family (b = -0.16, p = .031), friends (b = -0.16, p = .024), and significant others (b = -0.09, p = .001); higher stress (b = 0.34, p < .001) and depressive symptoms (b = 0.31, p < .001), and increased likelihood of an unwanted pregnancy (b = 0.30, p = .009). Significant associations with tobacco use (b = 0.36, p = .023) and premature birth (b = 0.35, p = .007) did not survive correction for multiple comparisons and there were no significant associations with alcohol use, low birth weight, or unplanned pregnancy. CONCLUSION: Results suggest that women with ADHD symptoms could benefit from earlier, more regular screening for mental health difficulties and greater mental health support during pregnancy.

Patterns of adverse childhood experiences and associations with prenatal substance use and poor infant outcomes in a multi-country cohort of mothers: a latent class analysis.

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.

Perceived stress during the prenatal period: assessing measurement invariance of the Perceived Stress Scale (PSS-10) across cultures and birth parity.

Maternal prenatal stress places a substantial burden on mother's mental health. Expectant mothers in low- and middle-income countries (LMICs) have thus far received less attention than mothers in high-income settings. This is particularly problematic, as a range of triggers, such as exposure to traumatic events (e.g. natural disasters, previous pregnancy losses) and adverse life circumstances (e.g. poverty, community violence), put mothers at increased risk of experiencing prenatal stress. The ten-item Perceived Stress Scale (PSS-10) is a widely recognised index of subjective experience of stress that is increasingly used in LMICs. However, evidence for its measurement equivalence across settings is lacking. This study aims to assess measurement invariance of the PSS-10 across eight LMICs and across birth parity. This research was carried out as part of the Evidence for Better Lives Study (EBLS, vrc.crim.cam.ac.uk/vrcresearch/EBLS). The PSS-10 was administered to N = 1,208 expectant mothers from Ghana, Jamaica, Pakistan, the Philippines, Romania, South Africa, Sri Lanka and Vietnam during the third trimester of pregnancy. Confirmatory factor analysis suggested a good model fit of a two-factor model across all sites, with items on experiences of stress loading onto a negative factor and items on perceived coping onto a positive factor. Configural and metric, but not full or partial scalar invariance, were established across all sites. Configural, metric and full scalar invariance could be established across birth parity. On average, first-time mothers reported less stress than mothers who already had children. Our findings indicate that the PSS-10 holds utility in assessing stress across a broad range of culturally diverse settings; however, caution should be taken when comparing mean stress levels across sites.

Taxine alkaloid poisoning successfully supported with venoarterial extracorporeal membrane oxygenation: a case report.

BACKGROUND: Ingestion of the berries of the European yew tree can result in fatal cardiac arrhythmias. CASE SUMMARY: A 53-year-old female presented to our emergency department following ingestion of ∼200 European yew tree berries. At presentation, she was in cardiogenic shock due to a mixture of tachy- and bradyarrhythmias including ventricular tachycardia, atrial fibrillation with slow ventricular response and prolonged ventricular conduction, and periods of asystole. She was referred to a specialist cardiac centre and promptly established on mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (V-A ECMO) by a retrieval team. Following resolution of her arrhythmias, she was weaned from V-A ECMO after 4 days of support and was discharged home with full neurological recovery on Day 12. DISCUSSION: Poisoning can lead to acute reversible but potentially fatal cardiogenic shock. We believe that access to prompt initiation of V-A ECMO was key to this patient's survival.

Aging alters the metabolic flux signature of the ER-unfolded protein response in vivo in mice.

Age is a risk factor for numerous diseases, including neurodegenerative diseases, cancers, and diabetes. Loss of protein homeostasis is a central hallmark of aging. Activation of the endoplasmic reticulum unfolded protein response (UPRER ) includes changes in protein translation and membrane lipid synthesis. Using stable isotope labeling, a flux "signature" of the UPRER in vivo in mouse liver was developed by inducing ER stress with tunicamycin and measuring rates of both proteome-wide translation and de novo lipogenesis. Several changes in protein synthesis across ontologies were noted with age, including a more dramatic suppression of translation under ER stress in aged mice as compared with young mice. Binding immunoglobulin protein (BiP) synthesis rates and mRNA levels were increased more in aged than young mice. De novo lipogenesis rates decreased under ER stress conditions in aged mice, including both triglyceride and phospholipid fractions. In young mice, a significant reduction was seen only in the triglyceride fraction. These data indicate that aged mice have an exaggerated metabolic flux response to ER stress, which may indicate that aging renders the UPRER less effective in resolving proteotoxic stress.

ER Unfolded Protein Response in Liver In Vivo Is Characterized by Reduced, Not Increased, De Novo Lipogenesis and Cholesterol Synthesis Rates with Uptake of Fatty Acids from Adipose Tissue: Integrated Gene Expression, Translation Rates and Metabolic Fluxes.

The unfolded protein response in the endoplasmic reticulum (UPRER) is involved in a number of metabolic diseases. Here, we characterize UPRER-induced metabolic changes in mouse livers in vivo through metabolic labeling and mass spectrometric analysis of lipid and proteome-wide fluxes. We induced UPRER by tunicamycin administration and measured synthesis rates of proteins, fatty acids and cholesterol, as well as RNA-seq. Contrary to reports in isolated cells, hepatic de novo lipogenesis and cholesterogenesis were markedly reduced, as were mRNA levels and synthesis rates of lipogenic proteins. H&E staining showed enrichment with lipid droplets while electron microscopy revealed ER morphological changes. Interestingly, the pre-labeling of adipose tissue prior to UPRER induction resulted in the redistribution of labeled fatty acids from adipose tissue to the liver, with replacement by unlabeled glycerol in the liver acylglycerides, indicating that the liver uptake was of free fatty acids, not whole glycerolipids. The redistribution of adipose fatty acids to the liver was not explicable by altered plasma insulin, increased fatty acid levels (lipolysis) or by reduced food intake. Synthesis of most liver proteins was suppressed under UPRER conditions, with the exception of BiP, other chaperones, protein disulfide isomerases, and proteins of ribosomal biogenesis. Protein synthesis rates generally, but not always, paralleled changes in mRNA. In summary, this combined approach, linking static changes with fluxes, revealed an integrated reduction of lipid and cholesterol synthesis pathways, from gene expression to translation and metabolic flux rates, under UPRER conditions. The reduced lipogenesis does not parallel human fatty liver disease. This approach provides powerful tools to characterize metabolic processes underlying hepatic UPRER in vivo.

Nonviolent Discipline Options for Caregivers and Teachers: A Systematic Overview of the Evidence.

Violence against children is a widespread problem with devastating consequences, and corporal punishment is a risk factor for more serious forms of physical abuse. One reason for the persistence of corporal punishment may be the lack of awareness of positive disciplinary alternatives. Nonviolent options offered to caregivers and teachers must be effective in addressing challenging behavior, or they may be rejected in favor of a return to physical punishment. There is an urgent need to determine which discipline options are evidence-supported and what that evidence says so that robust alternatives to corporal punishment can be made available. The primary objective of this research was to find, and explore the state of the science on, individual nonviolent interventions for challenging behavior, in so doing forming a "tool kit" for use by caregivers and teachers. A systematic overview of systematic reviews was conducted. Included systematic reviews were peer-reviewed and published in English between 1999 and 2018. Screening, quality assessment using AMSTAR, and data extraction were performed independently by two reviewers. A total of 223 reviews were included, covering data from 3,921 primary studies. A wide range of evidence-supported interventions exist, many of which have been found effective with severely challenging behavior. Important positive outcomes shown suggest that the use of these tools should be promoted not only for the prevention of violence but also for optimum child development. More research is needed on the use of these methods in home situations and on de-escalation skills.