PCB DISRUPTION OF GUT AND HOST HEALTH: IMPLICATIONS OF PREBIOTIC NUTRITIONAL INTERVENTION

Exposure to environmental pollutants poses numerous risk factors for human health, including increasing incidence of cardiovascular disease and diabetes. Persistent organic pollutants, such as polychlorinated biphenyls (PCBs) have been strongly linked to the development of these chronic inflammatory diseases and the primary route of exposure is through consumption of contaminated food products. Thus, the gastrointestinal tract is susceptible to the greatest levels of these pollutants and is an important facet to study. The first two hypotheses of this dissertation tested that exposure to PCBs disrupts gut microbiota directly (in vitro) and within a whole body system. PCB exposure disrupted microbial metabolism and production of metabolites (i.e. short chain fatty acids) in vitro. These disruptions in microbial populations were consistent in our mouse model of cardiometabolic disease, where we observed reductions in microbial diversity, an increase in the putative pro-inflammatory ratio of Firmicutes to Bacteroidetes, and reductions in beneficial microbial populations in exposed mice. Furthermore, observed greater inflammation was observed both within the intestines and peripherally in PCB exposed mice as well as disruptions in circulating markers associated with glucose homeostasis. Nutritional interventions high in prebiotic dietary fiber such as inulin may be able to attenuate the toxic effects of pollutant exposure. To test the hypothesis that consumption of the prebiotic inulin can decrease PCB-induced disruption in gut microbial and metabolic homeostasis, LDLr-\- mice were fed a diet containing inulin and exposed to PCB 126. Mice fed an inulin-containing diet and exposed to PCBs exhibited improved glucose tolerance, lower hepatic inflammation and steatosis, and distinct differences in gut microbial populations. Overall, these data suggests that nutritional intervention, specifically prebiotic consumption, may reduce pollutant-induced disease risk

Editorial Perspective: Misaligned incentives in mental health research - the case for Registered Reports.

Current incentive structures reward mental health researchers for producing positive, novel, and clean results. This can promote questionable research practices which contribute to a distorted evidence base, in turn limiting progress in mental health research. Registered Reports (RRs) offer a solution to realign the incentives towards conducting high-quality, rigorous, and accurate studies, by preventing publication and reporting biases. However, the uptake of RRs in mental health research has so far been limited. This editorial perspective highlights the advantages of RRs for mental health research, before discussing potential challenges and how they can be addressed. Greater uptake of RRs in mental health research could help to promote a fairer research culture, limit publication bias and questionable research practices, and ultimately, improve understanding of mental health

Triangulating evidence on the role of perceived versus objective experiences of childhood adversity in psychopathology

Childhood adversities, such as maltreatment, bullying, and socioeconomic deprivation, are well-established risk factors for psychopathology. Recent evidence suggests that it is the perceived, rather than objective (i.e., actual) experience of childhood adversity which is associated with psychopathology (Danese & Widom, 2020). However, it is unclear whether perceptions of childhood adversity cause psychopathology, as this cannot be tested ethically or feasibly with randomised controlled trials. Triangulation can instead be used to improve causal inference in observational research, by integrating evidence across multiple approaches with different sources of bias

Early risk factors for joint trajectories of bullying victimisation and perpetration

Bullying victimisation is a prevalent stressor associated with serious health problems. To inform intervention strategies, it is important to understand children’s patterns of involvement in bullying victimisation and perpetration across development, and identify early risk factors for these developmental trajectories. We analysed data from the Millennium Cohort Study (N = 14,525; 48.6% female, 82.6% White), a representative birth cohort of British children born in 2000–2002 across the UK. Bullying victimisation and perpetration were assessed via child, mother, and teacher reports at ages 5, 7, 11, and 14 years. Early risk factors (child emotional, cognitive, and physical vulnerabilities, and adverse family environments) were assessed at ages 9 months, 3, and 5 years. Using k-means for longitudinal data, we identified five joint trajectories of victimisation and perpetration across ages 5, 7, 11, and 14: uninvolved children (59.78%), early child victims (9.96%), early adolescent victims (15.07%), early child bullies (8.01%), and bully- victims (7.19%). Individual vulnerabilities (e.g., emotional dysregulation, cognitive difficulties) and adverse family environments (maternal psychopathology, low income) in pre-school years independently forecast multiple trajectories of bullying involvement. Compared to victims, bully-victims were more likely to be male, have cognitive difficulties, and experience harsh discipline and low income. Interventions addressing these risk factors (e.g., via accessible mental health care, stigma-based interventions, or programs to support low-income families) may help to prevent bullying involvement and its associated sequelae

Research Review: A guide to computing and implementing polygenic scores in developmental research

The increasing availability of genotype data in longitudinal population- and family-based samples provides opportunities for using polygenic scores (PGS) to study developmental questions in child and adolescent psychology and psychiatry. Here, we aim to provide a comprehensive overview of how PGS can be generated and implemented in developmental psycho(patho)logy, with a focus on longitudinal designs. As such, the paper is organized into three parts: First, we provide a formal definition of polygenic scores and related concepts, focusing on assumptions and limitations. Second, we give a general overview of the methods used to compute polygenic scores, ranging from the classic approach to more advanced methods. We include recommendations and reference resources available to researchers aiming to conduct PGS analyses. Finally, we focus on the practical applications of PGS in the analysis of longitudinal data. We describe how PGS have been used to research developmental outcomes, and how they can be applied to longitudinal data to address developmental questions

Impact of California table grapes on systemic inflammation, insulin resistance, and hepatic steatosis in mice fed an American-type diet

The incidence of obesity is increasing worldwide, currently affecting over 400 million people. With obesity, expansion of white adipose tissue (WAT) contributes to a chronic, low-grade inflammatory response that is associated with the formation of complications such as type 2 diabetes, cardiovascular disease, and hypertension. One potential method of reducing chronic inflammation associated with obesity is through consumption of table grapes, which contain fiber and are rich in phytochemicals with potential health promoting properties. Several clinical trials and animal studies have demonstrated that consumption of grape products (i.e. grape seed extract, grape juice, or California powdered table grapes) can reduce oxidative stress, insulin resistance, and inflammation, as well as improve heart health. However, there is still much to be elucidated concerning the mechanisms by which grapes or grape products exert beneficial effects and which compounds within grapes are active in the mediation of these effects. Additionally, the influence of grape polyphenols and fiber on gut microbiota and the link of this with improvements in adiposity, systemic inflammation and insulin resistance are unclear. Therefore, the specific aims of this research were to (i) determine the extent to which California table grapes attenuate body fat accumulation, systemic inflammation, and insulin resistance, and impact gut microbiota in mice fed and American type diet rich in butter (Aim 1), and (ii) identify the key bioactive fraction(s) responsible for reducing adiposity, inflammation, and insulin resistance, and modulating gut microbiota in mice fed an American-type diet rich in four types of saturated fat (Aim 2). In Aim 1, grape consumption at one or both levels (i.e. 3% or 5% w/w) attenuated accumulation of body and liver fat, but these lipid lowering effects were not associated in improvements in glucose tolerance or markers of inflammation in WAT. Alterations in microbial species (i.e. reductions in deleterious sulfidogenic bacteria and increases in beneficial bacteria) were observed in grape-fed mice. Taken together these data demonstrate that consuming grapes results in attenuations in adiposity and hepatic steatosis, and also alterations gut microbial populations in mice fed a butter-rich diet. In Aim 2, consumption of the extractable polyphenol fraction (EP) alone or with the non-extractable polyphenol fraction (EP+NEP), but not powdered grapes (GP), reduced adiposity, liver and plasma triglycerides, markers of inflammation within WAT, and improved insulin sensitivity in mice fed a diet rich in saturated fat from four sources. Taken together, these data demonstrate that (i) consumption of polyphenols extracted from powdered grapes is effective at preventing the complications of diet-induced obesity, and that (ii) the effects of powdered grapes differ based on the amount and source of dietary fat. Overall, the findings from Aim 1 and Aim 2 are anticipated to contribute to the development of novel dietary strategies using grapes or grape products to manage or treat diet-induced obesity and associated conditions. Further research studies, including clinical trials, are still warranted to determine the applicability of these findings to the human population

Protecting against researcher bias in secondary data analysis:Challenges and potential solutions

Analysis of secondary data sources (such as cohort studies, survey data, and administrative records) has the potential to provide answers to science and society’s most pressing questions. However, researcher biases can lead to questionable research practices in secondary data analysis, which can distort the evidence base. While pre-registration can help to protect against researcher biases, it presents challenges for secondary data analysis. In this article, we describe these challenges and propose novel solutions and alternative approaches. Proposed solutions include approaches to (1) address bias linked to prior knowledge of the data, (2) enable pre-registration of non-hypothesis-driven research, (3) help ensure that pre-registered analyses will be appropriate for the data, and (4) address difficulties arising from reduced analytic flexibility in pre-registration. For each solution, we provide guidance on implementation for researchers and data guardians. The adoption of these practices can help to protect against researcher bias in secondary data analysis, to improve the robustness of research based on existing data

Narrative analysis to track the development of clinical reasoning during residency

Purpose: Reflective narratives are valuable pedagogical tools that document and develop clinical reasoning. The purpose of this study was to investigate (through thematic analysis of reflective narratives) whether residents who were exposed to a specific clinical reasoning strategy showed development in the type and number of reasoning strategies used over the course of residency training. Methods: This retrospective analysis used narrative research and thematic analysis of reflective narratives written by five residents over the course of a 12-month orthopaedic residency program. Narrative research involves the analysis of stories that are in text form. Residents were introduced into the clinical reasoning strategies (CRS) model, which describes eight types of reasoning strategies used by expert physical therapists: diagnostic, narrative, intervention procedures, interactive, collaborative, reasoning about teaching, predictive, and ethical reasoning. Researchers coded resident narratives for the types of CRS used by residents, and then analyzed the code frequency to describe the development of resident clinical reasoning. Results: Researchers identified seven of the eight CRS strategies in resident narratives: diagnostic, narrative, reasoning about intervention procedures, interactive, collaborative, reasoning about teaching, and predictive reasoning. Residents used an average of 4.8 CRS at the beginning of residency and 5.8 at the end of the residency training. Reasoning about diagnostic and intervention procedures were used most frequently. Collaborative reasoning showed the most development, with 100% of the residents leveraging collaborative reasoning by the end of the residency. Conclusion: Narratives serve as valuable pedagogical tools to help residents engage in reflective processes and understand the context of caring for their patients. This study illustrates using qualitative data analysis to evaluate the development of clinical reasoning skills throughout residency training. Clinical narratives can both foster and provide valuable insights into the development of clinical reasoning skills

Childhood Maltreatment and Mental Health Problems:A Systematic Review and Meta-Analysis of Quasi-Experimental Studies

Objective: Childhood maltreatment is associated with mental health problems, but the extent to which this relationship is causal remains unclear. To strengthen causal inference, the authors conducted a systematic review and meta-analysis of quasi-experimental studies examining the relationship between childhood maltreatment and mental health problems. Methods: A search of PubMed, PsycINFO, and Embase was conducted for peer-reviewed, English-language articles from database inception until January 1, 2022. Studies were included if they examined the association between childhood maltreatment and mental health problems using a quasi-experimental method (e.g., twin/sibling differences design, children of twins design, adoption design, fixed-effects design, random-intercept cross-lagged panel model, natural experiment, propensity score matching, or inverse probability weighting). Results: Thirty-four quasi-experimental studies were identified, comprising 54,646 independent participants. Before quasi-experimental adjustment for confounding, childhood maltreatment was moderately associated with mental health problems (Cohen’s d=0.56, 95% CI=0.41, 0.71). After quasi-experimental adjustment, a small association between childhood maltreatment and mental health problems remained (Cohen’s d=0.31, 95% CI=0.24, 0.37). This adjusted association between childhood maltreatment and mental health was consistent across different quasi-experimental methods, and generalized across different psychiatric disorders. Conclusions: These findings are consistent with a small, causal contribution of childhood maltreatment to mental health problems. Furthermore, the findings suggest that part of the overall risk of mental health problems in individuals exposed to maltreatment is due to wider genetic and environmental risk factors. Therefore, preventing childhood maltreatment and addressing wider psychiatric risk factors in individuals exposed to maltreatment could help to prevent psychopathology