Elder Abuse and Depressive Symptoms: The Mediating Role of Loneliness in Older Adults.

BACKGROUND: Elder abuse (EA), depressive symptoms, and loneliness represent a growing risk to the health, well-being, and premature mortality of older adults. However, the role of loneliness in the relationship between EA and depressive symptoms has not yet been examined. AIMS: To investigate the associations between these constructs and to explore the possible mediating role of loneliness in the relationship between EA and depressive symptoms in a representative sample of older Mexican people. METHODS: A representative community-dwelling survey of older adults aged 60 and older was conducted in two cities in Mexico (Mexico City and Xalapa) in 2018-2019. Measurements of EA, loneliness, depressive symptoms, health, and sociodemographic data were collected. Regression and mediation models were tested to analyze the associations between these variables. RESULTS: The prevalence of EA was 16.3%, loneliness was 50%, and depressive symptoms were 25.5%. The odds ratio (OR) for the occurrence of depressive symptoms was 2.7 when the combined effects of EA and loneliness were considered. The proportion of the effect that could explain the mediating role of loneliness was 31%. CONCLUSION: To effectively reduce depressive symptoms in older individuals affected by emotional or psychological abuse and neglect, it is crucial to address both the mediating influence of loneliness and EA itself in therapeutic and preventive interventions.

Indirect Effects of Neighbourhood Socioeconomic Status on Preterm Birth Risk in an Argentine Population.

BACKGROUND: Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to determine the indirect effects of neighbourhood socioeconomic status (NSES) on the risk of spontaneous PTB. METHODS: We carried out a retrospective case-control study including sociodemographic and obstetric data of multigravid women who gave birth at a maternity hospital in Tucumán, Argentina, between 2005 and 2010: 949 women without previous PTB nor pregnancy loss who delivered at term and 552 who had spontaneous PTB. NSES was estimated from the Unsatisfied Basic Needs index of census data. Variables selected through penalised regressions were used to create a data-driven Bayesian network; then, pathways were identified and mediation analyses performed. RESULTS: Maternal age less than 20 years mediated part of the protective effect of high NSES on spontaneous PTB [natural indirect effect (NIE) -0.0125, 95% confidence interval (CI) (-0.0208, -0.0041)] and on few prenatal visits (< 5) [NIE - 0.0095, 95% CI (-0.0166, -0.0025)]. These pathways showed greater sensitivity to unobserved confounders that affect the variables mediator-outcome in the same direction, and exposure-mediator in the opposite direction. They did not show sensitivity to observed potential confounders, nor to the parameterization used to define NSES. Meanwhile, urinary tract infections showed a trend in mediating the effect of low NSES on spontaneous PTB [NIE 0.0044, 95% CI (-0.0006, 0.0093), P 0.0834]. CONCLUSIONS: High NSES has protective indirect effects on spontaneous PTB risk, mainly associated with a lower frequency of teenage pregnancy.

The role of monitoring skills in mediating the association between parent's hazardous alcohol consumption and adolescents' drinking.

BACKGROUND: This study aimed to investigate whether parental monitoring skills mediate the effect of hazardous parental alcohol consumption on adolescents' lifetime alcohol use. METHODS: This three wave longitudinal study was conducted with 884 families (n = 1,768 participants) to evaluate the effectiveness of a family-based drug prevention program for adolescents and parents across 12 Brazilian cities. We used structural equation mediation modeling to analyze the effect of hazardous parental alcohol consumption at baseline on adolescents' lifetime alcohol use at 12-month follow-up, mediated by parental monitoring skills latent dimension at 6-month follow-up. RESULTS: We found a significant indirect effect of parents' hazardous alcohol use on adolescents' alcohol use through parental monitoring (OR:1.18, 95%CI:1.02;1.36). CONCLUSION: Our finding underscores the importance of comprehensive preventive family alcohol approaches targeting adolescent alcohol use, which should consider both parental drinking behavior and monitoring practices.

Tooth loss and depression in Chilean participants of the National Health Survey 2016-2017: Oral and social functions mediation analysis.

BACKGROUND: Previous studies have indicated the association between poor oral health and depression in adults. This study evaluated oral and social functions contribution to the association between tooth loss and depressive symptoms in Chilean individuals. METHODS: We used data from the Chilean National Health Survey. The number of remaining teeth (≤19 versus ≥20 teeth) and anterior tooth losses were the exposure variables. Outcome was depression, measured through a self-report question and with the Composite International Diagnostic Interview - Short Form (CIDI SF). Mediating variables were determined by five questions, including problems regarding "speaking", "pain and suffering", "eating", "daily activities", and "social relationships". We performed logistic regression models adjusted by multiple confounders variables. Finally, we calculated indirect, direct effect, total effect, and the proportion mediated (PM). RESULTS: We included 5383 participants. The self-reported depression and suspected depression prevalence were 22,1 % and 14,0 % respectively. The total effect of fewer remaining teeth (≤19) on self-reported depression was 1.21 (95 % CI 1.02-1.44), and 1.09 (95 % CI 0.90-1.33) for suspected depression. All five variables of oral and social functions significantly mediated the association between tooth loss and depression. Feeling uncomfortable when speaking or eating discomfort were the most significant mediators. LIMITATIONS: The mediation analysis should be interpreted with caution due to the cross-sectional design. CONCLUSIONS: Deterioration of oral and social functions was a significant mediator in the association between tooth loss and depression, in particular feeling uncomfortable when speaking or eating. This mechanism should be considered in interventions to improve mental health.

The Alcohol Harm Paradox in Periodontitis.

Individuals of lower socioeconomic position (SEP) experience a greater rate of alcohol-related harms, yet they consume equal or lower amounts of alcohol than higher-SEP individuals. This phenomenon, called the "alcohol harm paradox" (AHP), gained attention recently, and different mechanisms have been proposed to explain it. Since both SEP and alcohol have been suggested to be associated with periodontitis risk, we conducted a secondary analysis using data from the National Health and Nutrition Examination Survey 2011 to 2012 and 2013 to 2014 cycles, aiming to examine 1) whether the association between alcohol consumption and periodontitis is modified by SEP and 2) the extent to which the effect of SEP inequalities on periodontitis is mediated by and/or interacts with alcohol consumption. We set educational attainment as the main SEP proxy and tested the poverty income ratio in subsequent sensitivity analyses. Effect measure modification analysis was employed, considering heavy drinking as exposure, and causal mediation analysis based on the potential outcome's framework decomposed the effect of SEP on periodontitis in proportions attributable to mediation and interaction. Models were fitted using binary logistic regression and adjusted for sex, ethnicity, age, body mass index, smoking status, diabetes, binge drinking, and regular preventive dental visits. The analytical sample comprised 4,057 participants. After adjusting for covariates, less educated heavy drinkers presented 175% (odds ratio, 2.75; 95% confidence interval [CI], 2.04-3.72) higher odds of periodontitis than their counterparts, and super-additive associations were found (relative excess risk due to interaction: 1.35; 95% CI, 0.49-2.20). Additionally, -69.5% (95% CI, -122.1% to -16.8%) of the effects of education on periodontitis were attributable to interaction with heavy drinking, consistent with the AHP. No contribution was found for the mechanism of mediation. Heavy drinking disproportionately impacts the occurrence of periodontitis in lower-SEP individuals. Lower-SEP individuals seem to experience differential effects of heavy drinking on periodontitis.

Tobacco advertising and oral health among never smokers: the mediating role of secondhand smoke exposure.

OBJECTIVE: To determine whether the association between tobacco advertising (TA) exposure and poor self-rated oral health (SROH) is mediated through secondhand smoke (SHS) exposure in Brazilian adults who have never smoked. METHODS: Secondary cross-sectional analysis of The Brazilian National Health Survey 2019 data. The daily, weekly, or monthly exposure to SHS at home or at work was set as the mediator. Mediation analysis within a counterfactual approach used adjusted binary logistic regressions for both poor SROH and SHS exposure, to estimate the natural direct effect (NDE), natural indirect effect (NIE) through SHS exposure, and marginal total effect (MTE) of TA exposure on poor SROH. To assess the robustness of the results, we calculated the E-value for the MTE. RESULTS: The sample comprised 53,295 never smoker adults. The MTE of TA exposure on poor SROH was 1.09 (1.03, 1.16), with the indirect effect through SHS exposure responsible for only 16.6% of the total (NIE: 1.01 [1.01, 1.02] and NDE: 1.08 [1.02, 1.14]). An effect of 1.42 would be required for an unmeasured confounder to explain away the association between TA and SROH. CONCLUSION: More individuals exposed to TA have poor SROH than those unexposed, with secondhand smoke exposure explaining only a small portion of this effect. Upstream tobacco policies should consider oral health outcomes.

The effect of conflict-related violence intensity and alcohol use on mental health: The case of Colombia.

We investigated the causal impact of conflict-related violence on individual mental health and its potential pathways in Colombia. Using data from before and after the 2016 peace accord between the Colombian government and the Revolutionary Armed Forces of Colombia (FARC), we adopted a difference-in-differences empirical design combined with instrumental variables estimation. We also used formal mediation analysis to investigate a possible mediating role of alcohol consumption in the relationship between conflict exposure and mental health. Our results did not support the hypothesis that changes in exposure to conflict violence after the peace accord causally led to any changes in individual mental health. We were unable to identify a statistically significant mediating effect of alcohol consumption in the relationship between exposure to conflict violence and mental health.

The role of differential exposure and susceptibility to heavy drinking linking income inequalities and tooth loss: An investigation of the alcohol harm paradox using a four-way decomposition analysis.

OBJECTIVES: To examine the extent to which the effect of income inequalities on tooth loss is attributable to differential exposure and susceptibility to heavy drinking in older Brazilian adults. METHODS: We conducted a secondary analysis using data from The Brazilian Longitudinal Study of Ageing (ELSI-Brazil 2015-2016), a nationally representative sample of community-dwelling people aged 50 years and over. Causal mediation analysis based on the counterfactual outcome framework decomposed the effect of income on tooth loss mediated by heavy drinking into four components (four-way decomposition): controlled direct effect (neither mediation nor interaction), reference interaction (interaction only), mediated interaction (both mediation and interaction) and pure indirect effect (mediation only). Proportions of effect attributable to each component were calculated to estimate the differential exposure (the sum of the third and fourth components) and differential susceptibility (the sum of the second and third components) to heavy drinking. RESULTS: The analytical sample comprised 8114 participants. After adjusting for covariates, 7.3% (95% CI: 3.8%; 10.9%) and -39.5% (95% CI: -75.8%; -3.3%) of the effects of income on tooth loss were attributable to differential exposure and susceptibility to heavy drinking, respectively, consistent with the alcohol harm paradox. When setting non-functional dentition as outcome, only the effect of differential susceptibility remained (-81.7% [95% CI: -128.2%; -35.2%]). CONCLUSION: Our findings suggest that individuals of low-income groups appear to be more susceptible to the effects of heavy drinking on tooth loss.

Work ability of school servants and the mediating effects between personal characteristics, work conditions, and sickness absence1.

BACKGROUND: School servants are professionals involved with cleaning and feeding activities in schools. Exposed to conditions of physical and psychosocial overload at work, they may face situations of morbidity and functional restrictions. OBJECTIVE: To evaluate personal and work characteristics and work ability index (WAI) of school servants in Brazil and test the mediating effect of WAI in the duration of sickness absence. METHODS: 163 Brazilian school servants participated in this cross-sectional study, that including the self-completion of a sociodemographic questionnaire, information about the Work Environment, the Protocol of Psychosocial Risks at Work's Evaluation, and the Work Ability Index. Also was collected, in a secondary health database, information about sickness absence. A linear regression model was constructed to identify the predictors of the duration of absence, followed by the analysis of mediation with the Path Analysis method. RESULTS: The study found that the WAI partially mediates the relation of the personal characteristics and the work conditions with the duration of absence of the school servants. The predictors included the organizational aspects of work, mental exhaustion, physical damage, health self-evaluation, availability of personal protective equipment, and the need to assume inadequate postures at work. These predictors explained 33% of the duration of absence and 53% of the WAI of these workers. CONCLUSION: This study indicated that inadequate working conditions and low WAI impact in the sickness absence, increasing by 33% the length of time off work of school servants.

O papel mediador da dependência de mídia social e da qualidade do sono na associação entre tempo de uso de mídia social e sintomas depressivos em universitários / The mediating role of social media addiction and sleep quality in the association between social media usage and depressive symptoms in university students / El papel mediador de la adicción a las redes sociales y la calidad del sueño en la asociación entre el tiempo de uso de las redes sociales y los síntomas depresivos en estudiantes universitarios

Resumo: O aumento do uso de mídias sociais e sua associação com sintomas depressivos, especialmente em jovens adultos, tem gerado a necessidade do entendimento de como ocorre tal associação para subsidiar políticas de redução de danos e agravos. Nesse sentido, este estudo objetivou verificar o efeito mediador da dependência de mídias sociais e da qualidade do sono na associação entre o tempo de uso de mídias sociais e sintomas depressivos em universitários brasileiros. Trata-se de um estudo transversal, realizado com 2.823 universitários, que forneceram informações referentes ao tempo de uso de mídias sociais, à dependência de mídias sociais, aos sintomas depressivos e à qualidade do sono. A análise de mediação, ajustada por fatores de confusão, foi realizada por meio do software PROCESS para SPSS, para obtenção do efeito total (c), direto (c') e indiretos (EI1, EI2 e EI3). Os resultados identificaram associação entre o tempo de uso de mídias sociais e os sintomas depressivos, mediada pela dependência de mídias sociais (EI1 = 20%) e pela qualidade do sono (EI1 = 40%). Os resultados permitem ampliar o conhecimento acerca dos mecanismos que influenciam mutuamente a relação entre o tempo de uso de mídias sociais e os sintomas depressivos, auxiliando na adoção de estratégias de redução de danos decorrentes do uso excessivo de mídias sociais.

Abstract: Increase in time spent on social media and its association with depressive symptoms, especially among young adults, has generated the need to understand how this association occurs in order to support the development of policies to reduce harm and complications. In view of this fact, this study aimed to assess the mediating effect of social media addiction and sleep quality on the association between time spent on social media and depressive symptoms in Brazilian university students. This is a cross-sectional study conducted with 2,823 university students, who provided information regarding time spent on social media, social media addiction, depressive symptoms and sleep quality. The mediation analysis, adjusted for confounding factors, was performed using the PROCESS macro for SPSS to obtain the total (c), direct (c'), and indirect effects (EI1, EI2, and EI3). The results identified an association between time spent on social media and depressive symptoms, mediated by social media addiction (EI1 = 20%) and sleep quality (EI1 = 40%). These findings help expand knowledge about the mechanisms that mutually influence the relationship between time spent on social media and depressive symptoms, supporting the adoption of strategies to reduce harm resulting from excessive social media use.

Resumen: El aumento del uso de las redes sociales y su asociación con síntomas depresivos, especialmente en adultos jóvenes, ha generado la necesidad de comprender cómo se produce esta asociación como una forma de apoyar las políticas de reducción de daños y afecciones. En ese sentido, el presente estudio tuvo como objetivo verificar el efecto mediador de la adicción a las redes sociales y de la calidad del sueño en la asociación entre el tiempo de uso de las redes sociales y los síntomas depresivos en estudiantes universitarios brasileños. Se trata de un estudio transversal, realizado con 2.823 estudiantes universitarios, quienes brindaron información respecto al tiempo de uso de las redes sociales, adicción a las redes sociales, síntomas depresivos y calidad del sueño. El análisis de mediación, ajustado por factores de confusión, se realizó por medio del software PROCESS para SPSS, para obtener el efecto total (c), directo (c') e indirectos (EI1, EI2 y EI3). Los resultados identificaron una asociación entre el tiempo de uso de las redes sociales y los síntomas depresivos, mediada por adicción a las redes sociales (EI1 = 20%) y la calidad del sueño (EI1 = 40%). Los resultados permiten ampliar el conocimiento acerca de los mecanismos que influyen mutuamente en la relación entre tiempo de uso de las redes sociales y los síntomas depresivos, ayudando a adoptar estrategias para reducir los daños resultantes del uso excesivo de las redes sociales.

Healthy Eating as Potential Mediator of Inverse Association between Purpose in Life and Waist Circumference: Emerging Evidence from US and Chilean Cohorts.

High sense of purpose in life, a fundamental domain of eudaimonic well-being, has been consistently associated with lower risk for various obesity-related chronic diseases. Although this psychological feature correlates with some health behaviors as potential mediators, its association with healthy eating remains less explored. In addition, studies of these psycho-behavioral and health relationships in the South American population are lacking. This research sought to assess: (1) the cross-sectional association between self-reported purpose in life and overall healthy eating patterns, and (2) healthy food intake as a potential mediator of the inverse relationship between purpose in life and waist circumference. Data collected of 2060 US adults from the MIDUS study (5 ± 12 years, 55% women, mostly white people, and 42.5% obese) and 223 Chilean adults from the CHILEMED study (46.6 ± 9 years, 58.3% women, and 71.3% obese) were used. Anthropometric and sociodemographic variables were collected. Sense of purpose was assessed using the purpose in life subscale of the Ryff's psychological well-being questionnaire. Diet quality was evaluated using healthy eating or low-fat diet indexes, according to extant food intake data in each cohort. The relationship between these variables was estimated by bivariate and multivariate linear regressions with appropriate adjustments. To establish whether a better diet quality could mediate a link of purpose in life and improved nutritional status (assessed by waist circumference), the association between these three variables was tested by bootstrapping-based mediation analysis. Our results show significant associations of sense of purpose with healthy eating and low-fat dietary patterns in both US and Chilean cohorts, respectively, even after adjusting for sociodemographic variables. According to the mediation analysis, the relationship between sense of purpose and waist circumference, as an indicator of abdominal obesity, appears to be partially mediated by healthier food intake in both samples. In conclusion, our findings suggest a plausible mechanism underlying the favorable impact of this well-being dimension on physical health. Given its protective effects, interventions aimed at increasing purpose in life may facilitate adherence to better dietary patterns, which, in turn, will reduce the risk for obesity-related chronic diseases.

Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample.

BACKGROUND: Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample. METHODS: Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43). RESULTS: We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (ß = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (ß = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition. CONCLUSION: The association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.

Orientação sexual e sintomas depressivos: papel mediador da autoestima e satisfação com a vida / Sexual orientation and depressive symptoms: mediating role of self-esteem and life satisfaction / Orientación sexual y síntomas depresivos: papel mediador de la autoestima y la satisfacción con la vida

Objetivo: verificar se autoestima e satisfação com a vida exercem efeitos mediadores na relação entre orientações sexuais minoritárias e sintomatologia depressiva em amostra de pós-graduandos stricto sensu. Método: estudo analítico, transversal, conduzido com 321 pós-graduandos stricto sensu entre março/abril de 2021. Utilizou-se o Patient Health Questionnaire-9 para avaliação de sintomas depressivos, Escala de Autoestima de Rosemberg e Escala de Satisfação com a Vida. Análises de mediação simples foram conduzidas por meio da macro PROCESS. Resultados: pós-graduandos de orientações sexuais minoritárias apresentaram maior severidade de sintomas depressivos e menores indicadores de autoestima e satisfação com a vida do que seus pares heterossexuais. Autoestima e satisfação com a vida mediaram parcialmente a relação entre orientação sexual e severidade de sintomas depressivos em uma proporção de, respectivamente, 48,26% e 37,54%. Conclusão: autoestima e satisfação com a vida apresentaram-se como importantes mediadores da relação entre orientações sexuais minoritárias e sintomas depressivos entre pós-graduandos(AU)

Objective: to verify whether self-esteem and satisfaction with life exert mediating effects on the relationship between minority sexual orientations and depressive symptoms in a sample of graduate students. Method: analytical, cross-sectional study conducted with 321 Brazilian graduate students between March/April 2021. The Patient Health Questionnaire-9 was used to assess depressive symptoms, was used too, Rosemberg´s Self-Esteem Scale and the Life Satisfaction Scale. Simple mediation analyzes were conducted using the PROCESS macro. Results: graduate students with minority sexual orientations had more severe depressive symptoms and lower indicators of self-esteem and life satisfaction than their heterosexual peers. Self-esteem and satisfaction with life partially mediated the relationship between sexual orientation and severity of depressive symptoms in a proportion of, respectively, 48.26% and 37.54%. Conclusion: self-esteem and life satisfaction were important mediators of the relationship between minority sexual orientations and depressive symptoms among graduate students(AU)

Objetivo: verificar si la autoestima y la satisfacción con la vida ejercen efectos mediadores en la relación entre las orientaciones sexuales minoritarias y la sintomatología depresiva en una muestra de estudiantes de posgrado stricto sensu. Método: estudio transversal analítico realizado junto a 321 estudiantes de posgrado stricto sensu entre marzo y abril de 2021. Para evaluar los síntomas depresivos, se utilizó el Patient Health Questionnaire-9, la Escala de Autoestima de Rosemberg y la Escala de Satisfacción con la Vida. Los análisis de mediación simple se realizaron utilizando la macro PROCESS. Resultados: los estudiantes de posgrado con orientaciones sexuales minoritarias presentaron síntomas depresivos más severos y menores indicadores de autoestima y satisfacción con la vida que sus pares heterosexuales. La autoestima y la satisfacción con la vida mediaron parcialmente la relación entre la orientación sexual y la severidad de los síntomas depresivos en una proporción de, respectivamente, 48,26% y 37,54%. Conclusión: la autoestima y la satisfacción con la vida fueron importantes mediadores de la relación entre la orientación sexual minoritaria y los síntomas depresivos entre estudiantes de posgrado(AU)

Sleep Quality as a Mediator of Burnout, Stress and Multisite Musculoskeletal Pain in Healthcare Workers: A Longitudinal Study.

This study aimed to verify whether sleep quality is a mediator of the relationship between burnout, stress and multisite pain in healthcare workers in a longitudinal study with 12 months of follow-up during the COVID-19 pandemic. Online questionnaires were used for data collection. The sociodemographic questionnaire contained personal and occupational data. The short version of the Copenhagen Psychosocial Questionnaire (COPSOQ II-Br) was used to assess burnout and stress. The Pittsburgh Sleep Quality Index (PSQI-Br) assessed sleep quality over one month. The Nordic Musculoskeletal Questionnaire (NMQ) aimed to identify the presence of multisite musculoskeletal pain in the last 12 months and the last 7 days. Mediation analysis was used to verify whether the effect of the predictor variables (burnout and stress) on the dependent variable (number of pain sites in the last 12 months and 7 days) was due to an intervening variable (sleep quality). Stress and burnout were associated with multisite pain in healthcare workers in the last 12 months and the last 7 days. Sleep quality was a significant mediator of this association in the last 12 months, indicating that some of the association between burnout, stress and multisite pain can be explained by poor sleep quality. Thus, a comprehensive approach to long-term multisite pain should consider psychosocial aspects such as burnout, stress and sleep quality.

Mediation Analysis of Waist Circumference in the Association of Gut Microbiota with Insulin Resistance in Children.

BACKGROUND: Persistent gut microbiota (GM) imbalance has been associated with metabolic disease development. This study evaluated the mediating role of waist circumference in the association between GM and insulin resistance (IR) in children. METHODS: This cross-sectional study included 533 children aged between 6 and 12. The anthropometry, metabolic markers, and relative abundance (RA) of five intestinal bacterial species were measured. Path coefficients were estimated using path analysis to assess direct, indirect (mediated by waist circumference), and total effects on the association between GM and IR. RESULTS: The results indicated a positive association mediated by waist circumference between the medium and high RA of S. aureus with homeostatic model assessments for insulin resistance (HOMA-IR) and for insulin resistance adiponectin-corrected (HOMA-AD). We found a negative association mediated by waist circumference between the low and medium RA of A. muciniphila and HOMA-IR and HOMA-AD. Finally, when we evaluated the joint effect of S. aureus, L. casei, and A. muciniphila, we found a waist circumference-mediated negative association with HOMA-IR and HOMA-AD. CONCLUSIONS: Waist circumference is a crucial mediator in the association between S. aureus and A. muciniphila RA and changes in HOMA-IR and HOMA-AD scores in children.

The Indirect Effect of #Tamojunto2.0 Program on Bullying Through Reduction of Alcohol Use Initiation.

PURPOSE: The Brazilian version of the prevention program Unplugged, #Tamojunto, has had a positive effect on bullying prevention. However, the curriculum has recently been revised, owing to its negative effects on alcohol outcomes. This study evaluated the effect of the new version, #Tamojunto2.0, on bullying. For adolescents exposed to the school-based program #Tamojunto2.0, we investigated (1) whether the prevalence of bullying victimization and perpetration was reduced, (2) whether this reduction was moderated by gender, and (3) whether the program's effect on bullying was mediated by adolescents' alcohol use. METHODS: A cluster randomized controlled trial was conducted using 5,208 eighth-grade students from 73 Brazilian public schools. Baseline data were collected before program implementation, and follow-up data were collected nine months later. We used a multilevel mixed-effects model to examine the effect of #Tamojunto2.0 on bullying, and a moderation model to test the moderating effect of gender on program outcomes. A mediation analysis was performed to determine lifetime alcohol use as a mediator of the intervention effect on bullying. RESULTS: We found that the positive effect of #Tamojunto2.0 on bullying victimization (ß = -0.019, 95% confidence interval = -0.035; -0.002) and perpetration (ß = -0.027, 95% confidence interval = -0.051; -0.004) was mediated by a decrease in alcohol use, but not moderated by gender. DISCUSSION: #Tamojunto2.0 program can be indirectly effective in the prevention of bullying by decreasing adolescents' alcohol use. Moreover, alcohol and drug use prevention programs might also affect bullying outcomes through mediation, and we suggest that future studies consider this.

Body Adiposity Partially Mediates the Association between FTO rs9939609 and Lower Adiponectin Levels in Chilean Children.

Children carrying the minor allele 'A' at the fat mass and obesity-associated protein (FTO) gene have higher obesity prevalence. We examined the link between FTO rs9939609 polymorphism and plasma adiponectin and the mediating role of body adiposity, in a cross-sectional study comprising 323 children aged 6-11 years. Adiponectin and FTO genotypes were assessed using a commercial kit and a real-time polymerase chain reaction with high-resolution melting analysis, respectively. Body adiposity included body mass index z-score, body fat percentage and waist-to-hip ratio. To investigate adiponectin (outcome) associations with FTO and adiposity, linear regressions were implemented in additive models and across genotype categories, adjusting for sex, age and Tanner's stage. Using mediation analysis, we determined the proportion of the association adiponectin-FTO mediated by body adiposity. Lower adiponectin concentrations were associated with one additional risk allele (ßadditive = -0.075 log-µg/mL [-0.124; -0.025]), a homozygous risk genotype (ßAA/TT = -0.150 [-0.253; -0.048]) and a higher body mass index z-score (ß = -0.130 [-0.176; -0.085]). Similar results were obtained for body fat percentage and waist-to-hip ratio. Body adiposity may mediate up to 29.8% of the FTO-adiponectin association. In conclusion, FTO rs9939609-related differences in body adiposity may partially explain lower adiponectin concentrations. Further studies need to disentangle the biological pathways independent from body adiposity.

Mediation Analysis in Manual Therapy Research.

Objective: The purpose of this study was to illustrate the applicability of mediation analysis in the manual therapy field by assessing whether pain intensity, duration of pain, or the change in systolic blood pressure mediated the heart rate variability (HRV) of patients with musculoskeletal pain who received manual therapy. Methods: A secondary data analysis from a 3-arm, parallel, randomized, placebo-controlled, assessor-blinded, superiority trial was performed. Participants were randomized into spinal manipulation, myofascial manipulation, or placebo groups. Cardiovascular autonomic control was inferred from resting HRV variables (low-high frequency power ratio; LF/HF) and blood pressure responsiveness to a sympathoexcitatory stimulus (cold pressor test). Pain intensity and duration were assessed. Mediation models analyzed whether pain intensity, duration, or blood pressure independently affected the improvement of the cardiovascular autonomic control of patients with musculoskeletal pain after intervention. Results: The first assumption of mediation was met for LF/HF with statistical evidence of a total effect of spinal manipulation, as compared with placebo on HRV outcomes (ß = 0.77 [0.17-1.30]); second and third assumptions showed no statistical evidence of a relationship between the intervention and pain intensity (ß = -5.30 [-39.48 to 28.87]), pain intensity, and LF/HF (ß = 0.00 [-0.01 to 0.01]). Conclusion: In this study of causal mediation analysis, the baseline pain intensity, duration of pain, and responsiveness of the systolic blood pressure to a sympathoexcitatory stimulus did not mediate the effects of the spinal manipulation on the cardiovascular autonomic control of patients with musculoskeletal pain. Accordingly, the immediate effect of spinal manipulation on the cardiac vagal modulation of patients with musculoskeletal pain may more likely be related to the intervention rather than the mediators investigated.

A Causal Mediation Analysis for Investigating the Effect of a Randomized Cash-Transfer Program in Nicaragua.

Mediation analysis can be applied to data from randomized trials of health and social interventions to draw causal inference concerning their mechanisms. We used data from a cluster-randomized trial in Nicaragua, fielded between 2000 and 2002, to investigate whether the impact of providing access to a conditional cash-transfer program on child nutritional outcomes was mediated by child health check-ups and household dietary diversity. In a sample of 443 children 6-35 months old, we estimated the controlled direct (CDE) effect of random assignment on measured height-for-age z scores had we intervened so that all children received a health check-up and had the same level of household dietary diversity, using inverse-probability weighted marginal structural models to account for mediator-outcome confounding. Sensitivity analyses corrected the CDE for potential nondifferential error in the measurement of dietary diversity. Treatment assignment increased height-for-age z score by 0.37 (95% CI: 0.05, 0.69) standard deviations. The CDE was 0.20 (95% CI: -0.17, 0.57) standard deviations, suggesting nearly one-half of the program's impact on child nutrition would be eliminated had we intervened on these factors, although estimates were relatively imprecise. This study provides an illustration of how causal mediation analysis can be applied to examine the mechanisms of multifaceted interventions.

Changes in alcohol beliefs mediate the effects of a school-based prevention program on alcohol use among Brazilian adolescents.

OBJECTIVE: To investigate the mechanisms of the #Tamojunto2.0 program that mediated the prevention of lifetime alcohol and drug use, including drug knowledge, behavioral beliefs, attitudes, decision-making skills, and refusal skills. METHODS: A cluster-randomized controlled trial was conducted in 73 public middle schools in three Brazilian cities. The sample included 5208 students (49.4 % girls; Mage = 13.2 years). The intervention group attended twelve #Tamojunto2.0 lessons conducted by their previously trained teachers. The control group did not receive any intervention. Data were collected pre-intervention and at the 9-months follow-up. We performed multiple mediation models (for the whole sample, users, and non-users) with a post-estimation adjustment to standard errors to account for nesting. We analyzed all available mediators simultaneously according to each drug: alcohol, binge drinking, tobacco, marijuana, and inhalant lifetime use. To handle missing data, we used the "full-information maximum-likelihood" paradigm. RESULTS: Outcomes in the whole sample and among non-users showed that #Tamojunto2.0 indirectly prevented lifetime alcohol use and binge drinking by increasing negative and non-positive alcohol beliefs. Only the direct effect on decreasing lifetime alcohol consumption was statistically significant. However, an indirect increase in binge drinking was observed through knowledge about alcohol, but the direct effect was not statistically significant. No effects were reported for marijuana, tobacco, or inhalants. Among users, no statistically significant effects were found for alcohol or drug use. CONCLUSIONS: The results suggest that the #Tamojunto2.0 program was only effective in delaying alcohol consumption via increasing negative and non-positive alcohol beliefs. It seems that mediating mechanisms vary depending on contextual characteristics, differences in socializing among adolescents, features of the educational systems, psychosocial conditions, or, fidelity issues of program implementation.