Joe C. Wen School of Population & Public Health

Discrimination is associated with negative mental health outcomes for Latina/o adolescents. While Latino/a adolescents experience discrimination from a number of sources and across contexts, little research considers how the source of discrimination and the context in which it occurs affect mental health outcomes among Latina/o children of immigrants. We examined the association between source-specific discrimination, racial or ethnic background of the source, and school ethnic context with depressive symptoms for Latina/o adolescents of immigrant parents. Using multilevel linear regression with time-varying covariates, we regressed depressive symptoms on source-specific discrimination, racial or ethnic background of the source of discrimination, and school percent Latina/o. Discrimination from teachers (β = 0.06, p < .05), students (β = 0.05, p < .05), Cubans (β = 0.19, p < .001), and Latinas/os (β = 0.19, p < .001) were positively associated with depressive symptoms. These associations were not moderated by school percent Latina/o. The findings indicate a need to reduce discrimination to improve Latina/o adolescents' mental health.

Effective clearance of neurotoxic amyloid-beta (Aβ) from the brain is a critical process to prevent Alzheimer's disease (AD). One major clearance mechanism is Aβ transcytosis mediated by low-density lipoprotein receptor-related protein 1 (LRP1) in capillary endothelial cells. A marked loss of endothelial LRP1 is found in AD brains and is believed to significantly impair Aβ clearance. Recently, we demonstrated that pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, significantly down-regulated LRP1 in human primary microvascular endothelial cells (MVECs). In this study, we sought to determine the underlying molecular mechanism by which IL-1β led to LRP1 loss in MVECs. Reduced LRP1 protein and transcript were detected up to 24 h post-exposure and returned to the baseline levels after 48 h post-exposure with 1 ng/ml IL-1β. This reduction was in part mediated by microRNA-205-5p, -200b-3p, and -200c-3p, as these microRNAs were concomitantly upregulated in MVECs exposed to IL-1β. Synthetic microRNA-205-5p, -200b-3p, and -200c-3p mimics recapitulated LRP1 loss in MVECs without IL-1β, and their synthetic antagomirs effectively reversed IL-1β-mediated LRP1 loss. Importantly, we found that the expression of these three microRNAs was controlled by NF-κB as pharmacological NF-κB inhibitor, BMS-345541, inhibited the IL-1β-mediated upregulation of these microRNAs and rescued LRP1 expression. siRNA-mediated silencing of IκB in MVECs elevated microRNA-200b-3p and decreased LRP1 transcript, partially confirming our overall findings. In conclusion, our study provides a mechanism by which pro-inflammatory IL-1β instigates the suppression of LRP1 expression in MVECs. Our findings could implicate spatiotemporal loss of LRP1 and impairment of the LRP1-mediated clearance mechanism by endothelial cells.

BackgroundMalaria reactive case detection is the testing and, if positive, treatment of close contacts of index cases. It is included in national malaria control programmes of countries in the Greater Mekong Subregion to accelerate malaria elimination. Yet the value of reactive case detection in the control and elimination of malaria remains controversial because of the low yield, limited evidence for impact, and high demands on resources.MethodsData from the epidemiological assessments of large mass drug administration (MDA) studies in Myanmar, Vietnam, Cambodia and Laos were analysed to explore malaria infection clustering in households. The proportion of malaria positive cases among contacts screened in a hypothetical reactive case detection programme was then determined. The parasite density thresholds for rapid diagnostic test (RDT) detection was assumed to be > 50/µL (50,000/mL), for dried-blood-spot (DBS) based PCR > 5/µL (5000/mL), and for ultrasensitive PCR (uPCR) with a validated limit of detection at 0.0022/µL (22/mL).ResultsAt baseline, before MDA, 1223 Plasmodium infections were detected by uPCR in 693 households. There was clustering of Plasmodium infections. In 637 households with asymptomatic infections 44% (278/637) had more than one member with Plasmodium infections. In the 132 households with symptomatic infections, 65% (86/132) had more than one member with Plasmodium infections. At baseline 4% of households had more than one Plasmodium falciparum infection, but three months after MDA no household had more than one P. falciparum infected member. Reactive case detection using DBS PCR would have detected ten additional cases in six households, and an RDT screen would have detected five additional cases in three households among the 169 households with at least one RDT positive case. This translates to 19 and 9 additional cases identified per 1000 people screened, respectively. Overall, assuming all febrile RDT positive patients would seek treatment and provoke reactive case detection using RDTs, then 1047 of 1052 (99.5%) Plasmodium infections in these communities would have remained undetected.ConclusionReactive case detection in the Greater Mekong subregion is predicted to have a negligible impact on the malaria burden, but it has substantial costs in terms of human and financial resources.

PURPOSE: Young adult childhood cancer survivors (YACCSs) are often impacted by cancer-related cognitive impairment (CRCI) and psychological distress. Using the Project Forward Cohort, we evaluated the relationship between CRCI and substance use behaviors. METHODS: YACCSs were surveyed between 2015 and 2018 (N = 1,106, female = 50.8%, Hispanic = 51.5%, median age = 25.5 years). Associations between CRCI and substance use (tobacco, binge drinking, marijuana, prescription drug misuse, and e-cigarette/vaporizer) were examined in multivariate logistic or log-binomial regressions, adjusting for child at diagnosis (0-14 years), years since diagnosis, sex, race/ethnicity, cancer type, and treatment intensity. Mediation analysis was performed to determine opportunities for interventions. RESULTS: CRCI was reported by 144 (13.0%) survivors. The highest prevalence was observed in CNS cancers (25.4%) and leukemia (13.3%) survivors. After covariate adjustment, CRCI was associated with 2.26 times the odds of prior 30-day vaping (95% CI, 1.24 to 4.11; P = .007). Mediators with significant indirect effects in the CRCI-vaping relationship include depressive symptoms (Center for Epidemiological Studies Depression Scale) and having two or more cancer-related late effects (P < .05). CONCLUSION: CRCI among YACCSs was associated with reports of vaping. Oncologists should screen for vaping behavior if CRCI is apparent. Increasing access to long-term follow-up clinics, addressing physical and mental health issues, and monitoring and educating on vaping and other substance use behaviors is recommended to improve the long-term health of YACCSs.

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.

Discrimination is associated with negative mental health outcomes for Latina/o adolescents. While Latino/a adolescents experience discrimination from a number of sources and across contexts, little research considers how the source of discrimination and the context in which it occurs affect mental health outcomes among Latina/o children of immigrants. We examined the association between source-specific discrimination, racial or ethnic background of the source, and school ethnic context with depressive symptoms for Latina/o adolescents of immigrant parents. Using multilevel linear regression with time-varying covariates, we regressed depressive symptoms on source-specific discrimination, racial or ethnic background of the source of discrimination, and school percent Latina/o. Discrimination from teachers (β = 0.06, p < .05), students (β = 0.05, p < .05), Cubans (β = 0.19, p < .001), and Latinas/os (β = 0.19, p < .001) were positively associated with depressive symptoms. These associations were not moderated by school percent Latina/o. The findings indicate a need to reduce discrimination to improve Latina/o adolescents' mental health.

BackgroundElective abortions show a secular decline in high income countries. That general pattern, however, may mask meaningful differences—and a potentially rising trend—among age, income, and other racial/ethnic groups. We explore these differences in Denmark, a high-income, low-fertility country with excellent data on terminations and births.MethodsWe examined monthly elective abortions (n = 225,287) from 1995 to 2009, by maternal age, parity, income level and mother’s country of origin. We applied time-series methods to live births as well as spontaneous and elective abortions to approximate the denominator of pregnancies at risk of elective abortion. We used linear regression methods to identify trend and seasonal patterns.ResultsDespite an overall declining trend, teenage women show a rising proportion of pregnancies that end in an elective termination (56% to 67%, 1995 to 2009). Non-Western immigrant women also show a slight increase in incidence. Heightened economic disadvantage among non-Western immigrant women does not account for this rise. Elective abortions also show a sustained “summer peak” in June, July and August. Low-income women show the most pronounced summer peak.ConclusionsIdentification of the causes of the increase over time in elective abortion among young women, and separately among non-Western immigrant women, represents key areas of further inquiry. The unexpected increase over time in elective abortions among teens and non-Western immigrants in Denmark may signal important social and cultural impediments to contraception. The summer peak in abortions among low-income women, moreover, conflicts with the conventional assumption that the social and demographic composition of mothers who electively end their pregnancy remains stable within a calendar year.

Recordings of smartphone use for contacts are increasingly being used as alternative or supplementary measurement methods for social interactions and social relations in the health sciences. Less work has been done to understand how these measures compare with widely used survey-based information. Using data from the Copenhagen Network Study, we investigated whether derived survey and smartphone measures on two widely studied concepts; Social integration and Tie strength were associated. The study population included 737 college students (mean age 21.6 years, Standard deviation: 2.6), who were followed with surveys and continuous recordings of smartphone usage over a one-month period. We derived self-reported and smartphone measures of social integration (social role diversity, social network size), and tie strength (contact frequency, duration and tie reciprocity). Logistic regression models were used to assess the associations between smartphone derived and self-reported measures adjusting for gender, age and co-habitation. Larger call and text message networks were associated with having a high self-reported social role diversity, and a high self-reported social contact frequency was likewise associated with having both frequent call and text message interactions, longer call duration and a higher level of reciprocity in call and text message communication. Self-reported aspects of social relations and smartphone measures of social interactions have considerable overlap supporting a measurement of similar underlying concepts.

PURPOSE: Young adult childhood cancer survivors (YACCSs) are often impacted by cancer-related cognitive impairment (CRCI) and psychological distress. Using the Project Forward Cohort, we evaluated the relationship between CRCI and substance use behaviors. METHODS: YACCSs were surveyed between 2015 and 2018 (N = 1,106, female = 50.8%, Hispanic = 51.5%, median age = 25.5 years). Associations between CRCI and substance use (tobacco, binge drinking, marijuana, prescription drug misuse, and e-cigarette/vaporizer) were examined in multivariate logistic or log-binomial regressions, adjusting for child at diagnosis (0-14 years), years since diagnosis, sex, race/ethnicity, cancer type, and treatment intensity. Mediation analysis was performed to determine opportunities for interventions. RESULTS: CRCI was reported by 144 (13.0%) survivors. The highest prevalence was observed in CNS cancers (25.4%) and leukemia (13.3%) survivors. After covariate adjustment, CRCI was associated with 2.26 times the odds of prior 30-day vaping (95% CI, 1.24 to 4.11; P = .007). Mediators with significant indirect effects in the CRCI-vaping relationship include depressive symptoms (Center for Epidemiological Studies Depression Scale) and having two or more cancer-related late effects (P < .05). CONCLUSION: CRCI among YACCSs was associated with reports of vaping. Oncologists should screen for vaping behavior if CRCI is apparent. Increasing access to long-term follow-up clinics, addressing physical and mental health issues, and monitoring and educating on vaping and other substance use behaviors is recommended to improve the long-term health of YACCSs.

Discrimination is associated with negative mental health outcomes for Latina/o adolescents. While Latino/a adolescents experience discrimination from a number of sources and across contexts, little research considers how the source of discrimination and the context in which it occurs affect mental health outcomes among Latina/o children of immigrants. We examined the association between source-specific discrimination, racial or ethnic background of the source, and school ethnic context with depressive symptoms for Latina/o adolescents of immigrant parents. Using multilevel linear regression with time-varying covariates, we regressed depressive symptoms on source-specific discrimination, racial or ethnic background of the source of discrimination, and school percent Latina/o. Discrimination from teachers (β = 0.06, p < .05), students (β = 0.05, p < .05), Cubans (β = 0.19, p < .001), and Latinas/os (β = 0.19, p < .001) were positively associated with depressive symptoms. These associations were not moderated by school percent Latina/o. The findings indicate a need to reduce discrimination to improve Latina/o adolescents' mental health.

Interparental conflict is a common source of psychosocial stress in the lives of children. The purpose of this study was to examine the association between recent interparental conflict and one component of the physiological stress response system, the hypothalamic-pituitary-adrenal (HPA)-axis. Parents of 42 children (ages 8-13 years) completed daily diaries of interparental conflict for 8 weeks. At the end of the 8 weeks, youth participated in the Trier Social Stress Test for Children (TSST-C) while providing 2 pre- and 4 poststress salivary cortisol samples. Youth whose fathers reported a pattern of increasing interparental conflict over the past 8 weeks demonstrated an exaggerated HPA-axis response to acute stress. Mother-reported interparental conflict was not associated with children's HPA-axis responses without accounting for fathers' reports. When accounting for fathers' reports, the offspring of mothers reporting higher average daily interparental conflict demonstrated an attenuated HPA-axis response to the stressor. By estimating both average exposure and recent patterns of change in exposure to conflict, we address the circumstances that may prompt attenuation versus sensitization of the HPA-axis in the context of interparental conflict. We conclude that the HPA-axis is sensitive to proximal increases in interparental conflict which may be one pathway through which stress affects health across development, and that incorporating father's reports is important to understanding the role of the family environment in stress responses. This study further demonstrates the value of using intensive repeated measures and multiple reporters to characterize children's psychosocial environment. (PsycINFO Database Record