COVID-19 Vaccine Side Effects and Long-Term Neutralizing Antibody Response : A Prospective Cohort Study.

BACKGROUND: Concern about side effects is a common reason for SARS-CoV-2 vaccine hesitancy. OBJECTIVE: To determine whether short-term side effects of SARS-CoV-2 messenger RNA (mRNA) vaccination are associated with subsequent neutralizing antibody (nAB) response. DESIGN: Prospective cohort study. SETTING: San Francisco Bay Area. PARTICIPANTS: Adults who had not been vaccinated against or exposed to SARS-CoV-2, who then received 2 doses of either BNT162b2 or mRNA-1273. MEASUREMENTS: Serum nAB titer at 1 month and 6 months after the second vaccine dose. Daily symptom surveys and objective biometric measurements at each dose. RESULTS: 363 participants were included in symptom-related analyses (65.6% female; mean age, 52.4 years [SD, 11.9]), and 147 were included in biometric-related analyses (66.0% female; mean age, 58.8 years [SD, 5.3]). Chills, tiredness, feeling unwell, and headache after the second dose were each associated with 1.4 to 1.6 fold higher nAB at 1 and 6 months after vaccination. Symptom count and vaccination-induced change in skin temperature and heart rate were all positively associated with nAB across both follow-up time points. Each 1 °C increase in skin temperature after dose 2 was associated with 1.8 fold higher nAB 1 month later and 3.1 fold higher nAB 6 months later. LIMITATIONS: The study was conducted in 2021 in people receiving the primary vaccine series, making generalizability to people with prior SARS-CoV-2 vaccination or exposure unclear. Whether the observed associations would also apply for neutralizing activity against non-ancestral SARS-CoV-2 strains is also unknown. CONCLUSION: Convergent self-report and objective biometric findings indicate that short-term systemic side effects of SARS-CoV-2 mRNA vaccination are associated with greater long-lasting nAB responses. This may be relevant in addressing negative attitudes toward vaccine side effects, which are a barrier to vaccine uptake. PRIMARY FUNDING SOURCE: National Institute on Aging.

Prenatal air pollution exposure in relation to the telomere-mitochondrial axis of aging at birth: A systematic review.

BACKGROUND: Telomere length (TL) and mitochondrial DNA (mtDNA) are central markers of vital biological mechanisms, including cellular aging. Prenatal air pollution exposure may impact molecular markers of aging leading to adverse health effects. OBJECTIVE: To perform a systematic review on human population-based studies investigating the association between prenatal air pollution exposure and TL or mtDNA content at birth. METHODOLOGY: Searches were undertaken on PubMed and Web of Science until July 2023. The framework of the review was based on the PRISMA-P guidelines. RESULTS: Nineteen studies studied prenatal air pollution and TL or mtDNA content at birth. Studies investigating TL or mtDNA content measured at any other time or did not evaluate prenatal air pollution were excluded. Twelve studies (including 4381 participants with study sample range: 97 to 743 participants) investigated newborn TL and eight studies (including 3081 participants with study sample range: 120 to 743 participants) investigated mtDNA content at birth. Seven studies focused on particulate matter (PM2.5) exposure and newborn TL of which all, except two, showed an inverse association in at least one of the gestational trimesters. Of the eight studies on mtDNA content, four focused on PM2.5 air pollution with two of them reporting an inverse association. For PM2.5 exposure, observations on trimester-specific effects were inconsistent. Current literature showing associations with other prenatal air pollutants (including nitrogen oxides, sulfur dioxide, carbon monoxide and ozone) is inconsistent. CONCLUSION: This review provides initial evidence that prenatal PM2.5 exposure impacts the telomere-mitochondrial axis of aging at birth. The current evidence did not reveal harmonious observations for trimester-specific associations nor showed consistent effects of other air pollutants. Future studies should elucidate the specific contribution of prenatal exposure to pollutants other than PM in relation to TL and mtDNA content at birth, and the potential later life health consequences.

Pre-COVID respiratory sinus arrhythmia moderates associations between COVID-19 stress and child externalizing behaviors: Testing neurobiological stress theories.

Exposure to stress related to the COVID-19 pandemic contributes to psychopathology risk, yet not all children are negatively impacted. The current study examined a parasympathetic biomarker of stress sensitivity, respiratory sinus arrhythmia (RSA), as a moderator of the effects of exposure to pandemic stress on child internalizing and externalizing behaviors in a sample of children experiencing economic marginalization. Three to five years pre-pandemic, when children were preschool-aged, RSA during baseline and a challenging parent-child interaction were collected. Mid-pandemic, between November 2020 and March 2021, children's exposure to pandemic stress and internalizing and externalizing behaviors were collected. Results demonstrated that children who, pre-pandemic, demonstrated blunted parasympathetic reactivity (i.e., no change in RSA relative to baseline) during the dyadic challenge exhibited elevated risk for externalizing behaviors mid-pandemic. Further, this risk was greatest for children exposed to high and moderate levels of pandemic stress. Consistent with diathesis stress and polyvagal frameworks, these conditional effects suggest that blunted parasympathetic reactivity in response to stress in early childhood may escalate the development of externalizing behaviors following stress exposure at school age.

Ebola Virus Disease Sensitization: Community-Driven Efforts in Sierra Leone.

The 2014-2016 West Africa Ebola outbreak was the largest in history, resulting in approximately 11,000 deaths. Despite the outbreak's eventual end, national and international health sensitization and containment efforts were subject to criticism. This study investigates disease-related knowledge and beliefs, as well as trusted sources of health information among EVD-survivors and their family members, highlighting the importance of community-informed public health responses. Participants (n = 134) were adults who were either EVD-infected, affected families/caregivers, or community leaders. In-depth interviews and focus groups explored EVD-related experiences, including health effects, stigma, and community relationships. Using a grounded theory and thematic content analysis approach, transcripts were coded for evidence of health sensitization, as well as compliance with mitigation measures and trusted sources of information. Participants displayed a high level of knowledge around EVD and reported compliance with mandated and personal prevention measures. Levels of health sensitization and subsequent reintegration of survivors were reported to be largely the products of community-based efforts, rather than the top-down, national public health response. Primary sources of trusted information included EVD survivors acting as peer educators; local leaders; and EVD sensitization by community health workers. This study highlights the importance of a community-based response for increasing the effectiveness of public health campaigns. Participants expressed that relying on the experiences of trusted cultural insiders led to a deeper understanding of Ebola compared to top-down public health campaigns, and helped infected and affected community members reintegrate. Future public health efforts should incorporate community-based participatory approaches to address infectious disease outbreaks.

Impact of prenatal tobacco smoking on infant telomere length trajectory and ADHD symptoms at 18 months: a longitudinal cohort study.

BACKGROUND: Prenatal maternal tobacco smoking is a predictor of child attention-deficit/hyperactivity disorder (ADHD) and is associated with offspring telomere length (TL). In this study, we examine the relationship between maternal prenatal smoking, infant TL, and maternal report of early childhood symptoms of ADHD. METHODS: One-hundred and eighty-one mother-infant dyads were followed prospectively for the infant's first 18 months of life. Prenatal smoking was assessed from maternal report and medical records. TL was measured from infant buccal swab DNA obtained across the first 18 months of life. ADHD symptoms were obtained from maternal report on the Child Behavior Check List. Multiple regression models tested the relation between prenatal smoking and both ADHD symptoms and infant TL. Additional analyses tested whether the change in infant TL influenced the relation between prenatal smoking and ADHD symptoms. RESULTS: Sixteen percent of mothers reported prenatal smoking. Infant TL at 4, 12, and 18 months of age were correlated. Consistent with previous cross-sectional studies linking shorter offspring TL to maternal prenatal smoking, maternal prenatal smoking predicted greater telomere shortening from four to 18 months of infant age (ß = - 5.797, 95% CI [-10.207, -1.386]; p = 0.010). Maternal depression was positively associated with both prenatal smoking (odds ratio (OR): 4.614, 95% CI [1.733, 12.282]; p = 0.002) and child ADHD symptoms (ß = 4.713, 95% CI [2.073, 7.354]; p = 0.0006). To prevent confounding, analyses examined the relation between TL, ADHD symptoms, and prenatal smoking only in non-depressed mothers. In non-depressed mothers, infant TL attrition across the first 18 months moderated the relation between smoking and child ADHD. CONCLUSIONS: The findings extend previous studies linking prenatal smoking to shorter infant TL by providing data demonstrating the effect on TL trajectory. The relation between prenatal smoking and early infant ADHD symptoms was moderated by the change in TL. The findings provide novel initial evidence suggesting that TL dynamics are one mechanistic pathway influencing the relation between maternal prenatal smoking and ADHD.

Racial Differences in the Risk of Prenatal Depression Among Women Experiencing Childhood and Adult Stressors.

INTRODUCTION: Stress exposure during a woman's own childhood and adulthood likely elevate risk of prenatal depression (PND). However, most PND screening tools fail to assess for events prior to conception. This study examined the differential effects of adverse childhood experiences (ACE) and adult life stressors on PND. METHODS: This cross-sectional study was conducted among 199 racially diverse pregnant women, ages 18 to 43, recruited from clinics and ongoing university-based studies between 2012 and 2018. The ACE Scale assessed maternal childhood trauma exposure. Validated scales examining subjective stressors assessed for chronic adult stressors. PND was assessed with the Edinburgh Depression Scale, with the Rini Pregnancy-Related Anxiety Scale as a covariate. Associations were measured using multivariable linear regression modeling. Results were stratified by self-identified Black or white race. RESULTS: Among 199 participants, mean age was 26.8 years and 67.8% were Black. Controlling for age, race, education, and prenatal anxiety, all participants reporting both childhood trauma and adult stressors were at increased risk for PND (p < 0.0001). PND risk was increased among Black women with childhood stressors (p < 0.01) or three or more adult stressors (p < 0.0001) and among White women following any number of adult stressors (p < 0.001). DISCUSSION: These findings highlight the importance of cumulative exposure to stress and trauma across the life span as indicators of risk for PND. Black and white participants had differential development of risk, depending on timing and number of exposures. Prenatal depression risk screening during routine prenatal care should include an assessment of current and historical trauma and stressors.

Linking preschoolers' parasympathetic activity to maternal early adversity and child behavior: An intergenerational perspective.

Increasing evidence suggests intergenerational effects of maternal early adversity on offspring self-regulation. Prior work has demonstrated associations between maternal adverse childhood experiences (ACEs) and infant respiratory sinus arrhythmia (RSA), a parasympathetic biomarker associated with emotional and behavioral self-regulation. The present study examined these associations and additional potential pathways including children's violence exposure and maternal psychopathology among 123 biological mother-child dyads. Families were low-income and oversampled for violence exposure; children were 3-5 years old. RSA was examined during dyadic interaction using latent growth curve modeling (LGCM). On average, females exhibited greater RSA reactivity. Greater RSA withdrawal across the interaction was associated with greater child negative affect during the interaction, linking RSA reactivity to concurrent child behavior. Consistent with previous findings among infants, high maternal ACEs were associated with lower child RSA at task initiation but not with RSA reactivity across the interaction. Findings suggest that the association between high maternal ACEs and a lower set point for offspring RSA persists into the early childhood period, beyond the influence of maternal psychopathology and children's own violence exposure. These data provide further evidence for the biological embedding of maternal early adversity across generations as well as for the relevance of RSA to child behavioral regulation.

Vision, Aphasia, Neglect Assessment for Large Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: Vision, Aphasia, Neglect (VAN) is a large vessel occlusion (LVO) screening tool that was initially tested in a small study where emergency department (ED) nurses were trained to perform VAN assessment on stroke code patients. We aimed to validate the VAN assessment in a larger inpatient dataset. METHODS: We utilized a large dataset and used National Institute of Health Stroke Scale (NIHSS) performed by physicians to extrapolate VAN. VAN was compared to NIHSS greater than or equal to 6 and established prehospital LVO screening tools including Rapid Arterial Occlusion Evaluation scale (RACE), Field Assessment Stroke Triage for Emergency Destination (FAST-ED), and Cincinnati Pre-hospital Stroke Scale (CPSS). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under receiver operating characteristics curve was calculated to estimate the predictive value of LVO. RESULTS: VAN was comparable in sensitivity (79% versus 80%) and NPV (88% versus 87%) to NIHSS greater than or equal to 6. It was superior in specificity (69% versus 57%), PPV (53% versus 46%) and accuracy to NIHSS greater than or equal to 6 (72% versus 64%) with significant receiver operating curve (.74 versus .69, P = .02). VAN also had comparable area under the curve when compared to RACE, FAST-ED, and CPSS however slightly lower accuracy (69%-73%) compared to RACE (76%), FAST-ED (77%), and CPSS (75%). VAN had the highest NPV among all screening assessments (88%). CONCLUSIONS: VAN is a simple screening tool that can identify LVOs with adequate accuracy in hospital setting. Future studies need to be conducted in prehospital setting to validate its utility to detect LVOs in the field.

Life Course Approaches to the Causes of Health Disparities.

Reducing health disparities requires an understanding of the mechanisms that generate disparities. Life course approaches to health disparities leverage theories that explain how socially patterned physical, environmental, and socioeconomic exposures at different stages of human development shape health within and across generations and can therefore offer substantial insight into the etiology of health disparities. Life course approaches are informed by developmental and structural perspectives. Developmental perspectives emphasize how socially patterned exposures to risk factors during sensitive life stages shift health trajectories, whereas structural perspectives emphasize how social identity and position within socially patterned environments disproportionately allocate risk factors and resources, resulting in altered health trajectories. We conclude that the science of health disparities will be advanced by integrating life course approaches into etiologic and intervention research on health disparities. The following 4 strategies are offered to guide in this process: (1) advance the understanding of multiple exposures and their interactions, (2) integrate life course approaches into the understanding of biological mechanisms, (3) explore transgenerational transmission of health disparities, and (4) integrate life course approaches into health disparities interventions.

Vision, Aphasia, Neglect Assessment to Predict Neurosurgical Intervention in Patients with Nontraumatic Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: The Vision, Aphasia, and Neglect (VAN) screening tool is a simple bedside test developed to identify patients with large vessel occlusion stroke. In the setting of intracerebral hemorrhage (ICH), there are very few bedside predictors of need for neurosurgical interventions other than age and Glasgow Coma Scale (GCS). We aimed to assess the utility of the VAN screening tool in predicting the need for neurosurgical intervention in patients with ICH. METHODS: We accessed sensitivity, specificity, positive predictive value, negative predictive value (NPV), and area under receiver operating characteristics curve of VAN for identifying ICH patients who require neurosurgical intervention. RESULTS: Among 228 ICH patients, 176 were VAN positive and 52 were VAN negative. On unadjusted analyses, VAN positive patients had a significantly higher ICH volume, GCS score, and National Institutes of Health Stroke Scale score (P < .001 for all). As compared to VAN negative patients, significantly higher proportion of VAN positive ICH patients (15.4% versus 32.4%) underwent a neurosurgical procedure such as external ventricular drain (EVD) and/or hematoma evacuation with craniotomy or craniectomy. The VAN screening tool had high sensitivity and NPV (100%) in predicting the need for craniectomy or hematoma evacuation, but had lower sensitivity (87.7%) for any neurosurgical procedure, as 15.4% of VAN negative patients received EVD. CONCLUSIONS: Our study suggests that VAN screening tool can identify high-risk ICH patients who are more likely to undergo craniotomy or craniectomy but is less sensitive to rule out need for EVD.

Caregiving Disruptions Affect Growth and Pubertal Development in Early Adolescence in Institutionalized and Fostered Romanian Children: A Randomized Clinical Trial.

OBJECTIVES: To determine the effects of foster care vs institutional care, as well as disruptions in the caregiving environment on physical development through early adolescence. STUDY DESIGN: This was a randomized controlled trial of 114 institutionalized, though otherwise healthy, children from 6 orphanages and 51 never institutionalized control children living in birth families (family care group) in Bucharest, Romania. Children were followed from baseline (21 months, range 5-31) through age 12 years for caregiving disruptions and growth trajectories and through age 14 years for pubertal development. RESULTS: Children randomized to the foster care group showed greater rates of growth in height, weight, and body mass index (BMI) through age 12 years than institutionalized group. Tanner development was delayed in institutionalized group boys compared with foster care group and family care group boys at 12 but not 14 years. There were no differences in Tanner development and age of menarche among foster care group, institutionalized group, and family care group girls at ages 12 and 14 years. More disruptions in caregiving between 30 months and 12 years moderated decreases in growth rates of height in foster care group and weight in foster care group and institutionalized group across age. institutionalized group boys with ≥2 disruptions showed lower Tanner scores at age 12 vs institutionalized group and foster care group boys with <2 disruptions. foster care group girls with ≥2 disruptions had higher Tanner scores at age 14 vs foster care group girls with <2 disruptions. Age of menarche was not affected by caregiving disruptions. CONCLUSIONS: For children who experienced early institutionalization, stable placement within family care is essential to ensuring the best outcomes for physical developmental. TRIAL REGISTRATION: clinicaltrials.gov: NCT00747396.

The development of the cortisol response to dyadic stressors in Black and White infants.

Acute reactivity of the stress hormone cortisol is reflective of early adversity and stress exposure, with some studies finding that the impact of adversity on the stress response differs by race. The objectives of the current study were to characterize cortisol reactivity to two dyadically based stress paradigms across the first year of life, to examine cortisol reactivity within Black and White infants, and to assess the impact of correlates of racial inequity including socioeconomic status, experiences of discrimination, and urban life stressors, as well as the buffering by racial socialization on cortisol patterns. Salivary cortisol reactivity was assessed at 4 months of age during the Still Face paradigm (N = 207) and at 12 months of age across the Strange Situation procedure (N = 129). Infants demonstrated the steepest recovery after the Still Face paradigm and steepest reactivity to the Strange Situation procedure. Race differences in cortisol were not present at 4 months but emerged at 12 months of age, with Black infants having higher cortisol. Experiences of discrimination contributed to cortisol differences within Black infants, suggesting that racial discrimination is already "under the skin" by 1 year of age. These findings suggest that race-related differences in hypothalamic-pituitary-adrenal reactivity are present in infancy, and that the first year of life is a crucial time period during which interventions and prevention efforts for maternal-infant dyads are most likely able to shape hypothalamic-pituitary-adrenal reactivity thereby mitigating health disparities early across the life course.

Secreted Oral Epithelial Cell Membrane Vesicles Induce Epstein-Barr Virus Reactivation in Latently Infected B Cells.

UNLABELLED: In the oral epithelium, peripheral stores of Epstein-Barr virus (EBV) are transmitted from infiltrating B cells to epithelial cells. Once the virus is transmitted to epithelial cells, the highly permissive nature of this cell type for lytic replication allows virus amplification and exchange to other hosts. Since the initial transfer of EBV from B cells to epithelial cells requires transitioning of the B-cell to a state that induces virus reactivation, we hypothesized that there might be epithelium-specific signals that allow the infiltrating B cells to sense the appropriate environment to initiate reactivation and begin this exchange process. We previously found that the epithelium-specific miR-200 family of microRNAs promotes EBV lytic replication. Here we show that there are high levels of miR-200 family members in oral and tonsillar epithelia and in saliva. Analysis of cultured oral epithelial cells (OKF6) showed that they actively secrete membrane vesicles (exosomes) that are enriched with miR-200 family members. Coculturing of EBV-positive B cells with OKF6 cells induced viral reactivation. Further, treatment of EBV-positive B cells with OKF6 cell-derived membrane vesicles promoted reactivation. Using a cell system that does not naturally express miR-200 family members, we found that enforced expression of a miR-200 family member produced membrane vesicles that were able to induce the lytic cascade in EBV-positive B cells. We propose that membrane vesicles secreted by oral and tonsillar epithelial cells may serve as a tissue-specific environmental cue that initiates reactivation in B cells, promoting the transfer of virus from peripheral B-cell stores to the oral epithelium to facilitate virus amplification and exchange to other hosts. IMPORTANCE: Epstein-Barr virus (EBV) is an important human pathogen that is causally associated with several lymphomas and carcinomas. The switch from latency to the lytic cycle is critical for successful host infection and for EBV pathogenesis. Although the EBV lytic cycle can be triggered by certain agents in vitro, the mechanisms that signal reactivation in vivo are poorly understood. We previously reported that endogenously expressed miR-200 family members likely play a role in facilitating the lytic tendencies of EBV in epithelial cells. Here we show that membrane vesicles secreted from oral epithelial cells contain miR-200 family members and that they can be transmitted to proximal EBV-positive B cells, where they trigger reactivation. We propose that this intercellular communication pathway may serve as a sensor mechanism for infiltrating B cells to recognize an appropriate environment to initiate reactivation, thereby allowing the exchange of virus to the oral epithelium.

Differences in placental telomere length suggest a link between racial disparities in birth outcomes and cellular aging.

BACKGROUND: Health disparities begin early in life and persist across the life course. Despite current efforts, black women exhibit greater risk for pregnancy complications and negative perinatal outcomes compared with white women. The placenta, which is a complex multi-tissue organ, serves as the primary transducer of bidirectional information between the mother and fetus. Altered placental function is linked to multiple racially disparate pregnancy complications; however, little is known about racial differences in molecular factors within the placenta. Several pregnancy complications, which include preeclampsia and fetal growth restriction, exhibit racial disparities and are associated with shorter placental telomere length, which is an indicator of cellular stress and aging. Cellular senescence and telomere dynamics are linked to the molecular mechanisms that are associated with the onset of labor and parturition. Further, racial differences in telomere length are found in a range of different peripheral tissues. Together these factors suggest that exploration of racial differences in telomere length of the placenta may provide novel mechanistic insight into racial disparities in birth outcomes. OBJECTIVE: This study examined whether telomere length measured in 4 distinct fetally derived tissues were significantly different between black and white women. The study had 2 hypotheses: (1) that telomere length that is measured in different placental tissue types would be correlated and (2) that across all sampled tissues telomere length would differ by race. STUDY DESIGN: In a prospective study, placental tissue samples were collected from the amnion, chorion, villus, and umbilical cord from black and white singleton pregnancies (N=46). Telomere length was determined with the use of monochrome multiplex quantitative real-time polymerase chain reaction in each placental tissue. Demographic and pregnancy-related data were also collected. Descriptive statistics characterized the sample overall and among black and white women separately. The overall impact of race was assessed by multilevel mixed-effects linear regression models that included empirically relevant covariates. RESULTS: Telomere length was correlated significantly across all placental tissues. Pairwise analyses of placental tissue telomere length revealed significantly longer telomere length in the amnion compared with the chorion (t=-2.06; P=.043). Overall telomere length measured in placenta samples from black mothers were significantly shorter than those from white mothers (ß=-0.09; P=.04). Controlling for relevant maternal and infant characteristics strengthened the significance of the observed racial differences (ß=-0.12; P=.02). Within tissue analyses revealed that the greatest difference by race was found in chorionic telomere length (t=-2.81; P=.007). CONCLUSION: These findings provide the first evidence of racial differences in placental telomere length. Telomere length was significantly shorter in placental samples from black mothers compared with white mothers. Given previous studies that have reported that telomere length, cellular senescence, and telomere dynamics are molecular factors that contribute to the rupture of the amniotic sac, onset of labor, and parturition, our findings of shorter telomere length in placentas from black mothers suggest that accelerated cellular aging across placental tissues may be relevant to the increased risk of preterm delivery in black pregnancies. Our results suggest that racial differences in cellular aging in the placenta contribute to the earliest roots of health disparities.

Shaping long-term primate development: Telomere length trajectory as an indicator of early maternal maltreatment and predictor of future physiologic regulation.

The molecular, neurobiological, and physical health impacts of child maltreatment are well established, yet mechanistic pathways remain inadequately defined. Telomere length (TL) decline is an emerging molecular indicator of stress exposure with definitive links to negative health outcomes in maltreated individuals. The multiple confounders endemic to human maltreatment research impede the identification of causal pathways. This study leverages a unique randomized, cross-foster, study design in a naturalistic translational nonhuman primate model of infant maltreatment. At birth, newborn macaques were randomly assigned to either a maltreating or a competent control mother, balancing for sex, biological mother parenting history, and social rank. Offspring TL was measured longitudinally across the first 6 months of life (infancy) from peripheral blood. Hair cortisol accumulation was also determined at 6, 12, and 18 months of age. TL decline was greater in animals randomized to maltreatment, but also interacted with biological mother group. Shorter TL at 6 months was associated with higher mean cortisol levels through 18 months (juvenile period) when controlling for relevant covariates. These results suggest that even under the equivalent social, nutritional, and environmental conditions feasible in naturalistic translational nonhuman primate models, early adverse caregiving results in lasting molecular scars that foreshadow elevated health risk and physiologic dysregulation.

When mothering goes awry: Challenges and opportunities for utilizing evidence across rodent, nonhuman primate and human studies to better define the biological consequences of negative early caregiving.

This article is part of a Special Issue "Parental Care".Across mammalian species, mothers shape socio-emotional development and serve as essential external regulators of infant physiology, brain development, behavior patterns, and emotional regulation. Caregiving quality, consistency and predictability shape the infant's underlying neurobiological processes. Although the requirements for "optimal" caregiving differ across species, the negative long-term consequences of the absence of needed caregiving (e.g. neglect) or the presence of harmful/aversive caregiving (e.g. physical abuse), are translatable across species. Recognizing the significant potential of cross species comparisons in terms of defining underlying mechanisms, effective translation requires consideration of the evolutionary, ecological, and fundamental biological and developmental differences between and among species. This review provides both an overview of several success stories of cross-species translations in relation to negative caregiving and a template for future studies seeking to most effectively define the underlying biological processes and advance research dedicated to mitigating the lasting negative health consequences of child maltreatment.

Role of Direct and Indirect Violence Exposure on Externalizing Behavior in Children.

The objective of this study was to examine the association between externalizing behaviors and indirect violence exposure, assessed both within the household and at the community level, as well as the interaction effect of indirect and direct violence exposure. A sample of parents of children ages 4-15 who have not been referred or enrolled in child welfare (n = 82) were recruited from the greater New Orleans community. Externalizing behavior was assessed with the Child Behavior Checklist (CBCL). The child's indirect exposure to violence included witnessing community violence, witnessing physical assault, and witnessing fighting or domestic violence at home. Direct exposure to violence included the child experiencing physical aggression from a caregiver. All assessments were based on caregiver reports. To decrease potential for confounding, children were matched for analysis based on age, Hurricane Katrina exposure, and their propensity to be exposed to high indirect violence. Cumulative indirect exposure to violence was significantly positively correlated with CBCL scores. After controlling for key covariates, CBCL externalizing T score increased significantly by approximately 1.25 points for each level increase in indirect violence exposure (ß = 1.25, SE = 0.57, p = 0.027). There also was a significant interaction between indirect and direct exposure to violence in the association with CBCL score (ß = -0.08, SE = 0.03, p = 0.002). These findings extend previous research by demonstrating that exposure to both direct and cross-contextual indirect violence influences externalizing behaviors in children. Additionally, the findings suggest that community and household social environments are both important targets for interventions designed to decrease externalizing behaviors and improve long-term outcomes for youth at risk of exposure to violence.

DNA methylation at stress-related genes is associated with exposure to early life institutionalization.

OBJECTIVES: Differences in DNA methylation have been associated with early life adversity, suggesting that alterations in methylation function as one pathway through which adverse early environments are biologically embedded. This study examined associations between exposure to institutional care, quantified as the proportion of time in institutional care at specified follow-up assessment ages, and DNA methylation status in two stress-related genes: FKBP5 and SLC6A4. MATERIALS AND METHODS: We analyzed data from the Bucharest Early Intervention Project, which is a prospective study in which children reared in institutional settings were randomly assigned (mean age 22 months) to either newly created foster care or care as usual (to remain in their current placement) and prospectively followed. A group of children from the same geographic area, with no history of institutionalized caregiving, were also recruited. DNA methylation status was determined in DNA extracted from buccal epithelial cells of children at age 12. RESULTS: An inverse association was identified such that more time spent in institutional care was associated with lower DNA methylation at specific CpG sites within both genes. DISCUSSION: These results suggest a lasting impact of early severe social deprivation on methylation patterns in these genes, and contribute to a growing literature linking early adversity and epigenetic variation in children. Am J Phys Anthropol 161:84-93, 2016.. © 2016 Wiley Periodicals, Inc.

Measuring the Developing Therapeutic Relationship Between Pregnant Women and Community Health Workers Over the Course of the Pregnancy in a Study Intervention.

The Scale to Assess the Therapeutic Relationship in Community Mental Health Care (STAR) is a frequently-administered tool for measuring therapeutic relationships between clinicians and patients. This manuscript tested the STAR's psychometric properties within a community health worker (CHW)-led intervention study involving pregnant and postpartum women. Women (n = 141) enrolled in the study completed the 12-item participant STAR survey (STAR-P) at two time points over the course of pregnancy and at two time points after delivery. The factor structure of the STAR-P proved to be unstable with this population. However, a revised 9-item STAR-P revealed a two-factor model of positive and negative interactions, and demonstrated strong internal consistency at postpartum time points. The revised STAR-P shows strong psychometric properties, and is suitable for use to evaluate the relationship developed between CHWs and pregnant and postpartum women in an intervention program.

Setting the trajectory: racial disparities in newborn telomere length.

OBJECTIVE: To explore racial differences in newborn telomere length (TL) and the effect moderation of the sex of the infant while establishing the methodology for the use of newborn blood spots for TL analyses. STUDY DESIGN: Pregnant mothers were recruited from the Greater New Orleans area. TL was determined via monochrome multiplex quantitative real-time polymerase chain reaction on DNA extracted from infant blood spots. Demographic data and other covariates were obtained via maternal report before the infant's birth. Birth outcome data were obtained from medical records and maternal report. RESULTS: Black infants weighed significantly less than white infants at birth and had significantly longer TL than white infants (P=.0134), with the strongest effect observed in black female infants. No significant differences in gestational age were present. CONCLUSIONS: Significant racial differences in TL were present at birth in this sample, even after we controlled for a range of birth outcomes and demographic factors. Because longer initial TL is predictive of more rapid TL attrition across the life course, these findings provide evidence that, even at birth, biological vulnerability to early life stress may differ by race and sex.