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Epigenetic clocks have been widely used to predict disease risk in multiple tissues or cells. Their success as a measure of biological aging has prompted research on the connection between epigenetic pathways of aging and the socioeconomic gradient in health and mortality. However, studies examining social correlates of epigenetic aging have yielded inconsistent results. We conducted a comprehensive, comparative analysis of associations between various dimensions of socioeconomic status (SES) (education, income, wealth, occupation, neighborhood environment, and childhood SES) and eight epigenetic clocks in two large U.S. aging studies: The Multi-Ethnic Study of Atherosclerosis (MESA) (n=1,211) and the Health and Retirement Study (HRS) (n=4,018). In both studies, we found robust associations between SES measures in adulthood and the GrimAge and DunedinPoAm clocks (Bonferroni corrected p-value

Unemployment shocks from the COVID-19 pandemic have reignited concerns over the long-term effects of job loss on population health. Past research has highlighted the corrosive effects of unemployment on health and health behaviors. This study examines whether the effects of job loss on changes in body mass index (BMI) are moderated by genetic predisposition using data from the U.S. Health and Retirement Study (HRS). To improve detection of gene-by-environment (G × E) interplay, we interacted layoffs from business closures—a plausibly exogenous environmental exposure—with whole-genome polygenic scores (PGSs) that capture genetic contributions to both the population mean (mPGS) and variance (vPGS) of BMI. Results show evidence of genetic moderation using a vPGS (as opposed to an mPGS) and indicate genome-wide summary measures of phenotypic plasticity may further our understanding of how environmental stimuli modify the distribution of complex traits in a population.

Unemployment shocks from the COVID-19 pandemic have reignited concerns over the long-term effects of job loss on population health. Past research has highlighted the corrosive effects of unemployment on health and health behaviors. This study examines whether the effects of job loss on changes in body mass index (BMI) are moderated by genetic predisposition using data from the U.S. Health and Retirement Study (HRS). To improve detection of gene-by-environment (G x E) interplay, we interacted layoffs from business closures—a plausibly exogenous environmental exposure—with whole-genome polygenic scores (PGSs) that capture genetic contributions to both the population mean (mPGS) and variance (vPGS) of BMI. Results show evidence of genetic moderation using a vPGS (as opposed to an mPGS) and indicate genome-wide summary measures of phenotypic plasticity may further our understanding of how environmental stimuli modify the distribution of complex traits in a population.

Objective—This paper aims to review findings from a longitudinal study of prenatal methylenedioxymethamphetamine (MDMA, “ecstasy”) on infant development. Methods—In a prospective, longitudinal cohort design, we followed 28 MDMA-exposed and 68 non-MDMA-exposed infants from birth to 2 years of age. Women recruited voluntarily into a study of recreational drug use during pregnancy were interviewed to obtain type, frequency, and amount of recreational drug use. Their children were followed for a 2-year period after birth. A large number of drug and environmental covariates were controlled. Infants were seen at 1, 4, 12, 18, and 24 months using standardized normative tests of mental and motor development. Results—There were no differences between MDMA-exposed and non-MDMA-exposed infants at birth except that MDMA-exposed infants were more likely to be male. Motor delays were evident in MDMA infants at each age and amount of MDMA exposure predicted motor deficits at 12 months in a dose-dependent fashion. Conclusions—Prenatal MDMA exposure is related to fine and gross motor delays in the first 2 years of life. Follow-up studies are needed to determine long-term effects.

Objective The illicit recreational drug 3,4-methylenedioxymethamphetamine (MDMA) or Ecstasy has strong neurohormonal effects. When taken by recreational users at dance clubs and raves, it can generate an 800% increase in the stress hormone cortisol, whereas drug-free users show chronically raised levels of cortisol. The aim here is to critically debate this neurohormonal influence for the children of pregnant MDMA-using mothers. Methods High levels of cortisol are known to be damaging for neuropsychobiological well-being in adult humans. MDMA can damage foetal development in laboratory animals, and the prospective Drugs and Infancy Study was established to monitor the effects of MDMA taken recreationally by pregnant women. Results The Drugs and Infancy Study revealed that young mothers, who took MDMA during the first trimester of pregnancy, gave birth to babies with significant gross psychomotor retardation . These mothers would have experienced high levels of cortisol due to Ecstasy/MDMA use, and since cortisol can cross the placenta, this is likely to have also occurred in the foetus. Conclusions In terms of causation, the developmental problems may reflect a combination of neurotransmitter and neurohormonal effects on the hypothalamic–pituitary–adrenal axis, with serotonergic activity being influenced by the high levels of cortisol. Copyright © 2014 John Wiley & Sons, Ltd. key words—Ecstasy; MDMA; cortisol; stress; hormone; pregnancy

Background Many measures of infants' early cognitive development, including the BSID-II (The Bayley Scales of Infant Development), mix together test items that assess a number of different developmental domains including language, attention, motor functioning and social abilities, and some items contribute to the assessment of more than one domain. Consequently, the scales may lead to under- or over-estimates of cognitive abilities in some clinical samples and may not be the best measure to use for matching purposes.\ud Method To address this issue we created a modified form of the BSID-II (the BSID-M) to provide a ‘purer’ assessment of the general cognitive capacities in infants with Down syndrome (DS) from 6 to 18 months of age. We excluded a number of items that implicated language, motor, attentional and social functioning from the original measure. This modified form was administered to 17 infants with Down syndrome when 6, 12 and 18 months old and to 41 typically developing infants at 4, 7 and 10 months old. \ud Results The results suggested that the modified form continued to provide a meaningful and stable measure of cognitive functioning and revealed that DS infants may score marginally higher in terms of general cognitive abilities when using this modified form than they might when using the standard BSID-II scales. \ud Conclusions This modified form may be useful for researchers who need a ‘purer’ measure with which to match infants with DS and other infants with intellectual disabilities on cognitive functioning.

There has been limited study of how the constitutional characteristics of infants with Down syndrome (DS) influence the patterning of their relations with caregivers. To assess natural and perturbed interactions between infants with DS and their mothers, we tested ten 6-month-old infants with DS and 20 typically developing (TD) 4-month-old of similar mental age. Participants were videotaped with their mothers in a natural face-to-face interaction, a brief period when the mothers adopted a still-face, and a subsequent reengagement phase. There was little to distinguish the infants in the initial phase of natural interaction, but the mothers of infants with DS were more likely to show assertive warmth, and unlike in the case of mothers of TD infants, high maternal directiveness tended to be associated with lower levels of infant looking and lack of fussing. During the still-face episode, infants of both groups showed reduced looking and smiling, although infants with DS tended to show lower levels of fussing and fewer in this group showed fussing in the reengagement phase. Therefore DS infants were somewhat similar to TD infants of comparable mental age in being responsive to the still-face procedure, but showed indications of group differences in intense emotional reactivity.

Background:\ud Recreational use of 3,4 methylenedioxymethamphetamine (ecstasy, MDMA) is increasing worldwide. Its use by pregnant women causes concern due to potentially harmful effects on the developing fetus. MDMA, an indirect monoaminergic agonist and reuptake inhibitor, affects the serotonin and dopamine systems. Preclinical studies of fetal exposure demonstrate effects on learning, motor behavior, and memory. In the first human studies, we found prenatal MDMA exposure related to poorer motor development in the first year of life. In the present study we assessed the effects of prenatal exposure to MDMA on the trajectory of child development through 2 years of age. We hypothesized that exposure would be associated with poorer mental and motor outcomes.\ud \ud Materials and Methods:\ud The DAISY (Drugs and Infancy Study, 2003–2008) employed a prospective longitudinal cohort design to assess recreational drug use during pregnancy and child outcomes in the United Kingdom. Examiners masked to drug exposures followed infants from birth to 4, 12, 18, and 24 months of age. MDMA, cocaine, alcohol, tobacco, cannabis, and other drugs were quantified through a standardized clinical interview. The Bayley Scales (III) of Mental (MDI) and Motor (PDI) Development and the Behavior Rating Scales (BRS) were primary outcome measures. Statistical analyses included a repeated measures mixed model approach controlling for multiple confounders.\ud \ud Results:\ud Participants were pregnant women volunteers, primarily white, of middle class socioeconomic status, average IQ, with some college education, in stable partner relationships. Of 96 women enrolled, children of 93 had at least one follow-up assessment and 81 (87%) had ≥ two assessments. Heavier MDMA exposure (M = 1.3 ± 1.4 tablets per week) predicted lower PDI (p < .002), and poorer BRS motor quality from 4 to 24 months of age, but did not affect MDI, orientation, or emotional regulation. Children with heavier exposure were twice as likely to demonstrate poorer motor quality as lighter and non-exposed children (O.R. = 2.2, 95%, CI = 1.02–4.70, p < .05).\ud \ud Discussion:\ud Infants whose mothers reported heavier MDMA use during pregnancy had motor delays from 4 months to two years of age that were not attributable to other drug or lifestyle factors. Women of child bearing age should be cautioned about the use of MDMA and MDMA-exposed infants should be screened for motor delays and possible intervention.

Background In the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), newborns with asphyxial encephalopathy who received hypothermic therapy had improved neurologic outcomes at 18 months of age, but it is uncertain whether such therapy results in longer-term neurocognitive benefits. Methods We randomly assigned 325 newborns with asphyxial encephalopathy who were born at a gestational age of 36 weeks or more to receive standard care alone (control) or standard care with hypothermia to a rectal temperature of 33 to 34°C for 72 hours within 6 hours after birth. We evaluated the neurocognitive function of these children at 6 to 7 years of age. The primary outcome of this analysis was the frequency of survival with an IQ score of 85 or higher. Results A total of 75 of 145 children (52%) in the hypothermia group versus 52 of 132 (39%) in the control group survived with an IQ score of 85 or more (relative risk, 1.31; P = 0.04). The proportions of children who died were similar in the hypothermia group and the control group (29% and 30%, respectively). More children in the hypothermia group than in the control group survived without neurologic abnormalities (65 of 145 [45%] vs. 37 of 132 [28%]; relative risk, 1.60; 95% confidence interval, 1.15 to 2.22). Among survivors, children in the hypothermia group, as compared with those in the control group, had significant reductions in the risk of cerebral palsy (21% vs. 36%, P = 0.03) and the risk of moderate or severe disability (22% vs. 37%, P = 0.03); they also had significantly better motor-function scores. There was no significant between-group difference in parental assessments of children’s health status and in results on 10 of 11 psychometric tests. Conclusions Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.)

Background: The recreational drug MDMA (3,4-methylenedioxymethamphetamine) or ‘Ecstasy’ is associated with heightened psychiatric distress and feelings of depression. The Drugs and Infancy Study (DAISY) monitored the psychiatric symptom profiles of mothers who used Ecstasy/MDMA while pregnant, and followed them over the first year post-partum. Methods: We compared 28 young women whom took MDMA during their pregnancy with a polydrug control group of 68 women who took other psychoactive drugs while pregnant. The Brief Symptom Inventory (BSI) was completed for several periods: The first trimester of pregnancy; and 1, 4 and 12 months after childbirth. Recreational drug use was monitored at each time point. Results: During the first trimester of pregnancy, MDMA-using mothers reported higher depression scores than the polydrug controls. At 1 year after childbirth, their BSI depression scores were significantly lower, now closer to the control group values. At the same time point, their self-reported use of MDMA became nearly zero, in contrast to their continued use of Cannabis/marijuana, nicotine and alcohol. We found significant symptom reductions in those with BSI obsessive-compulsive and interpersonal sensitivity, following Ecstasy/MDMA cessation. Conclusions: The findings from this unique prospective study of young recreational drug-using mothers are consistent with previous reports of improved psychiatric health after quitting MDMA.

Postnatal depression and anxiety have been shown to increase the risk of disturbances in mother–child interaction and child development. Research into mechanisms has focused on genetics and maternal behavior; maternal cognitions have received little attention. Our aim was to experimentally determine if worry and rumination in mothers with generalized anxiety disorder (GAD) and major depressive disorder (MDD), diagnosed in the postnatal 6 months, interfered with maternal responsiveness to their 10-month old infants. Mothers (N = 253: GAD n = 90; MDD n = 57; control n = 106) and their infants were randomized to either a worry/rumination prime (WRP) or a neutral prime (NP); mother–infant interactions were assessed before and after priming. Type of priming was a significant predictor of maternal cognitions, with WRP resulting in more negative thoughts, higher thought recurrence and more self-focus relative to NP across the entire sample. Interaction effects between group and priming were significant for two parenting variables: Compared with controls, WRP had a more negative impact on maternal responsiveness to infant vocalization for GAD, and to a lesser extent for MDD; WRP led to decreased maternal vocalization for GAD. Also, mothers with GAD used stronger control after the NP than WRP, as well as compared with other groups, and overall post-priming, their children exhibited lower emotional tone and more withdrawal. Across the entire sample, WRP was associated with increased child vocalization relative to NP. This study demonstrated that disturbances in maternal cognitions, in the context of postnatal anxiety and to a lesser degree depression, play a significant role in mother–child interaction.

OBJECTIVE: A widely used illicit recreational drug among young adults, 3,4-methylenedioxymethamphetamine (MDMA) or ecstasy, is an indirect monoaminergic agonist/reuptake inhibitor affecting the serotonin system. Preclinical studies found prenatal exposure related to long-term learning and memory impairments. There are no studies of sequelae of prenatal MDMA exposure in humans, despite potential harmful effects to the fetus. METHODS: A total of 96 women in the United Kingdom (28 MDMA users; 68 non-MDMA) were interviewed about recreational drug use during pregnancy. Their infants were seen at 12 months using standardized assessments of cognitive, language, and motor development (Preschool Language Scale, Bayley Mental and Motor Development and Behavior Rating Scales [Mental Development Index, Psychomotor Development Index, Behavioral Rating Scale]). Mothers completed the Child Domain Scale of the Parenting Stress Index, The Home Observation of the Environment Scale (in interview), the Brief Symptom Inventory, and the Drug Abuse Screening Test. Women were primarily middle class with some university education, in stable partner relationships, and polydrug users. MDMA and other drug effects were assessed through multiple regression analyses controlling for confounding variables, and analysis of covariance comparing heavier versus lighter and nonexposed groups. RESULTS: Amount of prenatal MDMA exposure predicted poorer infant mental and motor development at 12 months in a dose-dependent manner. Heavily exposed infants were delayed in motor development. Lighter-exposed infants were comparable to nonexposed infants. There were no effects on language, emotional regulation, or parenting stress. CONCLUSIONS: Findings document persistent neurotoxic effects of heavier prenatal MDMA exposure on motor development through the first year of life.

While recreational drug use in UK women is prevalent, to date there is little prospective data on patterns of drug use in recreational drug-using women immediately before and during pregnancy. A total of 121 participants from a wide range of backgrounds were recruited to take part in the longitudinal Development and Infancy Study (DAISY) study of prenatal drug use and outcomes. Eighty-six of the women were interviewed prospectively while pregnant and/or soon after their infant was born. Participants reported on use immediately before and during pregnancy and on use over their lifetime. Levels of lifetime drug use of the women recruited were high, with women reporting having used at least four different illegal drugs over their lifetime. Most users of cocaine, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and other stimulants stopped using these by the second trimester and levels of use were low. However, in pregnancy, 64% of the sample continued to use alcohol, 46% tobacco and 48% cannabis. While the level of alcohol use reduced substantially, average tobacco and cannabis levels tended to be sustained at pre-pregnancy levels even into the third trimester (50 cigarettes and/or 11 joints per week). In sum, while the use of ‘party drugs’ and alcohol seems to reduce, levels of tobacco and cannabis use are likely to be sustained throughout pregnancy. The data provide polydrug profiles that can form the basis for the development of more realistic animal models.

With the number of elders rising and the incidence of cancer increasing with age, a discussion of cancer in older adults is critical for medical-surgical nurses. An understanding of how aging affects cancer incidence, etiology, biology, diagnosis, treatment, and patient response will help medical-surgical nurses provide quality, comprehensive care to elders with cancer. This includes the ability to assess age-related limitations and initiate intervention strategies as appropriate for older adults with cancer.

While five-month-old infants show orientation-specific sensitivity to changes in the motion and occlusion patterns of human point-light displays, it is not known whether infants are capable of binding a human representation to these displays. Furthermore, it has been suggested that infants do not encode the same physical properties for humans and material objects. To explore these issues we tested whether infants would selectively apply the principle of solidity to upright human displays. In the first experiment infants aged six and nine months were repeatedly shown a human point-light display walking across a computer screen up to 10 times or until habituated. Next, they were repeatedly shown the walking display passing behind an in-depth representation of a table, and finally they were shown the human display appearing to pass through the table top in violation of the solidity of the hidden human form. Both six- and nine-month-old infants showed significantly greater recovery of attention to this final phase. This suggests that infants are able to bind a solid vertical form to human motion. In two further control experiments we presented displays that contained similar patterns of motion but were not perceived by adults as human. Six- and nine-month-old infants did not show recovery of attention when a scrambled display or an inverted human display passed through the table. Thus, the binding of a solid human form to a display in only seems to occur for upright human motion. The paper considers the implications of these findings in relation to theories of infants' developing conceptions of objects, humans and animals.

Infants and young children with Down syndrome can be engaging and affectionate. It seems that in the early months of life their personal relations may be relatively 'spared' the effects of limitations in their capacities for information-processing. Yet how far is this the case as development proceeds? In this paper we discuss some ways in which social and cognitive development interact and mutually influence one another over the first year or so of life, and present preliminary findings from a longitudinal study of infants with and without Down syndrome. The evidence suggests that the development of 'triadic' (person-person-world) social interactions may be affected by limited information-processing capacities in infants with Down syndrome, through a complex socially-mediated developmental trajectory.

Patients who receive high-dose chemotherapy, such as induction regimens followed by high dose melphalan (HD-MEL) and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM), often develop oral mucositis (OM) that impairs adequate intake of fluids and nutrition, serves as a breeding ground for bacteria, leads to increased complexity and cost of care, and may interrupt or delay cancer treatment. Previous work by members of our team demonstrated that renal function and melphalan dose contribute to risk predisposition for oral mucositis. In this study we explored whether genetic variants along with baseline clinical characteristics contribute to risk for oral mucositis by conducting a genome-wide associations study (GWAS). Following strict data quality screening and genotyping using Illumina’s HumanOmni1-Quad v1.0 BeadChip, 892,589 SNPs were tested for association to OM. The analyses evaluated oral mucositis risk in three steps: 1) baseline clinical characteristics; 2) genetic factors (SNPs); and then 3) clinical characteristics combined with genetic factors. Among 972 Caucasian patients who participated in Total Therapy clinical trials (TT2, TT3, TT4) with HD-MEL and ASCT for newly diagnosed myeloma, 353 developed grades 2-4 OM and 619 developed grades 0-1 OM. The baseline sample characteristics included mean age 57.65 (SD 9.16); gender (male 63.68); mean estimated GFR 80.44 (SD 28.40); mean serum albumin 3.85 (SD 0.50); and mean melphalan dose 4.44 (SD 0.79) The combination of estimated glomerular filtration rate (GFR) with melphalan dose (mg/kg), serum albumin, and female gender predicted 67.2% of the risk for oral mucositis (grades 2-4). Analysis of the genetic data identified 11 SNPs significantly associated with Grade 2-4 oral mucositis. The SNPs are located in or near MMP13, JPH3, DHRS7C, CEP 192, CPEB1/CEBP, FBN2, ALDH1A1, DMRTA1/FLJ35282 and have functions related to gene regulation and transcription. We surmise that inflammatory pathways underlie the significance of these SNPs; for example, expression of MMP13 is upregulated in oral epithelial cells during inflammation and FBN2 contributes to wound healing, possibly related to TGFβ signaling and availability. Cyclophospamide (CTX) was part of the total therapy regimens and is known to be detoxified by dehydrogenases. SNP variations associated with aldehyde dehydrogenase 1A1 (ALDH1A1) may alter susceptibility to chemotherapy induced oral mucositis in the presence of HD-MEL, CTX, and other regimens. We postulate that SNPs associated with oral mucositis may influence gene expression through non-coding RNA, thus providing a pathway and novel drug target to prevent this deleterious treatment effect. We will test this hypothesis in future work. Disclosures: No relevant conflicts of interest to declare.

Aims: The present study assessed longitudinal outcomes in mental and motor development through 2 years in infants whose mothers used MDMA (Ecstasy) during pregnancy. Methods: Pregnant women in the United Kingdom (28 MDMA uses; 68 non-MDMA users) were interviewed about recreational drug use and their infants followed from birth to 4, 12, 18, and 24 months of age. Assessments included the Bayley Mental and Motor Scales of Development (MDI, PDI) and mothers completed the HOME, the Brief Symptom Inventory (BSI) and the Drug Abuse Screening Test (DAST). Women were polydrug users, of middle socioeconomic status, average IQ, and in stable relationships. All but one MDMA user discontinued use after the first trimester and users were divided into heavier and lighter groups based on a median split. Infant birth parameters were not different except more MDMA infants were male. Effects of MDMA outcomes over timewere assessed through amixedmodel analysis, controlling for covariates of other drug use, HOME environment, and gender. Results: There was a significant main effect of first trimester MDMA exposure on motor outcomes from 4 months to 2 years (F=11.3, p< .002) with more heavily MDMA-exposed children showing delays compared to lighter-exposed and non-exposed children (PDI =90.8 (SE=3.76) for MDMA vs.98.7 (SE=1.39) for lighter and non-exposed at 2 years). Mental outcomes were not affected. Conclusions: Prenatal MDMA exposure predicts poorer motor outcomes from 4 months to 2 years of age. Given the widespread recreational use of MDMA (Ecstasy), pregnant women should be cautioned about possible developmental effects in offspring. Financial support: Supported by grant DA14910-05 NIH – National Institute on Drug Abuse.