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Racial inequities in health are vast and well-documented, particularly regarding maternal and infant health. Sleep health, including but not limited to duration and quality, is central to overall health and well-being. However, research has not adequately addressed how racism embedded in structures and systems, in addition to individual experiences, may affect maternal health by impacting sleep. In this critical review, we aim to 1) synthesize findings, emphasizing collaborative studies within our group, 2) highlight gaps in knowledge, and 3) propose a theoretical framework and methodological approach for moving the field forward. Specifically, we focus on findings and future directions linking perinatal sleep, cardiovascular and immune function, and racial disparities in maternal health. Because too few studies look beyond individual-level determinants of sleep deficiencies among Black Americans, we assert a critical need for research that bridges multiple levels of analysis (e.g., individual, community, society) and provides recommendations for specific health parameters that researchers in this area can target. Although the need to understand and address perinatal health disparities is clear, the goal of identifying multilevel mechanisms underlying how racism in one's environment and daily life may interact to affect health extends far beyond pregnancy research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Problem: Obesity and preeclampsia both involve a pathological inflammatory response, which may be how obesity increases preeclampsia risk. Previous studies have failed to assess robust measurements of inflammatory markers across gestation, specifically in overweight/ obese women in the context of preeclampsia., Method of Study: We measured 20 inflammatory markers in plasma via multiplex assay (ThermoFisher Inflammation 20 plex Human ProcartaPlex Panel) across the three trimesters of pregnancy in an existing cohort of overweight and obese women who developed preeclampsia (n = 37) and without preeclampsia (n = 74). Mann-Whitney U tests examined differences in inflammatory marker concentrations between cases and controls. Repeated measures ANOVA tests were used to explore differences in inflammatory marker concentrations over time within cases and controls., Results: Pro-inflammatory markers (IL-1α, IL-1β, IL-6, IFN-α, IFN-γ, GM-CSF, IL-12p70, IL-17α, TNF-α, IL-8) and anti-inflammatory markers (IL-4, IL-10, IL-13) were higher in the first and second trimester in participants who later developed preeclampsia compared to those who did not (p < .05). Only TNF-α and IL-8 remained elevated in the third trimester. Inflammatory markers did not change across pregnancy in preeclampsia cases but did increase across pregnancy in controls., Conclusion: Our findings diverge from prior studies, predominantly of non-obese women, that report lower circulating concentrations of anti-inflammatory cytokines in preeclampsia versus normotensive pregnancy, particularly by late pregnancy. We posit that women with overweight and obesity who develop preeclampsia entered pregnancy with a heightened pro-inflammatory state likely related to obesity, which increased risk for preeclampsia. Further studies are needed to investigate if inflammatory maker profiles differ between obese and non-obese women., (© 2023 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Background: Advanced chronic liver disease is an increasing cause of premature morbidity and mortality in the UK. Portal hypertension is the primary driver of decompensation, including the development of ascites, hepatic encephalopathy and variceal haemorrhage. Non-selective beta blockers (NSBB) reduce portal pressure and are well established in the prevention of variceal haemorrhage. Carvedilol, a newer NSBB, is more effective at reducing portal pressure due to additional α-adrenergic blockade and has additional anti-oxidant, anti-inflammatory and anti-fibrotic effects., Aim: To summarise the available evidence on the use of beta blockers, specifically carvedilol, in cirrhosis, focussing on when and why to start METHODS: We performed a comprehensive literature search of PubMed for relevant publications., Results: International guidelines advise the use of NSBB in primary prophylaxis against variceal haemorrhage in those with high-risk varices, with substantial evidence of efficacy comparable with endoscopic band ligation (EBL). NSBB are also well established in secondary prophylaxis, in combination with EBL. More controversial is their use in patients without large varices, but with clinically significant portal hypertension. However, there is gathering evidence that NSBB, particularly carvedilol, reduce the risk of decompensation and improve survival. While caution is advised in patients with advanced cirrhosis and refractory ascites, recent evidence suggests that NSBB can continue to be used safely, and that premature discontinuation may be detrimental., Conclusions: With increasing evidence of benefit independent of variceal bleeding, namely retardation of decompensation and improvement in survival, it is time to consider whether carvedilol should be offered to all patients with advanced chronic liver disease., (© 2023 John Wiley & Sons Ltd.)

Purpose: The purpose of this study is to characterize mothers' experiences within a mother/infant dyad postpartum primary care program (Dyad) following gestational diabetes mellitus (GDM) to inform improvements in the delivery of care., Methods: A qualitative pilot study of women (n = 10) enrolled in a mother/infant Dyad program was conducted in a primary care practice at a large, urban academic medical center. Respondents were asked a series of open-ended questions about their experience with GDM, the Dyad program, and health behaviors. Interviews were audio-recorded, transcribed verbatim, and analyzed using ground theory with NVivo 12 Plus software., Results: Three key themes emerged: (1) Dyad program experience, (2) implementation of health behavior changes, and (3) acknowledgment of future GDM and type 2 diabetes mellitus (T2DM) health risks. Respondents felt that the program conveniently served mother and infant health care needs in a single appointment. Respondents also valued support from primary care providers when implementing health behavior changes. The Dyad program provided an opportunity for respondents to understand their current and future risk for developing GDM and T2DM., Conclusions: Postpartum women enrolled in the Dyad program received highly personalized primary care services. The results of our study will help integrate patient-centered strategies into models for GDM care to maintain patient engagement in postpartum clinical services.

Although Black American mothers and infants are at higher risk for morbidity and mortality than their White counterparts, the biological mechanisms underlying these phenomena remain largely unknown. To investigate the role that lifetime stressor exposure, perceived stressor severity, and systemic inflammatory markers might play, we studied how these factors were interrelated in 92 pregnant Black American women. We also compared inflammatory marker levels for women who did versus did not go on to give birth preterm. During the early third trimester, women completed the Stress and Adversity Inventory for Adults to assess the stressors they experienced over their lifetime. Women also provided blood samples for plasma interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor (TNF)-α quantification. Preterm births were identified by medical record review. Controlling for relevant covariates, there were significant positive associations between average levels of both overall and acute perceived stressor severity and plasma IL-1β levels. Controlling for perceived stress at assessment and exposure to racial discrimination did not affect these results. Mediation models revealed that exposure to more chronic stressors was related to higher plasma IL-1β levels, as mediated by higher average levels of overall perceived stressor severity. Exposure to fewer acute stressors was related to higher plasma IL-1β levels, as mediated by higher average levels of acute perceived stressor severity. Finally, women who went on to give birth preterm had higher levels of plasma IL-6. These data thus highlight the potential importance of assessing and addressing lifetime stressor exposure among mothers before and during maternal-infant care., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Thanks to the development of antiretroviral drugs and the implementation of routine perinatal prophylaxis, primarily containing zidovudine, modern-day rates of perinatal transmission of HIV are very low in developed countries. We present a case of perinatal transmission of HIV with extensive nucleoside reverse transcriptase inhibitor resistance as a reminder that perinatal transmission of resistance mutations can occur. This case calls for further investigation into the utility of using genotype to determine neonatal prophylaxis in the setting of maternal HIV drug resistance., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Improved understanding of perinatal psychoneuroimmunology is needed, particularly to combat the high rates of maternal and infant mortality witnessed among Black Americans. We compared the success of recruitment by advertisement, in person, or by phone during the course of a prospective cohort study of perinatal psychoneuroimmunology among Black American women. Over 24 months, 363 women were assessed and 96 were enrolled. Women recruited by phone were less likely to complete full screening than women recruited by advertisement (OR = 0.32, p < 0.01) or in person (OR = 0.19, p < 0.01). Women recruited by advertisement were less likely to complete full screening than women recruited in person (OR = 0.60, p = 0.05). Odds of unsuccessful contact were 13.2 and 11.5 times greater among women recruited by phone versus by advertisement or in person, respectively (p values ≤ 0.01). Women recruited by advertisement and in person showed similar odds of unsuccessful contact (OR = 0.87, p = 0.76). Odds of screening decline were similar following recruitment in person or by phone when contact was successful (OR = 0.85, p = 0.76). Focusing on eligible women (n = 142), those recruited in person were significantly less likely to enroll than those recruited by advertisement (OR = 0.28, p < 0.01; Fig. 4). Considering all women (n = 363), odds of enrollment did not significantly differ among the recruitment groups (p values ≥ 0.09). Most (93.8%) enrolled women consented to biological specimen banking. Findings from this brief report provide a starting point for perinatal scientists to critically consider not only how to maximize research efforts but also how research team actions may perpetuate or assuage the research mistrust introduced by long-standing social inequities., (© 2021. The New York Academy of Medicine.)

ABSTRACT Opportunistic infections (OIs) are the primary cause of HIV-related morbidity and mortality. To reduce the risk, the ART eligibility criteria were revised to start treatment before advanced disease onset. We evaluated the effect of 2014 HIV clinical guideline changes in Uganda on opportunistic infections and survival among Youth Living with HIV (YLWH). This retrospective cohort analysis used administrative data from the District Health Information System (DHIS2) and the national referral hospital, to compare YLWH, 15-24 years old, who started ART pre-guideline (January 2012-June 2014) and post-guideline (July 2014-December 2016). We assessed the effect using multivariable logistic and Cox Proportional Hazards regression models, respectively. Post-guideline youth had 18% and 30% lower adjusted odds of having an OI at 6 (aOR: 0.82, 95%CI: 0.67, 0.99), and 12 months (aOR: 0.70, 95%CI: 0.58, 0.85) after ART initiation, compared to pre-guideline youth. No significant differences were observed in survival probabilities (Z = 2.56, P -value = 0.11) and adjusted hazard ratios (aHR: 1.55, 95%CI: 0.46, 5.28). Early ART initiation reduced the risk of OIs among YLWH. However, given the existence of geographical and clinical variations in the endemicity, morbidity and mortality associated with different OIs, additional research is still needed.

Objective: Debate is ongoing regarding the need for universal endoscopic follow-up to ensure gastric ulcer healing. We aimed to assess the value of follow-up oesophago-gastro-duodenoscopies (OGDs) for gastric ulcer healing and stratify patients according to risk of malignancy by developing a risk score., Design/method: All patients in National Health Service (NHS) Lothian with an index OGD and a diagnosis of gastric ulcer between 1 January 2014 and 31 December 2018 were identified. Data were analysed with logistic regression to identify factors significantly associated with a diagnosis of cancer; a risk score was derived and externally validated., Results: 778 patients were identified and 60.3% (469/778) of patients had a follow-up OGD. 8.6% (66/778) of patients were diagnosed with cancer. No cases of cancer were found on follow-up OGD of a benign appearing ulcer with negative biopsies. Macroscopic suspicion of malignancy was present at index OGD in 100% (3/3) of those diagnosed with cancer on subsequent OGDs. Older age (p=0.014), increased ulcer size (p<0.001) and non-antral location (p=0.030) were significantly associated with malignancy. A risk score (area under the curve (AUC) 0.868, p<0.001, minimum score=0, maximum score=6) was derived from these variables. 78.0% of patients with malignant ulcers scored ≥3, only 15.8% with benign ulcers scored ≥3 (negative predictive value (NPV) 97.4%). External validation yielded an AUC of 0.862 (p<0.001) and NPV of 98.6%; 84.0% of those with malignant ulcers scored ≥3., Conclusion: Ulcers with a combination of macroscopically benign appearances, at least six negative biopsies and a low risk score do not necessarily need endoscopic follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Variceal haemorrhage is a severe complication of liver disease with high mortality. Human recombinant thrombin has gained popularity in the management of variceal haemorrhage. We report on the use of thrombin for gastric and ectopic varices at a regional tertiary care centre. This was a retrospective observational study. Patients with portal hypertension who received endoscopic injection of recombinant thrombin were identified and data collected on haemostasis and rebleeding rates, complications and mortality. Patients were grouped by indication for thrombin injection: gastric/oesophageal/ectopic varices and endoscopic band ligation (EBL)-induced ulceration. 155 patients (96M/59F, mean age 58.3 years) received endoscopic thrombin injection. Mean volume of thrombin injected at index endoscopy was 9.5 ml/2375IU. Initial haemostasis was achieved in 144 patients (92.9%). Rebleeding occurred in a total of 53 patients (36.8%) divided as follows: early rebleeding (<5 days from index endoscopy)-26 patients (18%); rebleeding within 30 days-42 patients (29.1%); delayed rebleeding (> 30 days)-11 patients (7.6%). There was statistically significant difference in rate of initial haemostasis between Child-Pugh A/B patients vs Child-Pugh C ( p = 0.046). There was no significant difference in rebleeding rates between different indication groups ( p = 0.78), by presence of cirrhosis or by Child-Pugh Score. All-cause mortality at 6 weeks was 18.7%; 1-year mortality 37.4% (median follow-up 48 months). There was no significant difference in mortality between groups ( p = 0.37). No significant adverse events or complications were reported. Thrombin is effective and safe for gastric varices and other portal-hypertension-related bleeding including oesophageal varices, ulcers secondary to EBL and ectopic varices.

Background: Among Black Americans, interpersonal racial discrimination is common. Stress, including following discrimination, contributes to pregnancy complications. In this secondary analysis, we provide data on associations among discrimination, stress, and their interaction across the life course and inflammation, perceived stress, and depressive symptoms during pregnancy., Methods: During the early third trimester, Black American women (n = 93) completed the Experiences of Discrimination Scale, the Stress and Adversity Inventory, the Perceived Stress Scale, and the Center for Epidemiological Studies Depression Inventory. Plasma interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and IL-β levels were quantified. Associations were examined by linear regression, controlling for demographic, behavioral, and clinical covariates., Results: Associations among racial discrimination and plasma IL-8, TNF-α, and IL-β levels depended upon average ratings of life course stress. When stress was low, discrimination in the mid tertile was associated with the highest levels of IL-8, TNF-α, and IL-β. Subscale analyses suggested that findings related to IL-8 were driven by chronic stress whereas findings related to TNF-α and IL-β were driven by acute stress. When examined together, greater discrimination but not greater life course stress was associated with higher prenatal perceived stress. In subscale analyses, the association between discrimination and prenatal perceived stress depended upon average ratings of life course acute stress. When acute stress was low, discrimination in the midtertile was associated with the highest levels of prenatal perceived stress. When acute stress was high, discrimination in the high tertile was associated with the highest levels of prenatal perceived stress. There were also direct associations among greater life course chronic stress, prenatal perceived stress, and prenatal depressive symptoms. Associations were attenuated when discrimination was included as a covariate., Conclusions: The current analyses suggest that, among Black Americans, prenatal inflammation, perceived stress, and depressive symptoms may be shaped by racial discrimination and stress across the life course. In many cases, associations among discrimination and prenatal parameters depended upon how stressful exposures to life course stressors had been rated. The data suggest the potential for adaptive plasticity under some stress and highlight the deleterious nature of compounding stress., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Offspring born preterm (ie, before 37 weeks of gestation) are more likely to die or experience long-standing illness than full-term offspring. Maternal genetic variants (ie, heritable, stable variations in the genetic code) and epigenetic modifications (ie, chemical modifications to the genetic code that can affect which genes are turned on or off) in response to stress have been implicated in preterm birth. Fetal genetic variants have been linked to preterm birth though the role of offspring epigenetics in preterm birth remains understudied. This systematic review synthesizes the literature examining associations among stress during pregnancy and epigenetic modifications to offspring DNA, with 25 reports identified. Ten reports examined DNA methylation (ie, addition/removal of methyl groups to/from DNA) across the epigenome. The remainder examined DNA methylation near genes of interest, primarily genes linked to hypothalamic-pituitary-adrenal axis function (NR3C1, FKBP51), growth/immune function (IGF2), and socioemotional regulation (SLC6A4, OXTR). The majority of reports noted associations among stress and offspring DNA methylation, primarily when perceived stress, anxiety, or depression served as the predictor. Findings suggest that differences in offspring epigenetic patterns may play a role in stress-associated preterm birth and serve as targets for novel interventions.

African Americans are at heightened risk for coronary heart disease (CHD), with biologic pathways poorly understood. We examined the role of allostatic load (AL) in the association of depressive symptoms with incident CHD among 2,670 African American men and women in the prospective Jackson Heart Study. Depressive symptoms were quantified using the Center for Epidemiologic Studies Depression Scale (CES-D). Incident CHD was ascertained by self-report, death certificate survey, and adjudicated medical record surveillance. Baseline AL was quantified using biologic parameters of metabolic, cardiovascular, immune, and neuroendocrine subsystems and as a combined meta-factor. Sequential models adjusted for demographic, socioeconomic, and behavioral covariates, stratified to examine differences by sex. Greater depressive symptomatology was associated with greater metabolic, cardiovascular, and immune AL (p-values≤0.036) and AL meta-factor z-scores (p = 0.007), with findings driven by observations among females. Each 1-point increase in baseline depressive symptomatology, and 1-SD increase in metabolic AL, neuroendocrine AL, and AL meta-factor z-scores was associated with 3.3%, 88%, 39%, and 130% increases in CHD risk, respectively (p-values <0.001). Neuroendocrine AL and AL meta-factor scores predicted incident CHD among males but not females in stratified analyses. Metabolic AL partially mediated the association of depressive symptoms with incident CHD (5.79% mediation, p = 0.044), a finding present among females (p = 0.016) but not males (p = 0.840). Among African American adults, we present novel findings of an association between depressive symptomatology and incident CHD, partially mediated by metabolic AL. These findings appear to be unique to females, an important consideration in the design of targeted interventions for CHD prevention., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Early life, including prenatal development and childhood, is a period of sensitivity, with potential for developmental programming under conditions of adversity. The intergenerational effects of early adversity have received attention, most often studied in relation to fetal development according to maternal exposures. Less often considered but critically important is the effect of early adversity on future prenatal risk (e.g., risk for preeclampsia, preterm birth), which threatens the health of mother and infant. The body's ability to turn collections of genes "on" or "off" across a range of tissues via receptor-driven transcription factors and epigenetic mechanisms (i.e., chemical modifications to the genome) in response to the perceived environment may help to explain such associations. This review aims to summarize discoveries surrounding the effects of early adversity on gene expression, emphasizing prenatal populations. First, we review findings from gene expression studies examining the effects of early adversity on various tissues known to contribute to prenatal health in adulthood. Next, we review several gene regulatory mechanisms thought to underlie differences in gene expression. Finally, we discuss potential implications for prenatal risk among early adversity-exposed mothers according to our current understanding of the biology that contributes to the development of prenatal syndromes., Competing Interests: Declaration of interest: None.

Background: A rapidly expanding literature suggests that individuals of the same chronological age show significant variation in biological age., Purpose: The purpose of this article is to review the literature surrounding epigenetic age as estimated by DNA methylation, involving the addition or removal of methyl groups to DNA that can alter gene expression without changing the DNA sequence., Methods: This state of the science literature review summarizes current approaches in epigenetic age determination and applications of aging algorithms., Findings: A number of algorithms estimate epigenetic age using DNA methylation markers, primarily among adults. Algorithm application has focused on determining predictive value for risk of disease and death and identifying antecedents to age acceleration. Several studies have incorporated epigenetic age to evaluate intervention effectiveness., Discussion: As the research community continues to refine aging algorithms, there may be opportunity to promote health from a precision health perspective., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Rationale: Psychological stress-induced cortisol elevations appear to contribute to preterm birth. Yet, some studies suggest that the biological ramifications of racial discrimination-associated stress are unique and may involve development of decreased glucocorticoid sensitivity despite normalized cortisol levels., Objective: In this study, we examined the effects of racial discrimination on maternal cortisol output, leukocyte glucocorticoid sensitivity, and the degree of correspondence between cortisol levels and birth timing in an African American cohort., Method: A generally healthy prospective cohort was enrolled at 28-32 weeks gestation (n = 91). The Experiences of Discrimination scale was administered, whole blood collected, and plasma cortisol levels, cytokine levels, and leukocyte counts quantified for examination of patterns of endogenous feedback., Results: Racial discrimination in the mid-tertile was associated with greater maternal cortisol levels than the bottom tertile among women reporting internalizing responses (b* = 0.68, p = 0.001). Decreased leukocyte glucocorticoid sensitivity was witnessed at greater frequencies of experiences of racial discrimination, as evidenced by decreased correspondence between maternal cortisol levels and plasma IL-8 levels, monocyte counts, and lymphocyte counts (p values ≤ 0.043). The association between maternal cortisol levels and birth timing differed by discrimination tertile (p values ≤ 0.005), with greater cortisol levels predictive of earlier birth among women without (b* = -0.59, p < 0.001) but not with racial discrimination (ps ≥ 0.497)., Conclusion: We provide novel evidence of decreased glucocorticoid sensitivity at increasing frequency of exposure to racial discrimination. Our findings suggest that the biology of preterm birth may depend upon racial discriminatory exposures, favoring pathways dependent upon glucocorticoid-induced increases in leukocyte tissue surveillance versus glucocorticoid resistance-associated inflammatory aberrations at increasing levels of exposure. Precision approaches to prenatal care are sorely needed to combat preterm birth, particularly among African American women, with efforts dependent upon further research examining the pathways contributing to the syndrome dependent upon the totality of an individual's exposures., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Compared to women who have given birth before (i.e., multiparas), those giving birth for the first time (i.e., primiparas) show higher cortisol levels. Psychological factors may play a role; hypothalamic-pituitary-adrenal activation is a well-described stress response. Primiparity also predicts greater risk for postpartum depression, which may be related to greater correspondence between cortisol and mood following prenatal cortisol elevations. The current study examined associations among parity, perinatal cortisol adaptation, pregnancy-specific distress, and postpartum mood., Methods: This longitudinal study assayed serum cortisol levels among 137 women at early, mid-, and late pregnancy and postpartum. Pregnancy-specific distress and depressive symptoms were assessed. Maternal age, race, body mass index, sleep quality, depressive symptoms, and sampling time of day were statistically controlled., Results: Primiparous women showed higher cortisol levels than multiparous women during mid- (χ 2  = 11.8, p < 0.01) and late pregnancy (χ 2  = 18.9, p < 0.01) and higher distress across pregnancy (F 1,126  = 22.1, p < 0.01). Mediation analyses demonstrated that the association between parity and prenatal cortisol (per area under the curve; AUC) was partially accounted for by distress (ab = 1.0, 95%CI [0.05, 2.9]). Prenatal cortisol (per AUC) did not predict postpartum depressive symptoms (b* = 0.03, p = 0.81), with no difference by parity (b* = 0.03, p = 0.91). At postpartum, a significant interaction between parity and cortisol (b* = 0.40, p = 0.03) revealed no significant association between cortisol and mood among multiparas (b* = -0.11, p = 0.28) but a trend toward a positive association among primiparas (b* = 0.24, p = 0.06)., Discussion: Cortisol levels and pregnancy-specific distress are higher in primiparas versus multiparas, with pregnancy-specific distress partially mediating the association between parity and cortisol levels. Cortisol levels and mood display correspondence at postpartum in primiparous but not multiparous women. While observational studies must be interpreted with caution due to potential unmeasured confounders, these findings suggest that future studies examining mechanisms underlying perinatal and postpartum hypothalamic-pituitary-adrenal perturbations and designing interventions aimed at preventing related complications should carefully consider potential differences by parity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Mothers and infants are at high risk for inadequate vitamin D status. Mechanisms by which vitamin D may affect maternal and infant DNA methylation are poorly understood., Objective: This study quantified the effects of vitamin D 3 supplementation on DNA methylation in pregnant and lactating women and their breastfed infants., Materials and Methods: In this randomized controlled pilot study, pregnant women received vitamin D 3 400 international units (IU) (n = 6; control) or 3,800 IU (n = 7; intervention) daily from late second trimester through 4-6 weeks postpartum. Epigenome-wide DNA methylation was quantified in leukocytes collected from mothers at birth and mother-infant dyads at 4-6 weeks postpartum., Results: At birth, intervention group mothers showed DNA methylation gain and loss at 76 and 89 cytosine-guanine (CpG) dinucleotides, respectively, compared to controls. Postpartum, methylation gain was noted at 200 and loss at 102 CpGs. Associated gene clusters showed strongest biologic relevance for cell migration/motility and cellular membrane function at birth and cadherin signaling and immune function at postpartum. Breastfed 4-6-week-old infants of intervention mothers showed DNA methylation gain and loss in 217 and 213 CpGs, respectively, compared to controls. Genes showing differential methylation mapped most strongly to collagen metabolic processes and regulation of apoptosis., Conclusions: Maternal vitamin D supplementation during pregnancy and lactation alters DNA methylation in mothers and breastfed infants. Additional work is needed to fully elucidate the short- and long-term biologic effects of vitamin D supplementation at varying doses, which could hold important implications for establishing clinical recommendations for prenatal and offspring health promotion.

Preterm birth (PTB) occurs among 1:11U.S. white women and 1:7.5 African American women and is a significant driver of racial disparities in infant mortality. Maternal stress is the most common clinical phenotype underlying spontaneous PTB. Specific patterns of stress and biological mediators driving PTB remain unclear. We examined the effect of childhood stress on birth timing among African American women and evaluated maternal cortisol elevation as a biological mediator. A prospective observational design was employed, with a single study visit at 28-32 weeks gestation and medical record review. The Stress and Adversity Inventory was administered, which provides a comprehensive estimate of childhood stress, stress in adulthood, and five core characteristic subscales (interpersonal loss, physical danger, humiliation, entrapment, role disruption). Venipuncture was performed between 11:00am and 4:00pm and plasma cortisol quantified by ELISA. Analyses controlled for stress in adulthood. Among a final sample of 89, cumulative childhood stress predicted birth timing (p=0.01). The association was driven by stress related to interpersonal loss and physical danger, with support for maternal cortisol as a biological mediator (ab=0.02, 95% CI [0.001, 0.045]; ab=0.02, 95% CI [0.001, 0.043], respectively). Results were similar, overall, in sub-group analyses among spontaneously laboring women (n=53); however, role disruption arose as an additional predictor, as mediated by cortisol elevations (ab=0.03, 95% CI [0.005, 0.074]). Of note, cortisol was no longer supported as a mediator linking physical danger to birth timing after adjusting for sleep quality and hours awake prior to venipuncture (ab=0.02, 95% CI [-0.0001, 0.046]). We provide preliminary evidence that, independent of stress in adulthood, childhood stress of specific core characteristics may shape birth timing, with cortisol elevation as a biological mediator. Further investigation is warranted and may bolster the development of biologically-informed screening tools for the prediction and targeted prevention of stress-related PTB., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests that inflammatory pathways differ by race; however, studies among African American women are lacking., Objectives: We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1β production., Methods: A candidate gene study using a prospective cohort design was used. We collected blood samples at 28-32 weeks of gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN single-nucleotide polymorphism (SNP) rs2637988 was genotyped, and lipopolysaccharide-stimulated IL-1Ra and IL-1β production was quantified. Medical record review determined timing of birth., Results: Women with GG genotype gave birth earlier than women with AA/AG genotypes (b* = .21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [-0.05, 0.13]). Women with GG genotype showed less inhibition of IL-1β production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = .93, p = .03). Greater IL-1β production at 28-32 weeks of pregnancy was marginally associated with earlier birth (b* = .21, p = .05)., Discussion: Women with GG genotype may be at risk for earlier birth because of diminished IL-1β inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions.

Objective: The functional role of the glottis in brass performance is poorly understood and controversial, particularly with respect to pedagogy. Technological limitations have prevented the non-invasive, systematic study of the glottis in the past, but developments in real-time magnetic resonance imaging (RT-MRI) allow representations of glottal movement during performance on a MRI-compatible horn to be recorded and quantified., Methods: We present RT-MRI data obtained on 6 advanced-level horn players from serial images acquired at an acquisition time of 33.3 ms as they performed sustained note exercises on three notes (concert Eb2, Eb4, and Bb4) at each of three dynamics (pp, mf, and ff) and a staccato exercise. An advanced-level trumpet player was also studied performing a modification of the staccato exercise designed to minimize vertical movement of the larynx. Glottal movements and positions in the coronal plane were analyzed using a customized MATLAB toolkit., Results: In sustained note playing, there is a significant influence of dynamic on the degree of glottal adduction/abduction. There is greater adduction with softer notes, and greater abduction with louder notes. In slow staccato playing, glottal closure accompanies the cessation of each note and persists until iteration of the next note in the sequence., Conclusions: We demonstrate that RT-MRI provides a suitable method to identify and quantify glottal movement during horn playing. We further show that there is a direct relationship between dynamic level and glottal adduction/abduction, and that the glottis is involved in performing notes during slow staccato playing.

Background: As a measure of obesity, body mass index (BMI; kg/m 2 ) is an imperfect predictor of health outcomes, particularly among African Americans. However, BMI is used to guide prenatal care. We examined racial differences in the predictive value of maternal BMI for physiologic correlates of obesity, serum interleukin (IL)-6 and C-reactive protein (CRP), as well as cesarean section and infant birth weight., Methods: One hundred five pregnant women (40 European American, 65 African American) were assessed during the second trimester. BMI was defined as per prepregnancy weight. Electrochemiluminescence and enzyme-linked immunosorbent assays were used to quantify IL-6 and CRP, respectively. Birth outcomes were determined by medical record review., Results: Women of both races classified as obese had higher serum IL-6 and CRP than their normal-weight counterparts (ps ≤ 0.01). However, among women with overweight, elevations in IL-6 (p < 0.01) and CRP (p = 0.06) were observed among European Americans, but not African Americans (ps ≥ 0.61). Maternal obesity was a significantly better predictor of cesarean section among European Americans versus African Americans (p = 0.03) and BMI was associated with infant birth weight among European Americans (p < 0.01), but not African Americans (p = 0.94). Effects remained after controlling for gestational age at delivery, gestational diabetes, and gestational weight gain as appropriate., Conclusions: BMI may be a less valid predictor of correlates of overweight/obesity among African Americans versus European Americans during pregnancy. This should be considered in epidemiological studies of maternal-child health. In addition, studies examining the comparative validity of alternative/complementary measures to define obesity in pregnancy are warranted to inform clinical care., Competing Interests: Author Disclosure Statement No competing financial interests exist.

Background: Brain-derived neurotrophic factor (BDNF) is implicated as a causal factor in major depression and is critical to placental development during pregnancy. Longitudinal data on BDNF across the perinatal period are lacking. These data are of interest given the potential implications for maternal mood and fetal growth, particularly among Black women who show ∼2-fold greater risk for delivering low birth weight infants., Methods: Serum BDNF, serum cortisol, and depressive symptoms (per CES-D) were assessed during each trimester and 4-11 weeks postpartum among 139 women (77 Black, 62 White). Low birth weight (<2500g) was determined via medical record., Results: Serum BDNF declined considerably from 1st through 3rd trimesters (ps≤0.008) and subsequently increased at postpartum (p<0.001). Black women exhibited significantly higher serum BDNF during the 1st trimester, 2nd trimester, and postpartum (ps≤0.032) as well as lower serum cortisol during the 2nd and 3rd trimester (ps≤0.01). Higher serum cortisol was concurrently associated with lower serum BDNF in the 2nd trimester only (p<0.05). Controlling for race, serum BDNF at both the 2nd and 3rd trimester was negatively associated with 3rd trimester depressive symptoms (ps≤0.02). In addition, women delivering low versus healthy weight infants showed significantly lower serum BDNF in the 3rd trimester (p=0.004). Women delivering low versus healthy weight infants did not differ in depressive symptoms at any time point during pregnancy (ps≥0.34)., Conclusions: Serum BDNF declines considerably across pregnancy in Black and White women, with overall higher levels in Blacks. Lower serum BDNF in late pregnancy corresponds with higher depressive symptoms and risk for low birth weight in Black and White women. However, the predictive value of serum BDNF in pregnancy is specific to within-race comparisons. Potential links between racial differences in serum BDNF and differential pregnancy-related cortisol adaptation require further investigation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Loss to follow-up (LTFU) is a critical factor in determining clinical outcomes in HIV treatment programs. Identifying modifiable factors of LTFU is fundamental for designing effective patient-retention interventions. We analyzed factors contributing to children LTFU from a treatment program to identify those that can be modified. A case-control study involving 313 children was used to compare the sociodemographic and clinical characteristics of children LTFU (cases) with those remaining in care (controls) at a large pediatric HIV care setting in Botswana. We traced children through caregiver contacts and those we found, we conducted structured interviews with patients' caregivers. Children <5 years were nearly twice as likely as older children to be LTFU (57·8% versus 30·9%, p <0 .01). Approximately half (47·6%, n = 51) of LTFU patients failed to further engage in care after just one clinic visit, as compared to less than 1% (n = 2) in the control group (p < 0.01). Children LTFU were more likely than controls to have advanced disease, greater immunosuppression, and not to be receiving antiretroviral therapy. Among interviewed patient caregivers, psychosocial factors (e.g., stigma, religious beliefs, child rebellion, disclosure of HIV status) were characteristics of patients LTFU, but not of controls. Socioeconomic factors (e.g., lack of transportation, school-related activities, forgetting appointments) were cited predominantly by the controls. Pediatric patients and their caregivers need to be targeted and engaged at their initial clinic visit, with special attention to children <5 years. Possible interventions include providing psychosocial support for issues that deter patients from engaging with The Clinic. Collaboration with community-based organizations focused on reducing stigma may be useful in addressing these complex issues., Competing Interests: statement: No potential conflict of interest was reported by the authors

Pregnancy is a period of considerable physiological adaption in neuroendocrine, cardiovascular, as well as immune function. Understanding of typical changes in inflammatory immune responses during healthy pregnancy is incomplete. In addition, despite considerable racial difference in adverse pregnancy outcomes, data are lacking on potential racial differences in such adaptation. This repeated measures prospective cohort study included 37 Black and 39 White women who provided blood samples during early, mid-, and late pregnancy and 8-10 weeks postpartum. Peripheral blood mononuclear cells were incubated with lipopolysaccharide (LPS) for 24h and supernatants assayed by electrochemiluminescence to quantify interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-1β, and IL-8 production. While no changes were observed in IL-8 production over time, significant increases in IL-6, TNF-α, and IL-1β production were observed from early to late pregnancy, with subsequent declines approaching early pregnancy values at postpartum (ps<0.05). Overall, inflammatory response patterns were highly similar among Black versus White women. However, Black women had greater TNF-α production during mid-pregnancy (p=0.002) and marginally lower IL-1β production at postpartum (p=0.054). These data show a clear trajectory of change in the inflammatory immune response across pregnancy and postpartum. In this cohort of generally healthy women, Black and White women exhibited minimal differences in LPS-stimulated cytokine production across the perinatal period. Future prospective studies in Black and White women with healthy versus adverse outcomes (e.g., preeclampsia, preterm birth) would inform our understanding of the potential role of immune dysregulation in pregnant women and in relation to racial disparities in perinatal health., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Preterm birth (PTB), or birth prior to 37 weeks gestation, impacts 11.5% of U.S. deliveries. PTB results in significant morbidity and mortality among affected children and imposes a large societal financial burden. Racial disparities in PTB are alarming. African American women are at more than 1.5 times the risk for PTB than white women. Unfortunately, the medical community's ability to predict who is at risk for PTB is extremely limited. History of a prior PTB remains the strongest predictor during a singleton gestation. Cervical length and fetal fibronectin measurement are helpful tools. However, usefulness is limited, particularly among the 95% of U.S. women currently pregnant and lacking a history of PTB. Therefore, preventive therapies do not reach a great number of women who may benefit from them. This manuscript, in response to the pressing need for predictors of PTB risk and elimination of racial disparities in PTB, presents a proposed bio-panel for use in predicting risk for spontaneous PTB among African American women. This bio-panel, measured each trimester, includes stimulated production of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist (Ra), soluble(s) TNF receptor(R) 1, and sTNFR2, and cortisol responsiveness. We hypothesize that greater IL-1β and TNF-α production, decreased IL-1Ra, sTNFR1, and sTNFR2 production, and decreased cortisol responsiveness at each time point as well as a more expedient alignment with this unfavorable profile over time will be associated with PTB. The choice to focus on inflammatory parameters is supported by data highlighting a crucial role for inflammation in labor. Specific inflammatory mediators have been chosen due to their potential importance in preterm labor among African American women. The bio-panel also focuses on inflammatory regulation (i.e., cytokine production upon ex vivo stimulation), which is hypothesized to provide insight into potential in vivo leukocyte responses and potential for initiation of a preterm inflammatory cascade. Production of receptor antagonists is also considered, as pro-inflammatory mediator effects can be greatly influenced by their balance with respective antagonists. Finally, leukocyte responsiveness to cortisol is included as a measure of cortisol's ability to convey anti-inflammatory signals. The development of a bio-panel predictive of risk for spontaneous PTB among African American women would represent a significant advancement. Available preventive therapies, namely progesterone supplementation, could be delivered to women deemed at risk. Further, the identification of biological predictors of PTB may uncover novel targets for preventive therapies., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Objective: Although nonphysician reentry transitions have been characterized in literature, little is known about the reentry physicians in general, or residents in particular. We conducted a qualitative study to explore pediatric residents' reentry, using reverse culture shock as a conceptual framework., Methods: Eighteen pediatric residents who completed global health experiences in Africa (9 categorical residents with 1-month elective, 9 global child health residents with 12-month training) participated in interviews that included a card-sort to solicit emotional responses consistent with the conceptual framework. Data in the form of interview transcripts were coded and analyzed according to principles of grounded theory., Results: All pediatric residents, despite variable time abroad, reported a range of emotional responses on reentry to residency. Global child health residents felt disconnection and frustration more intensely than categorical residents, whereas categorical residents felt invigoration more intensely than global child health residents. Although residents met with program leadership after their return, no resident described these meetings as a formal debriefing, and few described a deliberate strategy for processing emotions on reentry., Conclusions: Consistent with reverse culture shock, pediatric residents felt a range of emotions as they move toward a steady state of acculturating back into their residency program. Residency programs might consider creating safety nets to help cultivate support for residents when they reenter training., (Copyright © 2015 by the American Academy of Pediatrics.)

Objective: To determine whether labor-associated inflammatory markers differ between low-risk, nulliparous women in preactive vs active labor at hospital admission and over time., Study Design: Prospective comparative study of low-risk, nulliparous women with spontaneous labor onset at term (n = 118) sampled from 2 large Midwestern hospitals. Circulating concentrations of inflammatory markers were measured at admission and again 2 and 4 hours later: namely, neutrophil, and monocyte counts; and serum inflammatory cytokines (interleukin -1β, interleukin-6, tumor necrosis factor-α, interleukin-10) and chemokines (interleukin-8). Biomarker concentrations and their patterns of change over time were compared between preactive (n = 63) and active (n = 55) labor admission groups using Mann-Whitney U tests., Results: Concentrations of interleukin-6 and interleukin-10 in the active labor admission group were significantly higher than concentrations in the preactive labor admission group at all 3 time points. Neutrophil levels were significantly higher in the active group at 2 and 4 hours after admission. The rate of increase in neutrophils and interleukin-10 between admission and 2 hours later was faster in the active group (P < .001 and P = .003, respectively)., Conclusion: Circulating concentrations of several inflammatory biomarkers are higher and their rate of change over time since admission is faster among low-risk, nulliparous women admitted to hospitals in active labor, as compared with those admitted in preactive labor. More research is needed to determine if progressive changes in inflammatory biomarkers might be a useful adjunct to improving the assessment of labor progression and determining the optimal timing of labor admission., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: The timing of when a woman is admitted to the hospital for labor care following spontaneous contraction onset may be among the most important decisions that labor attendants make because it can influence care patterns and birth outcomes. The aims of this study were to estimate the percentage of low-risk, nulliparous women at term who are admitted to labor units prior to active labor and to evaluate the effects of the timing of admission (ie, preactive vs active labor) on labor interventions and mode of birth., Methods: Data from low-risk, nulliparous women with spontaneous labor onset at term gestation were merged from 2 prospective studies conducted at 3 large Midwestern hospitals. Baseline characteristics, labor interventions, and outcomes were compared between groups using Fisher's exact and Mann-Whitney U tests, as appropriate. Likelihoods for oxytocin augmentation, amniotomy, and cesarean birth were assessed by logistic regression., Results: Of the sample of 216 low-risk nulliparous women, 114 (52.8%) were admitted in preactive labor and 102 (47.2%) were admitted in active labor. Women who were admitted in preactive labor were more likely to undergo oxytocin augmentation (84.2% and 45.1%, respectively; odds ratio [OR], 6.5; 95% confidence interval [CI], 3.43-12.27) but not amniotomy (55.3% and 61.8%, respectively; OR, 0.8; 95% CI, 0.44-1.32) when compared to women admitted in active labor. The likelihood of cesarean birth was higher for women admitted before active labor onset (15.8% and 6.9%, respectively; OR, 2.6; 95% CI, 1.02-6.37)., Discussion: Many low-risk nulliparous women with regular, spontaneous uterine contractions are admitted to labor units before active labor onset, which increases their likelihood of receiving oxytocin and giving birth via cesarean. An evidence-based, standardized approach for labor admission decision making is recommended to decrease inadvertent admissions of women in preactive labor. When active labor cannot be diagnosed with relative certainty, observation before admission to the birthing unit is warranted., (© 2014 by the American College of Nurse-Midwives.)

A 22,500-Da antigen apparently specific to Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum has been identified by Western immunoblotting. By use of a dot immunoassay, this antigen was found in the urine of 64% of patients with AIDS and disseminated M. avium disease. It was not found in the urine of healthy control subjects. Detection of antigenuria might provide the basis for rapid diagnosis of M. avium disease in patients with AIDS.

The 39-43 residue polypeptide (amyloid beta protein, beta A4) deposited as amyloid in Alzheimer's disease (AD) is derived from a set of 695-770 residue precursors referred to as the amyloid beta A4 protein precursor (beta APP). In each of the 695, 751, and 770 residue precursors, the 43 residue beta A4 is an internal peptide that begins 99 residues from the COOH-terminus of the beta APP. Each holoform is normally cleaved within the beta A4 to produce a large secreted derivative as well as a small membrane associated fragment. Neither of these derivatives can produce amyloid because neither contains the entire beta A4 peptide. In this study, we employ cells stably transfected with full length beta APP695, beta APP751, or beta APP770 expression constructs to show that phorbol ester activation of protein kinase C substantially increases the production of secreted forms from each isoform. By increasing processing of beta APP in the secretory pathway, PKC phosphorylation may help to prevent amyloid deposition.