Exposure to prenatal stressors and infant autonomic nervous system regulation of stress.

OBJECTIVES: The purpose of this study was to determine the relationship between fetal exposure to maternal prenatal stressors and infant parasympathetic (PNS) and sympathetic (SNS) nervous function at 3 timepoints across the first year of life. BACKGROUND: Autonomic nervous system impairments may mediate associations between gestational exposure to stressors and later infant health problems. Heart rate variability (HRV) provides a sensitive index of PNS and SNS function. However, no studies have assessed longitudinal associations between prenatal stressors and infant HRV measures of both PNS and SNS over the first year of life. METHODS: During the third trimester of pregnancy, 233 women completed measures of life stressors and depression. At 1, 6 and 12 months of age, a stressor protocol was administered while infant electrocardiographic (ECG) data were collected from a baseline through a post-stressor period. HRV measures of PNS and SNS activity (HF, LF, LF/HF ratio) were generated from ECG data. We used multilevel regression to examine the aims, adjusting for maternal depression and neonatal morbidity. RESULTS: There were no associations between prenatal stressors and any baseline or reactivity HRV metric over the infant's first year of life. However, exposure to more stressors was associated with lower post-stressor LF HRV at both 6 (ß = -.44, p = .001) and 12 (ß = -.37, p = .005) months of age. CONCLUSIONS: Findings suggest potential alterations in development of the vagally mediated baroreflex function as a result of exposure to prenatal stressors, with implications for the infants' ability to generate a resilient recovery in response to stressors.

Prenatal exposure to social adversity and infant cortisol in the first year of life.

Exposure to social adversity has been associated with cortisol dysregulation during pregnancy and in later childhood; less is known about how prenatal exposure to social stressors affects postnatal cortisol of infants. In a secondary analysis of data from a longitudinal study, we tested whether a pregnant woman's reports of social adversity during the third trimester were associated with their infant's resting cortisol at 1, 6, and 12 months postnatal. Our hypothesis was that prenatal exposure to social adversity would be associated with elevation of infants' cortisol. Measures included prenatal survey reports of social stressors and economic hardship, and resting cortisol levels determined from infant saliva samples acquired at each postnatal timepoint. Data were analyzed using linear mixed effects models. The final sample included 189 women and their infants (46.56% assigned female sex at birth). Prenatal economic hardship was significantly associated with infant cortisol at 6 months postnatal; reports of social stressors were not significantly associated with cortisol at any time point. Factors associated with hardship, such as psychological distress or nutritional deficiencies, may alter fetal HPA axis development, resulting in elevated infant cortisol levels. Developmental changes unique to 6 months of age may explain effects at this timepoint. More work is needed to better comprehend the complex pre- and post-natal physiologic and behavioral factors that affect infant HPA axis development and function, and the modifying role of environmental exposures.

Postpartum symptoms of anxiety, depression and stress: differential relationships to women's cortisol profiles.

PURPOSE: Women are at high risk of stress, anxiety, and depression during the postpartum but the ways in which these different types of psychological distress are related to cortisol regulation is not clear. We examined the distinct association of each type of distress with women's average cortisol level, cortisol awakening response (CAR), cortisol decline across the day (diurnal slope), and overall amount of cortisol secretion across the day (AUCG). METHODS: At 6 months postpartum, a diverse group of 58 women completed measures of depression, anxiety, perceived stress, and life stressors. Each woman provided 4 salivary samples for cortisol assay from waking to bedtime on each of 2 consecutive days. Linear regressions were used to examine associations of stress, anxiety and depression to each of the 4 cortisol measures, controlling for number of stressful life events. RESULTS: Depressive symptoms were associated with less of a rise in the CAR (ß = -.46, p = 0.01), steeper diurnal slope (ß = .51, p = 0.006), and higher average cortisol level (ß = .42, p = .01). Women who met the clinical cutoff for an anxiety disorder had lower overall cortisol output (ß = -.29, p = 0.03). Stress was not related to any cortisol metric. CONCLUSIONS: Findings suggest that stress is less associated with cortisol alterations in the postpartum than are more severe types of psychological distress. Anxiety and depression may have distinct and opposite profiles of cortisol dysregulation. Results indicate that mental health assessment is critical even in the later postpartum so that interventions can be initiated to reduce emotional suffering and the risk of impaired cortisol regulation.

Engaging adolescents in research: Home self-collection of biological samples and health questionnaires.

Adolescent health research with biomarker data collection is limited due to difficulties in recruiting and engaging this age group. Thus, successful recruitment, engagement, and retention of adolescents in translational research are necessary to elucidate factors influencing mental and physical health conditions, uncover novel biomarkers, and expand prevention and treatment options. This paper describes strategies for effective recruitment and retention of adolescents in a research study, using a project examining depressive symptoms and the microbiome to illustrate these approaches. This cross-sectional study collected electronic self-reported survey data and self-collected biospecimens (stool and salivary samples) from adolescents 13-19 years old. All but two participants completed the questionnaires, with few missing responses. 94% provided at least one salivary sample and 89% supplied a stool sample. Participants were able to adhere to the study instructions. Using a participant-centered approach, our study successfully recruited and engaged the targeted 90 participants in self-collection of electronic survey data and biospecimens. Successful strategies of recruitment and retention included: 1) on-site clinic recruitment by research team, 2) active involvement of parents as appropriate, 3) use of electronic surveys and self-collection of biospecimens to foster control and ease of participation while addressing privacy concerns, 4) noninvasive collection of data on biospecimen, 5) frequent texting to communicate with participants, 6) flexibility in the pickup and transferring of biospecimens to accommodate adolescent schedules, 7) developmentally appropriate research, 8) participant reimbursement, and 9) sensitivity toward discussing stool sample materials. As a result of these strategies, adolescent participation in the research proved feasible.

Factors associated with mobile medical clinic use: a retrospective cohort study.

BACKGROUND: Mobile medical clinics have been used for decades to provide primary and preventive care to underserved populations. While several studies have examined their return on investment and impact on chronic disease management outcomes in the Mid-Atlantic and East Coast regions of the United States, little is known about the characteristics and clinical outcomes of adults who receive care aboard mobile clinics on the West Coast region. Guided by the Anderson Behavioral Model, this study describes the predisposing, enabling, and need factors associated with mobile medical clinic use among mobile medical clinic patients in Southern California and examines the relationship between mobile clinic utilization and presence and control of diabetes and hypertension. METHODS: We conducted a retrospective cohort study of 411 adults who received care in four mobile clinic locations in Southern California from January 1, 2018, to December 31, 2019. Data were collected from patient charts on predisposing (e.g., sex, race, age), enabling (e.g., insurance and housing status), and need (e.g., chronic illness) factors based on Andersen's Behavioral Model. Zero-truncated negative binomial regression was used to examine the association of chronic illness (hypertension and diabetes) with number of clinic visits, accounting for potential confounding factors. RESULTS: Over the course of the 2-year study period, 411 patients made 1790 visits to the mobile medical clinic. The majority of patients were female (68%), Hispanic (78%), married (47%), with a mean age of 50 (SD = 11). Forty-four percent had hypertension and 29% had diabetes. Frequency of mobile clinic utilization was significantly associated with chronic illness. Patients with hypertension and diabetes had 1.22 and 1.61 times the rate of mobile medical clinic visit than those without those conditions, respectively (IRR = 1.61, 95% CI, 1.36-1.92; 1.22, 95% CI, 1.02-1.45). CONCLUSIONS: Mobile clinics serve as an important system of health care delivery, especially for adults with uncontrolled diabetes and hypertension.

Societal stigma and mistreatment in healthcare among gender minority people: a cross-sectional study.

BACKGROUND: Gender minority (GM; individuals whose gender is not aligned with that traditionally associated with the sex that was assigned to them at birth) people have widely reported mistreatment in healthcare settings. Mistreatment is enacted by individuals within society who hold stigmatizing beliefs. However, the relationship between healthcare mistreatment and societal stigma (i.e., the degree to which society disapproves of GM people) is unclear and not measured consistently. METHODS: We analyzed data from 2,031 GM participants in The Population Research in Identity and Disparities for Equality (PRIDE) Study's 2019 Annual Questionnaire to determine whether societal stigma was associated with participants' past-year reports of mistreatment (defined as denial of healthcare services and/or lower quality care) in medical or mental healthcare settings. We created a proxy measure of societal stigma by incorporating variables validated in existing literature. Participants reported whether they had experienced mistreatment in medical and mental health settings independently. RESULTS: Healthcare denial and/or lower quality care during the past year was reported by 18.8% of our sample for medical settings and 12.5% for mental health settings. We found no associations between the societal stigma variables and past-year reports of healthcare denial and/or lower quality care in medical or mental healthcare settings. CONCLUSIONS: Although a high proportion of GM people reported past-year healthcare mistreatment in both medical and mental health settings, mistreatment had no relationship with societal stigma. Factors other than societal stigma may be more important predictors of healthcare mistreatment, such as healthcare workers' knowledge of and attitudes toward GM people. However, other measures of societal stigma, or different types of mistreatment, may show stronger associations. Identifying key factors that contribute to mistreatment can serve as targets for intervention in communities and healthcare settings.

Evidence for multi-copy Mega-NUMTs in the human genome.

The maternal mode of mitochondrial DNA (mtDNA) inheritance is central to human genetics. Recently, evidence for bi-parental inheritance of mtDNA was claimed for individuals of three pedigrees that suffered mitochondrial disorders. We sequenced mtDNA using both direct Sanger and Massively Parallel Sequencing in several tissues of eleven maternally related and other affiliated healthy individuals of a family pedigree and observed mixed mitotypes in eight individuals. Cells without nuclear DNA, i.e. thrombocytes and hair shafts, only showed the mitotype of haplogroup (hg) V. Skin biopsies were prepared to generate ρ° cells void of mtDNA, sequencing of which resulted in a hg U4c1 mitotype. The position of the Mega-NUMT sequence was determined by fluorescence in situ hybridization and two different quantitative PCR assays were used to determine the number of contributing mtDNA copies. Thus, evidence for the presence of repetitive, full mitogenome Mega-NUMTs matching haplogroup U4c1 in various tissues of eight maternally related individuals was provided. Multi-copy Mega-NUMTs mimic mixtures of mtDNA that cannot be experimentally avoided and thus may appear in diverse fields of mtDNA research and diagnostics. We demonstrate that hair shaft mtDNA sequencing provides a simple but reliable approach to exclude NUMTs as source of misleading results.

Stressors in health care and their association to symptoms experienced by gender diverse people.

OBJECTIVES: Many individuals whose gender does not align with the sex they were assigned at birth (gender diverse [GD] people) report stressful health care encounters. We examined the relationship of these stressors to symptoms of emotional distress and impaired physical functioning among GD people. STUDY DESIGN: This study was conducted using a cross-sectional design with data from the 2015 United States Transgender Survey. METHODS: Composite metrics of health care stressors and physical impairments were developed, and the Kessler Psychological Distress Scale (K-6) provided a measure of emotional distress. Linear and logistic regression were used to analyze the aims. RESULTS: A total of 22,705 participants from diverse gender identity subgroups were included. Participants who experienced at least one stressor in health care during the past 12 months had more symptoms of emotional distress (ß = 0.14, P < .001) and 85% greater odds of having a physical impairment (odds ratio = 1.85, P < .001). Transgender men exposed to stressors were more likely than transgender women to experience emotional distress and have a physical impairment, with other gender identity subgroups reporting less distress. Black participants exposed to stressful encounters reported more symptoms of emotional distress than White participants. CONCLUSIONS: The results suggest that stressful encounters in health care are associated with symptoms of emotional distress and greater odds of physical impairment for GD people, with transgender men and Black individuals being at greatest risk of emotional distress. The findings indicate the need for assessment of factors that contribute to discriminatory or biased health care for GD people, education of health care workers, and support for GD people to reduce their risk of stressor-related symptoms.

Symptoms of maternal psychological distress during pregnancy: sex-specific effects for neonatal morbidity.

OBJECTIVES: Maternal psychological distress during pregnancy has been associated with preterm birth. However, little is known about the relationship of a woman's psychological symptoms during pregnancy to the infant's morbidity at birth or any differential effects of these symptoms on female vs. male fetuses. Our research aims addressed these gaps. METHODS: A total of 186 women were enrolled between 24 and 34 weeks gestation when demographic information was acquired and they completed the Brief Symptom Inventory to measure psychological distress. Data on gestational age at birth, fetal sex, and neonatal morbidity was extracted from the medical record. To control for their effects, obstetric complications were also identified. Multiple linear regressions were computed to examine the aims, including interaction terms to measure moderating effects of fetal sex. RESULTS: Symptoms of maternal psychological distress were a significant predictor of neonatal morbidity but were not associated with gestational age. The interaction between symptom distress and fetal/infant sex was also significant for neonatal morbidity but not for gestational age. For boys, high levels of maternal symptom distress during pregnancy were associated with neonatal resuscitation, ventilatory assistance, and infection. Maternal distress was not associated with neonatal morbidity for girls. CONCLUSIONS: The male fetus may be more sensitive to effects of mothers' psychological symptoms than the female fetus. Further research is needed to confirm our findings and identify potential biological mechanisms that may be responsible for these sex differences. Findings suggest the importance of symptom screening and early intervention to reduce maternal distress and risk of neonatal morbidity.

The relationship between pharmacist emotional intelligence, occupational stress, job performance, and psychological affective well-being.

BACKGROUND: Emotional intelligence (EI) is known to improve teamwork, communication, and organizational commitment. The role of EI has also influenced pharmacists' ability to empathize, control emotions, and actively listen. Although EI's impact on work-related components, including occupational stress, job performance, and psychological affective well-being, has been studied, there are no data specific to the practice of pharmacy. OBJECTIVE: The primary objective of this study was to determine whether a significant correlation exists between pharmacist EI and work-related components. METHODS: A voluntary Qualtrics survey (Qualtrics, Provo, UT) was distributed electronically to all active pharmacists licensed by the Florida Board of Pharmacy, which included questions from valid and reliable assessment tools. Spearman correlations were used to examine the association between EI facets and dependent variables of occupational stress, job performance, and psychological affective well-being. A subanalysis was conducted to evaluate demographic data. Statistical significance was set at P < 0.05 for all tests. Incomplete survey responses were included in the analysis. RESULTS: A total of 942 responses were received and analyzed. Most of the respondents were aged 44 years or younger (42.5%), female (46.9%), identified as Caucasian (52.8%), and worked 31-40 hours weekly (20.6%). Most of the respondents reported a primary employment setting within community (29.3%) or hospital (18.6%) pharmacy. Higher EI correlated with lower levels of occupational stress, higher job performance, and higher psychological affective well-being. Secondary outcomes reported increased stress for both females and those practicing in the community setting; hospital-based pharmacists reported higher job performance and psychological affective well-being. Stress decreased with both age and years of experience. CONCLUSION: Higher EI may support overall wellness for pharmacists on the basis of the results of this study. Additional evaluation of demographic data, including practice settings, and a more robust cohort of participants would provide more insight in this area.

Molecular Mechanism of Sirtuin 1 Modulation by the AROS Protein.

The protein lysine deacylases of the NAD+-dependent Sirtuin family contribute to metabolic regulation, stress responses, and aging processes, and the human Sirtuin isoforms, Sirt1-7, are considered drug targets for aging-related diseases. The nuclear isoform Sirt1 deacetylates histones and transcription factors to regulate, e.g., metabolic adaptations and circadian mechanisms, and it is used as a therapeutic target for Huntington's disease and psoriasis. Sirt1 is regulated through a multitude of mechanisms, including the interaction with regulatory proteins such as the inhibitors Tat and Dbc1 or the activator AROS. Here, we describe a molecular characterization of AROS and how it regulates Sirt1. We find that AROS is a partly intrinsically disordered protein (IDP) that inhibits rather than activates Sirt1. A biochemical characterization of the interaction including binding and stability assays, NMR spectroscopy, mass spectrometry, and a crystal structure of Sirtuin/AROS peptide complex reveal that AROS acts as a competitive inhibitor, through binding to the Sirt1 substrate peptide site. Our results provide molecular insights in the physiological regulation of Sirt1 by a regulator protein and suggest the peptide site as an opportunity for Sirt1-targeted drug development.

Psychological and physiological stress and burnout among maternity providers in a rural county in Kenya: individual and situational predictors.

BACKGROUND: Stress and burnout among healthcare workers has been recognized as a global crisis needing urgent attention. Yet few studies have examined stress and burnout among healthcare providers in sub-Saharan Africa, and even fewer among maternity providers who work under very stressful conditions. To address these gaps, we examined self-reported stress and burnout levels as well as stress-related physiologic measures of these providers, along with their potential predictors. METHODS: Participants included 101 maternity providers (62 nurses/midwives, 16 clinical officers/doctors, and 23 support staff) in western Kenya. Respondents completed Cohen's Perceived Stress Scale, the Shirom-Melamed Burnout scale, and other sociodemographic, health, and work-related items. We also collected data on heart rate variability (HRV) and hair cortisol levels to assess stress-related physiologic responses to acute and chronic stress respectively. Multilevel linear regression models were computed to examine individual and work-related factors associated with stress, burnout, HRV, and cortisol level. RESULTS: 85% of providers reported moderate stress and 11.5% high stress. 65% experienced low burnout and 19.6% high burnout. Average HRV (measured as the root mean square of differences in intervals between successive heart beats: RMSSD) was 60.5 (SD = 33.0) and mean cortisol was mean cortisol was 44.2 pg/mg (SD = 60.88). Greater satisfaction with life accomplishments was associated with reduced stress (ß = - 2.83; CI = -5.47; - 0.18), while motivation to work excessively (over commitment) was associated with both increased stress (ß = 0.61 CI: 0.19, 1.03) and burnout (ß = 2.05, CI = 0.91, 3.19). Female providers had higher burnout scores compared to male providers. Support staff had higher HRV than other providers and providers under 30 years of age had higher HRV than those 30 and above. Although no association between cortisol and any predictor was statistically significant, the direction of associations was consistent with those found for stress and burnout. CONCLUSIONS: Most providers experienced moderate to high levels of stress and burnout. Individuals who were more driven to work excessively were particularly at risk for higher stress and burnout. Higher HRV of support staff and providers under age 30 suggest their more adaptive autonomic nervous system response to stress. Given its impact on provider wellbeing and quality of care, interventions to help providers manage stress are critical.

Maternal depressive symptoms, poverty, and young motherhood increase the odds of early depressive and anxiety disorders for children born prematurely.

Children born preterm, compared to term, are at risk for behavioral problems. However, the prevalence and predictors of internalizing disorders among children born preterm are unclear. The purpose of this study was to identify the prevalence of depressive and anxiety disorders at 2 years of age among children born preterm and determine the extent to which poverty, maternal depressive symptoms, or young motherhood increase the likelihood of these disorders. Mothers and their infants (N = 105) were recruited from two neonatal intensive care units affiliated with a major U.S. university. A sociodemographic questionnaire, the Patient Health Questionnaire-9, and the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition scale scores from the Preschool Child Behavior Checklist were used to measure primary variables. We examined mothers' family satisfaction and quality of caregiving as well as children's degree of prematurity, morbidity, gender, cognitive functioning, and motor function as covariates. Fifteen percent of children met criteria for an anxiety disorder and another 15% for depression. Maternal depressive symptoms increased the odds of children developing both anxiety and depression, whereas young motherhood was associated with child anxiety and poverty with child depression. Results indicate the need for mental health assessment of children born preterm during their first 2 years of life and the importance of early therapeutic and tangible support to vulnerable mothers and children.

Los niños nacidos prematuramente, comparados con los no prematuros, están bajo riesgo de problemas de comportamiento. Sin embargo, la prevalencia y factores de predicción de la internalización de los trastornos entre niños nacidos prematuramente no están claras. El propósito de este estudio fue identificar la prevalencia de trastornos depresivos y de ansiedad a los 2 años de edad entre niños nacidos prematuramente y determinar hasta dónde la pobreza, los síntomas depresivos maternos o la maternidad joven aumentan la probabilidad de estos trastornos. A las madres y sus infantes (N = 105) se les reclutó de 2 unidades de cuidados intensivos neonatales afiliadas con una importante universidad de los Estados Unidos. Un cuestionario sociodemográfico, el PHQ-9 y los puntajes de la escala DSM-5 de la Lista de Verificación de la Conducta Prescolar del Niño se usaron para medir las variables primarias. Examinamos la satisfacción familiar y la calidad de la prestación del cuidado de las madres, así como el grado de prematuridad, la morbilidad, el género, el funcionamiento cognitivo, y la función motora de los niños como covariables. Quince por ciento de los niños cumplía los criterios para un trastorno de ansiedad y otro 15% para depresión. Los síntomas depresivos maternos aumentaron las posibilidades de que los niños desarrollaran tanto ansiedad como depresión, mientras que la maternidad joven se asoció con la ansiedad del niño y la pobreza con la depresión del niño. Los resultados indican la necesidad de evaluar la salud mental de niños nacidos prematuramente durante sus dos primeros años de vida y la importancia del temprano apoyo terapéutico y tangible a las madres y niños vulnerables.

Les enfants nés prématurés, comparés aux enfants né à terme, sont à risque de problèmes de comportement. Cependant, la prévalence et les prédicteurs de troubles d'intériorisation chez les enfants nés avant-terme ne sont pas claires. Le but de cette étude était d'identifier la prévalence des troubles dépressifs et des troubles d'anxiété à l'âge de 2 ans chez des enfants nés avant terme et de déterminer dans quelle mesure la pauvreté, les symptômes dépressifs maternels ou le statue de jeune mère augmente la probablbilité de ces troubles. Des mères et leurs nourrissons (N = 105) ont été recrutées dans deux services de réanimation néonatale dans une CHU américaine importante. Un questionnaie sociodémographique, le PHQ-9 et les scores de l'échelle DSM-5 de la Checklist de Comportement de l'Enfant d'Âge Préscolaire ont été utilisés pour mesurer les variables primaires. Nous avons examiné la satisfaction familiale des mères et la qualité du mode de soin ainsi que le degré de prématurité des enfants, leur morbidité, le genre, le fonctionnement cognitif et la fonction motrice comme covariants. Quinze pourcent des enfants ont rempli les critères pour un trouble de l'anxiété et un autre 15% pour la dépression. Les symptômes dépressifs maternels ont augmenté les chances que les enfants développent à la fois de l'anxiété et de la dépression, alors que le fait d'être une jeune mère était lié à l'anxiété de l'enfant et la pauvreté avec la dépression de l'enfant. Les résultats indiquent le besoin d'une évaluation de la santé mentale des enfants nés avant terme durant les deux premières années de leur vie et l'importance d'un soutien thérapeutique précoce et tangile pour les mères et les enfants vulnérables.

Association of differential symptoms of stress to hair cortisol and cortisone concentrations among pregnant women in Kenya.

Objectives: The purpose of this study was to characterize the stress experienced by pregnant women in Kenya and assess the relationship between perceived stress and stress-related biomarkers of cortisol and cortisone.Background: Kenyan women are exposed to multiple stressors that may result in chronic stress. However, antenatal stress has not been examined and characterized in Kenya; nor has the relationship between pregnant women's self-reported stress and stress biomarkers been established.Methods: One hundred and fifty women were recruited between 22 and 28 weeks gestation. Participants completed the Perceived Stress Scale (PSS) and a sociodemographic questionnaire. Hair samples were obtained for analysis of cortisol and cortisone. Factor analysis was used to extract unique clusters of stress symptoms from items in the PSS. Regression models were computed to examine relationships of stress to cortisone and cortisol, controlling for obstetric risk.Results: Mean age of the women was 25 years (SD = 5, ±16-41). Their degree of perceived stress and cortisol/cortisone concentrations both indicated moderate levels of stress. There was no association between general perceived stress and either hair cortisol or cortisone. However, factor analysis of the PSS identified three clusters of stress symptoms and one cluster - a woman's negative frame of mind regarding life and inefficacy in handling its problems - was associated with higher levels of cortisone (ß= -.231, p = 0.011).Conclusions: Specific stress symptoms may have unique relationships to specific biomarkers and be more useful in assessment than general perceived stress. Assays of both hair cortisol and cortisone might enable a more comprehensive assessment of glucocorticoid activity and better prediction of health risks from stress.Lay summaryUnderstanding stress among rural pregnant Kenyan women may help in addressing risks during pregnancy that lead to adverse birth outcomes. Findings suggest that a woman's tendency to think negatively about life and to doubt her ability to handle life's problems are symptoms of stress that may contribute to higher levels of stress hormones. Assessing women's specific symptoms of stress and different stress hormones during pregnancy may more effectively identify women who need intervention to reduce their health risk.

Early life adversity and depressive symptoms predict cortisol in pregnancy.

Evidence suggests that exposure to early life adversity (ELA) programs the hypothalamic-pituitary-adrenal (HPA) axis to influence responses to later adversity and predisposes women to depression. However, few studies have examined whether ELA moderates the HPA cortisol response to adulthood adversity and depressive symptoms in pregnant women. The aims of this study were to determine (a) whether ELA, adulthood adversity, and depressive symptoms differentially predict patterns of cortisol and (b) whether ELA moderates the relationship of adulthood adversity or depressive symptoms to cortisol. This was a descriptive, cross-sectional study of pregnant women (N = 58, mean = 26.5 weeks gestation). Participants completed the Stress and Adversity Inventory and Edinburgh Depression Scale and collected salivary cortisol five times per day for 3 days to assess cortisol awakening response (CAR), diurnal cortisol slope, and cortisol area under the curve (AUC). ELA predicted a larger CAR, while depressive symptoms predicted a blunted CAR and higher cortisol AUC. Adulthood adversity predicted a blunted CAR and steeper diurnal slope, but only in women with high ELA. ELA also moderated the effect of depressive symptoms on diurnal slope. Early adversity and depressive symptoms appear to have significant effects on the HPA axis during pregnancy, with early adversity also moderating effects of depressive symptoms and adulthood adversity on cortisol regulation. Early adversity may be an important factor in identifying unique HPA phenotypes and risk for HPA axis dysregulation in pregnancy.

The prevalence, predictors and outcomes of guideline-directed medical therapy in patients with acute myocardial infarction undergoing PCI, an analysis from the PROMETHEUS registry.

OBJECTIVES: To investigate the prevalence, predictors and associations between guideline-directed medical therapy (GDMT) and clinical outcomes in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI) from eight academic centers in the United States. BACKGROUND: Evidence for GDMT in patients with AMI comes from randomized controlled trials. The use of GDMT in clinical practice is unknown in this setting. METHODS: PROMETHEUS is a multicenter observational registry comprising 19,914 patients with acute coronary syndrome (ACS) undergoing PCI. Patients with AMI were divided into two groups based on the prescription of GDMT or not (non-GDMT) at discharge. GDMT was defined according to American College of Cardiology/American Heart Association (ACC/AHA) class I recommendations, specifically, dual antiplatelet therapy, statin and beta-blocker for all AMI patients, and additional ACEI/ARB in patients with left ventricular ejection fraction (LVEF) less than 40%, hypertension, diabetes mellitus (DM) or chronic kidney disease (CKD). The primary endpoint was major adverse cardiovascular events (MACE) defined as a composite of all-cause death, MI, stroke or unplanned target vessel revascularization (TVR) at 1 year. RESULTS: Out of 4,834 patients with AMI, 3,356 (69.4%) patients were discharged on GDMT. Patients receiving GDMT were more often younger and male. Compared with non-GDMT patients, GDMT patients had a significantly lower frequency of comorbidities. Predictors of greater GDMT prescription at discharge were ST-segment elevation myocardial infarction (STEMI), and increased body mass index (BMI), whereas hypertension, prior PCI, anemia and CKD were associated with less GDMT prescription. At 1 year, the use of GDMT was associated with a significantly lower incidence of MACE (13.7% vs. 22.5%; adjusted HR 0.68; 95%CI 0.58-0.80; P < 0.001), death (3.7% vs. 9.4%; adjusted HR 0.61; 95%CI 0.46-0.80; P < 0.001), and unplanned TVR (8.4% vs. 11.3%; adjusted HR 0.76; 95%CI 0.61-0.96; P = 0.020). However, there were no significant differences in the incidence of MI (4.3% vs. 7.0%; adjusted HR 0.75; 95%CI 0.56-1.01; P = 0.056), stroke (1.5% vs. 2.0%; adjusted HR 0.79; 95%CI 0.47-1.34; P = 0.384) between the two groups. CONCLUSION: In a contemporary practice setting in the United States, GDMT was utilized in just over two-thirds of AMI patients undergoing PCI. Predictors of GDMT prescription at discharge included STEMI, BMI and absence of hypertension, CKD, anemia or prior PCI. Use of GDMT was associated with significantly lower risk of 1-year MACE and mortality.

Use of prasugrel and clinical outcomes in African-American patients treated with percutaneous coronary intervention for acute coronary syndromes.

OBJECTIVE: To investigate the use of prasugrel after percutaneous coronary intervention (PCI) in African American (AA) patients presenting with acute coronary syndrome (ACS). BACKGROUND: AA patients are at higher risk for adverse cardiovascular outcomes after PCI and may derive greater benefit from the use of potent antiplatelet therapy. METHODS: Using the multicenter PROMETHEUS observational registry of ACS patients treated with PCI, we grouped patients by self-reported AA or other races. Clinical outcomes at 90-day and 1-year included non-fatal myocardial infarction (MI), major adverse cardiac events (composite of death, MI, stroke, or unplanned revascularization) and major bleeding. RESULTS: The study population included 2,125 (11%) AA and 17,707 (89%) non-AA patients. AA patients were younger, more often female (46% vs. 30%) with a higher prevalence of diabetes mellitus, chronic kidney disease, and prior coronary intervention than non-AA patients. Although AA patients more often presented with troponin (+) ACS, prasugrel use was much less common in AA vs. non-AA (11.9% vs. 21.4%, respectively, P = 0.001). In addition, the use of prasugrel increased with the severity of presentation in non-AA but not in AA patients. Multivariable logistic regression showed AA race was an independent predictor of reduced use of prasugrel (0.42 [0.37-0.49], P < 0.0001). AA race was independently associated with a significantly higher risk of MI at 90-days and 1 year after PCI. CONCLUSIONS: Despite higher risk clinical presentation and worse 1-year ischemic outcomes, AA race was an independent predictor of lower prasugrel prescription in a contemporary population of ACS patients undergoing PCI.

Associations between use of prasugrel vs clopidogrel and outcomes by type of acute coronary syndrome: an analysis from the PROMETHEUS registry.

We sought to investigate the utilization of prasugrel and its association with outcomes relative to clopidogrel in three typical subgroups of ACS in a real-world setting. Prasugrel is superior to clopidogrel for reducing risk of ischemic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), but is associated with an increased risk of bleeding complications. PROMETHEUS was a retrospective multicenter observational study of 19,913 ACS patients undergoing PCI from 8 centers in the United States between 2010 and 2013. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause mortality, myocardial infarction, stroke or unplanned revascularization. The study cohort included 3285 (16.5%) patients with ST-segment elevation myocardial infarction (STEMI), 5412 (27.2%) patients with NSTEMI and 11,216 (56.3%) patients with unstable angina (UA). The frequency of prasugrel use at discharge was highest in STEMI and lowest in UA patients, 27.3% versus 22.2% versus 18.9% (p < 0.001). Use of prasugrel vs clopidogrel was associated with a lower rate of MACE in STEMI, NSTEMI, or UA at 1 year, but the differences were attenuated for all groups except for patients with UA (adjusted HR 0.81, 95% CI 0.69-0.94, p = 0.006) after propensity adjusted analysis. After adjustment, there was no difference in bleeding risk between prasugrel and clopidogrel for all groups at 1 year. STEMI patients were more likely to receive prasugrel compared to NSTEMI and UA patients. Prasugrel was associated with reduced adverse outcomes compared with clopidogrel in unadjusted analyses, findings that were largely attenuated upon adjustment and suggest preferential use of prasugrel in low vs high risk patients.

Systematic review: Self-rated health of Arab immigrants in the United States.

PURPOSE: A systematic review was conducted to understand self-rated health (SRH) of Arab immigrants in the United States (U.S.). BACKGROUND: Arab immigrants are one of the fastest growing populations in the United States. There is some evidence that Arab immigrants face health issues including low SRH. However, no study has been done to synthesize research on SRH of Arab immigrants. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to guide this review. A search was conducted on seven databases. RESULTS: Six studies met the systematic review criteria. The available evidence indicated that rates of fair/poor SRH among Arab immigrants ranged between 4.66% and 41%. Arabic-speaking immigrants, women, older immigrants, and socioeconomically disadvantaged immigrants had the highest rates of fair/poor SRH. IMPLICATIONS: Health care providers need to assess patient's SRH and identify barriers to optimal health and health practices related to SRH of Arab immigrants.

"Thoughts Can Kill You": Characterization of Mental Health Symptoms by Ugandan Grandparent-Caregivers in the HIV/AIDS Era.

Studies of caregiving provided to HIV/AIDS orphans by sub-Saharan African grandparents have found that it has physical, financial, and emotional consequences. Our study extended this research by identifying and characterizing the symptoms experienced by Ugandan grandparent- caregivers, particularly as related to the caregiving role, loss and grief. Grounded theory methodology was used to conduct and analyze audio-recorded, semi-structured interviews with 32 grandparents. Findings revealed a cluster of biopsychosocial distress symptoms, especially anguish (driven by traumatic anxiety and disbelief), depression, and somatic symptoms that were linked primarily to psychological distress. The impact of cultural practices and beliefs on these symptoms was also identified. Results have implications for public health, research, and policy changes needed to alleviate symptoms of biopsychosocial distress among Uganda grandparent-caregivers.