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Context: Androgen excess (AE)-related symptoms can vary widely and may appear across the life course., Objective: We assessed the prevalence of signs of potential AE and heterogeneity by demographic/health characteristics., Methods: We used data of 24 435 participants who consented and enrolled during November 2019 to December 2022 in a US digital cohort to evaluate the prevalence and heterogeneity of self-reported signs of potential AE: possible hirsutism (having thick coarse hair on ≥4 of 8 body locations), hair level on the chin, hair loss on top of the head, and moderate to severe acne., Results: The prevalence of possible hirsutism, having several/a lot of hair on the chin, significantly reduced hair/visible scalp on top of the head, and moderate to severe acne were 6.9%, 12.6%, 1.7%, and 31.8%, respectively. While possible hirsutism and moderate to severe acne decreased with age (range: 18-86 years), hair on the chin and hair loss on the head increased with age. Participants who self-identified as Hispanic or South Asian reported a higher prevalence of possible hirsutism (11.2%, 16.9%, vs 6.3% among non-Hispanic White participants). Participants with higher body mass index had a higher prevalence of possible hirsutism. Moderate to severe acne was more common among those with polycystic ovary syndrome. Possible hirsutism and hair loss were less common among participants using hormones for contraception., Conclusion: In this large cohort, signs of potential AE varied by demographic and health factors. These results could provide a new understanding of how potential AE may appear differently in diverse groups, informing future work to develop more inclusive evaluation at a population level., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: While it is known that vital signs and behaviors change during pregnancy, there is limited data on timing and scale of changes for sensor-derived health metrics across pregnancy and postpartum. Wearable technology provides an opportunity to understand physiologic and behavioral changes across pregnancy with greater detail, more frequent measurements, and improved accuracy. The aim of this study is to describe changes in physiologic and behavioral sensor-based health metrics during pregnancy and postpartum in the Apple Women's Health Study (AWHS) and their relationship to demographic factors., Methods: The Apple Women's Health Study is a digital, longitudinal, observational study that includes U.S. residents with an iPhone and Apple Watch. We evaluated changes from pre-pregnancy through delivery and postpartum for sensor-derived health metrics. Minimum required data samples per day, week and overall were data element specific, and included 12 weeks prior to pregnancy start, and 12 weeks postpartum for pregnancies lasting between 24 and 43 weeks., Findings: A total of 757 pregnancies from 733 participants were included. Resting heart rate (RHR) increased across pregnancy, peaking in the third trimester (pre-pregnancy median RHR 65.0 beats per minute [BPM], interquartile range [IQR] 60.0-70.2 B.M. third trimester median RHR 75.5 B.M. IQR 69.0-82.0 B.M., with a decrease prior to delivery and nadir postpartum (postpartum median RHR 62.0 B.M. IQR 57.0-66.0 B.M.. Heart rate variability (HRV) decreased from pre-pregnancy (39.9 milliseconds, IQR 32.6-48.3 milliseconds), reaching a nadir in the third trimester (29.9 milliseconds, IQR 25.2-36.4 milliseconds), before rebounding in the last weeks of pregnancy. Measures of activity, such as exercise minutes, stand minutes, step count and Cardio Fitness were all decreased in each trimester compared to pre-pregnancy, with their nadirs postpartum. Total sleep duration increased slightly in early pregnancy (pre-pregnancy 7.2 hours, IQR 6.7-7.7 hours; 1st trimester 7.4 hours, IQR 6.8-7.9 hours), with the lowest sleep duration postpartum (6.2 hours, IQR 5.4-6.8 hours)., Interpretation: Resting heart rate increased during pregnancy, with a decrease prior to delivery, while heart rate variability decreased across pregnancy, with an upward trend before delivery. Behavioral metrics, such as exercise and sleep, showed decreasing trends during and after pregnancy. These data provide a foundation for understanding normal pregnancy physiology and can facilitate hypothesis generation related to physiology, behavior, pregnancy outcomes and disease., (© 2024 The Authors.)

Objective: In this discussion, we build the case for why climate change is an emerging threat to perinatal mental health., Method: A search of current literature on perinatal and maternal mental health and extreme weather events was conducted in PubMed/MEDLINE and Web of Science databases. Only articles focusing on maternal mental health were included in this narrative review., Results: The perinatal period represents a potentially challenging timeframe for women for several reasons. Necessary role adjustments (reprioritization), changes in one's ability to access pre-birth levels (and types) of social support, fluctuating hormones, changes in body shape, and possible complications during pregnancy, childbirth, or postpartum are just a few of the factors that can impact perinatal mental health. Trauma is also a risk factor for negative mood symptoms and can be experienced as the result of many different types of events, including exposure to extreme weather/natural disasters., Conclusion: While the concepts of "eco-anxiety," "climate despair," and "climate anxiety" have garnered attention in the mainstream media, there is little to no discussion of how the climate crisis impacts maternal mental health. This is an important omission as the mother's mental health impacts the family unit as a whole., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Early menarche is associated with adverse health outcomes. Trends toward earlier menarche have been observed in the US, but data remain limited on differences by sociodemographic factors and body mass index (BMI). Time from menarche to cycle regularity is another understudied early-life characteristic with health implications., Objectives: To evaluate the temporal trends and disparities in menarche and time to regularity and explore early-life BMI as a mediator., Design, Setting, and Participants: This ongoing cohort study enrolled participants from an ongoing mobile application-based US cohort from November 14, 2019, to March 20, 2023., Exposures: Birth year (categorized as 1950-1969, 1970-1979, 1980-1989, 1990-1999, and 2000-2005)., Main Outcomes and Measures: Main outcomes were age at menarche and time to regularity, which were self-recalled at enrollment. In addition, early (aged <11 years), very early (aged <9 years), and late (aged ≥16 years) age at menarche was assessed., Results: Among the 71 341 female individuals who were analyzed (mean [SD] age at menarche, 12.2 [1.6] years; 2228 [3.1%] Asian, 3665 [5.1%] non-Hispanic Black, 4918 [6.9%] Hispanic, 49 518 [69.4%] non-Hispanic White, and 8461 [11.9%] other or multiple races or ethnicities), 5223 were born in 1950 to 1969, 12 226 in 1970 to 1979, 22 086 in 1980 to 1989, 23 894 in 1990 to 1999, and 7912 in 2000 to 2005. The mean (SD) age at menarche decreased from 12.5 (1.6) years in 1950 to 1969 to 11.9 (1.5) years in 2000 to 2005. The number of individuals experiencing early menarche increased from 449 (8.6%) to 1223 (15.5%), the number of individuals experiencing very early menarche increased from 31 (0.6%) to 110 (1.4%), and the number of individuals experiencing late menarche decreased from 286 (5.5%) to 137 (1.7%). For 61 932 participants with reported time to regularity, the number reaching regularity within 2 years decreased from 3463 (76.3%) to 4075 (56.0%), and the number not yet in regular cycles increased from 153 (3.4%) to 1375 (18.9%). The magnitude of the trend toward earlier menarche was greater among participants who self-identified as Asian, non-Hispanic Black, or other or multiple races (vs non-Hispanic White) (P = .003 for interaction) and among participants self-rated with low (vs high) socioeconomic status (P < .001 for interaction). Within a subset of 9865 participants with data on BMI at menarche, exploratory mediation analysis estimated that 46% (95% CI, 35%-61%) of the temporal trend in age at menarche was explained by BMI., Conclusions and Relevance: In this cohort study of 71 341 individuals in the US, as birth year increased, mean age at menarche decreased and time to regularity increased. The trends were stronger among racial and ethnic minority groups and individuals of low self-rated socioeconomic status. These trends may contribute to the increase in adverse health outcomes and disparities in the US.

Importance: Polycystic ovary syndrome (PCOS), characterized by irregular menstrual cycles and hyperandrogenism, is a common ovulatory disorder. Having an irregular cycle is a potential marker for cardiometabolic conditions, but data are limited on whether the associations differ by PCOS status or potential interventions., Objective: To evaluate the association of PCOS, time to regularity since menarche (adolescence), and irregular cycles (adulthood) with cardiometabolic conditions., Design, Setting, and Participants: This cross-sectional study used a large, US-based digital cohort of users of the Apple Research application on their iPhone. Eligibility criteria were having ever menstruated, living in the US, being at age of consent of at least 18 years (or 19 years in Alabama and Nebraska or 21 years in Puerto Rico), and being able to communicate in English. Participants were enrolled between November 14, 2019, and December 13, 2022, and completed relevant surveys., Exposures: Self-reported PCOS diagnosis, prolonged time to regularity (not spontaneously establishing regularity within 5 years of menarche), and irregular cycles., Main Outcomes and Measures: The primary outcome was self-reported cardiometabolic conditions, including obesity, prediabetes, type 1 and 2 diabetes, high cholesterol, hypertension, metabolic syndrome, arrhythmia, congestive heart failure, coronary artery disease, heart attack, heart valve disease, stroke, transient ischemic attack (TIA), deep vein thrombosis, and pulmonary embolism measured using descriptive statistics and logistic regression to estimate prevalence odds ratios (PORs) and 95% CIs. Effect modification by lifestyle factors was also estimated., Results: The study sample (N = 60 789) had a mean (SD) age of 34.5 (11.1) years, with 12.3% having PCOS and 26.3% having prolonged time to regularity. Among a subset of 25 399 participants who completed the hormonal symptoms survey, 25.6% reported irregular cycles. In covariate-adjusted logistic regression models, PCOS was associated with a higher prevalence of all metabolic and several cardiovascular conditions, eg, arrhythmia (POR, 1.37; 95% CI, 1.20-1.55), coronary artery disease (POR, 2.92; 95% CI, 1.95-4.29), heart attack (POR, 1.79; 95% CI, 1.23-2.54), and stroke (POR, 1.66; 95% CI, 1.21-2.24). Among participants without PCOS, prolonged time to regularity was associated with type 2 diabetes (POR, 1.24; 95% CI, 1.05-1.46), hypertension (POR, 1.09; 95% CI, 1.01-1.19), arrhythmia (POR, 1.20; 95% CI, 1.06-1.35), and TIA (POR, 1.33; 95% CI, 1.01-1.73), and having irregular cycles was associated with type 2 diabetes (POR, 1.36; 95% CI, 1.08-1.69), high cholesterol (POR, 1.17; 95% CI, 1.05-1.30), arrhythmia (POR, 1.21; 95% CI, 1.02-1.43), and TIA (POR, 1.56; 95% CI, 1.06-2.26). Some of these associations were modified by high vs low body mass index or low vs high physical activity., Conclusions and Relevance: These findings suggest that PCOS and irregular cycles may be independent markers for cardiometabolic conditions. Early screening and intervention among individuals with irregular menstrual cycles may be beneficial.

Competing Interests: Declaration of competing interest This study received funding from Apple Inc. The funding source provided platforms and software for data collection and participated in writing the manuscript. It played no role in the analysis and interpretation of data or in the decision to submit. The research was also supported in part by the Intramural Research Program of the National Institutes of Health, Z01ES103333. Support for A.M.Z.J. was provided by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institute of Health. H.L., J.P.O., M.A.W., R.H., B.A.C., A.M.Z.J., and S.M. declare no support from any organization for the submitted work. C.L.C. and T.F.C. are employed by Apple Inc. and own Apple Inc. stock. No financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Menstrual characteristics are important signs of women's health. Here we examine the variation of menstrual cycle length by age, ethnicity, and body weight using 165,668 cycles from 12,608 participants in the US using mobile menstrual tracking apps. After adjusting for all covariates, mean menstrual cycle length is shorter with older age across all age groups until age 50 and then became longer for those age 50 and older. Menstrual cycles are on average 1.6 (95%CI: 1.2, 2.0) days longer for Asian and 0.7 (95%CI: 0.4, 1.0) days longer for Hispanic participants compared to white non-Hispanic participants. Participants with BMI ≥ 40 kg/m 2 have 1.5 (95%CI: 1.2, 1.8) days longer cycles compared to those with BMI between 18.5 and 25 kg/m 2 . Cycle variability is the lowest among participants aged 35-39 but are considerably higher by 46% (95%CI: 43%, 48%) and 45% (95%CI: 41%, 49%) among those aged under 20 and between 45-49. Cycle variability increase by 200% (95%CI: 191%, 210%) among those aged above 50 compared to those in the 35-39 age group. Compared to white participants, those who are Asian and Hispanic have larger cycle variability. Participants with obesity also have higher cycle variability. Here we confirm previous observations of changes in menstrual cycle pattern with age across reproductive life span and report new evidence on the differences of menstrual variation by ethnicity and obesity status. Future studies should explore the underlying determinants of the variation in menstrual characteristics., (© 2023. The Author(s).)

Background: Use of menstrual tracking data to understand abnormal bleeding patterns has been limited because of lack of incorporation of key demographic and health characteristics and confirmation of menstrual tracking accuracy., Objective: This study aimed to identify abnormal uterine bleeding patterns and their prevalence and confirm existing and expected associations between abnormal uterine bleeding patterns, demographics, and medical conditions., Study Design: Apple Women's Health Study participants from November 2019 through July 2021 who contributed menstrual tracking data and did not report pregnancy, lactation, use of hormones, or menopause were included in the analysis. Four abnormal uterine bleeding patterns were evaluated: irregular menses, infrequent menses, prolonged menses, and irregular intermenstrual bleeding (spotting). Monthly tracking confirmation using survey responses was used to exclude inaccurate or incomplete digital records. We investigated the prevalence of abnormal uterine bleeding stratified by demographic characteristics and used logistic regression to evaluate the relationship of abnormal uterine bleeding to a number of self-reported medical conditions., Results: There were 18,875 participants who met inclusion criteria, with a mean age of 33 (standard deviation, 8.2) years, mean body mass index of 29.3 (standard deviation, 8.0), and with 68.9% (95% confidence interval, 68.2-69.5) identifying as White, non-Hispanic. Abnormal uterine bleeding was found in 16.4% of participants (n=3103; 95% confidence interval, 15.9-17.0) after accurate tracking was confirmed; 2.9% had irregular menses (95% confidence interval, 2.7-3.1), 8.4% had infrequent menses (95% confidence interval, 8.0-8.8), 2.3% had prolonged menses (95% confidence interval, 2.1-2.5), and 6.1% had spotting (95% confidence interval, 5.7-6.4). Black participants had 33% higher prevalence (prevalence ratio, 1.33; 95% confidence interval, 1.09-1.61) of infrequent menses compared with White, non-Hispanic participants after controlling for age and body mass index. The prevalence of infrequent menses was increased in class 1, 2, and 3 obesity (class 1: body mass index, 30-34.9; prevalence ratio, 1.31; 95% confidence interval, 1.13-1.52; class 2: body mass index, 35-39.9; prevalence ratio, 1.25; 95% confidence interval, 1.05-1.49; class 3: body mass index, >40; prevalence ratio, 1.51; 95% confidence interval, 1.21-1.88) after controlling for age and race/ethnicity. Those with class 3 obesity had 18% higher prevalence of abnormal uterine bleeding compared with healthy-weight participants (prevalence ratio, 1.18; 95% confidence interval, 1.02-1.38). Participants with polycystic ovary syndrome had 19% higher prevalence of abnormal uterine bleeding compared with participants without this condition (prevalence ratio, 1.19; 95% confidence interval, 1.08-1.31). Participants with hyperthyroidism (prevalence ratio, 1.34; 95% confidence interval, 1.13-1.59) and hypothyroidism (prevalence ratio, 1.17; 95% confidence interval, 1.05-1.31) had a higher prevalence of abnormal uterine bleeding, as did those reporting endometriosis (prevalence ratio, 1.28; 95% confidence interval, 1.12-1.45), cervical dysplasia (prevalence ratio, 1.20; 95% confidence interval, 1.03-1.39), and fibroids (prevalence ratio, 1.14; 95% confidence interval, 1.00-1.30)., Conclusion: In this cohort, abnormal uterine bleeding was present in 16.4% of those with confirmed menstrual tracking. Black or obese participants had increased prevalence of abnormal uterine bleeding. Participants reporting conditions such as polycystic ovary syndrome, thyroid disease, endometriosis, and cervical dysplasia had a higher prevalence of abnormal uterine bleeding., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

COVID-19 vaccination may be associated with change in menstrual cycle length following vaccination. We estimated covariate-adjusted differences in mean cycle length (MCL), measured in days, between pre-vaccination cycles, vaccination cycles, and post-vaccination cycles within vaccinated participants who met eligibility criteria in the Apple Women's Health Study, a longitudinal mobile-application-based cohort of people in the U.S. with manually logged menstrual cycles. A total of 9652 participants (8486 vaccinated; 1166 unvaccinated) contributed 128,094 cycles (median = 10 cycles per participant; inter-quartile range: 4-22). Fifty-five percent of vaccinated participants received Pfizer-BioNTech's mRNA vaccine, 37% received Moderna's mRNA vaccine, and 8% received the Johnson & Johnson/Janssen (J&J) vaccine. COVID-19 vaccination was associated with a small increase in MCL for cycles in which participants received the first dose (0.50 days, 95% CI: 0.22, 0.78) and cycles in which participants received the second dose (0.39 days, 95% CI: 0.11, 0.67) of mRNA vaccines compared with pre-vaccination cycles. Cycles in which the single dose of J&J was administered were, on average, 1.26 days longer (95% CI: 0.45, 2.07) than pre-vaccination cycles. Post-vaccination cycles returned to average pre-vaccination length. Estimated follicular phase vaccination was associated with increased MCL in cycles in which participants received the first dose (0.97 days, 95% CI: 0.53, 1.42) or the second dose (1.43 days, 95% CI: 1.06, 1.80) of mRNA vaccines or the J&J dose (2.27 days, 95% CI: 1.04, 3.50), compared with pre-vaccination cycles. Menstrual cycle change following COVID-19 vaccination appears small and temporary and should not discourage individuals from becoming vaccinated., (© 2022. The Author(s).)

Background: Prospective longitudinal cohorts assessing women's health and gynecologic conditions have historically been limited., Objective: The Apple Women's Health Study was designed to gain a deeper understanding of the relationship among menstrual cycles, health, and behavior. This paper describes the design and methods of the ongoing Apple Women's Health Study and provides the demographic characteristics of the first 10,000 participants., Study Design: This was a mobile-application-based longitudinal cohort study involving survey and sensor-based data. We collected the data from 10,000 participants who responded to the demographics survey on enrollment between November 14, 2019 and May 20, 2020. The participants were asked to complete a monthly follow-up through November 2020. The eligibility included installed Apple Research app on their iPhone with iOS version 13.2 or later, were living in the United States, being of age greater than 18 years (19 in Alabama and Nebraska, 21 years old in Puerto Rico), were comfortable in communicating in written and spoken English, were the sole user of an iCloud account or iPhone, and were willing to provide consent to participate in the study., Results: The mean age at enrollment was 33.6 years old (±standard deviation, 10.3). The race and ethnicity was representative of the US population (69% White and Non-Hispanic [6910/10,000]), whereas 51% (5089/10,000) had a college education or above. The participant geographic distribution included all the US states and Puerto Rico. Seventy-two percent (7223/10,000) reported the use of an Apple Watch, and 24.4% (2438/10,000) consented to sensor-based data collection. For this cohort, 38% (3490/9238) did not respond to the Monthly Survey: Menstrual Update after enrollment. At the 6-month follow-up, there was a 35% (3099/8972) response rate to the Monthly Survey: Menstrual Update. 82.7% (8266/10,000) of the initial cohort and 95.1% (2948/3099) of the participants who responded to month 6 of the Monthly Survey: Menstrual Update tracked at least 1 menstrual cycle via HealthKit. The participants tracked their menstrual bleeding days for an average of 4.44 (25%-75%; range, 3-6) calendar months during the study period. Non-White participants were slightly more likely to drop out than White participants; those remaining at 6 months were otherwise similar in demographic characteristics to the original enrollment group., Conclusion: The first 10,000 participants of the Apple Women's Health Study were recruited via the Research app and were diverse in race and ethnicity, educational attainment, and economic status, despite all using an Apple iPhone. Future studies within this cohort incorporating this high-dimensional data may facilitate discovery in women's health in exposure outcome relationships and population-level trends among iPhone users. Retention efforts centered around education, communication, and engagement will be utilized to improve the survey response rates, such as the study update feature., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Faculty development for nurse and physician educators has a limited evidence base in high income countries, and very little research from low- and middle-income countries. Health professions educators in many global settings do not receive training on how to educate effectively., Objective: To pilot and assess a faculty development program aimed at nurse and physician educators at a teaching hospital in rural Haiti., Methods: We developed a program covering a total of 22 topics in health professions education, including applied learning theory as well as nurse and physician targeted topics. We assessed impact through participant assessment of personal growth, participant evaluation of the program, knowledge testing pre and post program, and structured observations of program participants providing teaching during the program., Findings: Nineteen out of 37 participants completed the program. While participant reviews were uniformly positive, a pre- and post-test on general educational topics showed no significant change, and the effort to institute observation and feedback of teaching did not succeed., Conclusions: Our project showcases some benefits of faculty development, while also demonstrating the challenges of instituting faculty development in situations where participants have limited time and resources. We suspect more benefits may emerge as the program evolves to fit the learners and setting., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

Objective: To quantify the proportion of postpartum venous thromboembolism (VTE) readmissions, including those that occur at different hospitals from index admission, and describe risk factors for this outcome., Design: Retrospective observational study., Setting: US hospitals included in the Nationwide Readmissions Database., Sample: A total of 3 719 238 patients >14 years of age with a delivery-associated hospitalisation in 2014., Methods: Univariate analysis was performed to identify patient and hospital factors associated with readmissions. Significant factors were included in multivariate logistic regression to identify independent risk factors. Results were weighted for national estimates., Main Outcome Measures: Readmission with VTE to both index and different hospitals at 30, 60 and 90 days., Results: The VTE cumulative readmission rate was 0.053% (n = 1477), 0.063% (n = 1765) and 0.069% (n = 1938) at 30, 60 and 90 days, respectively. Patients were readmitted to different hospitals 31% of the time within 90 days. Risk factors for different hospital VTE readmission were unique and included younger age and initial admission to a small/medium-sized hospital. Initial admission to a for-profit hospital increased the likelihood of readmission to a different hospital., Conclusions: Nearly one in three postpartum VTEs are missed by the current quality metrics, with significant implications for outcomes and quality. For-profit hospitals have a significant portion of their VTE readmissions hidden, falsely lowering their readmission rates relative to public hospitals., Tweetable Abstract: US analysis shows 1 in 3 readmissions for postpartum venous thromboembolism currently missed., (© 2021 John Wiley & Sons Ltd.)

Extreme weather events (EWEs) are increasing in frequency and severity as the planet continues to become warmer. Resulting disasters have the potential to wreak havoc on the economy, infrastructure, family unit, and human health. Global estimates project that children will be disproportionately impacted by the changing climate - shouldering 88% of the related burdens. Exposure to EWEs in childhood is traumatic, with ramifications for mental health specifically. Symptoms of posttraumatic stress, depression, and anxiety have all been associated with childhood EWE exposure and have the potential to persist under certain circumstances. Conversely, many childhood survivors of EWE also demonstrate resilience and experience only transient symptoms. While the majority of studies are focused on the effects resulting from one specific type of disaster (hurricanes), we have synthesized the literature across the various types of EWEs. We describe psychological symptoms and behavior, the potential for long-term effects, and potential protective factors and risk factors. What this paper adds Climate change-related phenomena such as extreme weather events (EWEs) have the potential to impact mood and behavior in children. Posttraumatic stress (PTS) is the most common mental health consequence in child survivors of EWEs. PTS is often comorbid with depression and/or anxiety in this group., (© 2021 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Background: Postpartum maternal functioning has the potential to affect the quality of interaction between mother and child. A proper assessment of maternal functioning requires a comprehensive and accurate tool. The objective of this study was to prepare a Persian version of the Barkin Index of Maternal Functioning (BIMF) and evaluate its psychometric properties in order to determine its applicability in Iranian mothers., Methods: The BIMF was translated into Persian and then culturally adapted for Iranian women. After evaluating face and content validity, to perform factor analysis, a cross-sectional study was conducted using the Persian version of BIMF. The data was collected from two unique groups of 250 mothers (in all 500 mothers) who had infants 2 to 12-months old and who were selected using a two-stage cluster sampling method. Factor analysis, Pearson's correlation, intra-class correlation coefficients (ICC), composite reliability (CR) and Cronbach's alpha were employed in order to evaluate structural validity and reliability., Results: Exploratory factor analysis resulted in a five-factor structure consisting of 20 items. Subsequently, confirmatory factor analysis (X 2 / df = 1.61, RMSEA = 0.050, GFI = 0.91, CFI = 0.91) confirmed that the Persian version had satisfactory goodness of fit. Reliability and internal consistency were confirmed with a CR of 0.77, an ICC of 0.87 and a Cronbach's alpha of 0.81., Conclusions: The findings indicated that the Persian version of the BIMF is a valid and reliable instrument for assessing maternal functioning among Iranian mothers.

Postpartum depression (PPD) has adverse effects on the mother's ability to work, her relationships, performance in other roles, and caregiving ability. The aim of this study was to compare levels of maternal functioning between mothers with depression symptoms and those without. The participants of this case-control study included 80 postpartum women ( n = 40 with depressive symptoms and n = 40 with no depressive symptoms) referred to health centers in Tabriz, Iran, in 2018-2019. The case and control groups were matched for the number of deliveries (first or second deliveries) and the type of delivery (vaginal or cesarean section). A sociodemographic questionnaire, Edinburgh Postpartum Depression Scale (EPDS), and Barkin Index of Maternal Functioning (BIMF) were used for data collection. The relationship between maternal functioning and depression was assessed by conducting independent t- tests and Pearson correlation tests in bivariate analysis and applying the general linear model (GLM) in a multivariate analysis. There was no statistically significant difference between the two groups in terms of sociodemographic information. The mean (SD) total scores of maternal functioning in the case (depressed) and control (non-depressed) groups were 63.4 (12.2) and 93.3 (13.0), respectively. According to the independent t- test, this value in the control group was significantly higher than that of the case group (mean difference: -30.0; 95% confidence interval: -35.6 to -24.3; p < 0.001). In terms of the domains of the BIMF, based on the independent t- test, the mean score of all domains in the control group was significantly higher than that of the case group, except for the mother-child interaction dimension ( p = 0.219). Based on the Pearson correlation test, there was significant negative correlation between the PPD score and total score of BIMF (r = -0.79, p < 0.001) and its domains (r = -0.81 to -0.54, p < 0.001). In addition, based on the GLM with adjusting the sociodemographic and obstetrics characteristics, the score of maternal functioning was significantly lower in the case group compared to the control group [β = -30.1; 95% CI: -36.8 to -23.4; p = 0.001]. The results of this study indicate that women with depressive symptoms have lower maternal functioning. Depressed women may find it difficult to perform their maternal duties and take care of themselves and other family members due to the burden of the depressive symptoms. Therefore, early diagnosis and treatment of postpartum depression can play an important role in improving daily maternal functioning.

Preexisting immunity against dengue virus or West Nile virus was previously reported to mediate antibody-dependent enhancement (ADE) of Zika virus (ZIKV) infection in a mouse model. We show here that ZIKV-immune plasma samples from both symptomatic and asymptomatic individuals mediated ZIKV ADE of infection in vitro and in mice. In a lethal infection model with a viral inoculum 10 times higher, both ADE and protection were observed, depending on the amount of infused immune plasma. In a vertical-transmission model, ZIKV-immune plasma infused to timed pregnant mice increased fetal demise and decreased the body weight of surviving fetuses. Depletion of IgG from an immune plasma abolished ADE of infection, and the presence of purified IgG alone mediated ADE of infection. Higher viral loads and proinflammatory cytokines were detected in mice treated with ZIKV-immune plasma samples compared to those receiving control plasma. Together, these data show that passive immunization with homotypic ZIKV antibodies, depending on the concentration, could either worsen or limit a subsequent ZIKV infection. IMPORTANCE Antibody-dependent enhancement (ADE) of virus infection is common to many viruses and is problematic when plasma antibody levels decline to subneutralizing concentrations. ADE of infection is especially important among flaviviruses, many of which are the cause of global health problems. Recently, human plasma samples immune to heterologous flaviviruses were shown to promote Zika virus (ZIKV) infection. Here we showed in immunocompromised mouse models that homologous immune plasma samples protect mice from subsequent infection at high antibody concentrations but that they mediate ADE of infection and increase ZIKV pathogenesis in adult mice and fetal demise during pregnancy at low concentrations., (Copyright © 2019 Shim et al.)

Zika virus is a mosquito-transmitted flavivirus and was first linked to congenital microcephaly caused by a large outbreak in northeastern Brazil. Although the Zika virus epidemic is now in decline, pregnancies in large parts of the Americas remain at risk because of ongoing transmission and the potential for new outbreaks. This review presents why Zika virus is still a complex and worrisome public health problem with an expanding spectrum of birth defects and how Zika virus and related viruses evade the immune response to injure the fetus. Recent reports indicate that the spectrum of fetal brain and other anomalies associated with Zika virus exposure is broader and more complex than microcephaly alone and includes subtle fetal brain and ocular injuries; thus, the ability to prenatally diagnose fetal injury associated with Zika virus infection remains limited. New studies indicate that Zika virus imparts disproportionate effects on fetal growth with an unusual femur-sparing profile, potentially providing a new approach to identify viral injury to the fetus. Studies to determine the limitations of prenatal and postnatal testing for detection of Zika virus-associated birth defects and long-term neurocognitive deficits are needed to better guide women with a possible infectious exposure. It is also imperative that we investigate why the Zika virus is so adept at infecting the placenta and the fetal brain to better predict other viruses with similar capabilities that may give rise to new epidemics. The efficiency with which the Zika virus evades the early immune response to enable infection of the mother, placenta, and fetus is likely critical for understanding why the infection may either be fulminant or limited. Furthermore, studies suggest that several emerging and related viruses may also cause birth defects, including West Nile virus, which is endemic in many parts of the United States. With mosquito-borne diseases increasing worldwide, there remains an urgent need to better understand the pathogenesis of the Zika virus and related viruses to protect pregnancies and child health., (Copyright © 2018. Published by Elsevier Inc.)

In the spring of 2017, a full-term infant with microcephaly was delivered in South Florida. During first trimester, the mother presented with fever, nausea, and vomiting. She reported no foreign travel for herself or her partner. The infant's neurologic, ophthalmologic, neuroradiologic, and audiologic findings were highly suggestive of congenital Zika syndrome (CZS), confirmed by IgM antibodies and plaque reduction neutralization test. New observations, including peripheral temporal retinal avascularity and peripapillary retinal nerve fiber layer thinning, are presented from this first known case of non-travel-associated CZS in the United States. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e93-e98.]., (Copyright 2018, SLACK Incorporated.)

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission.

Aim: This study was conducted to ascertain the knowledge and perceptions of the Zika virus among reproductive-aged women living in the first affected area of the United States with local mosquito-borne transmission., Methods: Reproductive-aged women were surveyed during the four weeks immediately following the announcement of local Zika virus transmission. The survey evaluated the participant's knowledge of Zika pathogenesis and transmission, sequelae of infection, epidemiology and public health information., Results: Fifty-nine women (age range 18-45) completed the survey. Most patients (n = 53, 89.8%) had received information about the Zika virus from the media rather than clinicians. In 93% of the questions, a high level of knowledge was demonstrated by the participants. Personal concern about becoming infected with the Zika virus was significantly higher in those considering pregnancy (n = 13, 86.7% vs n = 21, 47.7%; P = 0.01)., Conclusion: In the weeks following recognized local transmission of the Zika virus in the continental United States, reproductive-aged women had a high level of knowledge of the Zika virus, but those considering pregnancy harbored the greatest concern of personal risk of infection., (© 2017 Japan Society of Obstetrics and Gynecology.)

Zika virus infection during pregnancy can lead to congenital Zika syndrome. Implementation of screening programs and interpretation of test results can be particularly challenging during ongoing local mosquitoborne transmission. We conducted a retrospective chart review of 2,327 pregnant women screened for Zika virus in Miami-Dade County, Florida, USA, during 2016. Of these, 86 had laboratory evidence of Zika virus infection; we describe 2 infants with probable congenital Zika syndrome. Delays in receipt of laboratory test results (median 42 days) occurred during the first month of local transmission. Odds of screening positive for Zika virus were higher for women without health insurance or who did not speak English. Our findings indicate the increase in screening for Zika virus can overwhelm hospital and public health systems, resulting in delayed receipt of results of screening and confirmatory tests and the potential to miss cases or delay diagnoses.

Introduction In 2015, there was an outbreak of Zika virus in Brazil that spread throughout the Americas. The association of Zika virus with birth defects in infants born to infected pregnant women created concern for women of childbearing age. Social media is an important platform for health promotion, communication, and education on preventative methods during Zika virus outbreaks. Methods We evaluated the utility of social media on providing information regarding Zika virus. Facebook, Instagram, Twitter, and YouTube were utilized for our study. A search of the term "#Zikavirus" on Twitter and Instagram, and "Zika virus" on Facebook and YouTube was performed. The first 50 search results were analyzed from each source. Only English, Spanish, or Portuguese results were included. Results were categorized into three groups: "Useful", "Not Useful", or "Misleading". Results Search was conducted on December 17th, 2016, with 185 results. Forty (21.6%) were from Facebook, 50 (27%) from Twitter, 48 (25.9%) from YouTube, and 47 (25.4%) from Instagram. A total of 104 (56.22%) results were "Useful", 67 (36.2%) "Not Useful", and 14 (7.5%) were "Misleading". There were significantly more "Useful" results compared to "Not Useful" and "Misleading" results (Fisher's exact: p < 0.0001). Conclusion Social media is a useful resource for providing relevant information on Zika virus. Young women can utilize social media for Zika virus information. The role of social media in public health should be further investigated and established. Patient education interventions should focus on social media impact on behavior modification and education of public to recognize useful information., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine whether barriers to immediate post-placental intrauterine device (PPIUD) placement exist at the provider level., Study Design: Obstetrics providers at seven academic teaching hospitals in Massachusetts were asked to complete an electronic survey regarding their knowledge, experience, and opinions about immediate PPIUDs., Results: Eighty-two providers, including obstetricians, family medicine physicians, and midwives, completed the survey. Thirty-five (42.7%) reported experience placing an immediate PPIUD with the majority of them having placed three to five PPIUDs. Of participants who had never placed a PPIUD, the reason cited most frequently was inadequate training. Fewer than one-half (43.4%) correctly identified the PPIUD expulsion rate, whereas 75.9% knew the correct expulsion rate for interval IUD placement. The majority of providers responded that PPIUDs are acceptable in certain clinical scenarios., Conclusions: Overall, knowledge and experience with PPIUD placement is relatively low. As increasing numbers of states amend Medicaid policy to include reimbursement for immediate postpartum IUDs, additional education and training opportunities are needed., (Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.)

Background: Haiti has a chronic physician shortage, and the country has been facing an increased disease burden since the 2010 earthquake and the subsequent introduction of cholera. In such resource-challenged settings, access to postgraduate medical education often is limited due to inadequate financial, structural, and academic resources. A crucial component to improved health in Haiti is the expansion of continuing medical education (CME). To our knowledge there have been no previous studies investigating the continuing professional development needs of Haitian physicians working in this context., Objective: The objectives of this study are to describe the educational resources available to Haitian physicians and to understand their continuing professional development needs., Methods: We performed a needs and resource assessment of CME available to Haitian physicians using surveys and focus groups. We surveyed 62 physicians and led 3 focus groups. Questions gathered data on physicians' access to educational resources. Descriptive statistics were calculated from surveys, and focus group transcripts were manually reviewed for themes., Findings: In all, 82 conference attendees were invited to participate. Of these, 62 physicians completed the needs and resource assessment survey. Of the participants, 16% had a medical library at work and 31% had access to a computer at work. Educational conferences were available at work for 27% of participants, and 50% attended conferences outside of work. Less than half (45%) identified a clinical mentor. Focus group participants described inadequate tangible and reference resources, lack of colleague support, and lack of avenues for specialty training and employment., Conclusions: In this needs assessment, Haitian physicians identified lack of support for clinical decision making, poor access to CME activities, limited professional development, and absence of employment opportunities as key areas of need in support of their clinical and professional work., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Robotic-assisted laparoscopic surgery is increasingly used for the management of patients with gynecologic malignancies. The rate of portsite metastases in patients undergoing these procedures is unknown., Methods: We conducted a retrospective cohort analysis of a prospective database. A total of 220 women underwent robotic-assisted surgery from 2007 through 2011. Malignancy was detected in 145 cases, and 142 met the inclusion criteria with histologically proven cancer and robotically completed surgery. All women who underwent surgical treatment for their malignancies were followed up at the study site for oncology treatments., Results: There were 710 potential port sites for metastasis. We found that 2 of 142 patients each had a single port-site metastasis, for an overall rate of 1.41%, or 0.28% per trocar site. Recurrent disease was not isolated in the two patients found to have port-site metastases because both had concurrent sites of pelvic recurrence., Conclusion: The rate of port-site metastases in patients undergoing robotic-assisted laparoscopic surgery for gynecologic malignancies is similar to the published rate in the literature for traditional laparoscopic oncology.

Objective: To evaluate medical students in the United States at several medical schools regarding their knowledge of the global health burden of obstetric fistulas., Study Design: A cross-sectional survey was conducted in 8 schools across the United States over a period of 6 months. The survey was composed of 18 questions on epidemiology, pathology, and treatment of fistulas. It was a web-based module accessed through an emailed link. It was sent to 5,103 medical students' email addresses at the 8 institutions once a week for 4 weeks. SPSS paired student t tests was used for statistical analysis., Results: Of the 1,089 students from 8 medical schools that initially began the survey, 965 completed this voluntary and anonymous survey, with a 21% response rate and 19% completion rate. Overall the students averaged 11/18 (60.7%) correct on this survey. The knowledge of obstetric fistula improved, but not significantly, with increasing level of medical school education, with first-year medical students achieving 10/18 (55%) correct and senior medical students achieving 12/18 (67%) correct (p = 0.1)., Conclusion: U.S. medical students' knowledge of obstetric fistulas in developing countries does not increase significantly over 4 years of medical school education. While this condition presents largely in the developing world, given rapid globalization as well as increased international health experiences for U.S.-trained health professionals,further effort should be placed in improving medical student knowledge of this devastating condition.

Objective: To assess the underlying histology of HIV-infected women with minimally abnormal Pap tests compared to HIV-uninfected women by evaluating their colposcopic and histologic outcomes., Methods: Retrospective analysis was performed to identify HIV-infected women who had at least one cervical Pap test from 2002 through 2008 at Boston Medical Center. We identified women who underwent colposcopy within 6 months of a minimally abnormal Pap test (atypical squamous cells of undetermined significance with positive high-risk human papillomavirus testing [ASCUS/HPV+] or low-grade squamous intraepithelial lesion (LSIL)). Our outcome was the proportion of HIV-infected women with histologic cervical intraepithelial neoplasia 2 or worse (CIN2+). We then compared these outcomes to those of a cohort of HIV-uninfected women from the same institution., Results: There were 655 HIV-infected women who had Pap testing in the study time frame, and 146 (22%) had a minimally abnormal Pap test (ASCUS/HPV+ or LSIL). Of the 90 HIV-infected women who had subsequent colposcopy within 6 months, colposcopy was negative for 20 (22%), CIN1 for 41 (46%), and CIN2+ for the remaining 29 (32%). During the same time period, there were 747 HIV-uninfected women who underwent colposcopy within 6 months of a minimally abnormal Pap test. Colposcopy was negative for 336 (45%), CIN1 for 254 (34%), and CIN2+ for 157 (21%). After adjusting for differences in age and race, the HIV-infected women were more likely to have CIN2+ after a minimally abnormal Pap test (p=0.002) (adjusted odds ratio [OR] 2.17, 95% confidence interval [CI] 1.33-3.62). There were no diagnosed cases of cervical cancer., Conclusions: HIV-infected women have higher rates of underlying CIN2+ for minimally abnormal Pap tests compared with HIV-uninfected women.

Kaposi's sarcoma (KS) is the most common neoplasm in untreated AIDS patients and accounts for significant morbidity and mortality worldwide. We have recently reported that Notch signaling (which plays an important role in cell proliferation, apoptosis, and oncogenesis) is constitutively activated in KS tumor cells. Blockade of this activity using gamma-secretase inhibitors resulted in apoptosis of SLK cells, a KS tumor cell line; however, this apoptosis was preceded by a prolonged G(2)-M cell cycle arrest. This result led us to hypothesize that the cells were undergoing mitotic catastrophe, an abnormal mitosis that leads to eventual cell death. Here, we show that Notch inhibition in KS tumor cells using gamma-secretase inhibitors or Notch-1 small interfering RNA resulted in G(2)-M cell cycle arrest and mitotic catastrophe characterized by the presence of micronucleated cells and an increased mitotic index. Interestingly, Notch inhibition led to a sustained increase in nuclear cyclin B1, a novel observation suggesting that Notch signaling can modulate expression of this critical cell cycle protein. Further analysis showed the induction of cyclin B1 was due, at least in part, to increased nuclear factor-kappaB (NF-kappaB) activity, which was also required for the G(2)-M growth arrest after Notch inhibition. Taken together, these studies suggest that Notch inhibition can initiate aberrant mitosis by inducing NF-kappaB activity that inappropriately increases cyclin B1 resulting in cell death via mitotic catastrophe.

Background: In the A-HeFT (African-American Heart Failure Trial), treatment of African-American patients with New York Heart Association (NYHA) class III/IV heart failure (HF) with fixed-dose combination (FDC) of isosorbide dinitrate/hydralazine (I/H) reduced mortality and morbidity and improved patient reported functional status compared with standard therapy alone., Objective: To examine the benefit of FDC I/H in subgroups based on baseline drug therapy and to investigate whether ACE inhibitors and/or angiotensin receptor antagonists (angiotensin receptor blockers) [ARBs] or beta-adrenoceptor antagonists (beta-blockers) provided additional benefit in FDC I/H-treated African-American patients with HF., Study Design: The A-HeFT was a double-blind, placebo-controlled study enrolling 1050 patients stabilized on optimal HF therapies and with NYHA class III/IV HF with systolic dysfunction conducted during the years 2001-4 with up to 18 months follow-up. The primary endpoint was a composite of mortality, first HF hospitalization, and improvement of quality of life at 6 months. Secondary endpoints included mortality, hospitalizations, and change in quality of life. Prospective Kaplan-Meier survival analyses were used for differences between FDC I/H and placebo groups and retrospective analyses were conducted within FDC I/H-treated and placebo groups., Results: Subgroup analysis for mortality, event-free survival (death or first HF hospitalization), and HF hospitalization showed that FDC I/H, compared with placebo, was effective with or without ACE inhibitors or beta-blockers or other standard medications with all-point estimates favoring the FDC I/H group. Within the placebo-treated group, beta-blockers or ACE inhibitors and/or ARBs were efficacious in improving survival (hazard ratio [HR] 0.33; p<0.0001 for [beta]-blocker use and HR 0.39; p=0.01 for ACE inhibitor and/or ARB use). However, within the FDC I/H-treated group, use of beta-blockers, but not ACE inhibitors and/or ARBs, provided additional significant benefit for survival (HR 0.44; p=0.029 and HR 0.60; p=0.34, respectively), event-free survival (HR 0.62; p=0.034 and HR 0.72; p=0.29, respectively) and the composite score of death, HF hospitalization and change in quality of life (p=0.016 and p=0.13, respectively)., Conclusion: Based on the analysis of baseline medication use in the A-HeFT, FDC I/H was superior to placebo with or without beta-blockers or ACE inhibitor. However, beta-blockers but not ACE inhibitors and/or ARBs provided additional significant benefit in African-Americans with HF treated with FDC I/H. These analyses are hypotheses generating and their confirmation in clinical trials needs to be considered.

Our laboratory has recently demonstrated constitutive activation of the Notch signaling pathway in Kaposi's sarcoma tumor cells. As endothelial cells (EC) are believed to be the progenitor of these tumor cells, this study was designed to examine the effect of Notch activation on normal human EC. Recent reports suggest Notch activation induces EC growth arrest, and that this growth arrest may be linked to the establishment or maintenance of EC quiescence, the phenotype seen in contact-inhibited EC lining the vasculature. To gain further insight into Notch activation and quiescence, we first confirmed that Notch activation induced EC growth arrest. Next, we examined Notch activation in confluent, growth arrested EC (mimicking the cells lining the vasculature). In contrast to previous reports, we found confluent EC possess lower levels of activated Notch compared to proliferating control cells. Interestingly, these cells express elevated levels of Hes-1 protein (an immediate downstream target of Notch signaling) despite decreased Notch activation. Under these conditions, Hes-1 expression was mediated, at least in part, by a Notch-independent mechanism involving c-jun N-terminal protein kinase (JNK) signaling. This is the first report, to our knowledge, that JNK signaling can modulate Hes-1 expression in a Notch-independent manner.

Kaposi's sarcoma (KS) is a common neoplasm in HIV-1-infected individuals causing significant morbidity and mortality. Despite recent advances, the pathogenesis of this potentially life-threatening neoplasm remains unclear, and there is currently no cure for KS. Notch proteins are known to play a fundamental role in cell fate decisions including proliferation, differentiation, and apoptosis. It is, therefore, not surprising that Notch proteins have been implicated in tumorigenesis and appear to function as either oncogenes or tumor suppressor proteins depending on cellular context. In this report, we demonstrate elevated levels of activated Notch-1, -2, and -4 in KS tumor cells in vivo and in vitro compared to endothelial cells, the precursor of the KS cell. Notch activation was confirmed through luciferase reporter assays and localization of Hes (Hairy/Enhancer of Split)-1 and Hey (Hairy/Enhancer of Split related with YRPW)1 (primary targets of the Notch pathway) in KS cell nuclei. Studies using gamma-secretase inhibitors (GSI and LY-411,575), which block Notch activation, resulted in apoptosis in primary and immortalized KS cells. Similar studies injecting GSI into established KS cell tumors on mice demonstrated growth inhibition or tumor regression that was characterized by apoptosis in treated, but not control tumors. The results indicate that KS cells overexpress activated Notch and interruption of Notch signaling inhibits KS cell growth. Thus, targeting Notch signaling may be of therapeutic value in KS patients.

Kaposi sarcoma is considered a neoplasm of lymphatic endothelium infected with Kaposi sarcoma-associated herpesvirus. It is characterized by the expression of lymphatic lineage-specific genes by Kaposi sarcoma tumor cells. Here we show that infection of differentiated blood vascular endothelial cells with Kaposi sarcoma-associated herpesvirus leads to their lymphatic reprogramming; induction of approximately 70% of the main lymphatic lineage-specific genes, including PROX1, a master regulator of lymphatic development; and downregulation of blood vascular genes.

Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular morbidity in hypertensive patients. The effects of diuretics on LVH have raised controversies, but recent studies suggest that diuretics are able to reduce LVH in hypertensive patients, mainly through a reduction in ventricular diameter. The present multicenter open study was designed to test the effects of indapamide, a widely used nonthiazide diuretic, on LVH in patients with essential hypertension. Patients had to have mild-to-moderate essential hypertension (supine diastolic blood pressure [sDBP] 95 to 115 mm Hg) with echocardiographic evidence of LVH (left ventricular mass index [LVMI] > 130 g/m2 for men and > 110 g/m2 for women). After a 2 week placebo run-in period, eligible patients underwent a 6 month treatment with 2.5 mg indapamide daily. All echograms were performed by the same investigator before and after 6 months of indapamide. Clinical and biological acceptability and quality of life (visual analog scale) were also studied. One hundred and thirty patients were included in the study and 112 completed the trial. Indapamide induced a significant reduction i systolic and diastolic blood pressures. Indapamide induced a marked reduction in posterior wall thickness (from 12.1 +/- 2.0 to 11.2 +/- 1.6 mm) and in interventricular wall thickness (from 12.7 +/- 1.7 to 11.8 +/- 1.9 mm; each P < .001) and a slight decrease in left ventricular diameter (P = .049). This resulted in a 13% reduction in LVMI (from 161.9 +/- 37.9 to 140.7 +/- 33.8 g/m2, P < .001). Left ventricular fractional shortening remained unchanged. There was no significant relation between changes in LVMI and changes in systolic, diastolic, or mean blood pressure. No significant adverse clinical or biological effects were reported during the study. The increased score of the visual analog scale indicated that overall well-being was improved (P < .001). Our study indicates that indapamide, in addition to blood pressure control, is able to reduce LVH. This effect was achieved mainly through a reduction in wall thicknesses rather than in internal cavity diameter.

Background: Coronary artery disease strikes early and may prove particularly severe in persons of African-American descent. Therefore, we studied the lipid-lowering efficacy and safety of pravastatin sodium (20 mg/d), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in 245 African-American patients with primary hypercholesterolemia., Methods: After 4 weeks on an American Heart Association phase I low-fat diet, patients were randomized in a double-blind manner to either pravastatin or placebo in a 3:1 ratio., Results: After 12 weeks of pravastatin treatment, low-density lipoprotein cholesterol levels declined 25.8%, total cholesterol levels 20.3%, and triglyceride levels 6.2%, while high-density lipoprotein cholesterol levels remained essentially unchanged. Overall, 72% of pravastatin-treated patients achieved reductions in low-density lipoprotein cholesterol level in excess of 20%, and 44% attained declines in excess of 30% (both P < .01 vs placebo). Pravastatin was generally well tolerated in this population, with one patient (0.5%) exhibiting a reversible myopathy with creatine kinase elevations to 10 times the upper limit of normal. No substantial elevations of aminotransferase levels of two to three times the upper limit of normal occurred in either the pravastatin or the placebo group. Drug compliance was high, exceeding 90%., Conclusion: Pravastatin appears to be an effective and safe lipid-lowering agent and is the first 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor to be studied extensively in this underrepresented population.

Although vasomotor activity in small pulmonary vessels has been studied extensively in the past, using the concept of resistance to flow, information on the distensibility of these vessels is very sparse. In an attempt to reduce this deficit, we adapted a theoretical method developed for small systemic vessels, to estimate distensibility of pulmonary resistance vessels in experimental animals and man. Pressure-flow data from 11 dogs and 10 human subjects (5 control subjects and 5 patients with long-standing left heart failure) were used to calculate distensibility of small pulmonary vessels. The conductance, G, was calculated from these data as the ratio of blood flow to driving pressure. The slope of the relationship between the logarithm of G1/4 and the average distending pressure (ADP) provides a graphic picture of circumferential extensibility, E, defined as percent change in radius for an infinitesimal change in ADP. Results indicate that: (1) the value of E in dogs was 1.85 +/- .40 mmHg-1 for the control state, which decreased to 1.45 +/- .43 mmHg-1 during norepinephrine administration; however, the decrease in the value was not statistically significant (p = 0.53); (2) the value of E in control human subjects was 3.38 +/- .47 mmHg-1 and the value of E in patients with left heart failure was -0.64 +/- 0.39 mmHg-1; the difference was significant (P = .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: The purpose of the present study was to assess the influence of variations in the relative degree of dilation of left and right ventricular chambers on the clinical outcome of patients with dilated cardiomyopathy., Background: Dilated cardiomyopathy, a primary myocardial disease characterized by ventricular dilation and systolic dysfunction, is generally associated with a poor prognosis. However, considerable variability has been observed in the clinical course and the morphologic and hemodynamic features in individual patients., Methods: We evaluated 67 consecutive patients with dilated cardiomyopathy and without evidence of ischemic or primary valvular heart disease. On the basis of diastolic ventricular chamber area measurements obtained by echocardiography, patients were classified into two groups: 38 patients with a relatively equal degree of left and right ventricular dilation (LV congruent to RV) and 29 patients with predominant and disproportionate dilation of the left ventricle (LV > RV)., Results: The 67 patients ranged in age from 19 to 81 years (mean 56); 49 (73%) were male. The two subsets of patients with dilated cardiomyopathy did not differ with regard to age, left ventricular diastolic dimension, wall thickness and mass or ejection fraction. However, patients in the LV congruent to RV group showed more severe mitral and tricuspid regurgitation by Doppler echocardiography than did those in the LV > RV group (p = 0.01 for mitral and 0.004 for tricuspid regurgitation). Over the follow-up period of 2 to 60 months (mean 28), there were 19 deaths. Survival in the LV > RV group was significantly better than in the LV congruent to RV group (p = 0.03)., Conclusions: Patients with dilated cardiomyopathy represent a heterogeneous group with regard to both clinical outcome and the relative degree of left and right ventricular chamber dilation. Patients in the LV > RV subset appear to have better overall survival and less severe mitral and tricuspid regurgitation than do patients in the LV congruent to RV subset. Longitudinal studies are needed to determine whether these morphologic subsets in fact represent a continuum within the disease spectrum of dilated cardiomyopathy.

In order to evaluate the regulation of intracellular sodium and potassium balance, we investigated the Na+/K(+)-ATPase independent 22Na+ uptake and concentrations of Na+ in erythrocytes from eleven normal subjects. The experiments were performed with the purified erythrocyte suspensions in different assay buffers containing (i) 5 mEq/L KCl and varying amounts of NaCl (5 to 100 mEq/L); and (ii) a range of KCl (5 to 100 mEq/L) and a constant amount of NaCl (5 mEq/L). These erythrocyte suspensions were incubated at 37 degrees C for 30 minutes to assess ouabain insensitive 22Na+ uptake. Erythrocytes (2.0 x 10(9)/mL) showed an uptake of 2.03 to 0.88%, and 2.00 to 1.15% of the total 22Na+ present in the media under these experimental conditions, respectively. The 22Na+ uptake by erythrocytes was decreased by a gradual increase of either NaCl or KCl in the assay buffers. Erythrocytes in the experimental condition (i) showed an increase in intracellular sodium [Na+]i from 8.29 to 10.06 mEq/L. However in the condition (ii), KCl up to 20 mEq/L extracellularly caused a limited inhibition of [Na+]i accumulation (8.29 to 8.23 mEq/L), however, when KCl was raised extracellularly greater than 20 mEq/L it enhanced [Na+]i slowly (8.23 to 9.19 mEq/L). When NaCl 20, 50 and 100 mEq/L were replaced by an equivalent amount of KCl in the assay buffers, this extracellular K+ prevented 7, 6 and 10% [Na+]i accumulation, respectively. We also found that bicarbonate induced ouabain resistance 22Na+ influx was both inhibited and stimulated depending upon the amount of KCl in the assay media.(ABSTRACT TRUNCATED AT 250 WORDS)

Aim: To calculate the compliance of resistance vessels., Methods: Pressure-flow data (plethysmographic and sphygmomanometric) were obtained non-invasively from six normal and six hypertensive subjects, and the results were compared with similar data obtained previously from large blood vessels. The parameter used to represent compliance was extensibility (E), defined as the percentage change in radius for a given change in pressure., Results: The hand vessels of hypertensive subjects (E = 0.126 +/- 0.034/mmHg) were significantly stiffer (P < 0.02) than those of the normotensive subjects (E = 0.272 +/- 0.047/mmHg); and the values of E for the resistance vessels were larger than those for the large arteries.

The efficacy and safety of once-daily 2.5- or 5.0-mg methyclothiazide (MCTZ) added to once-daily 5.0-mg terazosin (TRZ) versus 5.0-mg TRZ alone was evaluated in this double-blind, multicenter study. All patients received TRZ during a 6-week titration period. Hypertensive patients (222) (mean blood pressure of 159/104 mm Hg) were randomized to one of three treatment groups: TRZ alone (N = 76); TRZ+MCTZ-2.5 mg (N = 74); and TRZ+MCTZ-5.0 mg (N = 72) for the 8-week double-blind period. Changes in the supine and standing SBP/DBP from preTRZ period were: TRZ alone (-4.8/-8.1 and -2.6/-6.1 mm Hg); TRZ+MCTZ-2.5 mg (-17.3/-12.4 and -16.0/-11.2 mm Hg); and TRZ+MCTZ-5.0 mg (-20.6/-14.4 and -23.3/-14.6 mm Hg). Blood pressure changes in the combination groups were significantly greater than those in the TRZ alone group. However, there were no statistically significant differences between the TRZ+MCTZ-2.5-mg and TRZ+MCTZ-5.0-mg groups. The combination of TRZ and MCTZ tends to mitigate the adverse effects on serum glucose, uric, potassium and lipids usually associated with thiazide diuretics. Thus, combination treatment that begins with TRZ and adds MCTZ is effective in lowering blood pressure without any significant adverse metabolic effects.

Contrary to opinions generally accepted in the past, CHD is very common in both African-American men and women, with incidence rates approaching those of US Caucasians. Higher prevalence of hypertension, diabetes, cigarette smoking, and obesity all contribute to the high level of CHD in African-Americans. Additional research is needed about the interrelations and management of various risk factors for CHD in African-Americans outside of the sudden death of African-Americans outside of the hospital is urgent, and special attention should be given to accessibility and use of health services by minority populations.

It is difficult to draw strong conclusions from the available data. One must simply accept the fact that vital statistics show that cardiovascular disease is the most common cause of death among black Americans. Health care providers, policymakers, and funding agencies should use this information to develop preventive and therapeutic strategies to conquer this dreadful disease.

Twenty normotensive and ten hypertensive black women taking oral contraceptive (OC) were studied. Age, body weight, family medical history of hypertension, length of OC use, and type of OC were comparable. At midcycle approximately 10-12 hours following OC intake, blood was drawn and the plasma was used to determine ethynylestradiol (EE2), caffeine, aldosterone (Aldo) and desoxycorticosterone (DOC) levels. The results showed that in hypertensive OC users, EE2 and caffeine levels were significantly higher (P less than .01) compared to normotensive OC users. While no significant differences were found in Aldo and DOC levels between hypertensive and normotensive OC users, OC users had higher levels of Aldo (P less than .01) compared to non-OC users.