[Special Issue on SEA Demographics] Response - Community Development

Response to Mark E. Pfeifer\u27s featured article

Progestins Related to Progesterone and Testosterone Elicit Divergent Human Endometrial Transcriptomes and Biofunctions.

Progestins are widely used for the treatment of gynecologic disorders and alone, or combined with an estrogen, are used as contraceptives. While their potencies, efficacies and side effects vary due to differences in structures, doses and routes of administration, little is known about their effects on the endometrial transcriptome in the presence or absence of estrogen. Herein, we assessed the transcriptome and pathways induced by progesterone (P4) and the three most commonly used synthetic progestins, medroxyprogesterone acetate (MPA), levonorgestrel (LNG), and norethindrone acetate (NETA), on human endometrial stromal fibroblasts (eSF), key players in endometrial physiology and reproductive success. While there were similar transcriptional responses, each progestin induced unique genes and biofunctions, consistent with their structural similarities to progesterone (P4 and MPA) or testosterone (LNG and NETA), involving cellular proliferation, migration and invasion. Addition of estradiol (E2) to each progestin influenced the number of differentially expressed genes and biofunctions in P4 and MPA, while LNG and NETA signatures were more independent of E2. Together, these data suggest different mechanisms of action for different progestins, with progestin-specific altered signatures when combined with E2. Further investigation is warranted for a personalized approach in different gynecologic disorders, for contraception, and minimizing side effects associated with their use

Rad-Hard, Miniaturized, Scalable, High-Voltage Switching Module for Power Applications Rad-Hard, Miniaturized

A paper discusses the successful development of a miniaturized radiation hardened high-voltage switching module operating at 2.5 kV suitable for space application. The high-voltage architecture was designed, fabricated, and tested using a commercial process that uses a unique combination of 0.25 micrometer CMOS (complementary metal oxide semiconductor) transistors and high-voltage lateral DMOS (diffusion metal oxide semiconductor) device with high breakdown voltage (greater than 650 V). The high-voltage requirements are achieved by stacking a number of DMOS devices within one module, while two modules can be placed in series to achieve higher voltages. Besides the high-voltage requirements, a second generation prototype is currently being developed to provide improved switching capabilities (rise time and fall time for full range of target voltages and currents), the ability to scale the output voltage to a desired value with good accuracy (few percent) up to 10 kV, to cover a wide range of high-voltage applications. In addition, to ensure miniaturization, long life, and high reliability, the assemblies will require intensive high-voltage electrostatic modeling (optimized E-field distribution throughout the module) to complete the proposed packaging approach and test the applicability of using advanced materials in a space-like environment (temperature and pressure) to help prevent potential arcing and corona due to high field regions. Finally, a single-event effect evaluation would have to be performed and single-event mitigation methods implemented at the design and system level or developed to ensure complete radiation hardness of the module

A Special Tribute to Anne Frank of the Southeast Asian Archive at the University of California, Irvine

Special tributes in honor of Anne Frank for her service to the field through the Southeast Asian Archive at UC, Irvine

Depression and its associated factors among pregnant women in central Vietnam.

To date, little attention has been given to prenatal depression, especially in low and middle-income countries. The aim of this research was to assess the prevalence of depression and its associated factors amongst pregnant women in a central Vietnamese city. This cross-sectional study included 150 pregnant women from 29 to 40 weeks of gestation, from eight wards of Hue city, via quota sampling from February to May 2019. We employed the Patient Health Questionnaire (PHQ-9) to assess depression. Findings suggest the need to provide routine screening of pregnant women in primary care for depressive symptoms and other mental health problems.This is part of the EBLS proejct of which Prof Eisner is PI. Botnar Fondation is the sponso

Intergenerational effects of violence on women's perinatal wellbeing and infant health outcomes: evidence from a birth cohort study in Central Vietnam.

BACKGROUND: Girls exposed to violence have a high risk of being victimized as adults and are more likely than non-abused women to have children who are treated violently. This intergenerational transmission may be especially serious when women suffer violence during pregnancy and early motherhood, as it impairs maternal wellbeing and infant health and development. This study examined the intergenerational effects of being exposed to childhood maltreatment (CM) and prenatal intimate partner violence (p-IPV) on perinatal mental distress and birth outcomes in central Vietnam. METHODS: A birth cohort study in Hue City, Vietnam was conducted with 150 women in the third trimester of pregnancy (Wave 1) and 3 months after childbirth (Wave 2). Using multivariable logistic regression models, augmented inverse-probability-weighted estimators and structural equation modelling (SEM), we analyzed a theoretical model by evaluating adjusted risk differences and pathways between CM, p-IPV and subsequent perinatal adversity and indicators of infant health problems. RESULTS: One in two pregnant women experienced at least one form of CM (55.03%) and one in ten pregnant women experienced both CM and p-IPV (10.67%). Mothers who experienced p-IPV or witnessed IPV as a child were approximately twice as likely to experience poor mental health during pregnancy [ARR 1.94, 95% CI (1.20-3.15)]. Infants had a two-fold higher risk of adverse birth outcomes (low birth weight, preterm birth, admission to neonatal intensive care) [ARR 2.45 95% CI (1.42, 4.25)] if their mothers experienced any form of p-IPV, with greater risk if their mothers were exposed to both CM and p-IPV [ARR 3.45 95% CI (1.40, 8.53)]. Notably, significant pathways to p-IPV were found via adverse childhood experience (ACE) events (β = 0.13), neighborhood disorder (β = 0.14) and partner support (β = - 1.3). CONCLUSION: These results emphasize the detrimental and prolonged nature of the effect of violence during childhood and pregnancy. Exposure to childhood maltreatment and violence during pregnancy increases the risk of maternal mental health difficulties and adverse birth outcomes. Antenatal care systems need to be responsive to women's previous experiences of violence and maternal mental health. The significant protective role of partner support and social support should also be considered when designing tailored interventions to address violence during pregnancy

Strategies for increasing impact, engagement, and accessibility in HIV prevention programs: suggestions from women in urban high HIV burden counties in the Eastern United States (HPTN 064)

Background Merely having the tools to end HIV is insufficient. Effectively ending the epidemic necessitates addressing barriers that impede engagement in biomedical and behavioral prevention and wide scale implementation and utilization of existing interventions. This qualitative study identifies suggestions for increasing access to, engagement in, and impact of HIV prevention among women living in cities in high HIV burden counties in the eastern US. Methods Data analyzed for the current study were collected via a qualitative sub-study within the HIV Prevention Trials Network Study 064 (HPTN 064), a multisite observational cohort study designed to estimate HIV incidence among women residing in communities with elevated HIV prevalence who also reported personal or partner characteristics associated with increased risk of HIV acquisition. Focus group and interview participants in the qualitative sub-study (N = 288) were from four cities in the eastern US. Results Thematic analyses revealed four themes describing women’s most frequently stated ideas for improving prevention efforts: 1) Promote Multilevel Empowerment, 2) Create Engaging Program Content, 3) Build “Market Demand”, and 4) Ensure Accessibility. We conducted additional analyses to identify contradictory patterns in the data, which revealed an additional three themes: 1) Address Structural Risk Factors, 2) Increase Engagement via Pleasure Promotion, 3) Expand Awareness of and Access to Prevention Resources. Conclusions Findings may be useful for enhancing women’s engagement in and uptake of behavioral and biomedical HIV prevention resources, improving policy, and addressing multilevel risk factors. Trial registration Clinicaltrials.gov: NCT00995176 , prospectively registered

Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs.

Transient delivery of CRISPR-Cas9 ribonucleoproteins (RNPs) into the central nervous system (CNS) for therapeutic genome editing could avoid limitations of viral vector-based delivery including cargo capacity, immunogenicity, and cost. Here, we tested the ability of cell-penetrant Cas9 RNPs to edit the mouse striatum when introduced using a convection-enhanced delivery system. These transient Cas9 RNPs showed comparable editing of neurons and reduced adaptive immune responses relative to one formulation of Cas9 delivered using AAV serotype 9. The production of ultra-low endotoxin Cas9 protein manufactured at scale further improved innate immunity. We conclude that injection-based delivery of minimally immunogenic CRISPR genome editing RNPs into the CNS provides a valuable alternative to virus-mediated genome editing

Socioecological factors influencing women\u27s HIV risk in the United States: qualitative findings from the women\u27s HIV SeroIncidence study (HPTN 064).

BACKGROUND: We sought to understand the multilevel syndemic factors that are concurrently contributing to the HIV epidemic among women living in the US. We specifically examined community, network, dyadic, and individual factors to explain HIV vulnerability within a socioecological framework. METHODS: We gathered qualitative data (120 interviews and 31 focus groups) from a subset of women ages 18-44 years (N = 2,099) enrolled in the HPTN 064 HIV seroincidence estimation study across 10 US communities. We analyzed data from 4 diverse locations: Atlanta, New York City (the Bronx), Raleigh, and Washington, DC. Data were thematically coded using grounded theory methodology. Intercoder reliability was assessed to evaluate consistency of team-based coding practices. RESULTS: The following themes were identified at 4 levels including 1) exosystem (community): poverty prevalence, discrimination, gender imbalances, community violence, and housing challenges; 2) mesosystem (network): organizational social support and sexual concurrency; 3) microsystem (dyadic): sex exchange, interpersonal social support, intimate partner violence; and 4) individual: HIV/STI awareness, risk taking, and substance use. A strong theme emerged with over 80 % of responses linked to the fundamental role of financial insecurity underlying risk-taking behavioral pathways. CONCLUSIONS: Multilevel syndemic factors contribute to women\u27s vulnerability to HIV in the US. Financial insecurity is a predominant theme, suggesting the need for tailored programming for women to reduce HIV risk. TRIAL REGISTRATION: Clinicaltrials.gov, NCT00995176