Baby's First Macrophage: Temporal Regulation of Hofbauer Cell Phenotype Influences Ligand-Mediated Innate Immune Responses across Gestation.

The importance of fetal placental macrophages (Hofbauer cell [HCs]) is underscored by their appearance 18 d postconception and maintenance through term; however, how human HCs evolve during healthy pregnancy and how microenvironment and ontogeny impact phenotype and function remain unknown. In this study, we comprehensively classify human HCs ex vivo, interrogate phenotypic plasticity, and characterize antiviral immune responses through gestation. Activated HCs were abundant in early pregnancy and decreased by term; molecular signatures emphasize inflammatory phenotypes early in gestation. Frequency of HCs with regulatory phenotypes remained high through term. Furthermore, term HCs exhibited blunted responses to stimulation, indicating reduced plasticity. IFN-λ1 is a key placental IFN that appeared less protective than IFN-α, suggesting a potential weakness in antiviral immunity. Ligand-specific responses were temporally regulated: we noted an absence of inflammatory mediators and reduced antiviral gene transcription following RIG-I activation at term despite all HCs producing inflammatory mediators following IFN-γ plus LPS stimulation. Collectively, we demonstrate sequential, evolving immunity as part of the natural history of HCs through gestation.

The COVID-19 pandemic's intersectional impact on work life, home life and wellbeing: an exploratory mixed-methods analysis of Georgia women's experiences during the pandemic.

BACKGROUND: Women have been especially impacted by the COVID-19 pandemic. This exploratory study aimed to characterize women's adverse experiences related to their work, home lives, and wellbeing during the height of the COVID-19 pandemic and to describe demographic differences of those lived experiences. METHODS: Using the validated Epidemic-Pandemic Impacts Inventory, we collected data from reproductive-aged women in the state of Georgia about their exposure to adverse events during the pandemic. A latent class analysis (LCA) was performed to identify subgroups of women reporting similar adverse experiences and describe their sociodemographic characteristics. An optional open-ended question yielded qualitative data that were analyzed thematically and merged with subgroup findings. Data were collected from September 2020 to January 2021. RESULTS: 423 individuals aged 18-49 completed the survey with 314 (74.2%) providing qualitative responses. The LCA yielded 4 subgroups: (1) a "low exposure" subgroup (n = 123, 29.1%) with relatively low probability of adverse experiences across domains (e.g. financial insecurity, health challenges, barriers to access to healthcare, intimate partner violence (IPV)); (2) a "high exposure" subgroup (n = 46, 10.9%) with high probability of experiencing multiple adversities across domains including the loss of loved ones to COVID-19; (3) a "caregiving stress" subgroup (n = 104, 24.6%) with high probability of experiencing challenges with home and work life including increased partner conflict; and (4) a "mental health changes" subgroup (n = 150, 35.5%) characterized by relatively low probability of adverse experiences but high probability of negative changes in mental health and lifestyle. Individuals in subgroups 1 and 4, which had low probabilities of adverse experiences, were significantly more likely to be non-Hispanic white. Individuals in subgroup 2 were more likely to identify with a sexual or racial/ethnic minority population. Inductive coding of qualitative data yielded themes such as stress, mental health, financial impact, and adaptation/resilience, providing context for pandemic-related adversity. CONCLUSION: Though many individuals in our sample experienced hardship, minority populations were unequally impacted by pandemic-related adversity in work life, home life, and wellbeing. Recovery and future emergency preparedness efforts in Georgia must incorporate support mechanisms for mental health and IPV, focusing especially on the intersectional needs of racial, ethnic, and sexual minorities.

The COVID-19 pandemic's impact on sexual and reproductive health in Georgia, USA: An exploration of behaviors, contraceptive care, and partner abuse.

OBJECTIVE: Assessing access to sexual and reproductive health care during the COVID-19 pandemic, experiences with intimate partner violence (IPV), and exploring sociodemographic disparities STUDY DESIGN: From September 2020 to January 2021, we recruited 436 individuals assigned female at birth (18-49 years.) in Georgia, USA for an online survey. The final convenience sample was n = 423; a response rate could not be calculated. Survey themes included: sociodemographic and financial information, access to contraceptive services/care, IPV, and pregnancy. Respondents who reported a loss of health insurance, difficulty accessing contraception, barriers to medical care, or IPV were characterized as having a negative sexual and reproductive health experience during the pandemic. We explored associations between sociodemographic variables and negative sexual and reproductive health experiences. RESULTS: Since March 2020, 66/436 (16%) of respondents lost their health insurance, and 45% (89/436) reported income loss. Of our sample, 144/436 people (33%) attempted to access contraception. The pandemic made contraceptive access more difficult for 38/144 (26%) of respondents; however, 106/144 (74%) said it had no effect or positive effect on access. Twenty-one respondents reported IPV (5%). COVID-19 amplified negative views of unplanned pregnancy. Seventy-six people (18%) reported at least 1 negative sexual and reproductive health experience during the pandemic; people in an urban setting and those identifying as homo/bisexual were more likely to report negative experiences (24%, 28% respectively). CONCLUSION: Urban and sexual minority populations had negative sexual and reproductive health experiences during COVID-19 more than their counterparts. The pandemic has shifted perspectives on family planning, likely due to the diverse impacts of COVID-19, including loss of health insurance and income. IMPLICATION: Females across Georgia reported varying impacts of the COVID-19's pandemic on their sexual and reproductive health care. These findings could be utilized to propose recommendations for care and intimate partner violence support mechanisms, tailored to urban and sexual minority populations.

ERα activity depends on interaction and target site corecruitment with phosphorylated CREB1.

The two transcription factors estrogen receptor α (ERα) and cyclic adenosine monophosphate (cAMP)-responsive element binding protein 1 (CREB1) mediate different signals, bind different response elements, and control different transcriptional programs. And yet, results obtained with transfected reporter genes suggested that their activities may intersect. We demonstrate here that CREB1 stimulates and is necessary for ERα activity on a transfected reporter gene and several endogenous targets both in response to its cognate ligand estrogen and to ligand-independent activation by cAMP. The stimulatory activity of CREB1 requires its DNA binding and activation by phosphorylation, and affects the chromatin recruitment of ERα. CREB1 and ERα are biochemically associated and share hundreds to thousands of chromatin binding sites upon stimulation by estrogen and cAMP, respectively. These shared regulatory activities may underlie the anti-apoptotic effects of estrogen and cAMP signaling in ERα-positive breast cancer cells. Moreover, high levels of CREB1 are associated with good prognosis in ERα-positive breast cancer patients, which may be because of its ability to promote ERα functions, thereby maintaining it as a successful therapeutic target.