Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair.

Drugs targeting the DNA damage response (DDR) are widely used in cancer therapy, but resistance to these drugs remains a major clinical challenge. Here, we show that SYCP2, a meiotic protein in the synaptonemal complex, is aberrantly and commonly expressed in breast and ovarian cancers and associated with broad resistance to DDR drugs. Mechanistically, SYCP2 enhances the repair of DNA double-strand breaks (DSBs) through transcription-coupled homologous recombination (TC-HR).

Association between per- and polyfluoroalkyl substances exposure and thyroid function biomarkers among females attending a fertility clinic.

Per- and polyfluoroalkyl substances (PFAS) exposure was associated with changes in thyroid function in pregnant mothers and the general population. Limited such evidence exists in other susceptible populations such as females with fertility problems. This cross-sectional study included 287 females seeking medically assisted reproduction at a fertility clinic in Massachusetts, United States, between 2005 and 2019.

Humoral profiles of toddlers and young children following SARS-CoV-2 mRNA vaccination.

Although young children generally experience mild symptoms following infection with SARS-CoV-2, severe acute and long-term complications can occur. SARS-CoV-2 mRNA vaccines elicit robust immunoglobulin profiles in children ages 5 years and older, and in adults, corresponding with substantial protection against hospitalizations and severe disease. Whether similar immune responses and humoral protection can be observed in vaccinated infants and young children, who have a developing and vulnerable immune system, remains poorly understood.

Maternal and Paternal Preconception Serum Concentrations of Per and Polyfluoroalkyl Substances in Relation to Birth Outcomes.

Prenatal per and polyfluoroalkyl substances (PFAS) exposure is associated with adverse birth outcomes. There is an absence of evidence on the relationship between maternal and paternal preconception PFAS exposure and birth outcomes. This study included 312 mothers and 145 fathers with a singleton live birth from a preconception cohort of subfertile couples seeking fertility treatment at a U.

Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity.

Maternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many mediated by in utero microglial programming. As microglia remain inaccessible throughout development, identification of noninvasive biomarkers reflecting fetal brain microglial programming could permit screening and intervention. We used lineage tracing to demonstrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells) in a mouse model of maternal diet-induced obesity, and single-cell RNA-seq to demonstrate shared transcriptional programs.

Effects of armed conflict on maternal and infant health: a mixed-methods study of Armenia and the 2020 Nagorno-Karabakh war.

Introduction: Armed conflict worldwide and across history has harmed the health of populations directly and indirectly, including generations beyond those immediately exposed to violence. The 2020 war between Armenia and Azerbaijan over Nagorno-Karabakh, inhabited by an ethnically Armenian population, provides an example of how conflict harmed health during COVID-19. We hypothesised that crises exposure would correspond to decreased healthcare utilisation rates and worse health outcomes for the maternal and infant population in Armenia, compounded during the pandemic.

Helping Us Grow Stronger (HUGS)/Abrazos: a community-based initiative improved perinatal mental health in an urban cohort.

Background: Targeted programs aimed at improving maternal mental health, particularly among those exposed to social determinants of health, are increasingly critical since the onset of the COVID-19 pandemic, yet the impact of such programs is poorly understood.

Objective: This study aimed to evaluate the impact of a novel, language-concordant community-based program on perinatal mental health.

Study Design: We conducted a prospective cohort study of peripartum individuals referred to a new community-based intervention known as Helping Us Grow Stronger (HUGS/Abrazos).

Comparison of vaginal microbiota between women with inflammatory bowel disease and healthy controls.

Background: The gut microbiota in patients with inflammatory bowel disease are perturbed in both composition and function. The vaginal microbiome and its role in the reproductive health of women with inflammatory bowel disease is less well described.

Objective: We aim to compare the vaginal microbiota of women with inflammatory bowel disease to healthy controls.

A diagnostic questionnaire for childbirth related posttraumatic stress disorder: a validation study.

Background: Labor and delivery can entail complications and severe maternal morbidities that threaten a woman's life or cause her to believe that her life is in danger. Women with these experiences are at risk for developing posttraumatic stress disorder. Postpartum posttraumatic stress disorder, or childbirth-related posttraumatic stress disorder, can become an enduring and debilitating condition.

Inhibition of the proline metabolism rate-limiting enzyme P5CS allows proliferation of glutamine-restricted cancer cells.

Glutamine is a critical metabolite for rapidly proliferating cells as it is used for the synthesis of key metabolites necessary for cell growth and proliferation. Glutamine metabolism has been proposed as a therapeutic target in cancer and several chemical inhibitors are in development or in clinical trials. How cells subsist when glutamine is limiting is poorly understood.

Evaluation of anti-biofilm effect of antimicrobial sonodynamic therapy-based periodontal ligament stem cell-derived exosome-loaded kojic acid on biofilm.

Antimicrobial sonodynamic therapy (aSDT) is an approach that uses ultrasound waves (UWs) and a sonosensitizer to generate reactive oxygen species (ROS) to damage microbial cells in biofilms. Using nano-carriers, such as exosomes (Exos), to deliver the sonosensitizer can potentially enhance the effectiveness of aSDT. aSDT can downregulate the expression of and genes, increasing the production of endogenous ROS and degradation of pre-formed biofilms.

Stressed target cancer cells drive nongenetic reprogramming of CAR T cells and solid tumor microenvironment.

The poor efficacy of chimeric antigen receptor T-cell therapy (CAR T) for solid tumors is due to insufficient CAR T cell tumor infiltration, in vivo expansion, persistence, and effector function, as well as exhaustion, intrinsic target antigen heterogeneity or antigen loss of target cancer cells, and immunosuppressive tumor microenvironment (TME). Here we describe a broadly applicable nongenetic approach that simultaneously addresses the multiple challenges of CAR T as a therapy for solid tumors. The approach reprograms CAR T cells by exposing them to stressed target cancer cells which have been exposed to the cell stress inducer disulfiram (DSF) and copper (Cu)(DSF/Cu) plus ionizing irradiation (IR).

Sex-specific impact of maternal obesity on fetal placental macrophages and cord blood triglycerides.

Introduction: Maternal obesity is associated with increased risk of offspring obesity and cardiometabolic disease. Altered fetoplacental immune programming is a potential candidate mechanism. Differences in fetal placental macrophages, or Hofbauer cells (HBCs), have been observed in maternal obesity, and lipid metabolism is a key function of resident macrophages that may be deranged in inflammation/immune activation.

Bacterial amylases enable glycogen degradation by the vaginal microbiome.

The human vaginal microbiota is frequently dominated by lactobacilli and transition to a more diverse community of anaerobic microbes is associated with health risks. Glycogen released by lysed epithelial cells is believed to be an important nutrient source in the vagina. However, the mechanism by which vaginal bacteria metabolize glycogen is unclear, with evidence implicating both bacterial and human enzymes.

The evolving role of DNA damage response in overcoming therapeutic resistance in ovarian cancer.

Epithelial ovarian cancer (EOC) is treated in the first-line setting with combined platinum and taxane chemotherapy, often followed by a maintenance poly (ADP-ribose) polymerase inhibitor (PARPi). Responses to first-line treatment are frequent. For many patients, however, responses are suboptimal or short-lived.

The complexity of genitourinary syndrome of menopause: number, severity, and frequency of vulvovaginal discomfort symptoms in women enrolled in a randomized trial evaluating treatment for genitourinary syndrome of menopause.

Objective: The aim of the study is to describe the location, severity, and frequency of genitourinary symptoms in postmenopausal women enrolled in a randomized trial of treatment for vulvovaginal discomfort.

Methods: This is a post hoc analysis of enrollment responses for participants in the MsFLASH Vaginal Health Trial. Participants were asked about the severity (0-3), frequency (in days per week) and location (vulvar or vaginal) of itch, dryness, pain/soreness, irritation, as well as severity and frequency of pain with penetration, vaginal discharge, urinary incontinence, and urinary urgency.

Bacterial vaginosis: a review of approaches to treatment and prevention.

Bacterial vaginosis (BV) is a common cause of vaginitis worldwide and is associated with serious reproductive health outcomes, including increased risk of preterm birth, sexually transmitted infections, and pelvic inflammatory disease. The current and only FDA-approved treatment regimens for BV are antibiotics, such as metronidazole and clindamycin. Antibiotics provide a short-term cure for bacterial vaginosis; however, fail to provide a consistent long-term cure for many women.

Association of Early Pregnancy Perfluoroalkyl and Polyfluoroalkyl Substance Exposure With Birth Outcomes.

Importance: Prenatal perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been linked to adverse birth outcomes. Previous research showed that higher folate concentrations are associated with lower blood PFAS concentrations in adolescents and adults. Further studies are needed to explore whether prenatal folate status mitigates PFAS-related adverse birth outcomes.

Long-term humoral signatures following acute pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children.

Background: Although most children experience mild symptoms during acute SARS-CoV-2 infection, some develop the severe post-COVID-19 complication, Multisystem Inflammatory Syndrome in Children (MIS-C). While acute presentations of COVID-19 and MIS-C have been well immunophenotyped, little is known about the lasting immune profile in children after acute illness.

Methods: Children 2 months-20 years of age presenting with either acute COVID-19 (n = 9) or MIS-C (n = 12) were enrolled in a Pediatric COVID-19 Biorepository at a single medical center.

Trauma and female reproductive health across the lifecourse: motivating a research agenda for the future of women's health.

The aetiology behind many female reproductive disorders is poorly studied and incompletely understood despite the prevalence of such conditions and substantial burden they impose on women's lives. In light of evidence demonstrating a higher incidence of trauma exposure in women with many such disorders, we present a set of interlinked working hypotheses proposing relationships between traumatic events and reproductive and mental health that can define a research agenda to better understand reproductive outcomes from a trauma-informed perspective across the lifecourse. Additionally, we note the potential for racism to act as a traumatic experience, highlight the importance of considering the interaction between mental and reproductive health concerns, and propose several neuroendocrinological mechanisms by which traumatic experiences might increase the risk of adverse health outcomes in these domains.

Humoral profiles of toddlers and young children following SARS-CoV-2 mRNA vaccination.

Although young children generally experience mild symptoms following infection with SARS-CoV-2, severe acute and long-term complications can occur. SARS-CoV-2 mRNA vaccines elicit robust immunoglobulin profiles in children ages 5 years and older, and in adults, corresponding with substantial protection against hospitalizations and severe disease. Whether similar immune responses and humoral protection can be observed in vaccinated infants and young children, who have a developing and vulnerable immune system, remains poorly understood.

FHL2 deficiency impairs follicular development and fertility by attenuating EGF/EGFR/YAP signaling in ovarian granulosa cells.

Female subfertility is an increasing reproductive issue worldwide, which is partially related to abnormal ovarian follicular development. Granulosa cells (GCs), by providing the necessary physical support and microenvironment for follicular development, play critical roles in maintaining female fertility. We previously showed that ectopic expression of four and a half LIM domains 2 (FHL2) promoted ovarian granulosa cell tumor progression.

Accelerated Longitudinal Weight Gain Among Infants With In Utero COVID-19 Exposure.

Context: Since the initial outbreak of coronavirus disease 2019 (COVID-19), a novel population of children with in utero exposure to maternal infection has emerged whose health outcomes are largely unknown.

Objective: To compare longitudinal growth trajectories among infants with vs without in utero COVID-19 exposure.

Methods: We conducted a longitudinal cohort study leveraging a prospectively enrolled perinatal biorepository among 149 infants with in utero COVID-19 exposure and 127 unexposed controls.