Reduced bioenergetics and mitochondrial fragmentation in human primary cytotrophoblasts induced by an EGFR-targeting chemical mixture.

Exposures to complex environmental chemical mixtures during pregnancy reach and target the feto-placental unit. This study investigates the influence of environmental chemical mixtures on placental bioenergetics. Recognizing the essential role of the epidermal growth factor receptor (EGFR) in placental development and its role in stimulating glycolysis and mitochondrial respiration in trophoblast cells, we explored the effects of chemicals known to disrupt EGFR signaling on cellular energy production.

Sex hormone trajectories and association to outcomes after out-of-hospital cardiac arrest.

Background: Outcomes and susceptibility to out-of-hospital cardiac arrest (OHCA) are known to differ by sex, yet little is known about changes in sex hormones after OHCA. We sought to determine the trajectory of sex hormones after OHCA and their association to survival and neurological outcome.

Methods: Plasma samples were collected from those that survived to hospital admission at four time points (1, 6, 24, and 48 h) and estrone, estradiol, progesterone, and testosterone concentrations were quantified via liquid chromatography-mass spectrometry.

Apolipoprotein E polymorphisms and female fertility in a transgenic mouse model of Alzheimer's disease.

Apolipoprotein E (APOE) is a major cholesterol carrier responsible for lipid transport and injury repair in the brain. The human APOE gene (h-APOE) has 3 naturally occurring alleles: ε3, the common allele; ε4, which increases Alzheimer's disease (AD) risk up to 15-fold; and ε2, the rare allele which protects against AD. Although APOE4 has negative effects on neurocognition in old age, its persistence in the population suggests a survival advantage.

Protein Misfolding in Pregnancy: Current Insights, Potential Mechanisms, and Implications for the Pathogenesis of Preeclampsia.

Protein misfolding disorders are a group of diseases characterized by supra-physiologic accumulation and aggregation of pathogenic proteoforms resulting from improper protein folding and/or insufficiency in clearance mechanisms. Although these processes have been historically linked to neurodegenerative disorders, such as Alzheimer's disease, evidence linking protein misfolding to other pathologies continues to emerge. Indeed, the deposition of toxic protein aggregates in the form of oligomers or large amyloid fibrils has been linked to type 2 diabetes, various types of cancer, and, in more recent years, to preeclampsia, a life-threatening pregnancy-specific disorder.

Work-Life Balance and Academic Productivity Among College of Medicine Faculty During the Evolution of the COVID-19 Pandemic: The New Normal.

Background: Work and home stress, productivity, and self-care of academic medicine faculty in Spring 2021 was contrasted to faculty's experience in the Spring of 2020, both of which were relatively compared with the prepandemic period.

Methods: A 93-question survey was sent to academic medicine faculty at an urban public university medical center in March 2020 and again in March 2021. Demographic, family, and academic characteristics, work distribution and productivity before and during the pandemic, perceived stress related to work and home activities, and self-care data compared with the prepandemic period were collected.

Surgical Instrument Designers and Inventors-Where are the Women?

Historically, surgical instruments were designed by men for male surgeons. Although instrumentation has changed with the changing paradigms of surgery, it has failed to adapt to the changing surgical workforce. Almost 30% of surgeons are female and nearly 90% of surveyed female surgeons report poor instrument design and associated musculoskeletal injuries from use.

PAPP-A as a screening tool for assessment of gestational age before medication abortion in an intended-use population.

Prior studies indicate that PAPP-A could serve as a marker of gestational age (GA) with the potential to determine eligibility for medication abortion. The authors validated the relationship between PAPP-A and GA in an actual-use population. The authors collected blood samples, medical histories and ultrasound-determined GA from patients presenting for abortion services.

Transcriptomics-Based Subphenotyping of the Human Placenta Enabled by Weighted Correlation Network Analysis in Early-Onset Preeclampsia With and Without Fetal Growth Restriction.

Background: Placental disorders contribute to pregnancy complications, including preeclampsia and fetal growth restriction (FGR), but debate regarding their specific pathobiology persists. Our objective was to apply transcriptomics with weighted gene correlation network analysis to further clarify the placental dysfunction in these conditions.

Methods: We performed RNA sequencing with weighted gene correlation network analysis using human placental samples (n=30), separated into villous tissue and decidua basalis, and clinically grouped as follows: (1) early-onset preeclampsia (EOPE)+FGR (n=7); (2) normotensive, nonanomalous preterm FGR (n=5); (2) EOPE without FGR (n=8); (4) spontaneous idiopathic preterm birth (n=5) matched for gestational age; and (5) uncomplicated term births (n=5).

Evaluation of a Maternal Plasma RNA Panel Predicting Spontaneous Preterm Birth and Its Expansion to the Prediction of Preeclampsia.

Preterm birth is the principal contributor to neonatal death and morbidity worldwide. We previously described a plasma cell-free RNA panel that between 16 and 20 weeks of pregnancy had potential to predict spontaneous preterm birth (sPTB) ≤ 32 weeks caused by preterm labor (PTL) or preterm premature rupture of membranes (PPROM). The present study had three objectives: estimate the RNA panel prognostic accuracy for PTL/PPROM ≤ 32 weeks in a larger series; improve accuracy by adding clinical characteristics to the predictive model; and examine the association of the RNA panel with preeclampsia.

Gender-differences of proceduralists in perception of hand-held surgical instrument fit - A cross-sectional survey.

Objective: Determining perception of hand size as it relates to instrument use and ability to perform a procedure in a diverse population of proceduralists across surgical and medical specialties.

Methods: Cross-sectional survey was distributed via electronic format to a convenience sample of surgeons/physicians. Secondary analysis included identified instrument use and choice of/perception of ability to learn and perform procedures.

A Novel Role for Plasminogen Activator Inhibitor Type-2 as a Hypochlorite-Resistant Serine Protease Inhibitor and Holdase Chaperone.

Plasminogen activator inhibitor type-2 (PAI-2), a member of the serpin family, is dramatically upregulated during pregnancy and in response to inflammation. Although PAI-2 exists in glycosylated and non-glycosylated forms in vivo, the majority of in vitro studies of PAI-2 have exclusively involved the intracellular non-glycosylated form. This study shows that exposure to inflammation-associated hypochlorite induces the oligomerisation of PAI-2 via a mechanism involving dityrosine formation.

Conformation-dependent anti-Aβ monoclonal antibody signatures of disease status and severity in urine of women with preeclampsia.

Prior research has shown that urine of women with preeclampsia (PE) contains amyloid-like aggregates that are congophilic (exhibit affinity for the amyloidophilic dye Congo red) and immunoreactive with A11, a polyclonal serum against prefibrillar β-amyloid oligomers, thereby supporting pathogenic similarity between PE and protein conformational disorders such as Alzheimer's and prion disease. The objective of this study was to interrogate PE urine using monoclonal antibodies with previously characterized A11-like epitopes. Over 100 conformation-dependent monoclonals were screened and three (mA11-09, mA11-89, and mA11-205) selected for further confirmation in 196 urine samples grouped as follows: severe features PE (sPE, n = 114), PE without severe features (mPE, n = 30), chronic hypertension (crHTN, n = 14) and normotensive pregnant control (P-CRL, n = 38).

Endocan, a Soluble Marker of Endothelial Cell Activation Is a Molecular Marker of Disease Severity in Women with Preeclampsia.

Endocan is a proteoglycan secreted by activated endothelium that regulates angiogenesis via interaction with hepatocyte growth factor (HGF). We hypothesized that women diagnosed with preeclampsia (PE) and/or fetal growth restriction (FGR) have elevated circulating endocan concentrations in direct relationship with severity of clinical manifestations. Serum concentration of endocan and HGF were analyzed in 224 women grouped as healthy pregnant controls (P-CRL, n = 77), PE with severe features (sPE, n = 83), chronic hypertension (crHTN: n = 36), idiopathic FGR (n = 18), and healthy non-pregnant controls (NP-CRL, n = 7).

Controversies in treatment practices of the mother-infant dyad at the limit of viability.

In the setting of threatened extreme preterm birth, balancing maternal and fetal risks and benefits in order to choose the best available treatment options is of utmost importance. Inconsistency in treatment practices for infants born between 22 and 24 weeks of gestatotional age may account for inter-hospital variation in survival rates with and without impairment. Most importantly, non-biased and accurate information must be presented to the family as soon as extremely preterm birth is suspected, including counseling on morbidities and mortality associated with delivery at the limits of viability.

Work-Life Balance and Productivity Among Academic Faculty During the COVID-19 Pandemic: A Latent Class Analysis.

For faculty in academic health sciences, the balance between research, education, and patient care has been impeded by the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to identify personal and professional characteristics of faculty to understand the impact of the pandemic on faculty and consequent policy implications. A 93-question survey was sent to faculty at a large urban public university and medical center.

Accuracy of anemia screening by point-of-care hemoglobin testing in patients seeking abortion.

Objective: Accurate and timely diagnosis of anemia in pregnancy is necessary for safe management of abortion care. Screening for anemia in abortion care is often accomplished using commercially-available point-of-care tests from capillary blood, but the validity of this test has not been investigated in the context of abortion care. We sought to determine the accuracy of a capillary hemoglobin (Hb) among pregnant patients seeking induced abortion.

Analytical Comparison of Pregnancy-Associated Plasma Protein-A (PAPP-A) Immunoassays for Biochemical Determination of Gestational Age.

Background: Accurate pregnancy dating is critical for maternal and child health and for counseling on safe and effective abortion methods. While last menstrual period and first trimester ultrasound are often used together to determine gestational age (GA), they have limited accuracy and availability, respectively. Prior studies have shown that pregnancy-associated plasma protein-A (PAPP-A) increases exponentially during pregnancy and has the potential to serve as a biochemical marker of GA.

Early pregnancy prediction of spontaneous preterm birth before 32 completed weeks of pregnancy using plasma RNA: transcriptome discovery and initial validation of an RNA panel of markers.

Objective: To compare the second-trimester plasma cell-free (PCF) transcriptome of women who delivered at term with that of women with spontaneous preterm birth (sPTB) at or before 32 weeks of gestation and identify/validate PCF RNA markers present by 16 weeks of gestation.

Design: Prospective case-control study.

Setting: Academic tertiary care centre.