Impact of Endocrine-Disrupting Chemicals, Climate, and Air Pollution on Pregnancy Outcomes: A Scoping Review.

Environmental pollutants, including endocrine-disrupting chemicals (EDCs), air pollution, and climate change, are increasingly recognized for their potential impact on pregnancy outcomes. EDCs, found in pesticides, industrial chemicals, and personal care products, are associated with preterm birth and fetal growth restriction, primarily through hormonal interference. Air pollution, notably PM, NO, and O, has been linked to increased rates of preterm birth, low birth weight, and stillbirth.

"To Be Vaccinated or Not to Be Vaccinated": Factors Influencing COVID-19 Vaccine Hesitancy and Future Vaccination Willingness Amongst US Women of Reproductive Age.

Background & Objectives: Growing data on the impact of herd immunity and susceptibility of unvaccinated persons to chronic COVID sequelae requires deeper understanding of vaccine stigma and hesitancy to facilitate population needs. Reproductive-aged women (18-45 years) were at a "vaccine paradox" during COVID-19 - hesitant to receive the vaccine, yet at increased risk for COVID infection. In this study, we sought to: identify demographic predictors, reasons, geographic location of vaccine hesitancy, and COVID-specific attributes that predict future vaccination willingness.

Minimizing higher-order aggregation maximizes iron mobilization by small molecules.

The natural product hinokitiol mobilizes iron across lipid bilayers at low concentrations and restores hemoglobinization in iron transporter protein-deficient systems. But hinokitiol fails to similarly mobilize iron at higher concentrations, limiting its uses in chemical biology and medicine. Here we show that at higher concentrations, hinokitiol:Fe(III) complexes form large, higher-order aggregates, leading to loss of transmembrane iron mobilization.

Probing Tissue Viscoelasticity With STL Ultrasound Shearwave Spectroscopy Using Cole-Cole Diagrams.

Objective: Viscoelasticity is mapped by dispersion in shearwave elastography. Incomplete spectral information of shearwaves is therefore used to estimate mechanical stiffness. We propose capturing the "full-waveform-information" of the shear wave spectra to better resolve complex shear modulus μ (ω).

Coronavirus Disease 2019 (COVID-19)-Related Stress and Menstrual Changes.

Objective: To evaluate how stress related to the coronavirus disease 2019 (COVID-19) pandemic has affected women's menstrual cycles. We hypothesized that women with high levels of COVID-19-related stress would have more menstrual changes compared with those with lower levels of stress.

Methods: Using a cross-sectional study design, we recruited a representative sample of U.

Pregnant Women Following Bariatric Surgery: a Focus on Maternal Mental Health and Its Impact on Birth Outcomes.

Purpose: Bariatric surgery is associated with elevated risks for adverse birth outcomes, such as small-for-gestational-age infants (SGA). Maternal mental health is a critical regulator of fetal growth, but it is largely overlooked in pregnant women post-surgery. This study aimed to examine the associations between maternal mental health and birth outcomes in pregnant women post-bariatric surgery.

The Geographical Correlation Between Historical Preterm Birth Disparities and COVID-19 Burden.

Similar to obstetric outcomes, rates of SARS-CoV-2 (COVID-19) infection are not homogeneously distributed among populations; risk factors accumulate in discrete locations. This study aimed to investigate the geographical correlation between pre-COVID-19 regional preterm birth (PTB) disparities and subsequent COVID-19 disease burden. We performed a retrospective, ecological cohort study of an upstate New York birth certificate database from 2004 to 2018, merged with publicly available community resource data.

Validations of the microchannel flow model for characterizing vascularized tissues.

The microchannel flow model postulates that stress-strain behavior in soft tissues is influenced by the time constants of fluid-filled vessels related to Poiseuille's law. A consequence of this framework is that changes in fluid viscosity and changes in vessel diameter (through vasoconstriction) have a measurable effect on tissue stiffness. These influences are examined through the theory of the microchannel flow model.

Associations Between Historically Redlined Districts and Racial Disparities in Current Obstetric Outcomes.

Importance: Despite much higher health care expenditure than comparable countries, striking racial and ethnic disparities exist in obstetric outcomes in the United States. A multifaceted exploration of the factors influencing these disparities, including the legacy of structural racism, is important to improve health outcomes for all.

Objective: To characterize the association of the historic racially discriminatory home loan practice of redlining with disparities in modern obstetric outcomes.

Improved Recognition of Maternal Deaths Using Modern Data Analytics.

Objective: To use a data-fusion approach to improve ascertainment of maternal deaths not detected with standard surveillance strategies.

Methods: We conducted a retrospective cohort study from the electronic health records of a tertiary medical center from 2011 to 2018. Cases of maternal death were identified in two ways: 1) using a standard medical informatics service query of hospital data and 2) using the TriNetX discovery tool as patients with a vital status of "deceased" and evidence of antecedent pregnancy exposure based on such factors as obstetric diagnostic codes or obstetric-related procedures.

"Provoked" feto-maternal hemorrhage may represent insensible cell exchange in pregnancies from 6 to 22 weeks gestational age.

Objective: To quantify spontaneous and provoked fetal to maternal cell exchange in the first half of pregnancy. Transfer of fetal red blood cells (FRBCs) into the maternal circulation during the first half of pregnancy is poorly characterized but of clinical relevance for miscarriage management and invasive procedures.

Study Design: Prospective, descriptive cohort study of women presenting for surgical termination of pregnancy with sonographically confirmed gestational age (GA).

Destination Therapy: Standardizing the Role of Palliative Medicine and Delineating the DT-LVAD Journey.

Context: Destination therapy (DT) patients face significant challenges as they transition from chronic left ventricular assist device (LVAD) support to comfort-oriented care. Integration of palliative medicine (PM) into the multidisciplinary team is important to facilitate advanced care planning (ACP) and improve quality of life (QoL).

Objectives: We evaluated the impact of a structured programmatic approach to the end-of-life (EOL) process in DT patients as measured by QoL surveys and the utilization of ACP.

Report from the Killer-cell Immunoglobulin-like Receptors (KIR) component of the 17th International HLA and Immunogenetics Workshop.

The goals of the KIR component of the 17th International HLA and Immunogenetics Workshop (IHIW) were to encourage and educate researchers to begin analyzing KIR at allelic resolution, and to survey the nature and extent of KIR allelic diversity across human populations. To represent worldwide diversity, we analyzed 1269 individuals from ten populations, focusing on the most polymorphic KIR genes, which express receptors having three immunoglobulin (Ig)-like domains (KIR3DL1/S1, KIR3DL2 and KIR3DL3). We identified 13 novel alleles of KIR3DL1/S1, 13 of KIR3DL2 and 18 of KIR3DL3.

Nitric Oxide-Releasing Macromolecule Exhibits Broad-Spectrum Antifungal Activity and Utility as a Topical Treatment for Superficial Fungal Infections.

Cutaneous and superficial fungal infections affecting the skin, nails, and hair of humans are caused primarily by dermatophytes of the genera and or by yeasts of the genera and Onychomycosis is a common fungal infection of the nail that frequently coexists with tinea pedis, the most prevalent mycotic skin infection. Efficacy rates for current topical onychomycosis therapies are hampered by low drug penetration across the nail plate, which is theoretically obviated with nitric oxide (NO)-based topical therapies. The Nitricil technology platform is comprised of polysiloxane-based macromolecules that stably release therapeutic levels of NO.

Andexanet alfa effectively reverses edoxaban anticoagulation effects and associated bleeding in a rabbit acute hemorrhage model.

Introduction: Increasing use of factor Xa (FXa) inhibitors necessitates effective reversal agents to manage bleeding. Andexanet alfa, a novel modified recombinant human FXa, rapidly reverses the anticoagulation effects of direct and indirect FXa inhibitors.

Objective: To evaluate the ability of andexanet to reverse anticoagulation in vitro and reduce bleeding in rabbits administered edoxaban.

Safety, pharmacokinetics, and reversal of apixaban anticoagulation with andexanet alfa.

Direct factor Xa (FXa) inhibitors lack a specific reversal agent for emergencies such as major bleeding or urgent surgery. Andexanet alfa, a modified, catalytically inactive, recombinant human FXa derivative, reverses anticoagulant effect by binding and sequestering FXa inhibitors. This original report of safety and dose-finding, phase 1 and 2 randomized, double-blind, placebo-controlled studies, investigated various doses of andexanet in healthy volunteers.

Preclinical safety and efficacy of andexanet alfa in animal models.

Essentials There is currently no approved reversal agent for factor Xa (FXa) inhibitors Andexanet alfa has been developed to reverse the anticoagulant effects of FXa inhibitors Andexanet reduced blood loss and anticoagulation markers in rivaroxaban-anticoagulated rabbits Andexanet was well tolerated in monkeys and rats, with no evidence of prothrombotic activity SUMMARY: Background Andexanet alfa is a recombinant modified form of factor Xa (FXa), designed to bind to and reverse the anticoagulant activity of FXa inhibitors. Objectives To evaluate the ability of andexanet to reverse the anticoagulant activity of rivaroxaban, and assess its pharmacokinetics (PK) and toxicity in animal models. Methods The effects of andexanet on blood loss, anti-FXa activity, rivaroxaban unbound plasma concentrations and other coagulation parameters were assessed in a rabbit liver laceration 'treatment' model.

PRT062607 Achieves Complete Inhibition of the Spleen Tyrosine Kinase at Tolerated Exposures Following Oral Dosing in Healthy Volunteers.

The spleen tyrosine kinase (SYK) regulates immune cell activation in response to engagement of a variety of receptors, making it an intriguing target for the treatment of inflammatory and autoimmune disorders as well as certain B-cell malignancies. We have previously reported on the discovery and preclinical characterization of PRT062607, a potent and highly selective inhibitor of SYK that exhibits robust anti-inflammatory activity in a variety of animal models. Here we present data from our first human studies aimed at characterizing the pharmacokinetics (PK), pharmacodynamics (PD), and safety of PRT062607 in healthy volunteers following single and multiple oral administrations.

Transitional Care and Adherence of Adolescents and Young Adults After Kidney Transplantation in Germany and Austria: A Binational Observatory Census Within the TRANSNephro Trial.

Transition from child to adult-oriented care is widely regarded a challenging period for young people with kidney transplants and is associated with a high risk of graft failure. We analyzed the existing transition structures in Germany and Austria using a questionnaire and retrospective data of 119 patients transferred in 2011 to 2012. Most centers (73%) confirmed agreements on the transition procedure.

The novel kinase inhibitor PRT062070 (Cerdulatinib) demonstrates efficacy in models of autoimmunity and B-cell cancer.

The heterogeneity and severity of certain autoimmune diseases and B-cell malignancies warrant simultaneous targeting of multiple disease-relevant signaling pathways. Dual inhibition of spleen tyrosine kinase (SYK) and Janus kinase (JAK) represents such a strategy and may elicit several benefits relative to selective kinase inhibition, such as gaining control over a broader array of disease etiologies, reducing probability of selection for bypass disease mechanisms, and the potential that an overall lower level suppression of individual targets may be sufficient to modulate disease activity. To this end, we provide data on the discovery and preclinical development of PRT062070 [4-(cyclopropylamino)-2-({4-[4-(ethylsulfonyl)piperazin-1-yl]phenyl}amino)pyrimidine-5-carboxamide hydrochloride], an orally active kinase inhibitor that demonstrates activity against SYK and JAK.

A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa.

Inhibitors of coagulation factor Xa (fXa) have emerged as a new class of antithrombotics but lack effective antidotes for patients experiencing serious bleeding. We designed and expressed a modified form of fXa as an antidote for fXa inhibitors. This recombinant protein (r-Antidote, PRT064445) is catalytically inactive and lacks the membrane-binding γ-carboxyglutamic acid domain of native fXa but retains the ability of native fXa to bind direct fXa inhibitors as well as low molecular weight heparin-activated antithrombin III (ATIII).