Isoquinolinequinone N-oxides with diverging mechanisms of action induce collateral sensitivity against multidrug resistant cancer cells.

Multidrug resistance (MDR) is a major challenge in cancer research. Collateral sensitizers, compounds that exploit the enhanced defense mechanisms of MDR cells as weaknesses, are a proposed strategy to overcome MDR. Our previous work reported the synthesis of two novel Isoquinolinequinone (IQQ) N-oxides that induce collateral sensitivity in MDR ABCB1-overexpressing non-small cell lung cancer (NSCLC) and colorectal cancer cells.

Contribution margins and utilization of transcatheter aortic valve replacement versus surgical aortic valve replacement in the Medicare population.

Background: Hospitals and health systems must balance the demand for transcatheter aortic valve replacement (TAVR) against financial sustainability. Patients may be eligible for both TAVR and surgical aortic valve replacement (SAVR), but financial realities for hospitals may affect differential access to those therapies. We sought to understand the landscape of costs and reimbursement for TAVR and SAVR in the US and to understand the association of procedural reimbursement with receipt of either.

A Multicenter Analysis of Aortic Root Replacement: Non-Native Chest Increases Risk of Post-Operative Mortality.

Objective: Re-do root replacement poses a significant technical challenge, increasing potential risk of morbidity and mortality. This multi-institution study compared outcomes in aortic root replacement stratified by chest surgery and aortic root history.

Methods: A retrospective review by the Western Aortic Collaborative was performed for three different aortic centers for patients who underwent non-emergent root replacement from 2017-2023 with exclusion of patients who underwent more than hemiarch replacement or who presented with acute or hyperacute aortic dissection.

Longitudinal evaluation of iron status during pregnancy: a prospective cohort study in a high-resource setting.

Background: Iron deficiency affects a large proportion of pregnant women worldwide, with potentially serious consequences for perinatal and infant outcomes, but well-powered, comprehensive analyses of longitudinal iron status during pregnancy are scarce.

Objectives: This study aimed to evaluate the longitudinal changes in iron biomarkers across pregnancy and prevalence of iron deficiency in primiparous women in a high-resource setting and propose early pregnancy iron status cutoffs that predict iron deficiency in the third trimester.

Methods: In a prospective cohort of primiparous women with low-risk, singleton pregnancies in Ireland, iron [ferritin, soluble transferrin receptors (sTfR), total body iron (TBI)] and inflammatory markers (C-reactive protein, α-glycoprotein) were measured at 3 study visits: 15, 20, and 33 wk of gestation.

BiP/GRP78 is a pro-viral factor for diverse dsDNA viruses that promotes the survival and proliferation of cells upon KSHV infection.

The Endoplasmic Reticulum (ER)-resident HSP70 chaperone BiP (HSPA5) plays a crucial role in maintaining and restoring protein folding homeostasis in the ER. BiP's function is often dysregulated in cancer and virus-infected cells, conferring pro-oncogenic and pro-viral advantages. We explored BiP's functions during infection by the Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic gamma-herpesvirus associated with cancers of immunocompromised patients.

Dark Photon Limits from Patchy Dark Screening of the Cosmic Microwave Background.

Dark photons that kinetically mix with the Standard Model photon give rise to new spectral anisotropies (patchy dark screening) in the cosmic microwave background (CMB) due to conversion of photons to dark photons within large-scale structure. We utilize predictions for this patchy dark screening signal to provide the tightest constraints to date on the dark photon kinetic mixing parameter [ϵ≲4.5×10^{-8} (95% confidence level)] over the mass range 10^{-13}  eV≲m_{A^{'}}≲10^{-11}  eV, almost an order of magnitude stronger than previous limits, by applying state-of-the-art component separation techniques to the cross-correlation of Planck CMB and unWISE galaxy survey data.

Predicting Admission to Neonatal Care Unit at Mid-Pregnancy and Delivery Using Data from a General Obstetric Population.

Objectives: Development and validation of risk prediction models at mid-pregnancy and delivery to predict admission to the neonatal care unit.

Methods: We used data from all singleton deliveries at Cork University Maternity Hospital (CUMH), Ireland during 2019. Admission to the neonatal care unit was assumed if length of stay in the unit was > 24 h.

mTOR activation induces endolysosomal remodeling and nonclassical secretion of IL-32 via exosomes in inflammatory reactive astrocytes.

Astrocytes respond and contribute to neuroinflammation by adopting inflammatory reactive states. Although recent efforts have characterized the gene expression signatures associated with these reactive states, the cell biology underlying inflammatory reactive astrocyte phenotypes remains under-explored. Here, we used CRISPR-based screening in human iPSC-derived astrocytes to identify mTOR activation a driver of cytokine-induced endolysosomal system remodeling, manifesting as alkalinization of endolysosomal compartments, decreased autophagic flux, and increased exocytosis of certain endolysosomal cargos.

Discovery of Potent Isoquinolinequinone -Oxides to Overcome Cancer Multidrug Resistance.

Multidrug resistance (MDR) of human tumors has resulted in an immediate need to develop appropriate new drugs. This work outlines the development of 20 potent IQQ -oxide derivatives in two isomeric families, both exhibiting nanomolar GI against human tumor cell lines. Preliminary NCI-60 tumor screening sees the C(6) isomers achieve a mean GI > 2 times lower than the corresponding C(7) isomers.

Prenatal stress impacts foetal neurodevelopment: Temporal windows of gestational vulnerability.

Prenatal maternal stressors ranging in severity from everyday occurrences/hassles to the experience of traumatic events negatively impact neurodevelopment, increasing the risk for the onset of psychopathology in the offspring. Notably, the timing of prenatal stress exposure plays a critical role in determining the nature and severity of subsequent neurodevelopmental outcomes. In this review, we evaluate the empirical evidence regarding temporal windows of heightened vulnerability to prenatal stress with respect to motor, cognitive, language, and behavioural development in both human and animal studies.

Cohort profile: Improved Pregnancy Outcomes via Early Detection (IMPROvED), an International Multicentre Prospective Cohort.

Background: Improved Pregnancy Outcomes via Early Detection (IMPROvED) is a multi-centre, European phase IIa clinical study. The primary aim of IMPROvED is to enable the assessment and refinement of innovative prototype preeclampsia risk assessment tests based on emerging biomarker technologies. Here we describe IMPROvED's profile and invite researchers to collaborate.

Pregnancy and birth complications and long-term maternal mental health outcomes: A systematic review and meta-analysis.

Background: Few studies have examined the associations between pregnancy and birth complications and long-term (>12 months) maternal mental health outcomes.

Objectives: To review the published literature on pregnancy and birth complications and long-term maternal mental health outcomes.

Search Strategy: Systematic search of Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (Embase), PsycInfo®, PubMed® and Web of Science from inception until August 2022.

Access to nutrition advice and knowledge, attitudes and practices of pregnant women in Ireland: A cross-sectional study.

Background: Healthy nutritional status, appropriate gestational weight gain and a balanced diet are important predictors of perinatal health outcomes. However, gaps exist in the translation of nutrition recommendations into dietary practices of women before and during pregnancy. The present study explored the relationship between access to nutrition advice, nutrition knowledge, attitudes and practices among pregnant women.

An altered gut microbiome in pre-eclampsia: cause or consequence.

Hypertensive disorders of pregnancy, including pre-eclampsia, are a leading cause of serious and debilitating complications that affect both the mother and the fetus. Despite the occurrence and the health implications of these disorders there is still relatively limited evidence on the molecular underpinnings of the pathophysiology. An area that has come to the fore with regard to its influence on health and disease is the microbiome.

Left Atrial Mechanics Following Preeclamptic Pregnancy.

Background: Preterm preeclampsia is a pregnancy complication associated with myocardial dysfunction and premature cardiovascular disease morbidity and mortality. Left atrial (LA) strain is a noninvasive index of left ventricular end diastolic pressure and an early marker of heart failure risk. This study aimed to evaluate LA strain during the postpartum period in participants with and without preterm preeclampsia and to assess whether this varied in the presence of hypertension, cardiac dysfunction or both.

Association between intrapartum fetal pulse oximetry and adverse perinatal and long-term outcomes: a systematic review and meta-analysis protocol.

Background: Current methods of intrapartum fetal monitoring based on heart rate, increase the rates of operative delivery but do not prevent or accurately detect fetal hypoxic brain injury. There is a need for more accurate methods of intrapartum fetal surveillance that will decrease the incidence of adverse perinatal and long-term neurodevelopmental outcomes while maintaining the lowest possible rate of obstetric intervention. Fetal pulse oximetry (FPO) is a technology that may contribute to improved intrapartum fetal wellbeing evaluation by providing a non-invasive measurement of fetal oxygenation status.

Comparative proteomic analysis of tail regeneration in the green anole lizard, .

As amniote vertebrates, lizards are the most closely related organisms to humans capable of appendage regeneration. Lizards can autotomize, or release their tails as a means of predator evasion, and subsequently regenerate a functional replacement. Green anoles () can regenerate their tails through a process that involves differential expression of hundreds of genes, which has previously been analyzed by transcriptomic and microRNA analysis.

Exposure to gestational diabetes mellitus increases subclinical inflammation mediated in part by obesity.

Gestational diabetes mellitus (GDM) is a frequent and serious complication of pregnancy, often associated with obesity. Metabolic dysfunction and metainflammation are evident in both obesity and GDM. In this cross-sectional study, we aimed at defining the direct contribution of the immune system in GDM, across the main metabolic tissues, specifically focussing on elucidating the roles of obesity and GDM to the clinical outcome.

The Association between Threatened Miscarriage and Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder in Offspring by Age 14 Years.

Objective: To examine the association between threatened miscarriage, and neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in offspring by age 14 years.

Methods: We used data from the Millennium Cohort Study, a nationally representative longitudinal study of children born in the UK. Data on threatened miscarriage and potential confounders were maternal-reported and collected at 9 months postpartum.

Hypertensive disorders of pregnancy and the risk of maternal dementia: a systematic review and meta-analysis.

Objective: Hypertensive disorders of pregnancy, including preeclampsia, are associated with an increased risk for maternal cardiovascular disease, stroke, and chronic kidney disease. However, their association with subsequent maternal dementia or cognitive impairment is less well understood. This study aimed to review and synthesize the published literature on hypertensive disorders of pregnancy and the subsequent risk for maternal dementia or cognitive impairment.

Immunoglobulin-like receptors in chickens: identification, functional characterization, and renaming to cluster homolog of immunoglobulin-like receptors.

The cluster homolog of immunoglobulin-like receptors (CHIRs), previously known as the "chicken homolog of immunogloublin-like receptors," represents is a large group of transmembrane glycoproteins that direct the immune response. However, the full repertoire of putatively activating, inhibitory, or dual function CHIRA, CHIRB, and CHIRAB on chickens' immune responses is poorly understood. Herein, the study objective was to determine the genes encoding CHIR proteins and predict their function by searching canonical protein structure.