Potentiating the effect of immunotherapy in pancreatic cancer using gas-entrapping materials.

Immune checkpoint inhibitors (ICIs) show limited success in treating pancreatic ductal adenocarcinoma (PDAC), largely due to immune evasion mechanisms, including downregulating expression of major histocompatibility complex class I (MHC-I). Our retrospective analysis demonstrated that smoking - a state of elevated CO exposure - is correlated with increased MHC I expression in pancreatic tumors. Here we tested our hypothesis that introducing exogenous CO augments the anti-cancer effects of immunotherapy.

A comparison of assessment tools for childcare centers in high vs. low resource settings.

Studies suggest issues may arise when using childcare setting assessment tools designed for high-resource settings in low-resource settings to assess and improve the quality of care, including placing disproportionate weight on features of the childcare environment that may not be available or culturally appropriate within the low-resource context. This study compares a novel assessment tool developed in and for low-income and low-resource settings with a standardized "gold standard" tool developed for use in high-resource settings. The study included a randomized sample of 34 childcare centers in a low-resource context that provided care for approximately 918.

RELAX (REducing Levels of AnXiety): a study protocol for a parallel two-arm randomised controlled trial evaluating a web-based early intervention for pregnant women with high levels of repetitive negative thinking to prevent escalating anxiety during pregnancy and after birth.

Background: Perinatal anxiety is common: up to 40% of pregnant women and new mothers experience high levels of anxiety. Given its prevalence, interventions that are low-intensity, highly accessible and cost-efficient, and target modifiable risk factors for anxiety are needed. Repetitive negative thinking (RNT)-such as worrying about ways things will go wrong in the future or ruminating about past negative events-is a risk factor for the development of anxiety.

Valsartan Rescues Suppressed Mitochondrial Metabolism during Insulin Resistance in C2C12 Myotubes.

Elevated circulating branched-chain amino acids (BCAA) have been linked with the severity of insulin resistance across numerous populations, implicating heightened BCAA metabolism as a potential therapy for insulin resistance. Recently, the angiotensin II type 1 receptor (AT1R) inhibitor Valsartan (VAL) was identified as a potent inhibitor of branched-chain alpha-keto acid dehydrogenase kinase (BCKDK), a negative regulator of BCAA metabolism. This work investigated the effect of VAL on myotube metabolism and insulin sensitivity under both insulin sensitive and insulin resistant conditions.

Long-term exposure to ambient PM and population health: evidence from linked census data.

Particulate matter suspended in the air that is comprised of microscopic particles with a diameter of 2.5μm or less (PM) is among the most impactful pollutants globally. Extensive evidence shows exposure to ambient PM is associated with a wide range of poor health outcomes.

Effect of mTORC Agonism via MHY1485 with and without Rapamycin on C2C12 Myotube Metabolism.

Unlabelled: The mechanistic target of rapamycin complex (mTORC) regulates protein synthesis and can be activated by branched-chain amino acids (BCAAs). mTORC has also been implicated in the regulation of mitochondrial metabolism and BCAA catabolism. Some speculate that mTORC overactivation by BCAAs may contribute to insulin resistance.

Modulation of diabetic wound healing using carbon monoxide gas-entrapping materials.

Diabetic wound healing is uniquely challenging to manage due to chronic inflammation and heightened microbial growth from elevated interstitial glucose. Carbon monoxide (CO), widely acknowledged as a toxic gas, is also known to provide unique therapeutic immune modulating effects. To facilitate delivery of CO, we have designed hyaluronic acid-based CO-gas-entrapping materials (CO-GEMs) for topical and prolonged gas delivery to the wound bed.

Prenatal exposure to particulate matter and infant birth outcomes: Evidence from a population-wide database.

There are growing concerns about the impact of pollution on maternal and infant health. Despite an extensive correlational literature, observational studies which adopt methods that seek to address potential biases due to unmeasured confounders draw mixed conclusions. Using a population database of births in Northern Ireland (NI) linked to localized geographic information on pollution in mothers' postcodes (zipcodes) of residence during pregnancy, we examine whether prenatal exposure to PM is associated with a comprehensive range of birth outcomes, including placental health.

Fructose Reduces Mitochondrial Metabolism and Increases Extracellular BCAA during Insulin Resistance in C2C12 Myotubes.

Unlabelled: Fructose is a commonly consumed monosaccharide implicated in developing several metabolic diseases. Previously, elevated branched-chain amino acids (BCAA) have been correlated with the severity of insulin resistance. Most recently, the effect of fructose consumption on the downregulation of BCAA catabolic enzymes was observed.

Correlation of fetal lung area with MRI derived pulmonary volume.

Background: Neonatal chest-Xray (CXR)s are commonly performed as a first line investigation for the evaluation of respiratory complications. Although lung area derived from CXRs correlates well with functional assessments of the neonatal lung, it is not currently utilised in clinical practice, partly due to the lack of reference ranges for CXR-derived lung area in healthy neonates. Advanced MR techniques now enable direct evaluation of both fetal pulmonary volume and area.

Gender and sex hormone effects on neonatal innate immune function.

Objectives: Scientific evidence provides a widened view of differences in immune response between male and female neonates. The X-chromosome codes for several genes important in the innate immune response and neonatal innate immune cells express receptors for, and are inhibited by, maternal sex hormones. We hypothesized that sex differences in innate immune responses may be present in the neonatal population which may contribute to the increased susceptibility of premature males to sepsis.

Healthcare utilization and left ventricular ejection fraction distribution in methamphetamine use associated heart failure hospitalizations.

Background: Although methamphetamine use associated heart failure (MU-HF) is increasing, data on its clinical course are limited due to a preponderance of single center studies and significant heterogeneity in the definition of MU-HF in the published literature. Our objective was to evaluate left ventricular ejection fraction (LVEF) distribution, methamphetamine use treatment engagement and postdischarge healthcare utilization among Veterans with heart failure hospitalization in the department of Veterans Affairs (VA) medical centers for MU-HF versus HF not associated with methamphetamine use (other-HF).

Methods: Observational study including a cohort of Veterans with a first heart failure hospitalization during 2007 - 2020 using data in the VA Corporate Data Warehouse.

Expression of , , and in the mature cochlea reprograms nonsensory cells into hair cells.

Mechanosensory hair cells of the mature mammalian organ of Corti do not regenerate; consequently, loss of hair cells leads to permanent hearing loss. Although nonmammalian vertebrates can regenerate hair cells from neighboring supporting cells, many humans with severe hearing loss lack both hair cells and supporting cells, with the organ of Corti being replaced by a flat epithelium of nonsensory cells. To determine whether the mature cochlea can produce hair cells in vivo, we reprogrammed nonsensory cells adjacent to the organ of Corti with three hair cell transcription factors: , , and We generated numerous hair cell-like cells in nonsensory regions of the cochlea and new hair cells continued to be added over a period of 9 wk.

Impact of formulation on solid oxygen-entrapping materials to overcome tumor hypoxia.

Tumor hypoxia, resulting from rapid tumor growth and aberrant vascular proliferation, exacerbates tumor aggressiveness and resistance to treatments like radiation and chemotherapy. To increase tumor oxygenation, we developed solid oxygen gas-entrapping materials (O-GeMs), which were modeled after clinical brachytherapy implants, for direct tumor implantation. The objective of this study was to investigate the impact different formulations of solid O-GeMs have on the entrapment and delivery of oxygen.

The BCKDH kinase inhibitor BT2 promotes BCAA disposal and mitochondrial proton leak in both insulin-sensitive and insulin-resistant C2C12 myotubes.

Elevated circulating branched-chain amino acids (BCAAs) have been correlated with the severity of insulin resistance, leading to recent investigations that stimulate BCAA metabolism for the potential benefit of metabolic diseases. BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid), an inhibitor of branched-chain ketoacid dehydrogenase kinase, promotes BCAA metabolism by enhancing BCKDH complex activity. The purpose of this report was to investigate the effects of BT2 on mitochondrial and glycolytic metabolism, insulin sensitivity, and de novo lipogenesis both with and without insulin resistance.

Genetic Variants of the Beta-Adrenergic Receptor Pathways as Both Risk and Protective Factors for Retinopathy of Prematurity.

Purpose: There is strong evidence that genetic factors influence retinopathy of prematurity (ROP), a neovascular eye disease. It has been previously suggested that polymorphisms in the genes involved in β-adrenergic receptor (ADRβ) pathways could protect against ROP. Antagonists for the ADRβ are actively tested in clinical trials for ROP treatment, but not without controversy and safety concerns.

Seasonality in land-ocean connectivity and local processes control sediment bacterial community structure and function in a High Arctic tidal flat.

Climate change is altering patterns of precipitation, cryosphere thaw, and land-ocean influxes, affecting understudied Arctic estuarine tidal flats. These transitional zones between terrestrial and marine systems are hotspots for biogeochemical cycling, often driven by microbial processes. We investigated surface sediment bacterial community composition and function from May to September along a river-intertidal-subtidal-fjord gradient.

A Cluster Randomized Trial of Primary Care Practice Redesign to Integrate Behavioral Health for Those Who Need It Most: Patients With Multiple Chronic Conditions.

Purpose: Patient outcomes can improve when primary care and behavioral health providers use a collaborative system of care, but integrating these services is difficult. We tested the effectiveness of a practice intervention for improving patient outcomes by enhancing integrated behavioral health (IBH) activities.

Methods: We conducted a pragmatic, cluster randomized controlled trial.

5-Aza-2'-deoxycytidine-mediated DNA hypomethylation with and without concurrent insulin resistance suppresses myotube mitochondrial capacity.

Type 2 diabetes is characterized by elevated blood glucose and reduced insulin sensitivity in target tissues. Moreover, reduced mitochondrial metabolism and expressional profile of genes governing mitochondrial metabolism (such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC-1α]) are also reduced during insulin resistance. Epigenetic regulation via DNA methylation of genes including PGC-1α may contribute to diminished mitochondrial capacity, while hypomethylation of PGC-1α (such as that invoked by exercise) has been associated with increased PGC-1α expression and favorable metabolic outcomes.