Integrated hepatic transcriptomics and metabolomics identify Pck1 as a key factor in the broad dysregulation induced by vehicle pollutants.

Background: Exposure to air pollution is associated with worldwide morbidity and mortality. Diesel exhaust (DE) emissions are important contributors which induce vascular inflammation and metabolic disturbances by unknown mechanisms. We aimed to determine molecular pathways activated by DE in the liver that could be responsible for its cardiometabolic toxicity.

Conditional ablation of MCU exacerbated cardiac pathology in a genetic arrhythmic model of CPVT.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic arrhythmic syndrome caused by mutations in the calcium (Ca) release channel ryanodine receptor (RyR2) and its accessory proteins. These mutations make the channel leaky, resulting in Ca-dependent arrhythmias. Besides arrhythmias, CPVT hearts typically lack structural cardiac remodeling, a characteristic often observed in other cardiac conditions (heart failure, prediabetes) also marked by RyR2 leak.

A Novel Case of Paraglottic Burkholderia Cepacia Complex Infection Mimicking a Laryngeal Malignancy.

The Burkholderia cepacia complex (BCC) is a rare pathogen typically causing respiratory illnesses in immunocompromised individuals. We present a novel case of BCC manifesting as a laryngeal abscess, mimicking a laryngeal malignancy in an immunocompetent patient. A 74-year-old male presented to the emergency department with acute respiratory failure and was emergently intubated, revealing abnormal supraglottic tissue.

Paracrine Signals in Calcified Conditioned Media Elicited Differential Responses in Primary Aortic Vascular Smooth Muscle Cells and in Adventitial Fibroblasts.

Our goal was to determine if paracrine signals from different aortic layers can impact other cell types in the diabetic microenvironment, specifically medial vascular smooth muscle cells (VSMCs) and adventitial fibroblasts (AFBs). The diabetic hyperglycemic aorta undergoes mineral dysregulation, causing cells to be more responsive to chemical messengers eliciting vascular calcification. Advanced glycation end-products (AGEs)/AGE receptors (RAGEs) signaling has been implicated in diabetes-mediated vascular calcification.

Genetic Inhibition of Mitochondrial Permeability Transition Pore Exacerbates Ryanodine Receptor 2 Dysfunction in Arrhythmic Disease.

The brief opening mode of the mitochondrial permeability transition pore (mPTP) serves as a calcium (Ca) release valve to prevent mitochondrial Ca (mCa) overload. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a stress-induced arrhythmic syndrome due to mutations in the Ca release channel complex of ryanodine receptor 2 (RyR2). We hypothesize that inhibiting the mPTP opening in CPVT exacerbates the disease phenotype.

HIV-1 Tat Upregulates the Receptor for Advanced Glycation End Products and Superoxide Dismutase-2 in the Heart of Transgenic Mice.

Cardiovascular disorder (CVD) is a common comorbidity in people living with HIV (PLWH). Although the underlying mechanisms are unknown, virotoxic HIV proteins, such as the trans-activator of transcription (Tat), likely contribute to CVD pathogenesis. Tat expression in mouse myocardium has been found to induce cardiac dysfunction and increase markers of endothelial toxicity.

Rap1a Activity Elevated the Impact of Endogenous AGEs in Diabetic Collagen to Stimulate Increased Myofibroblast Transition and Oxidative Stress.

Diabetics have an increased risk for heart failure due to cardiac fibroblast functional changes occurring as a result of AGE/RAGE signaling. Advanced glycation end products (AGEs) levels are higher in diabetics and stimulate elevated RAGE (receptor for AGE) signaling. AGE/RAGE signaling can alter the expression of proteins linked to extracellular matrix (ECM) remodeling and oxidative stressors.

Compositionally-Driven Formation Mechanism of Hierarchical Morphologies in Co-Deposited Immiscible Alloy Thin Films.

Co-deposited, immiscible alloy systems form hierarchical microstructures under specific deposition conditions that accentuate the difference in constituent element mobility. The mechanism leading to the formation of these unique hierarchical morphologies during the deposition process is difficult to identify, since the characterization of these microstructures is typically carried out post-deposition. We employ phase-field modeling to study the evolution of microstructures during deposition combined with microscopy characterization of experimentally deposited thin films to reveal the origin of the formation mechanism of hierarchical morphologies in co-deposited, immiscible alloy thin films.

RAGE Differentially Altered Responses in Vascular Smooth Muscle Cells and Adventitial Fibroblasts in Diabetes-Induced Vascular Calcification.

The Advanced Glycation End-Products (AGE)/Receptor for AGEs (RAGE) signaling pathway exacerbates diabetes-mediated vascular calcification (VC) in vascular smooth muscle cells (VSMCs). Other cell types are involved in VC, such as adventitial fibroblasts (AFBs). We hope to elucidate some of the mechanisms responsible for differential signaling in diabetes-mediated VC with this work.

Rap1a Regulates Cardiac Fibroblast Contraction of 3D Diabetic Collagen Matrices by Increased Activation of the AGE/RAGE Cascade.

Cardiovascular disease is a common diabetic complication that can arise when cardiac fibroblasts transition into myofibroblasts. Myofibroblast transition can be induced by advanced glycated end products (AGEs) present in the extracellular matrix (ECM) activating RAGE (receptor for advanced glycated end products) to elicit intracellular signaling. The levels of AGEs are higher under diabetic conditions due to the hyperglycemic conditions present in diabetics.

Rap1a Overlaps the AGE/RAGE Signaling Cascade to Alter Expression of α-SMA, p-NF-κB, and p-PKC-ζ in Cardiac Fibroblasts Isolated from Type 2 Diabetic Mice.

Cardiovascular disease, specifically heart failure, is a common complication for individuals with type 2 diabetes mellitus. Heart failure can arise with stiffening of the left ventricle, which can be caused by "active" cardiac fibroblasts (i.e.

Visual teaching aids improve patient understanding and reduce anxiety prior to a colectomy.

Background: Informed consent forms consist of large blocks of written information that may be difficult for patients to understand. Visual teaching aids are promising, however, they have not been studied as a pre-operative educational tool for common surgical procedures. We pilot tested the use of a visual teaching aid during the informed consent process for a colectomy.

Scottish Health Technologies Group: enhancing patient engagement.

Objectives: The Scottish Health Technologies Group (SHTG) provides evidence support and advice to the National Health Service in Scotland on the use of new and existing health technologies, which, although not medicines, are likely to have significant implications for people's care. The purpose of this paper is to highlight the developments that have taken place in the SHTG's patient involvement processes in the years 2017 to 2019, focusing primarily on specific engagement with patient organizations and considering how the new approaches have been received by stakeholders.

Methods: Feedback from patient organizations that participated in the SHTG submission process, alongside SHTG committee members' views on patient organizations contributions, was gathered primarily via online questionnaires.

Physical Activity Before, During, and After Chemotherapy for High-Risk Breast Cancer: Relationships With Survival.

Background: Although physical activity has been consistently associated with reduced breast cancer mortality, evidence is largely based on data collected at one occasion. We examined how pre- and postdiagnosis physical activity was associated with survival outcomes in high-risk breast cancer patients.

Methods: Included were 1340 patients enrolled in the Diet, Exercise, Lifestyle and Cancer Prognosis (DELCaP) Study, a prospective study of lifestyle and prognosis ancillary to a SWOG clinical trial (S0221).

Extracellular matrix components isolated from diabetic mice alter cardiac fibroblast function through the AGE/RAGE signaling cascade.

Individuals suffering from diabetes have an increased risk of developing cardiovascular complications such as heart failure. Heart failure can be a result of the stiffening of the left ventricle, which occurs when cardiac fibroblasts become "active" and begin to remodel the extracellular matrix (ECM). Fibroblast "activation" can be triggered by the AGE/RAGE signaling cascade.

Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221).

Purpose: Despite reported widespread use of dietary supplements during cancer treatment, few empirical data with regard to their safety or efficacy exist. Because of concerns that some supplements, particularly antioxidants, could reduce the cytotoxicity of chemotherapy, we conducted a prospective study ancillary to a therapeutic trial to evaluate associations between supplement use and breast cancer outcomes.

Methods: Patients with breast cancer randomly assigned to an intergroup metronomic trial of cyclophosphamide, doxorubicin, and paclitaxel were queried on their use of supplements at registration and during treatment (n =1,134).

Diesel Exhaust Induces Mitochondrial Dysfunction, Hyperlipidemia, and Liver Steatosis.

Objective: Air pollution is associated with increased cardiovascular morbidity and mortality, as well as dyslipidemia and metabolic syndrome. Our goal was to dissect the mechanisms involved. Approach and Results: We assessed the effects of exposure to air pollution on lipid metabolism in mice through assessment of plasma lipids and lipoproteins, oxidized fatty acids 9-HODE (9-hydroxyoctadecadienoic) and 13-HODE (13-hydroxyoctadecadienoic), lipid, and carbohydrate metabolism.

Persistent organic pollutants (POPs) increase rage signaling to promote downstream cardiovascular remodeling.

Exposure to environmental contaminants and consumption of a high, saturated fatty diet has been demonstrated to promote precursors for metabolic syndrome (hyperglycemia, hyperinsulinemia, and hypertriglyceridemia). The purpose of this study was to determine if exposure to the most prevalent environmental persistent organic pollutants (POPs) would act as causative agents to promote metabolic syndrome independent of dietary intake. We hypothesized that POPs will activate the advanced glycated end-product (AGE)-and receptor for AGE (RAGE) signaling cascade to promote downstream signaling modulators of cardiovascular remodeling and oxidative stress in the heart.

Associations between self-reported diet during treatment and chemotherapy-induced peripheral neuropathy in a cooperative group trial (S0221).

Background: The pathophysiology of chemotherapy-induced peripheral neuropathy (CIPN) is not well understood. Currently, dose reduction is the only recommendation for alleviating symptoms, often leading to premature treatment cessation. The primary aim of this analysis was to determine the association between components of diet during taxane treatment for breast cancer and change in CIPN symptoms over treatment.

Supplement Use and Chemotherapy-Induced Peripheral Neuropathy in a Cooperative Group Trial (S0221): The DELCaP Study.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) can interfere with daily function and quality of life, and there are no known preventive approaches. In a cohort of breast cancer patients receiving paclitaxel as part of a clinical trial (SWOG 0221), we examined the use of dietary supplements both before diagnosis and during treatment in relation to CIPN.

Methods: At registration to S0221, 1225 breast cancer patients completed questionnaires regarding the use of multivitamins and supplements before and at diagnosis.

Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci.

Objective: Taxane containing chemotherapy extends survival for breast cancer patients. However, taxane-induced peripheral neuropathy (TIPN) cannot be predicted, prevented or effectively treated. Using genome-wide analyses, we sought to identify common risk variants for TIPN.

The Role of AGE/RAGE Signaling in Diabetes-Mediated Vascular Calcification.

AGE/RAGE signaling has been a well-studied cascade in many different disease states, particularly diabetes. Due to the complex nature of the receptor and multiple intersecting pathways, the AGE/RAGE signaling mechanism is still not well understood. The purpose of this review is to highlight key areas of AGE/RAGE mediated vascular calcification as a complication of diabetes.