Rare germline variants in cancer-relevant genes are associated with breast cancer risk in young women with high-risk family history.

Introduction: It is incompletely understood why some women develop breast cancer 15-20 years earlier than the majority of women. We hypothesize that women with early-onset breast cancer and high-risk family history without germline pathogenic variants in cancer-predisposing genes (CPGs, n = 83) have a higher load of germline high functional impact variants (gHFI) in cancer hallmark genes (n = 1508) compared to healthy controls.

Methods: Germline whole exome sequencing data were analyzed from 5818 breast cancer cases from UKBiobank and from 94 young women with breast cancer without CPG pathogenic variants from the Yale Cancer Prevention Clinic, and compared to 149 controls from Yale GENERATIONS project and 56,917 controls from UKBiobank.

Proton Pump Inhibitor Usage in Urban vs. Rural Intensive Care Units: A Narrative Review of Implications for Standardization of Care.

Intensive care unit (ICU) patients frequently require and benefit from stress ulcer prophylaxis (SUP) using proton pump inhibitors (PPIs). Despite recognized benefits, PPIs are overutilized in patients who do not have high-risk factors predisposing them to clinically significant gastrointestinal bleeding (CSGIB), including mechanical ventilation and coagulopathy. This overuse increases the risk of adverse effects associated with PPIs.

The Novel Anticancer Aryl-Ureido Fatty Acid CTU Increases Reactive Oxygen Species Production That Impairs Mitochondrial Fusion Mechanisms and Promotes MDA-MB-231 Cell Death.

Cancer cell mitochondria are functionally different from those in normal cells and could be targeted to develop novel anticancer agents. The aryl-ureido fatty acid CTU (16({[4-chloro-3-(trifluoromethyl)phenyl]-carbamoyl}amino)hexadecanoic acid) is the prototype of a new class of targeted agents that enhance the production of reactive oxygen species (ROS) that disrupt the outer mitochondrial membrane (OMM) and kill cancer cells. However, the mechanism by which CTU disrupts the inner mitochondrial membrane (IMM) and activates apoptosis is not clear.

Detailed review of mortality reported following COVID-19 vaccination in Victoria, Australia: 2021-2023.

Introduction: The scale of the COVID-19 vaccine program, and appropriate focus on older individuals, emphasised monitoring of mortality as an important part of COVID-19 vaccine safety surveillance, noting many deaths temporally associated with vaccination may not be causally related. This cross-sectional study describes Victoria's vaccine safety service (SAEFVIC) process of reviewing mortality reports following COVID-19 vaccination, summarises report characteristics and identifies trends in mortality reporting.

Methods: Mortality cases reported to SAEFVIC following COVID-19 vaccination from 22 February 2021 to 22 February 2023 were included.

Comprehensive credit scoring datasets for robust testing: Out-of-sample, out-of-time, and out-of-universe evaluation.

This data article curates datasets from Freddie Mac's Single-Family Loan-Level Dataset (SFLLD) quarterly snapshots. The SFLLD tracks loan originations in the USA along with the ensuing repayment trends. This live dataset undergoes quarterly updates.

Carbon Chain Length in a Novel Anticancer Aryl-Urea Fatty Acid Modulates Mitochondrial Targeting, Reactive Oxygen Species Production and Cell Killing.

The cancer cell mitochondrion could be a promising target for the development of new anticancer agents. 16-([3-chloro-5-(trifluoromethyl)-phenyl]carbamoylamino)hexadecanoic acid (2) is a novel aryl-urea fatty acid that targets the mitochondrion in MDA-MB-231 breast cancer cells and activates cell death. In the present study, the relationships between alkyl chain length in 2 analogues, mitochondrial disruption and cell killing were evaluated.

Triphenylphosphonium-Conjugated Palmitic Acid for Mitochondrial Targeting of Pancreatic Cancer Cells: Proteomic and Molecular Evidence.

Pancreatic ductal adenocarcinoma (PDAC)'s resistance to therapies is mainly attributed to pancreatic cancer stem cells (PCSCs). Mitochondria-impairing agents can be used to hamper PCSC propagation and reduce PDAC progression. Therefore, to develop an efficient vector for delivering drugs to the mitochondria, we synthesized tris(3,5-dimethylphenyl)phosphonium-conjugated palmitic acid.

MiR-214-3p regulates Piezo1, lysyl oxidases and mitochondrial function in human cardiac fibroblasts.

Cardiac fibroblasts are pivotal regulators of cardiac homeostasis and are essential in the repair of the heart after myocardial infarction (MI), but their function can also become dysregulated, leading to adverse cardiac remodelling involving both fibrosis and hypertrophy. MicroRNAs (miRNAs) are noncoding RNAs that target mRNAs to prevent their translation, with specific miRNAs showing differential expression and regulation in cardiovascular disease. Here, we show that miR-214-3p is enriched in the fibroblast fraction of the murine heart, and its levels are increased with cardiac remodelling associated with heart failure, or in the acute phase after experimental MI.

FATAL ACUTE HEMOLYSIS FOLLOWING TRIAZOLE THERAPY IN AFRICAN PENGUINS ().

Aspergillosis is a major cause of morbidity and mortality in penguins, with triazole antifungal drugs being commonly used for prophylaxis and treatment. This report describes 15 cases of fatal hemolysis associated with liquid itraconazole and voriconazole formulations administered to African penguins () from four institutions. All penguins underwent stressful events (e.

Expanding the π-system of Fatty Acid-Anion Transporter Conjugates Modulates Their Mechanism of Proton Transport and Mitochondrial Uncoupling Activity.

Mitochondrial uncoupling by small molecule protonophores is a promising strategy for developing novel anticancer agents. Recently, aryl urea substituted fatty acids (aryl ureas) were identified as a new class of protonophoric anticancer agents. To mediate proton transport these molecules self-assemble into membrane-permeable anionic dimers in which intermolecular hydrogen bonds between the carboxylate and aryl-urea anion receptor delocalise the negative charge across the aromatic π-system.

The inositol-requiring enzyme 1 (IRE1) endoplasmic reticulum stress pathway promotes MDA-MB-231 cell survival and renewal in response to the aryl-ureido fatty acid CTU.

Current treatment options for triple-negative breast cancer (TNBC) are limited to toxic drug combinations of low efficacy. We recently identified an aryl-substituted fatty acid analogue, termed CTU, that effectively killed TNBC cells in vitro and in mouse xenograft models in vivo without producing toxicity. However, there was a residual cell population that survived treatment.

Omega-3 polyunsaturated fatty acid derived lipid mediators: a comprehensive update on their application in anti-cancer drug discovery.

Introduction: ω-3 Polyunsaturated fatty acids (PUFAs) have a range of health benefits, including anticancer activity, and are converted to lipid mediators that could be adapted into pharmacological strategies. However, the stability of these mediators must be improved, and they may require formulation to achieve optimal tissue concentrations.

Areas Covered: Herein, the author reviews the literature around chemical stabilization and formulation of ω-3 PUFA mediators and their application in anticancer drug discovery.

Anticoagulation in Patients with Premature Peripheral Artery Disease Undergoing Lower Extremity Revascularization.

Background: Premature peripheral artery disease (PAD), defined by lower extremity revascularization (LER) at age ≤ 50 years, is associated with poor major adverse limb events. The early onset of disease is thought to be influenced by genetic factors that regulate homeostasis of the vascular wall and coagulation. The aim of this study is to investigate the effect of anticoagulation as an adjunct to antiplatelet therapy on the outcomes of LER in patients with premature PAD.

Examining the Role of Nutrition in Cancer Survivorship and Female Fertility: A Narrative Review.

Female cancer survivors have a higher chance of experiencing infertility than females without a history of cancer diagnosis. This risk remains high despite advances in fertility treatments. There is a need to augment fertility treatments with cost-effective methods such as nutritional guidance to improve fertility chances.

PyDAP: Automated dental OPG beam area measurement using python and raspberry Pi camera.

Introduction: This study investigates if inexpensive computer hardware, open-source computer vision and a phosphor screen from disused CR (computed radiography) Cassette can be used to quantitatively assess beam shape and area.

Materials And Methods: The phosphor screen was affixed to a Carestream CS 8100 dental OPG system and the camera was mounted above the X-ray tube. Videos were acquired of the green light emissions during the tomographic irradiation.

Centralized Interactive Phenomics Resource: an integrated online phenomics knowledgebase for health data users.

Objective: Development of clinical phenotypes from electronic health records (EHRs) can be resource intensive. Several phenotype libraries have been created to facilitate reuse of definitions. However, these platforms vary in target audience and utility.

The Role of CYPs and Transporters in the Biotransformation and Transport of the Anti-hepatitis C Antiviral Agents Asunaprevir, Daclatasvir, and Beclabuvir: Impact of Liver Disease, Race and Drug-drug Interactions on Safety and Efficacy.

Asunaprevir, daclatasvir, and beclabuvir are direct-acting antiviral agents used in the treatment of patients infected with hepatitis C genotype 1b. This article reviews the biotransformation and disposition of these drugs in relation to the safety and efficacy of therapy. CYP3A4 and 3A5 catalyze the oxidative biotransformation of the drugs, while P-glycoprotein mediates their efflux from tissues.

The Role of Autophagy in Human Uveal Melanoma and the Development of Potential Disease Biomarkers and Novel Therapeutic Paradigms.

Autophagy is a form of programmed cell degradation that enables the maintenance of homeostasis in response to extracellular stress stimuli. Autophagy is primarily activated by starvation and mediates the degradation, removal, or recycling of cell cytoplasm, organelles, and intracellular components in eukaryotic cells. Autophagy is also involved in the pathogenesis of human diseases, including several cancers.

Pathology, microbiology, and genetic diversity associated with and novel spp. infections in southern sea otters ().

spp., including , are zoonotic bacterial pathogens that can cause morbidity and mortality in mammals, fish, reptiles, birds, and humans. The southern sea otter (SSO; ) is a federally-listed threatened species for which infectious disease is a major cause of mortality.

Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis.

Background: Hepatocellular carcinoma (HCC) remains a leading life-threatening health challenge worldwide, with pressing needs for novel therapeutic strategies. Sphingosine kinase 1 (SphK1), a well-established pro-cancer enzyme, is aberrantly overexpressed in a multitude of malignancies, including HCC. Our previous research has shown that genetic ablation of Sphk1 mitigates HCC progression in mice.

Psychotropic Medication Use in Children and Youth with Autism Enrolled in Medicaid.

Children with autism frequently present with complex mental health diagnoses and psychotropic medications are often a component of comprehensive biopsychosocial treatment plans for these conditions. The purpose of this study is to provide rates and patterns of psychotropic medication use, and predictors thereof, in children and youth with autism enrolled in Medicaid across the US. This study examined national Medicaid claims from 2008 to 2016 of all children and youth with autism ages 0-21 years enrolled in Medicaid.