Differential gene expression and protein-protein interaction network profiling of sulfur mustard-exposed rabbit corneas employing RNA-seq data and bioinformatics tools.

Sulfur mustard (SM) ocular exposure severely damages the cornea and causes vision impairment. At present, no specific therapy exists to mitigate SM-induced corneal injury and vision loss. This study performed transcriptome profiling of naïve, SM-damaged, and SM-undamaged rabbit corneas using RNA-seq analysis and bioinformatic tools to gain a better mechanistic understanding and develop SM-specific medical countermeasures.

Toxicological effects of ocular acrolein exposure to eyelids in rabbits in vivo.

Acrolein is a highly reactive volatile toxic chemical that injures the eyes and many organs. It has been used in wars and terrorism for wounding masses on multiple occasions and is readily accessible commercially. Our earlier studies revealed acrolein's toxicity to the cornea and witnessed damage to other ocular tissues.

Synthesis and preclinical evaluation of a novel fluorine-18 labeled small-molecule PET radiotracer for imaging of CXCR3 receptor in mouse models of atherosclerosis.

Background: CXCR3 is a chemokine receptor and is expressed in innate and adaptive immune cells. It promotes the recruitment of T-lymphocytes and other immune cells to the inflammatory site in response to the binding of cognate chemokines. Upregulation of CXCR3 and its chemokines has been found during atherosclerotic lesion formation.

Closing the gap between murine neutrophils and neutrophil-like cell lines.

Advantages of cloned Hoxb8 neutrophil-like cells are discussed and contrasted with weaknesses of human HL-60 and PLB-985 neutrophil-like cell lines, and shared and distinct features of primary murine and human neutrophils are summarized.

Central Auditory Processing Dysfunction in Service Members and Veterans: Treatment Considerations and Strategies.

Purpose: Military risk factors such as blast exposure, noise exposure, head trauma, and neurotoxin exposure place Service members and Veterans at risk for deficits associated with auditory processing dysfunction. However, there is no clinical guidance specific to the treatment of auditory processing deficits in this unique population. We provide an overview of available treatments and their limited supporting evidence for use in adults, emphasizing the need for multidisciplinary case management and interdisciplinary research to support evidence-based solutions.

Effect of Cognitive Behavioral Therapy for Insomnia on Alcohol Treatment Outcomes Among US Veterans: A Randomized Clinical Trial.

Importance: Three of 4 adults in treatment for alcohol use disorder (AUD) report symptoms of insomnia. Yet the first-line treatment for insomnia (cognitive behavioral therapy for insomnia, CBT-I) is often delayed until abstinence is established.

Objective: To test the feasibility, acceptability, and preliminary efficacy of CBT-I among veterans early in their AUD treatment and to examine improvement in insomnia as a mechanism for improvement in alcohol use outcomes.

Integrated "lab-on-a-chip" microfluidic systems for isolation, enrichment, and analysis of cancer biomarkers.

The liquid biopsy has garnered considerable attention as a complementary clinical tool for the early detection, molecular characterization and monitoring of cancer over the past decade. In contrast to traditional solid biopsy techniques, liquid biopsy offers a less invasive and safer alternative for routine cancer screening. Recent advances in microfluidic technologies have enabled handling of liquid biopsy-derived biomarkers with high sensitivity, throughput, and convenience.

Mustard Gas Exposure Actuates SMAD2/3 Signaling to Promote Myofibroblast Generation in the Cornea.

Sulfur mustard gas (SM) is a vesicating and alkylating agent used as a chemical weapon in many mass-casualty incidents since World War I. Ocular injuries were reported in >90% of exposed victims. The mechanisms underlying SM-induced blindness remain elusive.

Endothelial MRs Mediate Western Diet-Induced Lipid Disorders and Skeletal Muscle Insulin Resistance in Females.

Consumption of a Western diet (WD) consisting of excess fat and carbohydrates activates the renin-angiotensin-aldosterone system, which has emerged as an important risk factor for systemic and tissue insulin resistance. We recently discovered that activated mineralocorticoid receptors (MRs) in diet-induced obesity induce CD36 expression, increase ectopic lipid accumulation, and result in systemic and tissue insulin resistance. Here, we have further investigated whether endothelial cell (EC)-specific MR (ECMR) activation participates in WD-induced ectopic skeletal muscle lipid accumulation, insulin resistance, and dysfunction.

Corneal gene therapy: Structural and mechanistic understanding.

Cornea, a dome-shaped and transparent front part of the eye, affords 2/3rd refraction and barrier functions. Globally, corneal diseases are the leading cause of vision impairment. Loss of corneal function including opacification involve the complex crosstalk and perturbation between a variety of cytokines, chemokines and growth factors generated by corneal keratocytes, epithelial cells, lacrimal tissues, nerves, and immune cells.

Corneal Regeneration Using Gene Therapy Approaches.

One of the most remarkable advancements in medical treatments of corneal diseases in recent decades has been corneal transplantation. However, corneal transplants, including lamellar strategies, have their own set of challenges, such as graft rejection, delayed graft failure, shortage of donor corneas, repeated treatments, and post-surgical complications. Corneal defects and diseases are one of the leading causes of blindness globally; therefore, there is a need for gene-based interventions that may mitigate some of these challenges and help reduce the burden of blindness.

DEA-registered clinical pharmacist practitioners: Progressing practice to increase patient care access.

Purpose: This descriptive review aims to describe the impact of controlled substance prescriptive authority (CSPA) among Drug Enforcement Administration (DEA)-registered clinical pharmacist practitioners (pharmacists) within the Veterans Health Administration (VA). The practice perspectives of pharmacists with CSPA are also reviewed. A 3-part methodology included identification and query of DEA-registered pharmacists, practice impact data analysis, and time and motion prescribing analysis.

Dietary ketone ester attenuates the accretion of adiposity and liver steatosis in mice fed a high-fat, high-sugar diet.

The ketone diester, R,S-1,3-butanediol diacetoacetate (BD-AcAc), attenuates the accretion of adiposity and reduces hepatic steatosis in high-fat diet-induced obese mice when carbohydrate energy is removed from the diet to accommodate energy from the ester. Reducing carbohydrate energy is a potential confounder due to the well-known effects of carbohydrate restriction on components of energy balance and metabolism. Therefore, the current investigation was designed to determine whether the addition of BD-AcAc to a high-fat, high-sugar diet (with no reduction in carbohydrate energy) would attenuate the accretion of adiposity and markers of hepatic steatosis and inflammation.

Corneal injury is associated with stromal and vascular alterations within cranial dura mater.

The cornea and cranial dura mater share sensory innervation. This link raises the possibility that pathological impulses mediated by corneal injury may be transmitted to the cranial dura, trigger dural perivascular/connective tissue nociceptor responses, and induce vascular and stromal alterations affecting dura mater blood and lymphatic vessel functionality. In this study, using a mouse model, we demonstrate for the first time that two weeks after the initial insult, alkaline injury to the cornea leads to remote pathological changes within the coronal suture area of the dura mater.

Selective breeding for physical inactivity produces cognitive deficits altered hippocampal mitochondrial and synaptic function.

Physical inactivity is the 4th leading cause of death globally and has been shown to significantly increase the risk for developing Alzheimer's Disease (AD). Recent work has demonstrated that exercise prior to breeding produces heritable benefits to the brains of offspring, suggesting that the physical activity status of previous generations could play an important role in one's brain health and their subsequent risk for neurodegenerative diseases. Thus, our study aimed to test the hypothesis that selective breeding for physical inactivity, or for high physical activity, preference produces heritable deficits and enhancements to brain health, respectively.

Autophagy in dry eye disease: Therapeutic implications of autophagy modulators on the ocular surface.

Dry eye disease (DED) is a chronic ocular surface disorder, associated with inflammation, which can cause severe morbidity, visual compromise, and loss of quality of life, affecting up to 5-50% of the world population. In DED, ocular surface damage and tear film instability due to abnormal tear secretion lead to ocular surface pain, discomfort, and epithelial barrier disruption. Studies have shown the involvement of autophagy regulation in dry eye disease as a pathogenic mechanism along with the inflammatory response.

Multi-omic analysis of the cardiac cellulome defines a vascular contribution to cardiac diastolic dysfunction in obese female mice.

Coronary microvascular dysfunction (CMD) is associated with cardiac dysfunction and predictive of cardiac mortality in obesity, especially in females. Clinical data further support that CMD associates with development of heart failure with preserved ejection fraction and that mineralocorticoid receptor (MR) antagonism may be more efficacious in obese female, versus male, HFpEF patients. Accordingly, we examined the impact of smooth muscle cell (SMC)-specific MR deletion on obesity-associated coronary and cardiac diastolic dysfunction in female mice.

Novel Therapies for the Prevention of Fibrosis in Glaucoma Filtration Surgery.

Conjunctival fibrosis remains the major impediment to the success of glaucoma filtration surgery. Anti-metabolites remain the gold standard for mitigating post-surgical fibrosis, but they are associated with high complication rates and surgical failure rates. Establishing a more targeted approach to attenuate conjunctival fibrosis may revolutionize the surgical approach to glaucoma.

DOCK2 Promotes Asthma Development by Eliciting Airway Epithelial-Mesenchymal Transition.

Epithelial-mesenchymal transition (EMT) contributes to airway remodeling, a predominant feature of asthma. DOCK2 (dedicator of cytokinesis 2) is an innate immune signaling molecule involved in vascular remodeling. However, it is unknown if DOCK2 plays a role in airway remodeling during asthma development.

Synthesis and preclinical evaluation of a novel fluorine-18 labeled small-molecule PET radiotracer for imaging of CXCR3 receptor in mouse models of atherosclerosis.

CXCR3 is a chemokine receptor and is expressed on innate and adaptive immune cells. It promotes the recruitment of T-lymphocytes and other immune cells to the inflammatory site in response to the binding of cognate chemokines. Upregulation of CXCR3 and its chemokines has been found during atherosclerotic lesion formation.

Understanding common key indicators of successful and unsuccessful cancer drug trials using a contrast mining framework on ClinicalTrials.gov.

Clinical trials are essential to the process of new drug development. As clinical trials involve significant investments of time and money, it is crucial for trial designers to carefully investigate trial settings prior to designing a trial. Utilizing trial documents from ClinicalTrials.

Cardiovascular Disease in Obstructive Sleep Apnea: Putative Contributions of Mineralocorticoid Receptors.

Obstructive sleep apnea (OSA) is a chronic and highly prevalent condition that is associated with oxidative stress, inflammation, and fibrosis, leading to endothelial dysfunction, arterial stiffness, and vascular insulin resistance, resulting in increased cardiovascular disease and overall mortality rates. To date, OSA remains vastly underdiagnosed and undertreated, with conventional treatments yielding relatively discouraging results for improving cardiovascular outcomes in OSA patients. As such, a better mechanistic understanding of OSA-associated cardiovascular disease (CVD) and the development of novel adjuvant therapeutic targets are critically needed.

Emerging Links between Nonalcoholic Fatty Liver Disease and Neurodegeneration.

The association between liver and brain health has gained attention as biomarkers of liver function have been revealed to predict neurodegeneration. The liver is a central regulator in metabolic homeostasis. However, in nonalcoholic fatty liver disease (NAFLD), homeostasis is disrupted which can result in extrahepatic organ pathologies.

Preclinical models to study patient-derived circulating tumor cells and metastasis.

Circulating tumor cells (CTCs) that are detached from the tumor can be precursors of metastasis. The majority of studies focus on enumeration of CTCs from patient blood to predict recurrence and therapy outcomes. Very few studies have managed to expand CTCs to investigate their functional dynamics with respect to genetic changes, tumorigenic potential, and response to drug treatment.