Journal of Translational Science

BACKGROUND: Clinical research is a central mission of the University of Colorado Anschutz Medical Campus (CU-Anschutz). On March 18, 2020, due to rising COVID-19 rates and personal protective equipment (PPE) shortages, an emergency approval process for critical research essential to the care and safety of patients, including COVID-19 trials, was enacted. All other clinical research studies requiring face-to-face visits were placed on hold to protect participant and staff safety. METHODS: A clinical research TaskForce was rapidly assembled, consisting of a cross- section of campus clinical research operations leaders, including affiliate hospitals...

Although HSV-1 has been implicated in facial palsy for a long time, testing and treating for HSV is not routine. The lack of a meaningful demonstration of how HSV-1 would cause facial palsy has limited progress in this field. Herein we demonstrate that the depth of the lip HSV-1 infection defines the course of the disease, with deeper subcutaneous infection allowing virus access to the facial nerve and causing facial palsy. HSV-1 inoculated subcutaneously caused extensive facial paralysis in cotton rats Sigmodon hispidus , while virus inoculated in the same area of the lip by skin surface abrasion did not...

Background and aim: Hepatocellular carcinoma (HCC) biomarkers are limited, as even the best studied, alpha-fetoprotein (AFP), is elevated in no more than 50% of HCC patients. The aim was to evaluate several serum liver function tests in relation to survival and tumor characteristics in a large cohort of Turkish HCC patients. Methods: We retrospectively examined the serum levels of gamma glutamyl transpeptidase (GGT) in relation to patient survival. Results: Kaplan-Meier analysis showed that only GGT and albumin amongst liver function tests, were significantly associated with survival...

Introduction and aims: Hepatocellular carcinoma (HCC) is a consequence of chronic liver disease, particularly from hepatitis B or C and increasingly from obesity and metabolic syndrome. Since lipids are an important component of cell membranes and are involved in cell signaling and tumor cell growth, we wished to evaluate the relationship between HCC patient plasma lipids and maximum tumor diameter and other indices of HCC human biology. Methods: We examined prospectively-collected data from a multi-institutional collaborative Turkish HCC working group, from predominantly HBV-based patients, for plasma lipid profiles, consisting of triglycerides, total cholesterol, LDL-cholesterol (LDL) and HDL-cholesterol (HDL) and compared these with the associated patient maximum tumor diameter (MTD), portal vein thrombosis, alpha-fetoprotein (AFP) and also with patient survival...

Aging is a complex multidimensional process of progressive decline affecting multiple organ systems by a number of processes that are still not well understood. While many studies have focused on the approach of studying aging across multiple organs, assessment of the contribution of individual organs to overall aging processes is under appreciated. The ability to study and compare organs in the context of organismal aging has been documented recently using a geropathology grading platform in laboratory mice...

Diabetes is a global healthcare problem associated with enormous healthcare and personal costs. Despite glucose lowering agents that control glycaemia, both type 1 (T1D) and type (T2D) diabetes patients often develop microvascular complications that increase morbidity and mortality. Current interventions rely on careful glycemic control and healthy lifestyle choices, but these are ineffective at reversing or completely preventing the major microvascular complications, diabetic peripheral neuropathy (DPN), diabetic retinopathy (DR), and diabetic kidney disease (DKD)...

RATIONALE AND OBJECTIVE: Despite contribution of dyslipidemia to ischemic stroke, plasma lipidomic correlates of stroke in CKD is not studied. This study is aimed to identify plasma lipid alterations associated with stroke. STUDY DESIGN: Cross sectional. SETTING AND POPULATION: 214 participants of Clinical Phenotyping and Resource Biobank Core (CPROBE). Clinical data and plasma samples at the time of recruitment were obtained and used to generate lipidomic data by liquid chromatography/mass-spectrometry-based untargeted platform...

The current COVID-19 pandemic has presented unprecedented challenges to the world community. No effective therapies or vaccines have yet been established. Upon the basis of homologies to similar coronaviruses, several potential drug targets have been identified and are the focus of both laboratory and clinical investigation. The rationale for several of these drug candidates is presented in this review. Emerging clinical data has revealed that severe COVID-19 disease is associated with heightened inflammatory responses and a procoagulant state, suggesting that patient treatment strategies must extend beyond antiviral agents...

Objective: Obesity has reached epidemic proportions and is a strong risk factor for obstructive sleep apnea (OSA). However, the underlying mechanisms are poorly understood and current treatment strategies for OSA and obesity have critical limitations. Thus, establishment of an obesity-related large animal model with spontaneous OSA is imperative. Materials and methods: Natural and sedated sleep were monitored and characterized in 4 obese (body mass index - BMI>48) and 3 non-obese (BMI<40) minipigs...

Human cancers emerge from cancer stem cells (CSCs), which are resistant to cancer chemotherapeutic agents, radiation, and cell death. Moreover, autophagy provides the cytoprotective effect which contributes to drug resistance in these cells. Furthermore, much evidence shows that CSCs cause tumor initiation, progression, metastasis, and cancer recurrence. Various signaling pathways including the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), maternal embryonic leucine zipper kinase (MELK), NOTCH1, and Wnt/β-catenin as well as the CSC markers maintain CSC properties...

Objective: To determine whether sex, age, and body mass index are correlated with active glucagon-like-peptide 1 concentrations and to investigate glucagon-like-peptide 1 reproducibility during repeated oral glucose tolerance tests. Methods: Sixty-one healthy volunteers underwent four 2-hour repeated oral glucose tolerance tests approximately 1 week apart. Because this randomized same-subject crossover trial was designed to investigate effects of non-nutritive sweeteners, participants received 355 mL (12 ounces) of water or a beverage containing non-nutritive sweeteners 10 minutes prior to each oral glucose tolerance test...

Much of the recent gains in knowledge regarding the influence of patient genetics on medication pharmacokinetics (drug absorption, distribution, metabolism and elimination) how patients process medications) and pharmacodynamics (drug response) have been attributed to the technologic advances in genetic testing methodologies and the involvement of large clinical data sets and biobanks. Indeed, Genome Wide Association Studies (GWAS) and Phenome Wide Association Studies (PWAS) along with ever-evolving biomedical informatics techniques and the expansion of the -omics sciences ( e...

Introduction: Several markers of systemic inflammation, including blood C-reactive protein, platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) have been identified as independent prognosticators for hepatocellular carcinoma (HCC). Methods: To attempt to understand the significance of these markers, they were examined in relation to 4 tumour parameters, namely maximum tumour diameter (MTD), tumour multifocality, portal vein thrombosis (PVT) and blood alpha-fetoprotein (AFP) levels...

Introduction: Tumors over-expressing the human epithelial receptor 2 (HER2) or exhibiting amplification or mutation of its proto-oncogene have a poorer prognosis. Using trastuzumab and/or other HER2 targeted therapies can increase overall survival in patients with HER2(+) tumors making it critical to accurately identify patients who may benefit. We report on a Phase 0 study of the imaging agent, 111 In-CHX-A"-DTPA trastuzumab, in patients with known HER2 status to evaluate its safety and biodistribution and to obtain preliminary data regarding its ability to provide an accurate, whole-body, non-invasive means to determine HER2 status...

A variety of factors, whether extracellular (mutagens/carcinogens and viruses in the environment, chronic inflammation and radiation associated with the environment and/or electronic devices/machines) and/or intracellular (oxidative metabolites of food, oxidative stress due to inflammation, acid production, replication stress, DNA replication/repair errors, and certain hormones, cytokines, growth factors), pose a constant threat to the genomic integrity of a living cell. However, in the normal cellular environment multiple biological pathways including DNA repair, cell cycle, apoptosis and the immune system work in a precise, regulated (tightly controlled), timely and concerted manner to ensure genomic integrity, stability and proper functioning of a cell...

Background: Human Cytomegalovirus (HCMV) infection is problematic after kidney transplantation. Human mesangial cells along with human glomerular endothelial cells and podocytes constitute the renal glomerular vascular unit (GVU). HCMV infection of the GVU is poorly understood. Methods: GVU cells infectivity was analysed by microscopy and immunofluorescence. Cytokines profiles were measured by Luminex assays. Renal tissue analysis for HCMV infection was performed by immunohistochemistry...

Drug discovery and development (DDD) is a collaborative, dynamic process of great interest to researchers, but an area where there is a lack of formal training. The Drug Development Educational Program (DDEP) at New York University was created in 2012 to stimulate an improved, multidisciplinary DDD workforce by educating early stage scientists as well as a variety of other like-minded students. The first course of the program emphasizes post-compounding aspects of DDD; the second course focuses on molecular signaling pathways...

PhDs and post-doctoral biomedical graduates, in greater numbers, are choosing industry based careers. However, most scientists do not have formal training in business strategies and venture creation and may find senior management positions untenable. To fill this training gap, "Biotechnology Industry: Structure and Strategy" was offered at New York University School of Medicine (NYUSOM). The course focuses on the business aspects of translational medicine and research translation and incorporates the practice of business case discussions, mock negotiation, and direct interactions into the didactic...

The presence of cirrhosis poses an increased risk of both thrombosis and bleeding in individuals with chronic liver disease. This duality is a result of a dynamic disequilibrium between procoagulant and anticoagulant states in individuals with cirrhosis. The mechanism of this imbalance in cirrhosis remains unclear. It is known that the progression of cirrhosis leads to decreased synthetic function and a concurrent lack of natural anticoagulants. Other proposed mechanisms contributing to this hemostatic imbalance include decreased platelet production, increased platelet destruction from hypersplenism, decreased synthesis of Vitamin K-dependent and independent clotting factors and anticoagulant factors, and alterations in purinergic signaling pathways...

Life expectancy of individuals in both developed and undeveloped nations continues to rise at an unprecedented rate. Coupled to this increase in longevity for individuals is the rise in the incidence of chronic neurodegenerative disorders that includes Alzheimer's disease (AD). Currently, almost ten percent of the population over the age of 65 suffers from AD, a disorder that is presently without definitive therapy to prevent the onset or progression of cognitive loss. Yet, it is estimated that AD will continue to significantly increase throughout the world to impact millions of individuals and foster the escalation of healthcare costs...