515 results match your criteria: "Roudebush Veterans Administration Medical Center[Affiliation]"

Unique urine and serum metabolomic signature in patients with excessive alcohol use: An exploratory study.

Alcohol Clin Exp Res (Hoboken)

August 2024

Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Background: Excessive alcohol consumption has a multifaceted impact on the body's metabolic pathways and organ systems. The objectives of this study were to characterize global metabolomic changes and identify specific pathways that are altered in individuals with excessive alcohol use.

Methods: This exploratory study included 22 healthy controls with no known history of excessive alcohol use and 38 patients identified as using alcohol excessively.

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Background/aims: Alcohol-associated hepatitis (AH) mortality and risk factors have not been carefully studied in real-world settings. We examined the rate, temporal trend, and risk factors of mortality in AH.

Methods: We conducted a cohort study of individuals with AH diagnoses using medical claims data from Optum's Clinformatics® Data Mart (CDM).

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Mechanisms of Antihypertensive Effect of Chlorthalidone in Advanced Chronic Kidney Disease: A Causal Mediation Analysis.

Clin J Am Soc Nephrol

August 2024

Department of Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health, Indiana University Center for Aging Research, Indiana University School of Medicine, Regenstrief Institute, Indianapolis, Indiana.

Key Points: Chlorthalidone reduces the amount of fluid and the BP, but fluid volume reduction is not the cause of lowering of BP. It is not volume loss but the response to volume loss such as the synthesis of substances that lower BP is important.

Background: Chlorthalidone (CTD) in a chronic kidney disease randomized trial demonstrated a robust reduction in systolic BP in stage 4 CKD.

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Patients with chronic kidney disease (CKD) report high pain levels, but reduced renal clearance eliminates many analgesic options; therefore, 30-50% of CKD patients have chronic opioid prescriptions. Opioid use in CKD is associated with higher fracture rates. Opioids may directly alter bone turnover directly through effects on bone cells and indirectly via increasing inflammation.

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Article Synopsis
  • * Data from the Global Burden of Disease study revealed that in 2019 there were significant increases in ALD prevalence and incidence, particularly among the older age group (25-29), with varying trends across different regions.
  • * The findings suggest a growing public health concern regarding ALD in younger populations, highlighting the need for policies to reduce alcohol consumption and prevent disease.
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Article Synopsis
  • Alcohol consumption is linked to significant health issues worldwide, including alcohol use disorder (AUD), liver disease, and heart disease, contributing to increased disability and mortality rates, especially among lower socio-economic groups.
  • In 2019, AUD had the highest rate of disability-adjusted life years, with liver disease and alcohol-induced heart problems also notable, although some rates showed slight declines.
  • The burden of alcohol-related health complications is rising particularly in low and low-middle income countries, highlighting an urgent need for effective public health strategies to tackle these challenges.
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Low levels of microRNA (miR) 21 may explain the higher osteocyte apoptosis with Cx43-deficient and aged female mice. However, miR21 exerts a sex-divergent role in osteocytes, regulating bone mass and architecture through non-cell autonomous effects on osteoblasts and osteoclasts, via sex-specific regulation of osteocyte cytokine production. miR21 deficiency improves bone strength in females, and, to a higher extent, in male miR21-deficient mice.

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As international incidence of diabetes and diabetes-driven comorbidities such as chronic kidney disease (CKD) continue to climb, interventions are needed that address the high-risk skeletal fragility of what is a complex disease state. Romosozumab (Romo) is an FDA-approved sclerostin inhibitor that has been shown to increase bone mineral density and decrease fracture rates in osteoporotic patients with mild to severe CKD, but its effect on diabetes-weakened bone is unknown. We aimed to test Romo's performance in a model of combined diabetes and CKD.

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Background: Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis.

Methods: Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037).

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Non-invasive tests for alcohol-associated liver disease.

Hepatology

December 2024

Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Alcohol consumption is a global phenomenon and a major contributor to alcohol-associated liver disease (ALD). Detecting individuals at risk of ALD has been challenging, with only a small fraction of patients being identified at early stages compared to other chronic liver diseases. In response to this challenge, non-invasive tests (NITs) have become essential tools for the detection of ALD, offering opportunities for early identification and intervention to mitigate the disease burden.

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Background And Aims: The worldwide burden of cancer is increasing in younger populations. However, the epidemiology of primary liver cancer remains understudied in young adults compared to other cancer forms.

Approach And Results: This study analyzed data from the Global Burden of Disease study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years associated with primary liver cancer in the young (15-49 y), stratified by region, nation, sociodemographic index, and sex.

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Article Synopsis
  • Patients with chronic kidney disease (CKD) have a significantly higher risk of fractures due to changes in bone structure, specifically increased cortical porosity and diminished matrix hydration.
  • The study involved inducing CKD in mice and testing the effects of mechanical loading and a drug, raloxifene, on bone properties over ten weeks.
  • Results showed that combining mechanical loading with raloxifene treatment improved bone characteristics in CKD mice, leading to lower porosity and enhanced hydration, which could help reduce fracture risk.
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A Comparative Study of Large Language Models, Human Experts, and Expert-Edited Large Language Models to Neuro-Ophthalmology Questions.

J Neuroophthalmol

April 2024

Department of Ophthalmology (PDT, LAD, MRS, DAT, KDC, MCB, SAM, JJC), Mayo Clinic, Rochester, Minnesota; Departments of Ophthalmology (HEM) and Neurology & Neurological Sciences (HEM), Stanford University, Palo Alto, California; Department of Ophthalmology (KEL, MWK, DDM), Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana; Ophthalmology Service (KEL), Richard L. Roudebush Veterans' Administration Medical Center, Indianapolis, Indiana; Department of Ophthalmology and Visual Sciences (KEL), University of Louisville, Louisville, Kentucky; Midwest Eye Institute (KEL), Carmel, Indiana; Circle City Neuro-Ophthalmology (KEL), Carmel, Indiana; Department of Neurology (MWK, DDM), Indiana University, Indianapolis, Indiana; Department of Ophthalmology (MADN, OMD), Mayo Clinic, Scottsdale, Arizona; and Department of Ophthalmology (MLP, ERE), Mayo Clinic, Jacksonville, Florida.

Background: While large language models (LLMs) are increasingly used in medicine, their effectiveness compared with human experts remains unclear. This study evaluates the quality and empathy of Expert + AI, human experts, and LLM responses in neuro-ophthalmology.

Methods: This randomized, masked, multicenter cross-sectional study was conducted from June to July 2023.

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Skeletal fragility and high fracture rates are common in CKD. A key component of bone loss in CKD with secondary hyperparathyroidism is high bone turnover and cortical bone deterioration through both cortical porosity and cortical thinning. We hypothesized that RANKL drives high bone resorption within cortical bone leading to the development of cortical porosity in CKD (study 1) and that systemic inhibition of RANKL would mitigate the skeletal phenotype of CKD (study 2).

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Osteocytes and Paget's Disease of Bone.

Curr Osteoporos Rep

April 2024

Division of Hematology and Oncology, Department of Medicine, Indiana University, Indianapolis, IN, USA.

Purpose Of Review: To describe the contributions of osteocytes to the lesions in Paget's disease, which are characterized by locally overactive bone resorption and formation.

Recent Findings: Osteocytes, the most abundant cells in bone, are altered in Paget's disease lesions, displaying increased size, decreased canalicular length, incomplete differentiation, and less sclerostin expression compared to controls in both patients and mouse models. Pagetic lesions show increased senescent osteocytes that express RANK ligand, which drives osteoclastic bone resorption.

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MCJ (Methylation-Controlled J protein), an endogenous repressor of the mitochondrial respiratory chain, is upregulated in multiple liver diseases but little is known about how it is regulated. S-adenosylmethionine (SAMe), the biological methyl donor, is frequently depleted in chronic liver diseases. Here, we show that SAMe negatively regulates MCJ in the liver.

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Abaloparatide is more potent than teriparatide in restoring bone mass and strength in type 1 diabetic male mice.

Bone

April 2024

Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Central Arkansas Veterans Healthcare System, John L. McClellan Little Rock, AR, USA; Indiana University School of Medicine, Indianapolis, IN, USA; Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA. Electronic address:

This study investigated the efficacy of the two FDA-approved bone anabolic ligands of the parathyroid hormone receptor 1 (PTH1R), teriparatide or human parathyroid hormone 1-34 (PTH) and abaloparatide (ABL), to restoring skeletal health using a preclinical murine model of streptozotocin-induced T1-DM. Intermittent daily subcutaneous injections of equal molar doses (12 pmoles/g/day) of PTH (50 ng/g/day), ABL (47.5 ng/g/day), or vehicle, were administered for 28 days to 5-month-old C57Bl/6 J male mice with established T1-DM or control (C) mice.

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Multiple mechanisms activate GCN2 eIF2 kinase in response to diverse stress conditions.

Nucleic Acids Res

February 2024

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS4067 Indianapolis, Indiana 46202, USA.

Diverse environmental insults induce the integrated stress response (ISR), which features eIF2 phosphorylation and translational control that serves to restore protein homeostasis. The eIF2 kinase GCN2 is a first responder in the ISR that is activated by amino acid depletion and other stresses not directly related to nutrients. Two mechanisms are suggested to trigger an ordered process of GCN2 activation during stress: GCN2 monitoring stress via accumulating uncharged tRNAs or by stalled and colliding ribosomes.

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Apparent treatment-resistant hypertension is defined as an elevated BP despite the use of ≥3 antihypertensive medications from different classes or the use of ≥4 antihypertensives regardless of BP levels. Among patients receiving maintenance hemodialysis or peritoneal dialysis, using this definition, the prevalence of apparent treatment-resistant hypertension is estimated to be between 18% and 42%. Owing to the lack of a rigorous assessment of some common causes of pseudoresistance, the burden of true resistant hypertension in the dialysis population remains unknown.

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High levels of alcohol intake alter brain gene expression and can produce long-lasting effects. FK506-binding protein 51 (FKBP51) encoded by is a physical and cellular stress response gene and has been associated with alcohol consumption and withdrawal severity. has been previously linked to neurite outgrowth and hippocampal morphology, sex differences in stress response, and epigenetic modification.

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Objective: Medicare's Hospital Readmissions Reduction Program (HRRP) financially penalizes "excessive" postoperative readmissions. Concerned with creating a double standard for institutions treating a high percentage of economically vulnerable patients, Medicare elected to exclude socioeconomic status (SES) from its risk-adjustment model. However, recent evidence suggests that safety-net hospitals (SNHs) caring for many low-SES patients are disproportionately penalized under the HRRP.

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