Microvascular Disease, Peripheral Artery Disease, and Amputation.

Background: The mechanism of adverse limb events associated with peripheral artery disease remains incompletely understood. We investigated whether microvascular disease is associated with amputation in a large cohort of veterans to determine whether microvascular disease diagnosed in any location increases the risk of amputation alone and in concert with peripheral artery disease.

Methods: Participants in the Veterans Aging Cohort Study were recruited from April 1, 2003 through December 31, 2014.

Integrated stepped alcohol treatment for patients with HIV and alcohol use disorder: a randomised controlled trial.

Background: We examined the effectiveness of integrated stepped alcohol treatment (ISAT) on alcohol use and HIV outcomes among patients living with HIV and alcohol use disorder.

Methods: In this multisite, randomised controlled trial, conducted in five Veterans Affairs-based HIV clinics in the USA (Atlanta, GA; Brooklyn-Manhattan, NY; Dallas and Houston, TX; and Washington, DC), we recruited people living with HIV and an alcohol use disorder who were not otherwise receiving formal alcohol treatment. Patients were eligible if they were aged 18 years or older, HIV positive, English speaking, and met criteria for alcohol use disorder by the Diagnostic and Statistical Manual for Mental Disorders-IV criteria for alcohol abuse or dependence.

Advance Care Planning in Cognitively Impaired Older Adults.

Older adults with cognitive impairment face many healthcare challenges, chief among them participating in medical decision-making about their own health care. Advance care planning (ACP) is the process whereby individuals communicate their wishes for future care with their clinicians and surrogate decision-makers while they are still able to do so. ACP has been shown to improve important outcomes for individuals with cognitive impairment, but rates of ACP for these individuals are low because of individual-, clinician-, and system-related factors.

Recreational Marijuana Use and Acute Myocardial Infarction: Insights from Nationwide Inpatient Sample in the United States.

Background Marijuana is a widely used recreational substance. Few cases have been reported of acute myocardial infarction following marijuana use. To our knowledge, this is the first ever study analyzing the lifetime odds of acute myocardial infarction (AMI) with marijuana use and the outcomes in AMI patients with versus without marijuana use.

Risk of Acute Liver Injury After Statin Initiation by Human Immunodeficiency Virus and Chronic Hepatitis C Virus Infection Status.

Background: Patients with human immunodeficiency virus (HIV) and/or chronic hepatitis C virus (HCV) infection may be prescribed statins as treatment for metabolic/cardiovascular disease, but it remains unclear if the risk of acute liver injury (ALI) is increased for statin initiators compared to nonusers in groups classified by HIV/HCV status.

Methods: We conducted a cohort study to compare rates of ALI in statin initiators vs nonusers among 7686 HIV/HCV-coinfected, 8155 HCV-monoinfected, 17739 HIV-monoinfected, and 36604 uninfected persons in the Veterans Aging Cohort Study (2000-2012). We determined development of (1) liver aminotransferases >200 U/L, (2) severe ALI (coagulopathy with hyperbilirubinemia), and (3) death, all within 18 months.

The Starting Treatment for Ethanol in Primary care Trials (STEP Trials): Protocol for Three Parallel Multi-Site Stepped Care Effectiveness Studies for Unhealthy Alcohol Use in HIV-Positive Patients.

Unhealthy alcohol use is common among HIV-positive patients, yet effective evidence-based treatments are rarely provided in clinical settings providing HIV care. Further, given patient variability in response to initial treatments, stepped care approaches may be beneficial. We describe the rationale, aims and study design for the current StartingTreatment forEthanol inPrimary care Trials (STEP Trials); three parallel randomized controlled effectiveness trials being conducted in five Infectious Disease Clinics.

Association of COPD With Risk for Pulmonary Infections Requiring Hospitalization in HIV-Infected Veterans.

Background: Pulmonary infections remain more common in HIV-infected (HIV+) compared with uninfected individuals. The increase in chronic lung diseases among aging HIV+ individuals may contribute to this persistent risk. We sought to determine whether chronic obstructive pulmonary disease (COPD) is an independent risk factor for different pulmonary infections requiring hospitalization among HIV+ patients.

Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults.

Background: Although it has been shown that human immunodeficiency virus (HIV)-infected adults are at greater risk for aging-associated events, it remains unclear as to whether these events happen at similar, or younger ages, in HIV-infected compared with uninfected adults. The objective of this study was to compare the median age at, and risk of, incident diagnosis of 3 age-associated diseases in HIV-infected and demographically similar uninfected adults.

Methods: The study was nested in the clinical prospective Veterans Aging Cohort Study of HIV-infected and demographically matched uninfected veterans, from 1 April 2003 to 31 December 2010.

Incidence and clinical characteristics of lower urinary tract symptoms as a presenting symptom for patients with newly diagnosed bladder cancer.

Purpose: The incidence of lower urinary tract symptoms (LUTS) as the sole presenting symptom for bladder cancer has traditionally been reported to be low. The objective of this study was to evaluate the prevalence and clinical characteristics of newly diagnosed bladder cancer patients who presented with LUTS in the absence of gross or microscopic hematuria.

Materials And Methods: We queried our database of bladder cancer patients at the Atlanta Veteran's Affairs Medical Center (AVAMC) to identify patients who presented solely with LUTS and were subsequently diagnosed with bladder cancer.

Polymerase delta interacting protein 2 sustains vascular structure and function.

Objective: On the basis of previous evidence that polymerase delta interacting protein 2 (Poldip2) increases reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (Nox4) activity in vascular smooth muscle cells, we hypothesized that in vivo knockdown of Poldip2 would inhibit reactive oxygen species production and alter vascular function.

Approach And Results: Because homozygous Poldip2 deletion is lethal, Poldip2(+/-) mice were used. Poldip2 mRNA and protein levels were reduced by ≈50% in Poldip2(+/-) aorta, with no change in p22phox, Nox1, Nox2, and Nox4 mRNAs.

Natural antisense transcripts enhance bone formation by increasing sense IFITM5 transcription.

Interferon induced transmembrane protein 5 (IFITM5) has been recognized as an osteoblast differentiation factor. Its regulation, however, is still unclear. In this report, four novel naturally occurring antisense transcripts of rat IFITM2 and IFITM5 transcribed from the opposite strand of the IFITM gene locus, were isolated and characterized.

Adeno-associated viral delivery of a metabolically regulated insulin transgene to hepatocytes.

Transduction with a liver specific, metabolically responsive insulin transgene produces near-normal blood sugars in STZ-diabetic rats. To overcome the limited duration of hepatic transgene expression induced by E1A-deleted adenoviral vectors, we evaluated recombinant adeno-associated virus (rAAV2) for cell type specificity and glucose responsiveness in vitro. Co-infection of AAV2 containing the glucose responsive, liver-specific (GlRE)(3)BP-1 promoter with an empty adenovirus enhanced transduction efficiency, and shortened the duration of transgene expression in HepG2 hepatoma cells, but not primary hepatocytes.

Successful penile preservation surgery for large proximal penile carcinoma: 7-year follow-up.

We report the case of a 49-year-old man who presented with a 2-month history of a progressively enlarging squamous cell carcinoma on the skin of the proximal penile shaft. The patient refused penectomy and requested penile preservation. He was treated with wide surgical excision of the tumor, followed by a full-thickness vascularized scrotal skin flap.

Endoscopic enucleation of leiomyoma of the bladder.

A case of benign leiomyoma of the urinary bladder was discovered incidentally and treated successfully with endoscopic enucleation. We describe the technique of this new surgical approach and discuss its advantages. We recommend this minimally invasive approach over open surgical resection.

Role of transrectal ultrasonography in diagnosis and treatment of retained Foley catheter.

Retention of Foley balloon in the bladder or urethra is a troublesome complication that presents a challenge to the urologist. We describe a complicated case of Foley catheter balloon retention (and trauma) within the urethra in an orthopedic patient undergoing hemiarthroplasty. The Foley balloon failed to deflate with standard methods.

Mechanical strain differentially regulates endothelial nitric-oxide synthase and receptor activator of nuclear kappa B ligand expression via ERK1/2 MAPK.

Exercise promotes positive bone remodeling through controlling cellular processes in bone. Nitric oxide (NO), generated from endothelial nitric-oxide synthase (eNOS), prevents resorption, whereas receptor activator of nuclear kappa B ligand (RANKL) promotes resorption through regulating osteoclast activity. Here we show that mechanical strain differentially regulates eNOS and RANKL expression from osteoprogenitor stromal cells in a magnitude-dependent fashion.

M. tuberculosis induction of matrix metalloproteinase-9: the role of mannose and receptor-mediated mechanisms.

Mycobacterium tuberculosis (Mtb) infection induces the expression of matrix metalloproteinase-9 (MMP-9) in mouse lungs. In cultured human monocytic cells, Mtb bacilli and the cell wall glycolipid lipoarabinomannan (LAM) stimulate high levels of MMP-9 activity. Here, we explore the cellular mechanisms involved in the induction of MMP-9 by Mtb.

Regulation of serum-induced fibronectin expression by protein kinases, cytoskeletal integrity, and CREB.

Lung injury, characterized by the flooding of interstitial and alveolar spaces with serum proteins, induces the expression of fibronectin (FN). This cell-adhesive extracellular matrix (ECM) glycoprotein is believed to modulate inflammation and wound repair. Murine NIH/3T3 fibroblasts transfected with a 1.

Interleukin-1beta gene transcription in U937 cells is modulated by type I collagen and cytoskeletal integrity via distinct signaling pathways.

Type I collagen (Col), an extracellular matrix molecule highly expressed in injured tissues, stimulates interleukin-1beta (IL-1beta) expression in monocytic cells. Using U937 cells transfected with the human IL-1beta gene promoter connected to a reporter gene, we examined how the organizational state of the cytoskeleton modulates the expression of IL-1beta after Col stimulation. We found the same degree of stimulation of IL-1beta gene transcription in cells exposed to Col presented in different fashions (i.

Nucleotide sequence analysis of hypervariable junctions of Haemophilus influenzae pilus gene clusters.

Haemophilus influenzae pili are surface structures that promote attachment to human epithelial cells. The five genes that encode pili, hifABCDE, are found inserted in genomes either between pmbA and hpt (hif-1) or between purE and pepN (hif-2). We determined the sequence between the ends of the pilus clusters and bordering genes in a number of H.

Transcriptional regulation of the human interleukin 1beta gene by fibronectin: role of protein kinase C and activator protein 1 (AP-1).

Interleukin 1beta (IL-1beta) is a multifunctional polypeptide considered a key cytokine during inflammation. Fibronectin (FN), a matrix glycoprotein highly expressed in injured tissues, can induce expression of IL-1beta in human blood monocytic cells. Herein, we explore the intracellular signals and transcriptional mechanisms responsible for IL-1beta induction by FN using human promonocytic U937 cells transfected with the human IL-1beta promoter connected to a reporter gene.