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.

PPARγ attenuates hypoxia-induced hypertrophic transcriptional pathways in the heart.

Chronic hypoxia-induced pulmonary hypertension (PH) is characterized by increased pressure and resistance in the pulmonary vasculature and hypertrophy of the right ventricle (RV). The transcription factors, nuclear factor activated T-cells (NFAT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB/p65) contribute to RV hypertrophy (RVH). Because peroxisome proliferator-activated receptor gamma (PPARγ) activation attenuates hypoxia-induced PH and RVH, we hypothesized that PPARγ inhibits activation of RV hypertrophic transcriptional signaling mechanisms.

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.

Role of FKS Mutations in Candida glabrata: MIC values, echinocandin resistance, and multidrug resistance.

Candida glabrata is the second leading cause of candidemia in U.S. hospitals.

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.

Asthma and obstructive sleep apnea: clinical and pathogenic interactions.

Asthma and obstructive sleep apnea (OSA) are among the most prevalent chronic human diseases of the 21st century. They share several risk and aggravating factors such as obesity, smoking, gastroesophageal reflux, sinonasal disease or upper airway involvement, systemic inflammation, etc. Although the association between OSA and chronic obstructive pulmonary disease or "overlap syndrome" is better known and characterized, the association of asthma and OSA or "alternative overlap syndrome" is less clearly defined and understood.

Ethics and health policy of dialyzing a patient in a persistent vegetative state.

Each year, out-of-hospital cardiac arrests occur in approximately 300,000 Americans. Of these patients, less than 10% survive. Survivors often live with neurologic impairments that neurologists classify as anoxic-ischemic encephalopathy (AIE).

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.

Inhibition of renin-angiotensin system (RAS) reduces ventricular tachycardia risk by altering connexin43.

Renin-angiotensin system (RAS) activation is associated with arrhythmias. We investigated the effects of RAS inhibition in cardiac-specific angiotensin-converting enzyme (ACE) overexpression (ACE 8/8) mice, which exhibit proclivity to ventricular tachycardia (VT) and sudden death because of reduced connexin43 (Cx43). ACE 8/8 mice were treated with an ACE inhibitor (captopril) or an angiotensin receptor type-1 blocker (losartan).

A sodium channel pore mutation causing Brugada syndrome.

Background: Brugada and long QT type 3 syndromes are linked to sodium channel mutations and clinically cause arrhythmias that lead to sudden death. We have identified a novel threonine-to-isoleucine missense mutation at position 353 (T353I) adjacent to the pore-lining region of domain I of the cardiac sodium channel (SCN5A) in a family with Brugada syndrome. Both male and female carriers are symptomatic at young ages, have typical Brugada-type electrocardiogram changes, and have relatively normal corrected QT intervals.

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.

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.