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Isle of Wight, VA, United States

Fleischmann J.,Greater Los Angeles VA Healthcare System | Fleischmann J.,Research Division | Fleischmann J.,University of California at Los Angeles | Rocha M.A.,Research Division
PLoS ONE | Year: 2015

Candida albicans is an important polymorphic human pathogen. It can switch from a unicellular yeast form to germinating hypha, which may play a role in making it the successful pathogen it is. This hyphal transformation can be triggered by various extracellular stimuli, the most potent one being serum from any source. We have previously reported that Candida albicans transiently polyadenylates portions of both the large and small subunits of ribosomal RNA, shortly after serum exposure. Northern blots at the same time suggested that serum might induce a decrease in total ribosomal RNA. We have carried out a number of experiments to carefully assess this possibility and now report that serum significantly reduces ribosomal RNA in Candida albicans. Fluorometric measurements, Northern blotting and quantitative RT-PCR, have all confirmed this decrease. Timed experiments show that serum induces this decrease rapidly, as it was seen in as early as five minutes. Cell mass is not decreased as total cellular protein content remains the same and metabolic activity does not appear to slow, as assessed by XTT assay, and by the observation that cells form hyphal structures robustly. Another hyphal inducer, N-acetylglucosamine, also caused RNA decrease, but to a lesser extent. We also observed it in non-germinating yeast, such as Candida glabrata. The reason for this decrease is unknown and overall our data suggests that decrease in rRNA does not play a causal role in hyphal transformation. Rapid and significant decrease in a molecule so central to the yeast's biology is of some importance, and further studies, such as its effect on protein metabolism, will be required to better understand its purpose. © 2015, Public Library of Science. All rights reserved. Source

Kanwal F.,Baylor College of Medicine | Kramer J.R.,Baylor College of Medicine | Buchanan P.,Saint Louis University | Asch S.M.,Greater Los Angeles VA Healthcare System | And 5 more authors.
Gastroenterology | Year: 2012

Background & Aims: Ascites are the most common complication of cirrhosis. Evidence-based guidelines define the criteria and standards of care for patients with cirrhosis and ascites. However, little is known about the extent to which patients with ascites meet these standards. Methods: We evaluated the quality of ascites care, measured by 8 explicit Delphi panel-derived quality indicators, in 774 patients with cirrhosis and ascites, seen at 3 Veterans Affairs Medical Centers between 2000 and 2007. We also conducted a structured implicit review of patients' medical charts to determine whether patient refusal, outside care, or other justifiable exceptions to care processes account for nonadherence to the quality indicators. Results: Quality scores (maximum 100%) varied among individual indicators, ranging from 30% for secondary prophylaxis of spontaneous bacterial peritonitis, to 90% for assays for cell number and type in the paracentesis fluid. In general, care targeted at treatment was more likely to meet standards than preventive care. Only 33.2% (95% confidence interval [CI]: 29.9%-32.9%) of patients received all recommended care. Patients with no comorbidity (Deyo index 0 vs >3; odds ratio = 2.21; 95% CI: 1.43-3.43), who saw a gastroenterologist (odds ratio = 1.33; 95% CI, 1.01-1.74), or were seen in a facility with academic affiliation (odds ratio = 1.73; 95% CI: 1.29-2.35) received higher-quality care. Justifiable exceptions to indicated care, documented in charts, were common for patients with paracentesis after diagnosis with ascites, patients that received antibiotics for gastrointestinal bleeding, and patients that required diuretics. However, most patients did not have an explanation documented for nonadherence to recommended care. Conclusions: Health care quality, measured by whether patients received recommended services, was suboptimal for patients with cirrhosis-related ascites. Care that included gastroenterologists was associated with high quality. However, for some of the quality indicators, too many denominator exceptions existed to allow for accurate automated measurement. © 2012 AGA Institute. Source

Thames A.D.,University of California at Los Angeles | Arbid N.,Greater Los Angeles VA Healthcare System | Sayegh P.,University of California at Los Angeles
Addictive Behaviors | Year: 2014

Objective: With the recent debates over marijuana legalization and increases in use, it is critical to examine its role in cognition. While many studies generally support the adverse acute effects of cannabis on neurocognition, the non-acute effects remain less clear. The current study used a cross-sectional design to examine relationships between recent and past cannabis use on neurocognitive functioning in a non-clinical adult sample. Method: One hundred and fifty-eight participants were recruited through fliers distributed around local college campuses and the community. All participants completed the Brief Drug Use History Form, the Structured Clinical Interview for DSM-IV Disorders, and neurocognitive assessment, and underwent urine toxicology screening. Participants consisted of recent users (n=68), past users (n=41), and non-users (n=49). Results: Recent users demonstrated significantly (p<.05) worse performance than non-users across cognitive domains of attention/working memory (M=42.4, SD=16.1 vs. M=50.5, SD=10.2), information processing speed (M=44.3, SD=7.3 vs. M=52.1, SD=11.0), and executive functioning (M=43.6, SD=13.4 vs. M=48.6, SD=7.2). There were no statistically significant differences between recent users and past users on neurocognitive performance. Frequency of cannabis use in the last 4. weeks was negatively associated with global neurocognitive performance and all individual cognitive domains. Similarly, amount of daily cannabis use was negatively associated with global neurocognitive performance and individual cognitive domains. Conclusions: Our results support the widespread adverse effects of cannabis use on neurocognitive functioning. Although some of these adverse effects appear to attenuate with abstinence, past users' neurocognitive functioning was consistently lower than non-users. © 2014 Elsevier Ltd. Source

Morales S.A.,University of California at Los Angeles | Telander D.G.,UCD | Mareninov S.,University of California at Los Angeles | Nagy A.,Greater Los Angeles VA Healthcare System | And 3 more authors.
Experimental Eye Research | Year: 2012

Epithelial membrane protein 2 (EMP2) regulates collagen gel contraction by the retinal pigment epithelium cell line ARPE-19 by modulating FAK activation. Collagen gel contraction is one. in vitro model for an aberrant wound healing response, proliferative vitreoretinopathy (PVR), which occurs as a complication of severe ocular trauma. The purpose of this study is to investigate whether EMP2 specific recombinant diabody decreases activation of FAK and collagen gel contraction in ARPE-19. Anti-EMP2 diabody was recombinantly constructed from a human phage library-derived clone selected for reactivity against an extracellular domain of human EMP2. ARPE-19 cells were exposed to an anti-EMP2 or control diabody, and toxicity, adhesion, and migration were assessed respectively through toluidine blue exclusion, binding to collagen type 1, and a migration assay. Collagen gel contraction was assessed using an in vitro assay. FAK activation was evaluated using Western blot. Exposure to anti-EMP2 diabody, resulted in a 75% reduction in EMP2 protein levels at 4 h. No significant toxicity was observed with anti-EMP2 diabody at levels that maximally reduced EMP2. Anti-EMP2 diabody, but not control diabody, significantly reduced collagen gel contraction (p < 0.001), without changes in adhesion or migration. Concordantly, anti-EMP2 diabody as compared to a control diabody reduced collagen stimulated FAK activation (p = 0.01). Anti-EMP2 diabody decreases EMP2 protein levels, FAK activation, and collagen gel contraction by ARPE-19 cells without an adverse effect on cell survival. Modulation of EMP2 using anti-EMP2 diabody could be a new approach for targeting EMP2 and pathologic consequences associated with EMP2. © 2012 . Source

Kanwal F.,Saint Louis University | Kanwal F.,Saint Louis Medical Center | Hoang T.,Greater Los Angeles VA Healthcare System | Kramer J.R.,Baylor College of Medicine | And 8 more authors.
Gastroenterology | Year: 2011

Background & Aims: Patients with hepatitis C virus (HCV) infection are at risk for developing costly and morbid complications, although the actual prevalence of these complications is unknown. We examined time trends in the prevalence of cirrhosis and its related complications, such as hepatic decompensation and hepatocellular carcinoma (HCC). Methods: We calculated the annual prevalence of cirrhosis, decompensated cirrhosis, and HCC in a national sample of veterans diagnosed with HCV between 1996 and 2006. Patients with HCV who had at least one physician visit in a given calendar year were included in the analysis of prevalence for that year. We used direct standardization to adjust the prevalence of cirrhosis and related complications for increasing age of the cohort as well as sex and changes in clinical characteristics. Results: In this cohort, the number of individuals with HCV increased from 17,261 in 1996 to 106,242 in 2006. The prevalence of cirrhosis increased from 9% in 1996 to 18.5% in 2006. The prevalence of patients with decompensated cirrhosis doubled, from 5% in 1996 to 11% in 2006, whereas the prevalence of HCC increased approximately 20-fold (0.07% in 1996 to 1.3% in 2006). After adjustment, the time trend in the prevalence of cirrhosis (and its complications) was lower than the crude trend, although it still increased significantly. Conclusions: The prevalence of cirrhosis and HCC in HCV-infected patients has increased significantly over the past 10 years. An aging cohort of patients with HCV could partly explain our findings. Clinicians and health care systems should develop strategies to provide timely and effective care to this high-risk population of patients. © 2011 AGA Institute. Source

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