Faculty Bibliography

BACKGROUND: We performed this study 1) to determine the prevalence of community-associated extended spectrum beta-lactamase producing Enterobacteriaceae (ESBLPE) colonization and infection in New York City (NYC); 2) to determine the prevalence of newly-acquired ESBLPE during travel; 3) to look for similarities in contemporaneous hospital-associated bloodstream ESBLPE and travel-associated ESBLPE. METHODS: Subjects were recruited from a travel medicine practice and consented to submit pre- and post-travel stools, which were assessed for the presence of ESBLPE. Pre-travel stools and stools submitted for culture were used to estimate the prevalence of community-associated ESBLPE. The prevalence of ESBLPE-associated urinary tract infections was calculated from available retrospective data. Hospital-associated ESBLPE were acquired from saved bloodstream isolates. All ESBLPE underwent multilocus sequence typing (MLST) and ESBL characterization. RESULTS: One of 60 (1.7%) pre- or non-travel associated stool was colonized with ESBLPE. Among community-associated urine specimens, 1.3% of Escherichia coli and 1.4% of Klebsiella pneumoniae were identified as ESBLPE. Seven of 28 travelers (25.0%) acquired a new ESBLPE during travel. No similarities were found between travel-associated ESBLPE and hospital-associated ESBLPE. A range of imported ESBL genes were found, including CTX-M-14 and CTX-15. CONCLUSION: ESBL colonization and infection were relatively low during the study period in NYC. A significant minority of travelers acquired new ESBLPE during travel.

BACKGROUND: Recent reports highlight the incursion of community-associated MRSA within healthcare settings. However, knowledge of this phenomenon remains limited in Latin America. The aim of this study was to evaluate the molecular epidemiology of MRSA in three tertiary-care hospitals in Medellin, Colombia. METHODS: An observational cross-sectional study was conducted from 2008-2010. MRSA infections were classified as either community-associated (CA-MRSA) or healthcare-associated (HA-MRSA), with HA-MRSA further classified as hospital-onset (HAHO-MRSA) or community-onset (HACO-MRSA) according to standard epidemiological definitions established by the U.S. Centers for Disease Control and Prevention (CDC). Genotypic analysis included SCCmec typing, spa typing, PFGE and MLST. RESULTS: Out of 538 total MRSA isolates, 68 (12.6%) were defined as CA-MRSA, 243 (45.2%) as HACO-MRSA and 227 (42.2%) as HAHO-MRSA. The majority harbored SCCmec type IVc (306, 58.7%), followed by SCCmec type I (174, 33.4%). The prevalence of type IVc among CA-, HACO- and HAHO-MRSA isolates was 92.4%, 65.1% and 43.6%, respectively. From 2008 to 2010, the prevalence of type IVc-bearing strains increased significantly, from 50.0% to 68.2% (p = 0.004). Strains harboring SCCmec IVc were mainly associated with spa types t1610, t008 and t024 (MLST clonal complex 8), while PFGE confirmed that the t008 and t1610 strains were closely related to the USA300-0114 CA-MRSA clone. Notably, strains belonging to these three spa types exhibited high levels of tetracycline resistance (45.9%). CONCLUSION: CC8 MRSA strains harboring SCCmec type IVc are becoming predominant in Medellin hospitals, displacing previously reported CC5 HA-MRSA clones. Based on shared characteristics including SCCmec IVc, absence of the ACME element and tetracycline resistance, the USA300-related isolates in this study are most likely related to USA300-LV, the recently-described 'Latin American variant' of USA300.

BACKGROUND:Acute coronary syndromes (ACS; myocardial infarction or unstable angina) can induce posttraumatic stress disorder (PTSD), and ACS-induced PTSD may increase patients' risk for subsequent cardiac events and mortality. OBJECTIVE:To determine the prevalence of PTSD induced by ACS and to quantify the association between ACS-induced PTSD and adverse clinical outcomes using systematic review and meta-analysis. DATA SOURCES/METHODS:Articles were identified by searching Ovid MEDLINE, PsycINFO, and Scopus, and through manual search of reference lists. METHODOLOGY/PRINCIPAL FINDINGS/RESULTS:Observational cohort studies that assessed PTSD with specific reference to an ACS event at least 1 month prior. We extracted estimates of the prevalence of ACS-induced PTSD and associations with clinical outcomes, as well as study characteristics. We identified 56 potentially relevant articles, 24 of which met our criteria (N = 2383). Meta-analysis yielded an aggregated prevalence estimate of 12% (95% confidence interval [CI], 9%-16%) for clinically significant symptoms of ACS-induced PTSD in a random effects model. Individual study prevalence estimates varied widely (0%-32%), with significant heterogeneity in estimates explained by the use of a screening instrument (prevalence estimate was 16% [95% CI, 13%-20%] in 16 studies) vs a clinical diagnostic interview (prevalence estimate was 4% [95% CI, 3%-5%] in 8 studies). The aggregated point estimate for the magnitude of the relationship between ACS-induced PTSD and clinical outcomes (ie, mortality and/or ACS recurrence) across the 3 studies that met our criteria (N = 609) suggested a doubling of risk (risk ratio, 2.00; 95% CI, 1.69-2.37) in ACS patients with clinically significant PTSD symptoms relative to patients without PTSD symptoms. CONCLUSIONS/SIGNIFICANCE/CONCLUSIONS:This meta-analysis suggests that clinically significant PTSD symptoms induced by ACS are moderately prevalent and are associated with increased risk for recurrent cardiac events and mortality. Further tests of the association of ACS-induced PTSD and clinical outcomes are needed.

The popularity of smokeless tobacco (ST), or noncombusted tobacco, usually placed within the mouth to be chewed, sucked, or swallowed, is growing rapidly and its prevalence of use is rising globally, due (in part) to greater convenience, as allowable cigarette smoking areas are rapidly decreasing, and increased social acceptability. Though data are limited, ST usage has been directly linked to a number of adverse health outcomes. The potential role that immune dysfunction, including dysregulation of immune cells and their components, may play in the progression of these adverse health outcomes is only just beginning to emerge. Evidence suggesting reproductive outcomes, such as perinatal mortality, preterm birth, and reduced sperm viability, also exists in conjunction with ST use. Cardiovascular health may also be impacted by ST use, resulting in increased blood pressure and endothelial dysfunction, both of which may potentially lead to cardiovascular diseases. This review describes the toxicological implications associated with ST use, with emphasis on immune, reproductive, and cardiovascular outcomes. Epidemiological studies are discussed with respect to experimental studies to help develop the relationship between ST and disease pathology. This review also summarizes the gaps in ST knowledge and potential future directions that are needed to more fully delineate the complex systems driving the adverse health outcomes associated with its use.

ABSTRACT Primary care is understudied as a reentry drug and alcohol treatment setting. This study compared treatment retention and opioid misuse among opioid-dependent adults seeking buprenorphine/naloxone maintenance in an urban primary care clinic following release from jail versus community referrals. Postrelease patients were either (a) induced to buprenorphine in-jail as part of a clinical trial, or (b) seeking buprenorphine induction post release. From 2007 to 2008, N = 142 patients were new to primary care buprenorphine: n = 32 postrelease; n = 110 induced after community referral and without recent incarceration. Jail-released patients were more likely African American or Hispanic and uninsured. Treatment retention rates for postrelease (37%) versus community (30%) referrals were similar at 48 weeks. Rates of opioid positive urines and self-reported opioid misuse were also similar between groups. Postrelease patients in primary care buprenorphine treatment had equal treatment retention and rates of opioid abstinence versus community-referred patients

OBJECTIVE: Among current smokers, the proportion of Nondaily smokers is increasing. A better understanding of the characteristics and smoking behaviors of Nondaily smokers is needed. METHODS: We analyzed data from the New York City (NYC) Community Health Survey to explore Nondaily smoking among NYC adults. Univariate analyses assessed changes in Nondaily smoking over time (2002-2010) and identified unique characteristics of Nondaily smokers; multivariable logistic regression analysis identified correlates of Nondaily smoking in 2010. RESULTS: The proportion of smokers who engage in Nondaily smoking significantly increased between 2002 and 2010, from 31% to 36% (P = 0.05). A larger proportion of Nondaily smokers in 2010 were low income and made tax-avoidant cigarette purchases compared to 2002. Smoking behaviors significantly associated with Nondaily smoking in 2010 included smoking more than one hour after waking (AOR = 8.8, 95% CI (5.38-14.27)); buying "loosies" (AOR = 3.5, 95% CI (1.72-7.08)); attempting to quit (AOR = 2.3, 95% CI (1.36-3.96)). CONCLUSION: Nondaily smokers have changed over time and have characteristics distinct from daily smokers. Tobacco control efforts should be targeted towards "ready to quit" Nondaily smokers.

The four Rep proteins of adeno-associated virus (AAV) orchestrate all aspects of its viral life cycle, including transcription regulation, DNA replication, virus assembly, and site-specific integration of the viral genome into the human chromosome 19. All Rep proteins share a central SF3 superfamily helicase domain. In other SF3 members this domain is sufficient to induce oligomerization. However, the helicase domain in AAV Rep proteins (i.e. Rep40/Rep52) as shown by its monomeric characteristic, is not able to mediate stable oligomerization. This observation led us to hypothesize the existence of an as yet undefined structural determinant that regulates Rep oligomerization. In this document, we described a detailed structural comparison between the helicase domains of AAV-2 Rep proteins and those of the other SF3 members. This analysis shows a major structural difference residing in the small oligomerization sub-domain (OD) of Rep helicase domain. In addition, secondary structure prediction of the linker connecting the helicase domain to the origin-binding domain (OBD) indicates the potential to form α-helices. We demonstrate that mutant Rep40 constructs containing different lengths of the linker are able to form dimers, and in the presence of ATP/ADP, larger oligomers. We further identified an aromatic linker residue (Y224) that is critical for oligomerization, establishing it as a conserved signature motif in SF3 helicases. Mutation of this residue critically affects oligomerization as well as completely abolishes the ability to produce infectious virus. Taken together, our data support a model where the linker residues preceding the helicase domain fold into an α-helix that becomes an integral part of the helicase domain and is critical for the oligomerization and function of Rep68/78 proteins through cooperative interaction with the OBD and helicase domains.