Faculty Bibliography

Th17 cells are enriched in the gut mucosa and play a critical role in maintenance of the mucosal barrier and host defense against extracellular bacteria and fungal infections. During chronic human immunodeficiency virus (HIV) infection, Th17 cells were more depleted compared to Th1 cells, even when the patients had low or undetectable viremia. To investigate the differential effects of HIV infection on Th17 and Th1 cells, a culture system was used in which CCR6(+) CD4(+) T cells were sorted from healthy human peripheral blood and activated in the presence of interleukin 1beta (IL-1beta) and IL-23 to drive expansion of Th17 cells while maintaining Th1 cells. HIV infection of these cultures had minimal effects on Th1 cells but caused depletion of Th17 cells. Th17 loss correlated with greater levels of virus-infected cells and cell death. In identifying cellular factors contributing to higher susceptibility of Th17 cells to HIV, we compared Th17-enriched CCR6(+) and Th17-depleted CCR6(-) CD4 T cell cultures and noted that Th17-enriched CCR6(+) cells expressed higher levels of alpha4beta7 and bound HIV envelope in an alpha4beta7-dependent manner. The cells also had greater expression of CD4 and CXCR4, but not CCR5, than CCR6(-) cells. Moreover, unlike Th1 cells, Th17 cells produced little CCR5 ligand, and transfection with one of the CCR5 ligands, MIP-1beta (CCL4), increased their resistance against HIV. These results indicate that features unique to Th17 cells, including higher expression of HIV receptors and lack of autocrine CCR5 ligands, are associated with enhanced permissiveness of these cells to HIV.

Aim: To identify factors that affect outpatient colonoscopy attendance in a tertiary care center. Methods: A retrospective review of the electronic medical record system was performed for patients scheduled for outpatient colonoscopies from July to October 2008 at the Manhattan VA Hospital. Patient age, gender, ethnicity, marital status, gender of referring healthcare provider (HCP), distance from hospital (in miles), living situation (e.g. apartment vs. shelter, alone vs. with others), employment status, smoking history, appointment time, day of the week, month, proximity to holiday (in days), family history of gastrointestinal malignancy, prior colon procedures, indication for current procedure, comorbidities (diabetes, hypertension, hyperlipidemia, obesity, pathologies of the major organ systems, psychiatric disorders, and history of cancer) were compared. Statistical analysis using t- and +/-2-tests was performed, with p values 0.05 denoting statistical significance. Results: A total of 517 patients were identified, comprised of 358 patients who presented for their scheduled colonoscopies ("shows") and 159 patients who did not ("no shows"). Patients were more likely to attend their procedure if the referring HCP was female rather than male (p<0.001, Figure 1a). A higher percentage of employed patients presented at their scheduled time compared with patients who were not employed (p<0.005, Figure 1b). Fewer active smokers attended compared with non-smokers. A higher percentage of "shows" who quit smoking attended compared with that of "no shows" (p<0.05, Figure 1c). Patients were less likely to attend the morning time slots from 8-11:30am compared with the afternoon/ early evening time slots from 12-5:30pm (p<0.05, Figure 1d). Patients with neurological conditions (Figure 2, footnote) were less likely to show up at their scheduled appointments (p<0.05, Figure 1e). A greater percentage of "no shows" showed up for future outpatient colonoscopies at the VA Hospital compared with "shows" (p<0.00!

A 38-year-old man with a history of HIV infection virologically suppressed on antiretroviral therapy presents to his gastroenterologist for evaluation of iron deficiency anemia and weight loss. A diagnostic colonoscopy demonstrates a two-centimeter ulcerated mass in the cecum. Biopsies of the lesion return moderately differentiated adenocarcinoma that is wild type for the KRAS mutation by real-time PCR.

Understanding of the human microbiome continues to grow rapidly; however, reports on changes in the microbiome after HIV infection are still limited. This review surveys the progress made in methodology associated with microbiome studies and highlights the remaining challenges to this field. Studies have shown that commensal oral, gut, vaginal, and penile bacteria are vital to the health of the human immune system. Our studies on crosstalk among oral and gastrointestinal soluble innate factors, HIV, and microbes indicated that the oral and gut microbiome was altered in the HIV-positive samples compared to the negative controls. The importance of understanding the bacterial component of HIV/AIDS, and likelihood of "crosstalk" between viral and bacterial pathogens, will help in understanding the role of the microbiome in HIV-infected individuals and facilitate identification of novel antiretroviral factors for use as novel diagnostics, microbicides, or therapeutics against HIV infection.