Workup and conservative management of ileal conduit-vaginal fistulas: review of literature.

Ileal conduit-vaginal fistulas are a rare but challenging complication of urinary diversion. Here we identify risk factors and summarize the workup and conservative management strategies for this complication. We present two cases of elderly women with remote history of cancer who presented with persistent urinary leakage from the vagina several years after ileal conduit creation. Fistulas may be identified using dye or imaging with a loopogram and looposcopy. Correction of obstruction such as stomal stenosis or urinary diversion should be pursued to relieve pressure off the conduit. Minimally invasive management such as fulguration can result temporary relief; however, the recurrence rate is high

Gene Discovery and In Vivo Characterization of the Iridoid Biosynthesis Pathway in Nepeta

This thesis presents the characterization of the Nepeta iridoid biosynthetic pathway via gene discovery and the development of a functional genomics tool for in planta genetic characterization. The Lamiaceae plant family, colloquially known as the mint family, is well known for its chemical diversity and economical importance, especially amongst members of the Nepetoideae sub-family. Most members of this sub-family are well known for their diverse terpene-based natural products; however, one genus, Nepeta, is unique amongst the Nepetoideae for its ability to produce nepetalactone, an iridoid-scaffold compound known for its psychoactive effect on cats and potential use as a bio-based pest control in agriculture due to its influence on various insect species. Chemical profiling on Nepeta spp. and within varieties of a single species have revealed the production of different nepetalactone stereoisomers varies widely across plants. Previous work has identified Nepeta spp. biosynthetic enzymes that can synthesize different stereoisomers of nepetalactones in vitro. Work in this thesis also presents the gene discovery and biochemical characterization of the early steps of this pathway (Chapter 2). The role these biosynthetic genes play in planta leading to the synthesis of different stereochemical ratios of nepetalactone has not been addressed. This thesis presents the development of a virus-induced gene silencing (VIGS) tool for N. cataria (Chapter 3) to explore the in vivo function of the putative biosynthetic genes (Chapter 4). Simultaneously targeting a visual marker gene, magnesium chelatase subunit H (ChlH), and the genes involved in the production of the various nepetalactone stereoisomers, allows the precise selection of the tissue under the knockdown phenotype of VIGS and characterisation of this pathway in vivo. Furthermore, VIGS provides the possibility to untangle the mechanisms behind isomer regulation and gene expression in nepetalactone production, as well as to understand the effect of this pathway on other physiological processes

Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Background:Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and Findings:1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure.An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial Registration:http://www.ClinicalTrials.gov NCT00084136

Workup and conservative management of ileal conduit-vaginal fistulas: review of literature.

Ileal conduit-vaginal fistulas are a rare but challenging complication of urinary diversion. Here we identify risk factors and summarize the workup and conservative management strategies for this complication. We present two cases of elderly women with remote history of cancer who presented with persistent urinary leakage from the vagina several years after ileal conduit creation. Fistulas may be identified using dye or imaging with a loopogram and looposcopy. Correction of obstruction such as stomal stenosis or urinary diversion should be pursued to relieve pressure off the conduit. Minimally invasive management such as fulguration can result temporary relief; however, the recurrence rate is high