Vibrio cholerae is a gram-negative human intestinal pathogen that causes the diarrheal disease cholera. Humans acquire cholera by ingesting V. cholerae-contaminated food or water. Upon ingestion, V. cholerae encounters several barriers to colonization, including bile acid toxicity and antimicrobial products of the innate immune system. In many gram-negative bacteria, resistance to the antimicrobial effects of these products is mediated by RND (resistance-nodulation-division) family efflux systems. In this study we tested the hypothesis that the V. cholerae RND efflux systems are required for antimicrobial resistance and virulence. The six V. cholerae genes encoding RND efflux pumps were deleted from the genome of the O1 El Tor strain N16961, resulting in the generation of 14 independent RND deletion mutants, including one RND-null strain. Determination of the antimicrobial susceptibilities of the mutants revealed that the RND efflux systems were responsible for resistance to multiple antimicrobial compounds, including bile acids, antimicrobial peptides, and antibiotics. VexB (VC0164) was found to be the RND efflux pump primarily responsible for the resistance of V. cholerae to multiple antimicrobial compounds in vitro. In contrast, VexD (VC1757) and VexK (VC1673) encoded efflux pumps with detergent-specific substrate specificities that were redundant with VexB. A strain lacking VexB, VexD, and VexK was attenuated in the infant mouse model, and its virulence factor production was unaffected. In contrast, a V. cholerae RND-null strain produced significantly less cholera toxin and fewer toxin-coregulated pili than the wild type and was unable to colonize the infant mouse. The decreased virulence factor production in the RND-null strain was linked to reduced transcription of tcpP and toxT. Our findings show that the V. cholerae RND efflux systems are required for antimicrobial resistance, optimal virulence factor production, and colonization of the infant mouse.

The Vietnamese community and physicians serving that community need culturally appropriate education about type 2 diabetes and modern therapy for the disease.

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Phthalates are a group of chemicals used in a variety of products worldwide. Exposure to some phthalates is considered to be potentially harmful to human health. Measuring specific metabolites of the phthalates in urine is becoming popular in estimating human exposure to phthalates. In this study, a sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed for the simultaneous determination of 18 phthalate metabolites in human urine. A high efficiency core-shell column allows for a fast separation that is comparable to ultra high performance liquid chromatography (UHPLC) methods. An off-line solid-phase extraction (SPE) was used to clean up the sample matrix. The method detection limit defined as three times the signal to noise ratio in spiked pooled urine samples was achieved in the range of 0.03-1.4 ng mL À1 urine for the 18 target analytes.The developed method has been applied to measure the 18 phthalate metabolites in urine samples of 150 Canadian men. Eleven major metabolites associated with seven parent phthalates, namely diethylphthalate (DEP), bis(2-ethylhexyl) phthalate (DEHP), di-n-octylphthalate (DOP), di-n-butyl phthalate (DBP), diisobutyl phthalate (DiBP), butylbenzylphthalate (BBzP), and dimethylphthalate (DMP), were detected in these samples, among which the metabolites of DEP and DEHP dominated the distribution of all phthalate metabolites detected in the urine samples with mean values of 191.4 and 101.8 ng mL À1 in urine, respectively. The concentrations of phthalate metabolites in this study were found to be similar to those findings in the Canadian Health Measures Survey 2007-2009 (CHMS) andother international studies. The results also demonstrated that the developed method is a robust and reliable method for monitoring of phthalate metabolites in urine samples.

Acrokeratoelastoidosis is a rare palmoplantar keratoderma. We report the case of a 32-year old man with multiple keratotic papules and plaques on the peripheral margins of his hands and feet. Histopathologic evaluation showed compact orthokeratosis; Verhoeff van Gieson stain showed thin and fragmented elastic fibers. The differential diagnosis includes focal acral hyperkeratosis, which has a similar presentation but with normal elastic fibers. Treatment of acrokeratoelastoidosis is often disappointing, with minimal response to topical glucocorticoids, keratolytics, retinoids, cryotherapy, and lasers. Case synopsisHistory: A 32-year-old man presented to the Bellevue Hospital Center Dermatology Clinic for evaluation of multiple papules on his hands and feet that appeared over the past year. The affected areas were associated with a mildly pruritic and intermittently burning sensation. The lesions on his hands and feet developed around the same time and were increasing in number. The patient worked part-time as a construction worker and dishwasher and believed that the initial skin eruption occurred after exposures to various occupational chemicals and detergents. There was no history of trauma, hyperhidrosis, or prolonged exposure to the sun. Neither the patient nor his close contacts had a history of similar lesions. The patient was otherwise well with no relevant family or personal medical history. He was treated with urea 40% cream twice daily and clobetasol 0.05% ointment twice daily for three weeks without improvement. Physical examination:Multiple, 2-to-3-mm, tan, firm papules were clustered along the peripheral margins of the palms and soles. Laboratory: None.Histopathology: There is hyperkeratotic compact orthokeratosis. Within the dermis, a Verhoeff-van Gieson stain shows thinning and fragmentation of elastic fibers.