24 research outputs found

    Detection and Identification of Salmonella enterica, Escherichia coli, and Shigella spp. via PCR-ESI-MS: Isolate Testing and Analysis of Food Samples

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    An assay to identify the common food-borne pathogens Salmonella, Escherichia coli, Shigella, and Listeria monocytogenes was developed in collaboration with Ibis Biosciences (a division of Abbott Molecular) for the Plex-ID biosensor system, a platform that uses electrospray ionization mass spectroscopy (ESI-MS) to detect the base composition of short PCR amplicons. The new food-borne pathogen (FBP) plate has been experimentally designed using four gene segments for a total of eight amplicon targets. Initial work built a DNA base count database that contains more than 140 Salmonella enterica, 139 E. coli, 11 Shigella, and 36 Listeria patterns and 18 other Enterobacteriaceae organisms. This assay was tested to determine the scope of the assay\u27s ability to detect and differentiate the enteric pathogens and to improve the reference database associated with the assay. More than 800 bacterial isolates of S. enterica, E. coli, and Shigella species were analyzed. Overall, 100% of S. enterica, 99% of E. coli, and 73% of Shigella spp. were detected using this assay. The assay was also able to identify 30% of the S. enterica serovars to the serovar level. To further characterize the assay, spiked food matrices and food samples collected during regulatory field work were also studied. While analysis of preenrichment media was inconsistent, identification of S. enterica from selective enrichment media resulted in serovar-level identifications for 8 of 10 regulatory samples. The results of this study suggest that this high-throughput method may be useful in clinical and regulatory laboratories testing for these pathogens

    The insect pathogenic bacterium Xenorhabdus innexi has attenuated virulence in multiple insect model hosts yet encodes a potent mosquitocidal toxin

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    Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

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    Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

    <i>Helicobacter pylori</i>, HIV and Gastric Hypochlorhydria in the Malawian Population

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    <div><p>Background</p><p>HIV and <i>Helicobacter pylori</i> are common chronic infections in sub-Saharan Africa. Both conditions can predispose to gastric hypochlorhydria that may be a risk factor for enteric infections and reduced drug absorption. We have investigated to what extent HIV and <i>H</i>. <i>pylori</i> infections are associated with hypochlorhydria in a Malawian cohort of patients undergoing endoscopy.</p><p>Methods</p><p>104 sequential symptomatic adults referred for gastroscopy at Queen Elizabeth Central Hospital, Blantyre, Malawi, had blood taken for rapid HIV testing and fasting serum gastrin analysis. Gastric fluid was aspirated for pH testing, and gastric biopsies were taken.</p><p>Results</p><p>After 9/104 HIV-infected patients who were already established on anti-retroviral therapy were excluded, 17/95 (25.0%) were seropositive for untreated HIV, and 68/95 (71.6%) patients were <i>H</i>. <i>pylori</i> positive by histology. Hypochlorhydria (fasting gastric pH>4.0) was present in 55.8% (53/95) of patients. <i>H</i>. <i>pylori</i> infection was significantly associated with hypochlorhydria (OR 2.91, [1.02-7.75], p=0.046). While single infection with HIV was not significantly independently associated with hypochlorhydria. <i>H</i>. <i>pylori</i> and HIV co-infection was more strongly associated with hypochlorhydria (OR 6.25, [1.33-29.43], p=0.020) than either infection alone, suggesting an additive effect of co-infection. HIV infection was associated with higher serum gastrin levels (91.3pM vs. 53.1pM, p=0.040), while <i>H</i>. <i>pylori</i> infection was not (63.1pM vs. 55.1pM, p=0.610). Irrespective of <i>H</i>. <i>pylori</i> and HIV status, most patients (>90%) exhibited pangastritis. Only three patients had histological evidence of gastric atrophy, of which only one was HIV-infected.</p><p>Conclusion</p><p><i>H</i>. <i>pylori</i> infection was associated with fasting hypochlorhydria, while HIV was not independently associated. HIV and <i>H</i>. <i>pylori</i> co-infection, however, was more strongly associated with hypochlorhydria than <i>H</i>. <i>pylori</i> infection alone. The mechanism of this apparent additive effect between HIV and <i>H</i>. <i>pylori</i> remains unclear, but appears to be related to chronic pangastritis rather than gastric atrophy, and associated with hypergastrinaemia in HIV-infected individuals.</p></div
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