A Talaromyces fungal species with strong antimicrobial activity from Deception Island, Antarctica

Deception Island is well-known for harboring highly diverse microbial communities due to its unique volcanic environment in Antarctica. Most studies focused on bacteria, and relatively little was known about the fungal species on this island. The present study was aimed to determine the antimicrobial production and nutrient utilization profiles of a soil fungus from Deception Island, designated as Im33. Our findings showed that the strain had maximum mycelial growth and sporulation on malt-extract agar (MEA) medium, but it demonstrated the strongest antimicrobial activity in yeast extract-malt extract broth (YMB) medium. Phylogenetic analysis of the internal transcribed spacer 1 and 2 regions showed that it is a species belonging to the genus Talaromyces. It was resistant to cycloheximide concentrations up to 1,000 mg/L and exhibited broad-spectrum antimicrobial activity against Gram-positive and Gram-negative test pathogens, as well as being able to utilize a variety of carbon sources. This is the first report of a Talaromyces species from Deception Island. The capability of the strain to produce broad-spectrum antimicrobial compounds and various enzymes indicated that Antarctic fungi, like their bacterial counterparts, have adopted various adaptation strategies to compete and survive in the extreme environment

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

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

Effects of imperfect testing on presence-absence sampling plans

Sampling inspection plans are used in the food industry to determine whether a batch of food is contaminated or not. Testing for pathogens is mandatory in several foodstuffs because some bacteria pose a significant risk to human health, even when these are consumed in minute quantity. Test performance measures such as sensitivity and specificity are generally ignored in microbiological risk assessment and food quality assurance. In this research, we examine the impact of imperfect analytical tests on sampling inspection plans for presence-absence characteristics. We discuss several plausible scenarios and assess the risk for the consumers. The method is illustrated using data collected over 2 years for Cronobacter spp (formerly Enterobacter sakazakii) in skimmed milk powder. The probability of contamination and the test sensitivity and specificity are estimated using Bayesian methods. We examine the sampling plans proposed by the Codex Alimentarius and by the New Zealand's Ministry of Primary Industries for this pathogen. A cost analysis is performed to show the economic loss due to measurement errors. We describe the strengths and limitations of these plans under different conditions and propose a plan that could provide better protection to the consumers as well as to the producers.</p