Human-specific phages infecting Enterococcus host strain MW47: are they reliable microbial source tracking markers?

AIM: The aim of this study was to determine the morphological diversity and environmental survival of human-specific phages infecting Enterococcus faecium host strain MW47, to support their use as microbial source tracking (MST) markers. METHODS AND RESULTS: Twenty phages capable of infecting strain MW47 were propagated and their morphologies were determined using transmission electron microscopy (TEM), which revealed that a heterogeneous group of phages was able to infect strain MW47. Three distinct morphologies from two different families (Myoviridae and Siphoviridae) were observed. In situ inactivation experiments were subsequently conducted to determine their environmental persistence. CONCLUSION: The findings revealed a statistically significant link between morphology and the rate of inactivation, with phages belonging to the Myoviridae family demonstrating more rapid inactivation in comparison to those belonging to the Siphoviridae family. SIGNIFICANCE AND IMPACT OF STUDY: The results suggest that while Enterococcus MW47 phages appear to be a potentially valuable MST tools, significant variations in the persistence of the different phages mean that the approach should be used with caution, as this may adversely affect the reliability of the approach, especially when comparing MW47 phage levels or the presence across different matrices (e.g. levels in sediments or shellfish). This highlights the importance of elucidating the ecological characteristics of newly proposed MST markers before they are used in full-scale MST investigations.

Pegylated-asparaginase during induction therapy for adult acute lymphoblastic leukaemia: toxicity data from the UKALL14 trial.

Safety and efficacy data on pegylated asparaginase (PEG-ASP) in adult acute lymphoblastic leukaemia (ALL) induction regimens are limited. The UK National Cancer Research Institute UKALL14 trial NCT01085617 prospectively evaluated the tolerability of 1000 IU/m2 PEG-ASP administered on days 4 and 18 as part of a five-drug induction regimen in adults aged 25-65 years with de novo ALL. Median age was 46.5 years. Sixteen of the 90 patients (median age 56 years) suffered treatment-related mortality during initial induction therapy. Eight of the 16 died of sepsis in combination with hepatotoxicity. Age and Philadelphia (Ph) status were independent variables predicting induction death >40 versus ⩽40 years, odds ratio (OR) 18.5 (2.02-169.0), P=0.01; Ph- versus Ph+ disease, OR 13.60 (3.52-52.36), P<0.001. Of the 74 patients who did not die, 37 (50.0%) experienced at least one grade 3/4 PEG-ASP-related adverse event, most commonly hepatotoxicity (36.5%, n=27). A single dose of PEG-ASP achieved trough therapeutic enzyme levels in 42/49 (86%) of the patients tested. Although PEG-ASP delivered prolonged asparaginase activity in adults, it was difficult to administer safely as part of the UKALL14 intensive multiagent regimen to those aged >40 years. It proved extremely toxic in patients with Ph+ ALL, possibly owing to interaction with imatinib.

The application of phage-based faecal pollution markers to predict the concentration of adenoviruses in mussels (Mytilus edulis) and their overlying waters.

AIM: This study set out to determine whether phage-based indicators may provide a 'low-tech' alternative to existing approaches that might help maintain the microbial safety of shellfish and their overlying waters. METHODS AND RESULTS: Mussels and their overlying waters were collected biweekly from an estuary in southeast England over a 2-year period (May 2013-April 2015) (n = 48). Levels of bacterial indicators were determined using membrane filtration and most probable number methods and those of bacteriophages were determined by direct plaque assay. The detection of adenovirus was determined using real-time polymerase chain reaction. The results revealed that somatic coliphages demonstrated the most significant correlations with AdV F and G in mussels (ρ = 0·55) and overlying waters (ρ = 0·66), followed by GB124 phages (ρ = 0·43) while Escherichia coli showed no correlation with AdV F and G in mussels. CONCLUSION: This study demonstrates that the use of somatic coliphages and GB124 phages may provide a better indication of the risk of adenovirus contamination of mussels and their overlying waters than existing bacterial indicators. SIGNIFICANCE AND IMPACT OF THE STUDY: Phage-based detection may be particularly advantageous in low-resource settings where viral infectious disease presents a significant burden to human health.

Characterization of Hepatitis B and C Among Liver Transplant Recipients With Hepatocellular Carcinoma: An Analysis of the Nationwide Inpatient Sample Database.

INTRODUCTION: Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections account for most hepatocellular carcinoma (HCC) and subsequent liver transplant cases. Racial/ethnic disparities exist in access to liver transplantation and post-transplantation survival, and we sought to compare and explore potential disparities in HBV and HCV-related liver transplant populations. METHOD: The Nationwide Inpatient Sample database was used (2001 to 2010). RESULTS: In this study, 2269 liver transplant recipients were included: 56% HCV, 6% HBV, and 37% non-HV. HBV and HCV patients were mostly Asian/Pacific Islander (API) and white, respectively. Within HBV transplant recipients, the mean age was youngest in black patients (P = .02); variation of mean age was not seen within HCV patients. Regarding the transplant recipients' income and insurance, most API and white patients were in the highest income quartile, whereas most black and Hispanic patients were in the lowest income group (P < .001). The most common form of payer across all racial/ethnic groupings was private insurance (P < .001). The mean length of hospitalization was longest in Hispanic patients (P = .008); they had a significantly longer stay compared with white patients (P = .02). The liver transplantations were mostly performed in teaching hospitals, located in urban areas in the West region of the United States (P < .001). CONCLUSION: Differences were found in the HBV and HCV-associated liver transplant populations. More work needs to be done to elucidate disparities regarding black and Hispanic liver transplant recipients as they receive transplants at younger mean ages, are in lower income quartiles, and have longer lengths of hospitalization compared with other racial/ethnic groupings.

Fetal dosimetry from natural alpha-particle emitters.

The alpha-particle dose to human fetal bone marrow from natural exposure was investigated. The rate of calcification and the (210)Pb activity levels in fetal vertebrae showed that (210)Pb follows the uptake of calcium into the skeleton. Lead-210-supported (210)Po activity concentrations of up to 0.18 Bq kg(-1) were found in fetal lumbar vertebra. The mean chord length of the trabecular spaces in lumbar vertebra were 110-320 micrometer at 20- 40 weeks, in rib 130-180 micrometer at 20-35 weeks, and in sternum 190 micrometer at 35 weeks of gestation. In lumbar vertebra, up to 80% of marrow was within alpha-particle range (37 micrometer) of a bone surface. This resulted in a gestational equivalent dose to marrow from (210)Pb-supported (210)Po in bone of 8 and 24 micrometerSv when the contribution from all major natural alpha-particle-emitting radionuclides was considered. The mean distance of CD34(+) cells from the nearest bone surfaces in lumbar vertebra was 61 and 46 micrometer at mid- and late gestation, respectively. The mean cellular and nuclear diameters of CD34(+) cells were 5.5 and 3.8 micrometer respectively, and remained constant with gestational age. Few stem cells were hit by alpha particles at natural exposure; however, those that were hit received doses of up to 1.3 Gy.