A Population-Based Surveillance Study of Shared Genotypes of Escherichia coli Isolates from Retail Meat and Suspected Cases of Urinary Tract Infections.

There is increasing evidence that retail food may serve as a source of Escherichia coli that causes community-acquired urinary tract infections, but the impact of this source in a community is not known. We conducted a prospective, population-based study in one community to examine the frequency of recovery of uropathogenic E. coli genotypes from retail meat samples. We analyzed E. coli isolates from consecutively collected urine samples of patients suspected to have urinary tract infections (UTIs) at a university-affiliated health service and retail meat samples from the same geographic region. We genotyped all E. coli isolates by multilocus sequence typing (MLST) and tested them for antimicrobial susceptibility. From 2016 to 2017, we cultured 233 E. coli isolates from 230 (21%) of 1,087 urine samples and 177 E. coli isolates from 120 (28%) of 427 retail meat samples. Urine samples contained 61 sequence types (STs), and meat samples had 95 STs; 12 STs (ST10, ST38, ST69, ST80, ST88, ST101, ST117, ST131, ST569, ST906, ST1844, and ST2562) were common to both. Thirty-five (81%) of 43 meat isolates among the 12 STs were from poultry. Among 94 isolates in the 12 STs, 26 (60%) of 43 retail meat isolates and 15 (29%) of 51 human isolates were pan-susceptible (P < 0.005). We found that 21% of E. coli isolates from suspected cases of UTIs belonged to STs found in poultry. Poultry may serve as a possible reservoir of uropathogenic E. coli (UPEC). Additional studies are needed to demonstrate transmission pathways of these UPEC genotypes and their food sources.IMPORTANCE Community-acquired urinary tract infection caused by Escherichia coli is one of the most common infectious diseases in the United States, affecting approximately seven million women and costing approximately 11.6 billion dollars annually. In addition, antibiotic resistance among E. coli bacteria causing urinary tract infection continues to increase, which greatly complicates treatment. Identifying sources of uropathogenic E. coli and implementing prevention measures are essential. However, the reservoirs of uropathogenic E. coli have not been well defined. This study demonstrated that poultry sold in retail stores may serve as one possible source of uropathogenic E. coli This finding adds to a growing body of evidence that suggests that urinary tract infection may be a food-borne disease. More research in this area can lead to the development of preventive strategies to control this common and costly infectious disease

Film Boiling on Downward Quenching Hemisphere of Varying Sizes

Film boiling heat transfer coefficients for a downward-facing hemispherical surface are measured from the quenching tests in DELTA (Downward-boiling Experimental Laminar Transition Apparatus). Two test sections are made of copper to maintain low Biot numbers. The outer diameters of the hemispheres are 120 mm and 294 mm, respectively. The thickness of all the test sections is 30 mm. The effect of diameter on film boiling heat transfer is quantified utilizing results obtained from the test sections. The measured data are compared with the numerical predictions from laminar film boiling analysis. The measured heat transfer coefficients are found to be greater than those predicted by the conventional laminar flow theory on account of the interfacial wavy motion incurred by the Helmholtz instability. Incorporation of the wavy motion model considerably improves the agreement between the experimental and numerical results in terms of heat transfer coefficient. In addition, the interfacial wavy motion and the quenching process are visualized through a digital camera

Prandtl Number Dependent Natural Convection with Internal Heat Sources

Natural convection plays an important role in determining the thermal load from debris accumulated in the reactor vessel lower head during a severe accident. Recently, attention is being paid to the feasibility of external vessel flooding as a severe accident management strategy and to the phenomena affecting the success path for retaining the molten core material inside the vessel. The heat transfer inside the molten core material can be characterized by the strong buoyancy-induced flows resulting from internal heating due to decay of fission products. The thermo-fluid dynamic characteristics of such flow depend strongly on the thermal boundary conditions. The spatial and temporal variation of heat flux on the pool wall boundaries and the pool superheat are mainly characterized by the natural convection flow inside the molten pool. In general, the natural convection heat transfer phenomena involving the internal heat generation are represented by the modified Rayleigh number (Ra’), which quantifies the internal heat source and hence the strength of the buoyancy force. In this study, tests were conducted in a rectangular section 250 mm high, 500 mm long and 160 mm wide. Twenty-four T-type thermocouples were installed in the test section to measure temperatures. Four T-type thermocouples were used to measure the boundary temperatures. The thermocouples were placed in designated locations after calibration. A direct heating method was adopted in this test to simulate the uniform heat generation. The experiments covered a range of Ra' between 1.5x106 and 7.42x1015 and the Prandtl number (Pr) between 0.7 and 6.5. Tests were conducted with water and air as simulant. The upper and lower boundary conditions were maintained uniform. The results demonstrated feasibility of the direct heating method to simulate uniform volumetric heat generation. Particular attentions were paid to the effect of Pr on natural convection heat transfer within the rectangular pool

Critical Heat Flux in Inclined Rectangular Narrow Gaps

In light of the TMI-2 accident, in which the reactor vessel lower head survived the attack by molten core material, the in-vessel retention strategy was suggested to benefit from cooling the debris through a gap between the lower head and the core material. The GAMMA 1D (Gap Apparatus Mitigating Melt Attack One Dimensional) tests were conducted to investigate the critical heat flux (CHF) in narrow gaps with varying surface orientations. The CHF in an inclined gap, especially in case of the downward-facing narrow gap, is dictated by bubble behavior because the departing bubbles are squeezed. The orientation angle affects the bubble layer and escape of the bubbles from the narrow gap. The test parameters include gap sizes of 1, 2, 5 and 10 mm and the open periphery, and the orientation angles range from the fully downward-facing (180o) to the vertical (90o) position. The 15 ×35 mm copper test section was electrically heated by the thin film resistor on the back. The heater assembly was installed to the tip of the rotating arm in the heated water pool at the atmospheric pressure. The bubble behavior was photographed utilizing a high-speed camera through the Pyrex glass spacer. It was observed that the CHF decreased as the surface inclination angle increased and as the gap size decreased in most of the cases. However, the opposing results were obtained at certain surface orientations and gap sizes. Transition angles, at which the CHF changed in a rapid slope, were also detected, which is consistent with the existing literature. A semi-empirical CHF correlation was developed for the inclined narrow rectangular channels through dimensional analysis. The correlation provides with best-estimate CHF values for realistically assessing the thermal margin to failure of the lower head during a severe accident involving relocation of the core material

Multilocus Phylogenetic Study of the Scheffersomyces Yeast Clade and Characterization of the N-Terminal Region of Xylose Reductase Gene

Many of the known xylose-fermenting (X-F) yeasts are placed in the Scheffersomyces clade, a group of ascomycete yeasts that have been isolated from plant tissues and in association with lignicolous insects. We formally recognize fourteen species in this clade based on a maximum likelihood (ML) phylogenetic analysis using a multilocus dataset. This clade is divided into three subclades, each of which exhibits the biochemical ability to ferment cellobiose or xylose. New combinations are made for seven species of Candida in the clade, and three X-F taxa associated with rotted hardwood are described: Scheffersomyces illinoinensis (type strain NRRL Y-48827T  =  CBS 12624), Scheffersomyces quercinus (type strain NRRL Y-48825T  =  CBS 12625), and Scheffersomyces virginianus (type strain NRRL Y-48822T  =  CBS 12626). The new X-F species are distinctive based on their position in the multilocus phylogenetic analysis and biochemical and morphological characters. The molecular characterization of xylose reductase (XR) indicates that the regions surrounding the conserved domain contain mutations that may enhance the performance of the enzyme in X-F yeasts. The phylogenetic reconstruction using XYL1 or RPB1 was identical to the multilocus analysis, and these loci have potential for rapid identification of cryptic species in this clade

A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models

van Lengerich et al. developed a human TREM2 antibody with a transport vehicle (ATV) that improves brain exposure and biodistribution in mouse models. ATV:TREM2 promotes microglial energetic capacity and metabolism via mitochondrial pathways. Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer's disease (AD), suggesting that activation of this innate immune receptor may be a useful therapeutic strategy. Here we describe a high-affinity human TREM2-activating antibody engineered with a monovalent transferrin receptor (TfR) binding site, termed antibody transport vehicle (ATV), to facilitate blood-brain barrier transcytosis. Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced signaling compared to a standard anti-TREM2 antibody. In human induced pluripotent stem cell (iPSC)-derived microglia, ATV:TREM2 induced proliferation and improved mitochondrial metabolism. Single-cell RNA sequencing and morphometry revealed that ATV:TREM2 shifted microglia to metabolically responsive states, which were distinct from those induced by amyloid pathology. In an AD mouse model, ATV:TREM2 boosted brain microglial activity and glucose metabolism. Thus, ATV:TREM2 represents a promising approach to improve microglial function and treat brain hypometabolism found in patients with AD

Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia.

BACKGROUND: Genetic mutations underlying familial Alzheimer\u27s disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding of the immune response in the brain. METHODS: We engineered a novel App knock-in mouse model (App RESULTS: Leveraging multi-omics approaches, we discovered profound alteration of diverse lipids and metabolites as well as an exacerbated disease-associated transcriptomic response in microglia with high intracellular Aβ content. The App DISCUSSION: Our findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology

Biofortified Wheat Increases Dietary Zinc Intake: A Randomised Controlled Efficacy Study of Zincol-2016 in Rural Pakistan

A new variety of zinc biofortified wheat (Zincol-2016) was released in Pakistan in 2016. The primary aim of this study was to examine the effects of consuming Zincol-2016 wheat flour on biochemical and functional markers of zinc status in a population with widespread zinc deficiency. An individually-randomised, double-blind, placebo-controlled cross over design was used. Fifty households were recruited to participate in the study, with each household included at least one woman of reproductive age (16–49 years) who was neither pregnant nor breast feeding or currently taking nutritional supplements. All households were provided with control flour for an initial 2-week baseline period, followed by the intervention period where households were randomly allocated in a 1:1 ratio to receive biofortified flour (group A; n = 25) and control flour (group B; n = 25) for 8-weeks, then switched to the alternate flour for 8-weeks. The trial has been registered with the ISRCTN (https://www.isrctn.com), ID ISRCTN83678069. The primary outcome measure was plasma zinc concentration, and the secondary outcome measures were plasma selenium and copper concentrations, plasma copper:zinc ratio and fatty acid desaturase and elongase activity indices. Nutrient intake was assessed using 24-h dietary recall interviews. Mineral concentrations in plasma were measured using inductively coupled plasma mass spectrometry and free fatty acids and sphingolipids by mass spectrometry. Linear Mixed Model regression and General Linear Model with repeated measures were used to analyse the outcomes. Based on an average flour consumption of 224 g/day, Zincol-2016 flour provided an additional daily zinc intake of between 3.0 and 6.0 mg for white and whole grain flour, respectively. No serious adverse events were reported. This resulted in significant, increase in plasma zinc concentration after 4 weeks [mean difference 41.5 μg/L, 95% CI (6.9–76.1), p = 0.02]. This was not present after 8 weeks (p = 0.6). There were no consistent significant effects of the intervention on fatty acid desaturase and elongase activity indices. Regular consumption of Zincol-2016 flour increased the daily zinc intake of women of reproductive age by 30–60%, however this was not associated with a sustained improvement in indices of zinc status