Theragnostic Efficacy of K18 Response in Alcohol Use Disorder with Clinically Significant Fibrosis Using Gut-Liver Axis

(1) Background: Fibrosis in early-stage alcohol-associated liver disease (ALD) is commonly under-diagnosed in routine clinical practice. This study characterized the liver-injury and cell death response in alcohol use disorder (AUD) patients with ALD who also exhibited fibrosis and assessed the efficacy of standard of care (SOC) treatment in the improvement in liver injury. (2) Methods: Forty-eight heavy-drinking AUD patients aged 21–65 yrs. without clinical manifestations of liver injury were grouped by Fibrosis-4 (FIB-4) score, as negative (Gr.1 < 1.45, n = 21) or positive (Gr.2 ≥ 1.45, n = 27). Patients received 2-weeks (2 w) inpatient SOC. Data on demographics, drinking patterns, liver-injury, immune markers, and liver cell death (K18s) markers were analyzed at baseline (BL) and after 2 w SOC. (3) Results: Lifetime drinking (LTDH, yrs.) and acute heavy drinking (Heavy Drinking Days Past 90 Days [HDD90]) markers were significantly higher in Gr.2 vs. Gr.1. BL ALT, AST, AST:ALT and K18M65 were considerably higher in Gr.2. Dysregulated gut dysfunction and elevated immune activity were evident in Gr.2 characterized by TNF-α, IL-8 and LPS levels. After SOC, Gr.2 showed improvement in AST, ALT, AST/ALT ratio; and in the K18M65, K18M30 and K18M65/M30 ratio vs. Gr.1. The true positivity of BL IL-8 response to predict the improvement in K18M65 to normal levels among Gr.2 patients against those who did not have improvement after 2 w SOC was very high (AUROC = 0.830, p = 0.042). (4) Conclusions: Gut dysfunction, elevated cytokine response and necrotic liver cell death were elevated in AUD patients with early-stage ALD. K18 showed promise as a predictive theragnostic factor to differentiate among the AUD patients with early-stage ALD and baseline fibrosis who had improvement in liver injury against those who did not, by the levels of baseline IL-8.     

An efficient nonlinear circuit simulation technique

This paper proposes a novel method for the analysis and simulation of integrated circuits (ICs) with the potential to greatly shorten the IC design cycle. The circuits are assumed to be subjected to input signals that have widely separated rates of variation, e.g., in communication systems, an RF carrier modulated by a low-frequency information signal. The proposed technique involves two stages. Initially, a particular order result for the circuit response is obtained using a multiresolution collocation scheme involving cubic spline wavelet decomposition. A more accurate solution is then obtained by adding another layer to the wavelet series approximation. However, the novel technique presented here enables the reuse of results acquired in the first stage to obtain the second-stage result. Therefore, vast gains in efficiency are obtained. Furthermore, a nonlinear model-order reduction technique can readily be used in both stages making the calculations even more efficient. Results will highlight the efficacy of the proposed approach     

Ozone application in a modified screw conveyor to treat grain for insect pests, fungal contaminants, and mycotoxins

Recent efforts have focused on improving the application of ozone technology as a pest management tool for stored grain. This study evaluated the efficacy of a modified screw conveyor to treat grain with ozone in a continuous-flow system. The ozone concentration delivered into the screw conveyor was 47,800 ppm and the average retention time for a corn kernel moving through the system was 1.8 min. Under these conditions, 100% mortality of adult red flour beetle (Tribolium castaneum (Herbst)) and adult maize weevil (Sitophilus zeamais (Motsch.)) was achieved after three passes through the screw conveyor, which equated to a concentration × time (CT) product value of 258,120 ppm-min. The potential effectiveness of the continuous treatment to reduce mold on the surface of corn kernels was also explored. Aspergillus flavus counts were reduced by 96% in a single pass through the screw conveyor. Three passes through the screw conveyor reduced the mold count by more than 2-log units. Ozone treatment also reduced aflatoxin applied to the grain; however, the reduction was not sufficient enough to be of commercial value. The results of this study provide valuable information for estimating the parameters needed for effectively treating grain in a commercial scale continuous-flow treatment system.     

Manipulating the Level of Sensorimotor Stimulation during LI-rTMS Can Improve Visual Circuit Reorganisation in Adult Ephrin-A2A5-/- Mice

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has the potential to treat a variety of neurologic and psychiatric disorders. The extent of rTMS-induced neuroplasticity may be dependent on a subject’s brain state at the time of stimulation. Chronic low intensity rTMS (LI-rTMS) has previously been shown to induce beneficial structural and functional reorganisation within the abnormal visual circuits of ephrin-A2A5^-/- mice in ambient lighting. Here, we administered chronic LI-rTMS in adult ephrin-A2A5^-/- mice either in a dark environment or concurrently with voluntary locomotion. One day after the last stimulation session, optokinetic responses were assessed and fluorescent tracers were injected to map corticotectal and geniculocortical projections. We found that LI-rTMS in either treatment condition refined the geniculocortical map. Corticotectal projections were improved in locomotion+LI-rTMS subjects, but not in dark + LI-rTMS and sham groups. Visuomotor behaviour was not improved in any condition. Our results suggest that the beneficial reorganisation of abnormal visual circuits by rTMS can be significantly influenced by simultaneous, ambient visual input and is enhanced by concomitant physical exercise. Furthermore, the observed pathway-specific effects suggest that regional molecular changes and/or the relative proximity of terminals to the induced electric fields influence the outcomes of LI-rTMS on abnormal circuitry.     

Comparison of Soybean and Cottonseed Oils upon Hydrogenation with Nickel,Palladium and Platinum Catalysts

There is current interest in reducing the trans fatty acids (TFA) in hydrogenated vegetable oils because consumption of foods high in TFA has been linked to increased serum cholesterol content. In the interest of understanding the TFA levels, hydrogenation was carried out in this work on soybean oil and cottonseed oil at two pressures (2 and 5 bar) and 100 °C using commercially available Ni, Pd, and Pt catalysts. The TFA levels and the fatty acid profiles were analyzed by gas chromatography. The iodine value of interest is ~70 for all-purpose shortening and 95–110 for pourable oil applications. In all cases, higher hydrogen pressures produced lower levels of TFA. In the range of 70–95 iodine values for the hydrogenated products, the Pt catalyst gave the least TFA, followed closely by Ni, and then Pd, for both oils. For all three catalysts at 2- and 5-bar pressures and 70–95 iodine values, cottonseed oil contained noticeably less TFA than soybean oil; this is probably because cottonseed oil contains a lower total amount of olefin-containing fatty acids relative to soybean oil. Approximate kinetic modeling was also done on the hydrogenation data that provided additional confirmation of data consistency.     

Is the Jaw Bone Micro-Structure Altered in Response to Osteoporosis and Bisphosphonate Treatment? A Micro-CT Analysis

The aim of the study was to quantify the micro-architectural changes of the jaw bone in response to ovariectomy, exposed or not to bisphosphonate treatment. A total of 47 Wistar rats were ovariectomized (OVX) or sham-operated (shOVX) and exposed to osteoporosis preventive treatment for eight weeks either with bisphosphonates (alendronate, ALN; group OVX-ALN) three days/week at a dose of 2 mg/kg or with saline solution (untreated control condition; group OVX). The bone morphometric parameters of the trabecular jaw bone were assessed using ex vivo micro-computed tomography. The regions of interest investigated in the maxilla were the inter-radicular septum of the second molar and the tuber. The regions quantified in the mandible included the three molar regions and the condyle. A one-way analysis of variance followed by pairwise comparison using Tukey’s HSD and the Games–Howell test was conducted to explore significant differences between the groups. In the maxilla, OVX decreased the bone volume in the inter-radicular septum of the second molar. Bisphosphonate treatment was able to prevent this deterioration of the jaw bone. The other investigated maxillary regions were not affected by (un)treated ovariectomy. In the mandible, OVX had a significant negative impact on the jaw bone in the buccal region of the first molar and the inter-radicular region of the third molar. Treatment with ALN was able to prevent this jaw bone loss. At the condyle site, OVX significantly deteriorated the trabecular connectivity and shape, whereas preventive bisphosphonate treatment showed a positive effect on this trabecular bone region. No significant results between the groups were observed for the remaining regions of interest. In summary, our results showed that the effects of ovariectomy-induced osteoporosis are manifested at selected jaw bone regions and that bisphosphonate treatment is capable to prevent these oral bone changes.     

Toward Low-Cost,High-Energy Density,and High-Power Density Lithium-Ion Batteries

Reducing cost and increasing energy density are two barriers for widespread application of lithium-ion batteries in electric vehicles. Although the cost of electric vehicle batteries has been reduced by ~70% from 2008 to 2015, the current battery pack cost ($268/kWh in 2015) is still >2 times what the USABC targets ($125/kWh). Even though many advancements in cell chemistry have been realized since the lithium-ion battery was first commercialized in 1991, few major breakthroughs have occurred in the past decade. Therefore, future cost reduction will rely on cell manufacturing and broader market acceptance. This article discusses three major aspects for cost reduction: (1) quality control to minimize scrap rate in cell manufacturing; (2) novel electrode processing and engineering to reduce processing cost and increase energy density and throughputs; and (3) material development and optimization for lithium-ion batteries with high-energy density. Insights on increasing energy and power densities of lithium-ion batteries are also addressed.     

Enterococcal diversity in the environment of an Irish Cheddar-type cheesemaking factory.

Enterococci are natural residents of human and animal intestinal tracts and grow to high levels in a variety of artisanal cheeses. The aim of this study was to determine the diversity of enterococci in a farmhouse raw-milk cheese production unit. Putative enterococci were isolated from the faeces of all the cows and all the people associated with the cheesemaking, from the milk and cheese during manufacture and ripening and from the environment in three separate trials. Almost 1400 isolates were screened using a genus-specific primer. The results indicated that all the human, milk, curd and cheese isolates but only 33.7%, 6.7% and 4.4% of the bovine isolates from the three trials, respectively, were members of the genus Enterococcus. RAPD-PCR was used to type the enterococcal isolates. In general, only E. faecium was found in the bovine faeces while E. casseliflavus dominated the human faeces, milk and cheese followed by lower numbers of E. faecalis. Environmental sampling of the water in the milking parlour and rinses of the cows' teats, the bulk-milk storage tank and the milking machine corroborated these results as E. casseliflavus and E. faecalis were the only Enterococcus species found in these samples. The putative vancomycin-resistant enterococci (VRE), isolated in Trial 1, were shown to be Pediococcus spp. by genotypic and phenotypic analysis.     

Fluorescent polyacrylate derivate from 4-biphenylmethanol with UV-green emission

In this paper we report the synthesis of a new polyacrylate named poly(1,1?-BP4MA) which is a derivate from 4-biphenylmethanol monomer. Poly(1,1?-BP4MA) was obtained by solution and bulk polymerization techniques to yield polymers with high molecular weight and high solubility. The study of the optical properties showed that poly(1,1?-BP4MA) is a fluorescent material with emission in the UV-green region and it has similar quantum yield to tryptophan.