We sought to evaluate the effectiveness of a multi-component, case manager-led exacerbation prevention/management model for reducing emergency department visits. Secondary outcomes included hospitalisation, mortality, health-related quality of life, chronic obstructive pulmonary disease (COPD) severity, COPD self-efficacy, anxiety and depression.Two-centre randomised controlled trial recruiting patients with ≥2 prognostically important COPD-associated comorbidities. We compared our multi-component intervention including individualised care/action plans and telephone consults (12-weekly then 9-monthly) with usual care (both groups). We used zero-inflated Poisson models to examine emergency department visits and hospitalisation; Cox proportional hazard model for mortality.We randomised 470 participants (236 intervention, 234 control). There were no differences in number of emergency department visits or hospital admissions between groups. We detected difference in emergency department visit risk, for those that visited the emergency department, favouring the intervention (RR 0.74, 95% CI 0.63-0.86). Similarly, risk of hospital admission was lower in the intervention group for those requiring hospital admission (RR 0.69, 95% CI 0.54-0.88). Fewer intervention patients died (21 36) (HR 0.56, 95% CI 0.32-0.95). No differences were detected in other secondary outcomes.Our multi-component, case manager-led exacerbation prevention/management model resulted in no difference in emergency department visits, hospital admissions and other secondary outcomes. Estimated risk of death (intervention) was nearly half that of the control.

This study aimed to evaluate the usefulness of four microRNAs (miRNAs) in an acute pancreatic injury dog model. Acute pancreatitis was induced by infusion of cerulein for 2 h (7.5 μg/kg/h). The levels of well-known miRNAs, microRNA-216a (miR-216a) and microRNA-375 (miR-375), and new candidates microRNA-551b (miR-551b), and microRNA-7 (miR-7), were measured at 0, 0.5, 1, 2, 6, 12, and 24 h with serum amylase and lipase, and histopathological examination was performed. Among the four miRNAs, miR-216a and miR-375, and serum enzymes were significantly increased by cerulein treatment. The expression levels of miRNAs and serum enzymes peaked at 2–6 h with a similar pattern; however, the overall increases in miR-216a and miR-375 levels were much higher than those of the serum enzyme biomarkers. Increased levels of miR-216a and miR-375 were most highly correlated to the degree of individual histopathological injuries of the pancreas, and showed much greater dynamic response than serum enzyme biomarkers. Twenty-four-hour time-course analysis in this study revealed time-dependent changes of miRNA expression levels, from initial increase to decrease by predose level in acute pancreatitis. Our findings demonstrate that, in dogs, miR-216a and miR-375 have the potential to sensitively detect pancreatitis and reflect well the degree of pancreatic injury, whereas miR-551b and miR-7 do not.

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Drug-induced phospholipidosis (PL) is a storage disorder caused by the formation of phospholipid-drug complexes in lysosomes. Because of the diversity of PL between species, human cell-based assays have been used to predict drug-induced PL in humans. We established three-dimensional (3D) human liver organoids as described previously and investigated their liver characteristics through multiple analyses. Drug-induced PL was initiated in these organoids and in monolayer HepG2 cultures, and cellular changes were systemically examined. Organoids that underwent differentiation showed characteristics of hepatocytes rather than HepG2 cells. The organoids also survived under PL-inducing drug conditions for 48 h and maintained a more stable albumin secretion level than the HepG2 cells. More cytoplasmic vacuoles were observed in organoids and HepG2 cells treated with more potent PL-induced drugs, but to a greater extent in organoids than in HepG2 cells. Lysosome-associated membrane protein 2, a marker of lysosome membranes, showed a stronger immunohistochemical signal in the organoids. PL-distinctive lamellar bodies were observed only in amiodarone-treated organoids by transmission electron microscopy. Human liver organoids are thus more sensitive to drug-induced PL and less affected by cytotoxicity than HepG2 cells. Since PL is a chronic condition, these results indicate that organoids better reflect metabolite-mediated hepatotoxicity in vivo and could be a valuable system for evaluating the phospholipidogenic effects of different compounds during drug development.Int. J. Mol. Sci. 2020, 21, 2982 2 of 18 stages [6]. PL can occur in target organs without organ-related toxicity or physiological consequences [7], however, there are cases in which PL is observed with target organ toxicity [8]. Due to the uncertainty of the toxicological outcome of PL, drug-induced PL discovered in preclinical studies can have a detrimental impact on pharmaceutical development and delay the process. Fatal genetic disorders such as Niemann-Pick disease and Tay-Sachs disease [9,10] associated with PL have been described in humans, as has cell membrane damage leading to cell death. And other hepatic [11,12] cardiac [13,14], renal [15,16] pulmonary [17,18], eye [19], nervous [20], and skin [21] toxicities related to PL are known.Although drug-induced PL can be detected preclinically using in vivo systems such as animal models [3,[22][23][24], these types of studies are expensive, time-consuming, can raise ethical issues, and may not have specific toxicological relevance to humans. It has also been recommended that compounds that can lead to PL in humans should be identified and screened out in the early stages of drug discovery [25]. PL can be observed in any organ in the body, but the lung, liver, kidney, brain, spleen, and other lymphoid tissues are the most commonly involved sites [26]. To identify chemicals that provoke PL in humans, cell-based in vitro assays using various human liver cell types, such as HepG2 cells, HuH7 cells, and human pri...

BackgroundCurrent studies report that aberrations in epigenetic regulators or chromatin modifications are related to tumor development and maintenance. EZH2 (Enhancer of zeste homolog 2) is one of the catalytic subunits of Polycomb repressive complex 2, a crucial epigenetic regulator. EZH2 has a master regulatory function in such processes as cell proliferation, stem cell differentiation, and early embryogenesis. In humans, EZH2 is linked to oncogenic function in several carcinomas, including breast cancer, and dysregulation of EZH2 has been particularly associated with loss of differentiation and the development of poorly differentiated breast cancer. In our present study, we were interested in determining whether EZH2 is increased in canine mammary tumors, which show similarities to human breast cancer.ResultsInvestigation of the expression of EZH2 in canine mammary tumors revealed that EZH2 protein was overexpressed in canine mammary carcinomas, as in human breast cancer. In addition, the immunohistochemical expression level of EZH2 was associated with the degree of malignancy in canine mammary carcinoma. This is the first report to describe EZH2 expression in canine mammary tumors.ConclusionsBecause the expression of EZH2 was similar in canine mammary carcinoma and human breast cancer, spontaneous canine mammary tumors may be a suitable model for studying EZH2 and treatment development.

Abstract-Broadband Power Line Communications (PLC)technology allows the usage of electrical power supply networks for communications purposes, such as audio/video streaming and broadband internet access. The powerline has an inherent characteristic that is the cyclic variation of channel and noise with the phase of the AC line cycle. To achieve either high throughput or high robustness, we apply dynamic channel adaptation scheme that exploits the cyclic variation of powerline characteristics. In this paper, we introduce an expedient, dynamic channel adaptation which is robust against the short-time variation of the AC synchronized powerline channel and noise. We analyze the performance enhancement for the measured powerline channel and noise when the proposed adaptation scheme is applied to the Korean standard on high speed powerline communications.

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In this paper we present the abstraction model of physical (PHY) layer of an Orthogonal Frequency Division Multiplexing (OFDM)-based powerline communication (PLC) system. This paper describes the PHY abstraction methodology suitable to predict the PHY layer error performance in a realistic powerline channel environment including frequency-selective interference. The approach to predict the PHY layer performance and the process to obtain the detailed parameters of PHY abstraction models are presented. The parameters of developed PHY abstraction models for several modulation and coding schemes used in the OFDM-based PLC PHY layer are presented in this paper. The validation result of the proposed PHY abstraction methodology shows that the developed PHY abstraction model provides a high accuracy of error performance prediction for PLC channel models in the powerline noise environment. Therefore the developed PHY abstraction model can be used for the further system-level simulations or MAC simulations regarding both error performance prediction and for fast link adaptation purposes.