Genome-wide host responses against infectious laryngotracheitis virus vaccine infection in chicken embryo lung cells

<p>Abstract</p> <p>Background</p> <p>Infectious laryngotracheitis virus (ILTV; gallid herpesvirus 1) infection causes high mortality and huge economic losses in the poultry industry. To protect chickens against ILTV infection, chicken-embryo origin (CEO) and tissue-culture origin (TCO) vaccines have been used. However, the transmission of vaccine ILTV from vaccinated- to unvaccinated chickens can cause severe respiratory disease. Previously, host cell responses against virulent ILTV infections were determined by microarray analysis. In this study, a microarray analysis was performed to understand host-vaccine ILTV interactions at the host gene transcription level.</p> <p>Results</p> <p>The 44 K chicken oligo microarrays were used, and the results were compared to those found in virulent ILTV infection. Total RNAs extracted from vaccine ILTV infected chicken embryo lung cells at 1, 2, 3 and 4 days post infection (dpi), compared to 0 dpi, were subjected to microarray assay using the two color hybridization method. Data analysis using JMP Genomics 5.0 and the Ingenuity Pathway Analysis (IPA) program showed that 213 differentially expressed genes could be grouped into a number of functional categories including tissue development, cellular growth and proliferation, cellular movement, and inflammatory responses. Moreover, 10 possible gene networks were created by the IPA program to show intermolecular connections. Interestingly, of 213 differentially expressed genes, BMP2, C8orf79, F10, and NPY were expressed distinctly in vaccine ILTV infection when compared to virulent ILTV infection.</p> <p>Conclusions</p> <p>Comprehensive knowledge of gene expression and biological functionalities of host factors during vaccine ILTV infection can provide insight into host cellular defense mechanisms compared to those of virulent ILTV.</p

CD24 Expression and differential resistance to chemotherapy in triple-negative breast cancer.

Breast cancer (BC) is a leading cause of cancer-related death in women. Adjuvant systemic chemotherapies are effective in reducing risks of recurrence and have contributed to reduced BC mortality. Although targeted adjuvant treatments determined by biomarkers for endocrine and HER2-directed therapies are largely successful, predicting clinical benefit from chemotherapy is more challenging. Drug resistance is a major reason for treatment failures. Efforts are ongoing to find biomarkers to select patients most likely to benefit from chemotherapy. Importantly, cell surface biomarkers CD44+/CD24- are linked to drug resistance in some reports, yet underlying mechanisms are largely unknown. This study focused on the potential role of CD24 expression in resistance to either docetaxel or doxorubicin in part by the use of triple-negative BC (TNBC) tissue microarrays. In vitro assays were also done to assess changes in CD24 expression and differential drug susceptibility after chemotherapy. Further, mouse tumor xenograft studies were done to confirm in vitro findings. Overall, the results show that patients with CD24-positive TNBC had significantly worse overall survival and disease-free survival after taxane-based treatment. Also, in vitro cell studies show that CD44+/CD24+/high cells are more resistant to docetaxel, while CD44+/CD24-/low cells are resistant to doxorubicin. Both in vitro and in vivo studies show that cells with CD24-knockdown are more sensitive to docetaxel, while CD24-overexpressing cells are more sensitive to doxorubicin. Further, mechanistic studies indicate that Bcl-2 and TGF-βR1 signaling via ATM-NDRG2 pathways regulate CD24. Hence, CD24 may be a biomarker to select chemotherapeutics and a target to overcome TNBC drug resistance

Compatibility of the Incompatible: How Does Asymmetric Power Lead to Coexistence of Trust and Distrust in Adversarial Policy Networks?

Asymmetric power has been found to hinder the development of trust that is essential for structuring policy subsystems or networks. Using a multinomial logistic analysis of a local hydraulic fracturing policy network in New York, our findings indicate that (1) power imbalance affects the coexistence of trust and distrust and (2) power imbalance interacting with certain types of social relationships (policy communication, regulation, and knowledge exchange) leads to the coexistence of trust and distrust. We suggest three implications for the governance of policy networks and policy process literature: increasing levels of trust do not guarantee decreasing levels of distrust, asymmetric power has an impact on structuring “ambivalent” relations, and adversarial policy subsystems can take four structural forms depending on the levels of trust and distrust.1

Seeds of Distrust: Conflicts over Sustainable Development in a Local Fracking Policy Network in New York State

Pursuing economic, environmental and social sustainability requires networks endowed with persistent relationships between stakeholders. Networks serve as the vehicle to coordinate diverse policy goals among stakeholders. Within the networks, stakeholders inevitably experience some level of distrust due to the complexity and uncertainty of the unstructured problems on the sustainability. However, little is known about why stakeholders often distrust with one another in the networks. By analysing a local fracking policy network in NYS, we suggest that distrust is influenced by incongruent ecological worldviews, policy goals incongruence in the triple bottom line of sustainability, characterization framing, policy communications and knowledge exchange.1

Nimesulide-induced hepatotoxicity: A systematic review and meta-analysis.

OBJECTIVE:This study aimed to evaluate the risk for hepatotoxicity with nimesulide, a non-steroidal anti-inflammatory drug (NSAID) available in Republic of Korea but withdrawn from the market in several countries. METHODS:A systematic review and meta-analysis were conducted of studies retrieved from PubMed, EMBASE, Cochrane, the Research Information Sharing Service and ClinicalTrials.gov up to September 2017. All studies reporting nimesulide-associated hepatotoxicity in patients as compared with the unexposed or the exposed to other NSAIDs were included. Studies using spontaneous reporting databases were included to estimate reporting odds ratio (ROR) of hepatotoxicity associated with nimesulide exposure. The association between nimesulide use and hepatotoxicity was estimated using relative risk (RR) and ROR with 95% confidence interval (CI). RESULTS:A total of 25 observational studies were eligible for review. In a meta-analysis of five observational studies, nimesulide was significantly associated with hepatotoxicity [RR 2.21, 95% CI 1.72-2.83]. From studies using spontaneous reporting databases (n = 6), rates of reported hepatotoxicity were significantly higher in patients using nimesulide, compared with those treated with other NSAIDs [pooled ROR 3.99, 95% CI 2.86-5.57]. Of a total of 33 patients from case studies and series, the majority (n = 28, 84.8%) were female, and the mean age (± standard deviation) was 56.8 (± 15.6) years. Almost half of the patients on nimesulide (45.5%) either required liver transplantation or died due to fulminant hepatic failure, of whom a third developed hepatotoxicity within less than 15 days of nimesulide administration. CONCLUSIONS:Our study findings support previous reports of an increased risk for hepatotoxicity with nimesulide use and add to existing literature by providing risk estimates for nimesulide-associated hepatotoxicity. As the limited number of studies with primarily observational study designs were included in the analysis, more studies are needed to further describe the effects of dose and length of treatment on the risk for hepatotoxicity

Detection of paradoxical carbon dioxide gas embolism with opening of patent foramen ovale by perioperative transesophageal echocardiography during laparoscopic hepatectomy - A case report -

Background Due to its various advantages, laparoscopic surgery is preferred over laparotomy in patients who require hepatic resection. Carbon dioxide embolism—which occurs approximately ten times more often in laparoscopic hepatectomy than in general laparoscopic surgery—presents with insignificant symptoms and may be overlooked. Case A 70-year-old male with hepatic cell carcinoma underwent laparoscopic hepatectomy. Though his vital signs were stable during the initiation of surgery, they became unstable during the procedure. The surgeon detected portal vein rupture, and transesophageal echocardiography was subsequently performed. A large amount of gas in the heart chamber and paradoxical embolism through a patent foramen ovale due to a right-to-left shunt were observed. We treated the symptoms, and the surgery was completed without any further issues. Conclusions Active use of transesophageal echocardiography to identify and monitor heart functions during a suspected carbon dioxide embolism can significantly reduce morbidity and mortality associated with that embolism

Memory Access Pattern-Aware DRAM Controller Design for Mixed-Criticality Systems

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A Prototype Design and Development of the Smart Photovoltaic System Blind Considering the Photovoltaic Panel, Tracking System, and Monitoring System

This study aims to design and develop the prototype models of the smart photovoltaic system blind (SPSB). To achieve this objective, the study defined the properties in three ways: (i) the photovoltaic (PV) panel; (ii) the tracking system; and (iii) the monitoring system. First, the amorphous silicon PV panel was determined as a PV panel, and the width and length of the PV panel were determined to be 50 mm and 250 mm, respectively. Second, the four tracker types (i.e., fixed type, vertical single-axis tracker, horizontal single-axis tracker, and azimuth-altitude dual-axis tracker) was applied, as well as the direct tracking method based on the amount of electricity generated as a tracking system. Third, the electricity generation and environmental conditions were chosen as factors to be monitored in order to evaluate and manage the technical performance of SPSB as a monitoring system. The prototype model of the SPSB is designed and developed for providing the electricity generated from its PV panel, as well as for reducing the indoor cooling demands through the blind’s function, itself (i.e., blocking out sunlight)

A Nonrandomized Phase 2 Trial of EG-Mirotin, a Novel, First-in-Class, Subcutaneously Deliverable Peptide Drug for Nonproliferative Diabetic Retinopathy

Background and objectives: EG-Mirotin (active ingredient EGT022) targets nonproliferative diabetic retinopathy (NPDR), the early stage of retinopathy. EG-Mirotin reverses capillary damage before NPDR progresses to an irreversible stage. EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. Methods: In this open-label, single-arm, single-center, exploratory phase II study, 10 patients (20 eyes) received EG-Mirotin once a day (3 mg/1.5 mL sterile saline) for 5 days and were evaluated for ischemic index changes and safety. End of study was approximately 8 ± 1 weeks (57 ± 7 days) after the first drug administration. Results: EG-Mirotin injections were well tolerated, with no dose-limiting adverse events, serious adverse events, or deaths. Four treatment-emergent adverse events (TEAEs) unrelated to the investigational drug were observed in 2 out of 10 participants (20%) who had received the investigational drug. The overall average percent change in ischemic index at each evaluation point compared with baseline was statistically significant (Greenhouse–Geisser F = 9.456, p = 0.004 for the main effect of time), and a larger change was observed when the baseline ischemic index value was high (Greenhouse–Geisser F = 10.946, p = 0.002 for time × group interaction). Conclusions: The EG-Mirotin regimen established in this study was shown to be feasible and safe and was associated with a trend toward potential improvement in diabetes-induced ischemia and retinal capillary leakage