42 research outputs found

    Chronic Ketamine Administration Modulates Midbrain Dopamine System in Mice

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    Ketamine is an anesthetic and a popular abusive drug. As an anesthetic, effects of ketamine on glutamate and GABA transmission have been well documented but little is known about its long-term effects on the dopamine system. In the present study, the effects of ketamine on dopamine were studied in vitro and in vivo. In pheochromocytoma (PC 12) cells and NGF differentiated-PC 12 cells, ketamine decreased the cell viability while increasing dopamine (DA) concentrations in a dose-related manner. However, ketamine did not affect the expression of genes involved in DA synthesis. In the long-term (3 months) ketamine treated mice, significant increases of DA contents were found in the midbrain. Increased DA concentrations were further supported by up-regulation of tyrosine hydroxylase (TH), the rate limiting enzyme in catecholamine synthesis. Activation of midbrain dopaminergic neurons could be related to ketamine modulated cortical-subcortical glutamate connections. Using western blotting, significant increases in BDNF protein levels were found in the midbrain, suggesting that perhaps BDNF pathways in the cortical-subcortical connections might contribute to the long-term ketamine induced TH upregulation. These data suggest that long-term ketamine abuse caused a delayed and persistent upregulation of subcortical DA systems, which may contribute to the altered mental status in ketamine abusers

    Knowledge Domains and Emerging Trends of Osteoblasts-Osteoclasts in Bone Disease From 2002 to 2021: A Bibliometrics Analysis and Visualization Study

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    BackgroundOsteoblasts-Osteoclasts has been a major area in bone disease research for a long time. However, there are few systematic studies in this field using bibliometric analysis. We aimed to perform a bibliometric analysis and visualization study to determine hotspots and trends of osteoblasts-osteoclasts in bone diseases, identify collaboration and influence among authors, countries, institutions, and journals, and assess the knowledge base to develop basic and clinical research in the future.MethodsWe collected articles and reviews for osteoblasts-osteoclasts in bone diseases from the Web of Science Core Collection. In addition, we utilized scientometrics software (CiteSpace5.8 and VOSviewer1.6.18) for visual analysis of countries/regions, institutions, authors, references, and keywords in the field.ResultsIn total, 16,832 authors from 579 institutions in 73 countries/regions have published 3,490 papers in 928 academic journals. The literature in this field is rapidly increasing, with Bone publishing the most articles, whereas Journal of Bone and Mineral Research had the most co-cited journals. These two journals mainly focused on molecular biology and the clinical medicine domain. The countries with the highest number of publications were the US and China, and the University of Arkansas for Medical Sciences was the most active institution. Regarding authors, Stavros C. Manolagas published the most articles, and Hiroshi Takayanagi had the most co-cited papers. Research in this field mainly includes molecular expression and regulatory mechanisms, differentiation, osteoprotection, inflammation, and tumors. The latest research hotspots are oxidative stress, mutation, osteocyte formation and absorption, bone metabolism, tumor therapy, and in-depth mechanisms.ConclusionWe identified the research hotspots and development process of osteoblasts-osteoclasts in bone disease using bibliometric and visual methods. Osteoblasts-osteoclasts have attracted increasing attention in bone disease. This study will provide a valuable reference for researchers concerned with osteoblasts-osteoclasts in bone diseases

    Common Minor Histocompatibility Antigen Discovery Based upon Patient Clinical Outcomes and Genomic Data

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    BackgroundMinor histocompatibility antigens (mHA) mediate much of the graft vs. leukemia (GvL) effect and graft vs. host disease (GvHD) in patients who undergo allogeneic stem cell transplantation (SCT) [1], [2], [3], [4]. Therapeutic decision making and treatments [5] based upon mHAs will require the evaluation of multiple candidate mHAs and the selection of those with the potential to have the greatest impact on clinical outcomes. We hypothesized that common, immunodominant mHAs, which are presented by HLA-A, B, and C molecules, can mediate clinically significant GvL and/or GvHD, and that these mHAs can be identified through association of genomic data with clinical outcomes.Methodology/Principal FindingsBecause most mHAs result from donor/recipient cSNP disparities, we genotyped 57 myeloid leukemia patients and their donors at 13,917 cSNPs [6]. We correlated the frequency of genetically predicted mHA disparities with clinical evidence of an immune response and then computationally screened all peptides mapping to the highly associated cSNPs for their ability to bind to HLA molecules. As proof-of-concept, we analyzed one predicted antigen, T4A, whose mHA mismatch trended towards improved overall and disease free survival in our cohort. T4A mHA mismatches occurred at the maximum theoretical frequency for any given SCT. T4A-specific CD8+ T lymphocytes (CTLs) were detected in 3 of 4 evaluable post-transplant patients predicted to have a T4A mismatch.Conclusions/SignificanceOur method is the first to combine clinical outcomes data with genomics and bioinformatics methods to predict and confirm a mHA. Refinement of this method should enable the discovery of clinically relevant mHAs in the majority of transplant patients and possibly lead to novel immunotherapeutics [5]

    Impacts of demand uncertainty on retailer's dominance and manufacturer-retailer supply chain cooperation

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    Recent studies in marketing and distribution channels have shown that the balance of power between manufacturers and retailers is shifting. Based on this observation, we investigate a two-echelon supply chain with a manufacturer and a retailer in this paper. We first develop retailer-dominant non-cooperative game models by introducing a sensitivity of retailer's order quantity to manufacturer's wholesale price; then we analyze two cooperative scenarios, in which the Nash bargaining model is utilized to implement profit sharing between the manufacturer and the retailer. Under the assumption that the manufacturer and the retailer are risk-neutral, we find that the manufacturer and the retailer can bargain to cooperate at any level of retail-market demand uncertainty with exogenous retail price. However, the cooperation is conditional on retail-market demand uncertainty with endogenous retail price: it can be implemented if the fluctuation of retail-market demand is relatively small, and the measure of retail-market demand uncertainty does not exceed an upper bound. Theoretical and numerical analyses show that the retailer's dominance over the manufacturer increases with the increase in the sensitivity of retailer's order quantity to manufacturer's wholesale price under a limitation of retail-market demand uncertainty. Numerical analyses also show that the retailer's dominance decreases with the increase in retail-market demand uncertainty.Supply chain cooperation Retailer's dominance Demand uncertainty Nash bargaining model Newsvendor problem

    Outcomes of endoscopic and open resection of sinonasal malignancies: a systematic review and meta-analysis

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    Objective: To compare the efficacy of endoscopic and open resection of sinonasal malignancies. Methods: The search was performed using PubMed (1950–2020), Embase (1974–2020), the Cochrane library, and the website clinicaltrials.gov. The hazard ratio, HR, 95% confidence interval, CI, of the rates of overall survival and disease-free survival and the demographic characteristics of the included studies were extracted and analyzed. Pooled analysis was conducted with the studies’ individual patient data, using log-rank test, Kaplan–Meier survival, and Cox regression analysis. Results: Of 1939 articles retrieved, 23 articles were included. Overall, 1373 cases were incorporated into the final analysis, 653 (47.56%) of which underwent the surgery through an endoscopic approach, whereas 720 (52.44%) cases utilized the open approach. The overall survival was comparable between endoscopic and open resection (HR = 0.84 [95% CI: 0.65–1.07], p = 0.16; random effects analysis). Pooled analysis with Cox regression revealed signifcant differences in overall survival (HR = 0.568 [95%CI:0.380-0.849], p = 0.006) and disease-free survival (HR = 0.628 [95%CI:0.424-0.929], p = 0.02) between endoscopic and open approaches. Conclusion: The aggregated evidence suggests the survival outcome of endoscopic resection is comparable or greater than that of open resection of sinonasal malignancies

    Suspension of Australian National Electricity Market in 2022 Necessitates Mechanism Evolution Ensuring Power Supply Security

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    The National Electricity Market (NEM) in Australia was suspended during June 15-23, 2022, with a primary attribution to the lack of available generation capacity. This incident is noteworthy because it was the first market suspension in NEM's history and took place in a major energy exporting country. In this letter, we review the outline and impacts of the incident. From the perspectives of market regulation, electricity supply, and electricity demand, we identify three underlying causes of the market suspension and offer four recommendations for the market mechanism evolution to ensure power supply security
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