General Anesthetics Inhibit Erythropoietin Induction under Hypoxic Conditions in the Mouse Brain

Background: Erythropoietin (EPO), originally identified as a hematopoietic growth factor produced in the kidney and fetal liver, is also endogenously expressed in the central nervous system (CNS). EPO in the CNS, mainly produced in astrocytes, is induced under hypoxic conditions in a hypoxia-inducible factor (HIF)-dependent manner and plays a dominant role in neuroprotection and neurogenesis. We investigated the effect of general anesthetics on EPO expression in the mouse brain and primary cultured astrocytes. Methodology/Principal Findings: BALB/c mice were exposed to 10 % oxygen with isoflurane at various concentrations (0.10–1.0%). Expression of EPO mRNA in the brain was studied, and the effects of sevoflurane, halothane, nitrous oxide, pentobarbital, ketamine, and propofol were investigated. In addition, expression of HIF-2a protein was studied by immunoblotting. Hypoxia-induced EPO mRNA expression in the brain was significantly suppressed by isoflurane in a concentration-dependent manner. A similar effect was confirmed for all other general anesthetics. Hypoxia-inducible expression of HIF-2a protein was also significantly suppressed with isoflurane. In the experiments using primary cultured astrocytes, isoflurane, pentobarbital, and ketamine suppressed hypoxia-inducible expression of HIF-2a protein and EPO mRNA. Conclusions/Significance: Taken together, our results indicate that general anesthetics suppress activation of HIF-2 an

Animal influence on water, sanitation and hygiene measures for zoonosis control at the household level: A systematic literature review

Neglected zoonotic diseases (NZDs) have a significant impact on the livelihoods of the world’s poorest populations, which often lack access to basic services. Water, sanitation and hygiene (WASH) programmes are included among the key strategies for achieving the World Health Organization’s 2020 Roadmap for Implementation for control of Neglected Tropical Diseases (NTDs). There exists a lack of knowledge regarding the effect of animals on the effectiveness of WASH measures. This review looked to identify how animal presence in the household influences the effectiveness of water, hygiene and sanitation measures for zoonotic disease control in low and middle income countries; to identify gaps of knowledge regarding this topic based on the amount and type of studies looking at this particular interaction

Bayesian perspectives on mathematical practice

Mathematicians often speak of conjectures as being confirmed by evidence that falls short of proof. For their own conjectures, evidence justifies further work in looking for a proof. Those conjectures of mathematics that have long resisted proof, such as the Riemann hypothesis, have had to be considered in terms of the evidence for and against them. In recent decades, massive increases in computer power have permitted the gathering of huge amounts of numerical evidence, both for conjectures in pure mathematics and for the behavior of complex applied mathematical models and statistical algorithms. Mathematics has therefore become (among other things) an experimental science (though that has not diminished the importance of proof in the traditional style). We examine how the evaluation of evidence for conjectures works in mathematical practice. We explain the (objective) Bayesian view of probability, which gives a theoretical framework for unifying evidence evaluation in science and law as well as in mathematics. Numerical evidence in mathematics is related to the problem of induction; the occurrence of straightforward inductive reasoning in the purely logical material of pure mathematics casts light on the nature of induction as well as of mathematical reasoning

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

NLRP3 Inflammasome May Be a Biomarker for Risk Stratification in Patients with Acute Coronary Syndrome

De-Gang Mo,1 Lin Wang,2 Qian-Feng Han,1 Kang Yu,3 Jia-Hui Liu,1 Heng-Chen Yao1 1Department of Cardiology, Liaocheng People’s Hospital Affiliated to Shandong First Medical University, Liaocheng, People’s Republic of China; 2Cardiologic Color Doppler Room, Liaocheng People’s Hospital Affiliated to Shandong First Medical University, Liaocheng, People’s Republic of China; 3Department of Laboratory Medicine, Liaocheng People’s Hospital Affiliated to Shandong First Medical University, Liaocheng, People’s Republic of ChinaCorrespondence : Heng-Chen YaoDepartment of Cardiology, Liaocheng People’s Hospital Affiliated to Shandong First Medical University, Liaocheng, 252000, People’s Republic of China, Email [email protected]: Acute coronary syndrome (ACS) has a high incidence and mortality rate worldwide, which has a considerable negative impact on the global economy. This study aimed to identify a group of ACS patients at a high risk of recurrent adverse cardiac events using the plasma NLRP3 inflammasome.Patients and methods: ACS patients admitted to Liaocheng People’s Hospital between June 2021 and March 2022 were enrolled in this study. Patients were divided into low (levels < 3.84 ng/mL) and high (levels ≥ 3.84 ng/mL) groups based on the median NLRP3 inflammasome levels. The patients were divided into three groups according to the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P): low (scores ≤ 2 points), intermediate (scores = 3 points), and high (score ≥ 4 points) risk. We investigated the relationship between NLRP3 inflammasome and laboratory indicators. Additionally, we examined whether the NLRP3 inflammasome was an independent predictor of high TRS-2P and explored the applicability of the plasma NLRP3 inflammasome for predicting high TRS-2P.Results: Logistic regression analysis revealed that NLRP3 inflammasome was an independent predictor of high TRS-2P (odds ratio [OR]:2.013; 95% confidence interval [CI]: 1.174– 3.452). The area under the receiver operating characteristic curve value of the NLRP3 inflammasome was 0.674 (95% CI: 0.611– 0.737; P < 0.001).Conclusion: NLRP3 inflammasome levels are an independent predictive factor for high TRS-2P levels, which indicates that the NLRP3 inflammasome may help predict the prognosis of ACS patients.Keywords: NLRP3 inflammasome, biomarker, risk stratification, acute coronary syndrome, thrombolysis in myocardial infarction risk score for secondary prevention, TRS-2