View of Pakistani residents toward coronavirus disease (COVID-19) during a rapid outbreak: A rapid online survey

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Background: Coronavirus disease (COVID-19) is a deadly disease that is affecting most of the countries worldwide. Public understanding, including knowledge about signs and symptoms, mode of transmission, and hygiene of COVID-19, is vital for designing effective control strategies during a public health crisis. The current study is aimed at investigating the public’s perspective about COVID-19, including their knowledge, attitude, and practices. Methods: A rapid online survey comprising 22 items was administered during the rapid outbreak of COVID-19 in Pakistan. Questions were focused on the prevention, transmission, clinical features, and control of COVID-19. In addition, the attitudes and practices of the participants were explored. Descriptive statistics, Mann–Whitney tests, Kruskal–Wallis tests, and regression analysis were carried out during data analysis. Results: A total of 1257 respondents participated in this study. Most of the respondents had good knowledge (good = 64.8%, average = 30.5%, poor = 4.7%) of COVID-19. Gender, marital status, education, and residence were observed to have a significant association with the knowledge score. A vast majority of the survey respondents (77.0%) believed that COVID-19 would be controlled successfully in Pakistan. The practices of wearing a mask (85.8%) and handwashing (88.1%) were common among the participants. Conclusion: The participants demonstrated good knowledge and reasonable attitudes and practices toward most aspects of the COVID-19 outbreak. Improvements in certain areas could be made by mass-level education

Simultaneous thermoosmotic and thermoelectric responses in nanoconfined electrolyte solutions: Effects of nanopore structures and membrane properties

Hypothesis: Nanofluidic systems provide an emerging and efficient platform for thermoelectric conversion and fluid pumping with low-grade heat energy. As a basis of their performance enhancement, the effects of the structures and properties of the nanofluidic systems on the thermoelectric response (TER) and the thermoosmotic response (TOR) are yet to be explored. Methods: The simultaneous TER and TOR of electrolyte solutions in nanofluidic membrane pores on which an axial temperature gradient is exerted are investigated numerically and semi-analytically. A semi-analytical model is developed with the consideration of finite membrane thermal conductivity and the reservoir/entrance effect. Findings: The increase in the access resistance due to the nanopore-reservoir interfaces accounts for the decrease of short circuit current at the low concentration regime. The decrease in the thermal conductivity ratio can enhance the TER and TOR. The maximum power density occurring at the nanopore radius twice the Debye length ranges from several to dozens of mW K$^{-2}$ m$^{-2}$ and is an order of magnitude higher than typical thermo-supercapacitors. The surface charge polarity can heavily affect the sign and magnitude of the short-circuit current, the Seebeck coefficient, and the open-circuit thermoosmotic coefficient, but has less effect on the short-circuit thermoosmotic coefficient. Furthermore, the membrane thickness makes different impacts on TER and TOR for zero and finite membrane thermal conductivity.Comment: 38 pages, 10 figure

Perspective of Pakistani physicians towards hospital antimicrobial stewardship programs: A multisite exploratory qualitative study

© 2019 Raha Orfali et al. Plicosepalus is an important genus of the Loranthaceae family, and it is a semiparasitic plant grown in Saudi Arabia, traditionally used as a cure for diabetes and cancer in human and for increasing lactation in cattle. A flavonoid quercetin (P1), (-)-catechin (P2), and a flavane gallate 2S,3R-3,3′,4′,5,7-pentahydroxyflavane-5-O-gallate (P3) were isolated from the methanol extract of the aerial parts of P. curviflorus (PCME). The PCME and the isolated compounds were subjected to pharmacological assays to estimate peroxisome proliferator-activated receptors PPARα and PPARγ agonistic, anti-inflammatory, cytotoxic, and antimicrobial activities. Results proved for the first time the dual PPAR activation effect of the PCME and catechin (P2), in addition to the promising anti-inflammatory activity of the flavonoid quercetin (P1). Interestingly, both PCME and isolated compounds showed potent antioxidant activities while no antimicrobial effect against certain microbial strains had been reported from the extract and the isolated compounds. Based on the pharmacological importance of these compounds, an HPTLC validated method was developed for the simultaneous estimation of these compounds in PCME. It was found to furnish a compact and sharp band of compounds P1, P2, and P3 at Rf = 0.34, 0.47, and 0.65, respectively, using dichloromethane, methanol, and formic acid (90: 9.5: 0.5, (v/v/v)) as the mobile phase. Compounds P1, P2, and P3 were found to be 11.06, 10.9, 6.96 μg/mg, respectively, in PCME. The proposed HPTLC method offers a sensitive, precise, and specific analytical tool for the quantification of quercetin, catechin, and flavane gallates in P. curviflorus

Molecular subtypes based on centrosome-related genes can predict prognosis and therapeutic responsiveness in patients with low-grade gliomas

BackgroundAbnormalities in centrosome regulatory genes can induce chromosome instability, cell differentiation errors, and tumorigenesis. However, a limited number of comprehensive analyses of centrosome-related genes have been performed in low-grade gliomas (LGG).MethodsLGG data were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. The ConsensusClusterPlus” R package was used for unsupervised clustering. We constructed a centrosome-related genes (CRGs) signature using a random forest model, lasso Cox model, and multivariate Cox model, and quantified the centrosome-related risk score (centS). The prognostic prediction efficacy of centS was evaluated using a Receiver Operating Characteristic (ROC) curve. Immune cell infiltration and genomic mutational landscapes were evaluated using the ESTIMATE algorithm, single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm, and “maftools” R package, respectively. Differences in clinical features, isocitrate dehydrogenase (IDH) mutation, 1p19q codeletion, O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, and response to antitumor therapy between the high- and low-centS groups were explored. “pRRophetic” R packages were used for temozolomide (TMZ) sensitivity analysis. qRT-PCR verified the differential expression of the centrosomal gene team, the core of which is CEP135, between LGG cells and normal cells.ResultsTwo distinct CRG-based clusters were identified using consensus unsupervised clustering analysis. The prognosis, biological characteristics, and immune cell infiltration of the two clusters differed significantly. A well-performing centS signature was developed to predict the prognosis of patients with LGG based on 12 potential CRGs. We found that patients in the high-centS group showed poorer prognosis and lower proportion of IDH mutation and 1p19q codeletion compared to those in the low-centS group. Furthermore, patients in the high-centS group showed higher sensitivity to TMZ, higher tumor mutation burden, and immune cell infiltration. Finally, we identified a centrosomal gene team whose core was CEP135, and verified their differential expression between LGG cells and normal glial cells.ConclusionOur findings reveal a novel centrosome-related signature for predicting the prognosis and therapeutic responsiveness of patients with LGG. This may be helpful for the accurate clinical treatment of LGG

Autophagic Degradation Deficit Involved in Sevoflurane-Induced Amyloid Pathology and Spatial Learning Impairment in APP/PS1 Transgenic Mice

The adverse effects of anesthetics on elderly people, especially those with brain diseases are very concerning. Whether inhaled anesthetics have adverse effects on Alzheimer’s disease (AD), which is the most common form of dementia with brain degenerative changes, remains controversial. Autophagy, a crucial biological degradation process, is extremely important for the pathogenesis of AD. In this study, the inhaled anesthetic sevoflurane elicited many enlarged autolysosomes and impaired the overall autophagic degradation in the hippocampus of an AD mouse model, which is involved in the accumulation of amyloid-β (Aβ) and spatial learning deficits. However, rapamycin treatment counteracted all these effects. The results suggested that inhaled anesthetics may accelerate the pathological process of AD, and enlarged autolysosomes may be a new marker for prediction and diagnosis of the neurotoxicity of anesthetics in AD

TFEB Probably Involved in Midazolam-Disturbed Lysosomal Homeostasis and Its Induced β-Amyloid Accumulation

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases, and β-amyloid (Aβ) plays a leading role in the pathogenesis of AD. The transcription factor EB (TFEB), a main regulating factor of autophagy and lysosome biosynthesis, is involved in the pathogenesis of AD by regulating autophagy-lysosomal pathways. To date, the choice of anesthetics during surgery in patients with neurodegenerative diseases and evaluation of the effects and underlying mechanisms in these patients have rarely been reported. In this study, the HEK293-APP cells overexpressing APP and Hela cells were used. The cells were treated with midazolam at different concentrations and at different times, then lysosomes were stained by lysotracker and their morphology was observed under a fluorescence microscope. The number and size of lysosomes were analyzed using the ImageJ software. The levels of TFEB in the nucleus and APP-cleaved intracellular proteins were detected by nuclear separation and Western Blot. Finally, ELISA was used to detect the levels of Aβ40 and Aβ42 in the cells after drug treatment. We found that 30 μM midazolam decreased the number of lysosomes and increased its size in HEK293 and HeLa cells. However, 15 μM midazolam transiently disturbed lysosomal homeostasis at 24 h and recovered it at 36 h. Notably, there was no significant difference in the extent to which lysosomal homeostasis was disturbed between treatments of different concentrations of midazolam at 24 h. In addition, 30 μM midazolam prevents the transport of TFEB to the nucleus in either normal or starved cells. Finally, the intracellular C-terminal fragment β (CTFβ), CTFα, Aβ40 and Aβ42 levels were all significantly elevated in 30 μM midazolam-treated HKE293-APP cells. Collectively, the inhibition of TFEB transport to the nucleus may be involved in midazolam-disturbed lysosomal homeostasis and its induced Aβ accumulation in vitro. The results indicated the risk of accelerating the pathogenesis of AD by midazolam and suggested that TFEB might be a candidate target for reduction of midazolam-dependent neurotoxicity

Greenhouse gas emissions from U.S. crude oil pipeline accidents:1968 to 2020

Abstract Crude oil pipelines are considered as the lifelines of energy industry. However, accidents of the pipelines can lead to severe public health and environmental concerns, in which greenhouse gas (GHG) emissions, primarily methane, are frequently overlooked. While previous studies examined fugitive emissions in normal operation of crude oil pipelines, emissions resulting from accidents were typically managed separately and were therefore not included in the emission account of oil systems. To bridge this knowledge gap, we employed a bottom-up approach to conducted the first-ever inventory of GHG emissions resulting from crude oil pipeline accidents in the United States at the state level from 1968 to 2020, and leveraged Monte Carlo simulation to estimate the associated uncertainties. Our results reveal that GHG emissions from accidents in gathering pipelines (~720,000 tCO2e) exceed those from transmission pipelines (~290,000 tCO2e), although significantly more accidents have occurred in transmission pipelines (6883 cases) than gathering pipelines (773 cases). Texas accounted for over 40% of total accident-related GHG emissions nationwide. Our study contributes to enhanced accuracy of the GHG account associated with crude oil transport and implementing the data-driven climate mitigation strategies

Genetic and phenotypic profiling of single living circulating tumour cells from patients with microfluidics

Accurate prediction of the efficacy of immunotherapy for cancer patients through the characterization of both genetic and phenotypic heterogeneity in individual patient cells holds great promise in informing targeted treatments, and ultimately in improving care pathways and clinical outcomes. Here, we describe the nanoplatform for interrogating living cell host-gene and (micro-)environment (NICHE) relationships, that integrates micro- and nanofluidics to enable highly efficient capture of circulating tumor cells (CTCs) from blood samples. The platform uses a unique nanopore-enhanced electrodelivery system that efficiently and rapidly integrates stable multichannel fluorescence probes into living CTCs for in situ quantification of target gene expression, while on-chip coculturing of CTCs with immune cells allows for the real-time correlative quantification of their phenotypic heterogeneities in response to immune checkpoint inhibitors (ICI). The NICHE microfluidic device provides a unique ability to perform both gene expression and phenotypic analysis on the same single cells in situ, allowing us to generate a predictive index for screening patients who could benefit from ICI. This index, which simultaneously integrates the heterogeneity of single cellular responses for both gene expression and phenotype, was validated by clinically tracing 80 non–small cell lung cancer patients, demonstrating significantly higher AUC (area under the curve) (0.906) than current clinical reference for immunotherapy prediction