Carbon nanotube-coated recombinant human surfactant protein D reduces cell viability in an ovarian cancer cell line, SKOV3, and modulates mTOR pathway and pro-inflammatory cytokine response

Copyright © 2022 The Authors. Nanoparticles such as carbon nanotubes (CNTs) have various clinical and diagnostic applications as utilised for imaging and drug delivery. Therapeutic proteins/peptides can be loaded on CNT coronas to specifically hit immune cells in overdrive or uncontrolled malignant cells. Previously, it was reported that a recombinant version of human surfactant protein D (rfhSP-D) containing trimeric C-type lectin domains induced apoptosis in several tumour cells/cell lines, including SKOV3, which is an ovarian tumour cell line. Solid-phase rfhSP-D coated on a microtiter plate is considerably more potent in inducing apoptosis in breast tumour cells. We have immobilised highly purified, endotoxin-free rfhSP-D on CNTs and assessed its antiproliferative effect on SKOV3 cells. Biotinylated rfhSP-D-CNTs were phagocytosed by SKOV3 cells, followed by apoptosis in a time-dependent manner. Gene expression analysis revealed compromised mTOR complex as a mechanism of apoptosis. When rfhSP-D-CNTs were added to a culture system of SKOV3 cells, it produced a highly proinflammatory immune response that is likely anti-tumorigenic. Thus, rfhSP-D-CNT seems a worthwhile nanocarrier for testing in vivo using an animal model of orthotopic ovarian cancer.This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University, Riyadh, KSA, through the Research Funding Program (Grant No# FRP-1440-27)

Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: A multicenter cohort study

Background: Inhaled nitric oxide (iNO) is used as rescue therapy in patients with refractory hypoxemia due to severe COVID-19 acute respiratory distress syndrome (ARDS) despite the recommendation against the use of this treatment. To date, the effect of iNO on the clinical outcomes of critically ill COVID-19 patients with moderate-to-severe ARDS remains arguable. Therefore, this study aimed to evaluate the use of iNO in critically ill COVID-19 patients with moderate-to-severe ARDS. Methods: This multicenter, retrospective cohort study included critically ill adult patients with confirmed COVID-19 treated from March 01, 2020, until July 31, 2021. Eligible patients with moderate-to-severe ARDS were subsequently categorized into two groups based on inhaled nitric oxide (iNO) use throughout their ICU stay. The primary endpoint was the improvement in oxygenation parameters 24 h after iNO use. Other outcomes were considered secondary. Propensity score matching (1:2) was used based on the predefined criteria. Results: A total of 1598 patients were screened, and 815 were included based on the eligibility criteria. Among them, 210 patients were matched based on predefined criteria. Oxygenation parameters (PaO2, FiO2 requirement, P/F ratio, oxygenation index) were significantly improved 24 h after iNO administration within a median of six days of ICU admission. However, the risk of 30-day and in-hospital mortality were found to be similar between the two groups (HR: 1.18; 95% CI: 0.77, 1.82; p = 0.45 and HR: 1.40; 95% CI: 0.94, 2.11; p= 0.10, respectively). On the other hand, ventilator-free days (VFDs) were significantly fewer, and ICU and hospital LOS were significantly longer in the iNO group. In addition, patients who received iNO had higher odds of acute kidney injury (AKI) (OR (95% CI): 2.35 (1.30, 4.26), p value = 0.005) and hospital/ventilator-acquired pneumonia (OR (95% CI): 3.2 (1.76, 5.83), p value = 0.001). Conclusion: In critically ill COVID-19 patients with moderate-to-severe ARDS, iNO rescue therapy is associated with improved oxygenation parameters but no mortality benefits. Moreover, iNO use is associated with higher odds of AKI, pneumonia, longer LOS, and fewer VFDs

The Role of Pharmacists in Providing Pharmaceutical Care in Primary and Secondary Prevention of Stroke: A Systematic Review and Meta-Analysis

Pharmacists deliver pharmaceutical care in many different healthcare settings and are well-placed to support the prevention of stroke. However, their role and impact in this area is ill-defined. This systematic review aims to explore the pharmacists’ role in stroke prevention. Nine databases were searched for studies reporting pharmacist interventions in the management of primary and secondary ischaemic stroke prevention. Study quality was evaluated through Cochrane Risk of Bias and Joanna Briggs Institute (JBI) appraisal tools where possible. A narrative review was conducted and meta-analysis performed for studies with comparable outcomes. Of the 834 initial articles, 31 met inclusion criteria. Study designs were varied and included controlled trials, observational studies, audit reports and conference abstracts. Seven studies addressed the pharmacists’ role in primary prevention and 24 in secondary prevention. Pharmacist interventions reported were diverse and often multifactorial. Overall, 20 studies reported significant improvement in outcomes. Meta-analysis showed pharmacist interventions in emergency care significantly improved the odds of achieving thrombolytic therapy door to needle (DTN) times ≤45 min, odds ratio: 2.69 (95% confidence interval (CI): 1.95–3.72); p < 0.001. The pharmacists’ role is varied and spans the stroke treatment pathway, with the potential for a positive impact on a range of health-related outcomes

Genetic characterization of the highlander Tibetan population from Qinghai-Tibet Plateau revealed by X chromosomal STRs.

Tibetans are considered an East Asian ethnic group and primarily live in the high Tibetan plateau, the western Sichuan and Yunnan mountains of central and southern China, and areas throughout the Himalayas and around the Tibetan plateau. These people exhibit rare molecular machinery that allows them to adapt to hypoxic environments in the Qinghai-Tibet Plateau and make them a potential candidate for providing insights related to medical genetic, molecular medicine and human population studies. In the current study, we have genotyped 549 individuals with Investigator Argus X-12 Kit. For 12 X-STRs, a total of 174 unique alleles were found, among them DXS10134 and DXS10135 were the most polymorphic loci. All of the loci were in Hardy-Weinberg Equilibrium (HWE). The numbers of observed haplotypes in Highlander Tibetans males were 161,112, 96 and 108, respectively, whereas haplotype diversities (HD) were 0.9959, 0.9880, 0.9809 and 0.9873, respectively. The combined discrimination power for males (PDm) was 0.999 999 99701 and for females (PDf) was 0.999 999 999 999 9958. This study represents an extensive report on X chromosomal STR markers variation in the Highlander Tibetans population for forensic applications and population genetic studies

Environmentally Conscious Design of Upstream Crude Oil Supply Chain

In the past few decades, very rapid growth in environmental legislation has resulted in an increasing will of companies to address environmental thinking through their supply chain. In this context, great strides have been made to incorporate the environmental concerns, such as “green” and “sustainable” supply chains, along with the traditional economic indicators. To assess the environmental impacts, there is no agreement on a universal environmental metric. Hence, a plethora of indicators has been developed to measure environmental impacts. The environmental indicators (e.g., Eco-indicator 99) that are founded on the Life Cycle Assessment (LCA) framework and nowadays are becoming among the popular environmental assessment methodologies. The crude oil tankers and utilities consumptions are the main origins of emissions through the crude oil supply chain. The energy required for operating upstream facilities in the crude oil supply chain represents enormous energy consumption. Whereas, ships and oil tankers are of the highest polluting combustion origins, per unit of fuel used. As a result, environmentally conscious design of upstream crude oil supply chain has created intriguing new challenges for practitioners and the managers. In this work, we introduce an environmentally conscious mathematical model to design the Upstream Oil Supply Chain (i.e., oil field development, and crude oil transportation). The model configure the supply network, select the technologies, establish the pipeline network, and plan the oil tankers with optimizing the economic objective value (i.e., the net present value) and the environmental metric value (i.e., the standard Eco-indicator 99 value)