The Saudi Critical Care Society practice guidelines on the management of COVID-19 in the ICU: Therapy section

BACKGROUND: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). METHODS: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. RESULTS: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. CONCLUSION: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available

Phytosynthesis via wasted onion peel extract of samarium oxide/silver core/shell nanoparticles for excellent inhibition of microbes

The aqueous onion peel extract (OPE) was used to synthesize silver nanoparticles (Ag-onion), samarium oxide nanoparticles (Sm2O3-onion), and silver/samarium oxide core/shell nanoparticles (Ag@Sm2O3-onion). The produced nanoparticles were characterized by thermal gravimetric analysis (TGA), infrared spectra (FT-IR), absorption spectra (UV–Vis), energy band gap, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), zeta potential, and transmission electron microscopy (TEM). OPE and NPs were tested for the disinfection of some water microbes. XRD analysis exhibited an amorphous structure of samarium oxide in both Sm2O3-onion and Ag@ Sm2O3-onion. The isolated bacteria from the water sample were Bacillus subtilis (OQ073500) and Escherichia coli (MW534699), while the isolated fungi were Alternaria brassicae (MZ266540), Aspergillus flavus (MT550030), Aspergillus penicillioides (MW957971), Pythium ultimum (MW830915), Verticillium dahlia (MW830379), Fusarium acuminatum (MZ266538), Candida albicans (MW534712), and Candida parapsilosis (MW960416). High levels of antimicrobial activity were seen in both the nanoparticles and the aqueous onion peel extract. Based on experimental results, Ag@Sm2O3 demonstrated the highest activity as an effective disinfectant, indicating the effectiveness of the modification process

Preparation, structural characterization, optical, photoluminescence, AC electrical conductivity and broadband dielectric properties of WO3 reinforced PEG/CS blend for futuristic optoelectronic and energy storage devices

Polymer nanocomposites (PNCs) composed of biopolymers and metallic oxides are important classes of materials. In addition to the environmental and economic considerations, these materials became the best candidates for various industrial fields. In the current study, solution cast procedure is used to prepare polymer nanocomposites (PNCs) based on polyethylene glycol (PEG)/chitosan (CS) blend and varying concentrations of tungsten trioxide nanoparticles (WO3 NPs), as a nanofiller. TEM micrograph shows that WO3 NPs have particle sizes of 5–32 nm their shapes are cubic and spherical. The XRD results reveal the semicrystalline of PEG/CS blend through showing three distinct diffraction peaks at 2θ = 7.42°, 19.47° and 23.62° and the degree of crystallinity is decreased after the incorporation of WO3 NPs due to the formation of polymer-nanoparticle interactions as indicated by FTIR spectra. The values of optical energy bandgap (direct and indirect) reduce while the Urbach energy increases with raising the concentration of WO3 NPs in the PEG/CS matrix. The PEG/CS-WO3 films' PL spectra show a photoemission peak at about 387 nm, where this peak loses intensity and becomes broader due to the induced defects and increase of disordering within the nanocomposite films. Additionally, the results of the dielectric investigation show an increase in the dielectric constant, dielectric loss, and AC electrical conductivity, which may be a sign of an increase of charge carriers and the content of amorphous regions that assists the movement of charge carriers. The DC electrical conductivity and conduction mechanism are also reported. Argand plot shows a half semicircle implying the Debye-type relaxation mechanism. The experimental results suggest the use of PEG/CS-WO3 nanocomposites as a possible contender for futuristic energy storage and optoelectronic applications

The Anti-Rheumatic Drug, Leflunomide, Induces Nephrotoxicity in Mice via Upregulation of TGFβ-Mediated p53/Smad2/3 Signaling

Recent studies indicated renal toxicity and interstitial nephritis in patients receiving leflunomide (LEFN), but the exact mechanism is still unknown. The transforming growth factor β (TGFβ)/p53/Smad2/3 pathway crucially mediates renal fibrosis. We aimed to assess the nephrotoxic effect of LEFN in mice and the possible role of TGFβ-stimulated p53/SMAD2/3 signaling. The study design involved distributing sixty male albino mice into four groups: (i) vehicle-treated mice, (ii) LEFN (2.5 mg/kg), (iii) LEFN (5 mg/kg), and (iv) LEFN (10 mg/kg). The drug was given orally every 48 h and continued for 8 weeks. Blood samples were then taken from mice for the determination of kidney function parameters. Right kidneys were used for histopathologic staining and immunohistochemistry, whereas left kidneys were frozen and used for Western blot analysis of the target proteins, p-p53 and Smad2/3. Results indicated that chronic administration of LEFN in mice resulted in a four- and nine-fold increase in serum urea and creatinine levels, respectively. Kidney specimens stained with hematoxylin and eosin or periodic acid–Schiff showed significant histopathological manifestations, such as cellular irregularity, interstitial congestion, and moderate lymphocytic inflammatory infiltrate in mice treated with LEFN. Western blotting indicated upregulation of the p-p53/Smad2/3 proteins. LEFN, especially in the highest dose (10 mg/kg), produced prominent nephrotoxicity in mice. This toxicity is mediated through stimulating fibrotic changes through TGFβ-stimulated p53/Smad2/3 signaling and induction of glomerular and tubular apoptosis. An improved understanding of LEFN-induced nephrotoxicity would have great implications in the prediction, prevention, and management of leflunomide-treated rheumatic patients, and may warrant further clinical studies for following up these toxidromes

The Impact of Dietary Consumption of Palm Oil and Olive Oil on Lipid Profile and Hepatocyte Injury in Hypercholesterolemic Rats

A metabolic disease called hypercholesterolemia is connected to both oxidative damage and inflammation. The goal of the current investigation was to determine if olive oil and palm oil could prevent hypercholesterolemia-induced oxidative stress in the liver of rats fed a high-cholesterol diet (HCD). The experimental mice were given HCD for three months while also receiving 0.5 mL/kg of either palm or olive oil. Serum triglycerides, total cholesterol, LDL cholesterol, vLDL cholesterol, and the atherogenic index all significantly increased in HCD-fed rats, while HDL cholesterol significantly dropped. Additionally, HCD caused a notable rise in proinflammatory cytokines and serum transaminases in liver tissue. Additionally, HCD significantly increased the production of nitric oxide and lipid peroxidation in the liver while decreasing antioxidant enzymes. Treatment with palm and olive oils dramatically reduced the levels of pro-inflammatory cytokines and lipid peroxidation, improved antioxidant defenses, and considerably improved liver function indicators. Additionally, the examined oils dramatically decreased the expression of fatty acid synthase (FAS) in the liver of rats receiving HCD. In conclusion, HCD-fed rats exhibit significant antihyperlipidemic and cholesterol-lowering benefits from palm and olive oils. The improved antioxidant defenses, lower inflammation and lipid peroxidation, and altered hepatic FAS mRNA expression were the main mechanisms by which palm and olive oils produced their advantageous effects

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population