Effect of methotrexate hold on COVID-19 vaccine response in the patients with autoimmune inflammatory disorders: a systematic review and meta-analysis.

Immunosuppressants, such as methotrexate (MTX), can suppress the COVID-19 vaccine response in patients with autoimmune diseases. Thus, this study aims to evaluate the effects of MTX hold following COVID-19 vaccination on vaccine efficacy response. A systematic review and meta-analysis of relevant studies retrieved from Web of Science, SCOPUS, PubMed, and CENTRAL from inception until Oct 1, 2023, was conducted. Covidence was used to screen the eligible articles, and all relevant outcomes data were synthesized using risk ratios (RRs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) in meta-analysis models within RevMan 5.4. PROSPERO ID: CRD42024511628. Four studies with a total of 762 patients with autoimmune inflammatory disorders were included. Holding MTX following the COVID-19 vaccination for approximately 2 weeks was associated with significantly higher antibody titer (SMD: 0.70, 95% CI [0.54, 0.87], P < 0.00001). However, the flare rate was significantly higher in the MTX hold group based on CDAI > 10 or DAS28-CRP > 1.2 either after 1st dose (RR: 2.49 with 95% CI [1.39, 4.47], P = 0.002) or 2nd dose (RR: 2.16 with 95% CI [1.37, 3.41], P = 0.0009) and self-reported disease flare (RR: 1.71 with 95% CI [1.35, 2.17], P < 0.00001). Holding MTX for 2 weeks after the COVID-19 vaccination resulted in significantly higher antibody titer but also had a higher disease flare rate, necessitating cautious clinical monitoring during this period. There is still a need to investigate safer MTX hold duration, considering patients' vulnerability to COVID-19, disease status, and demographics while adopting this strategy.

Zeta potential changing self-nanoemulsifying drug delivery systems: A newfangled approach for enhancing oral bioavailability of poorly soluble drugs.

The mucus is a defensive barrier for different drug-loaded systems. To overcome this obstacle, the crucial factor is the surface charge. Due to mucus negative charge behavior; it was revealed that negatively charged formulations can move across mucus, whereas positively charged nanoformulations could not diffuse via mucus due to interactions. However, cellular intake of negatively charged nanoformulations to the epithelium by endocytosis is less prominent as compared to positively charged carriers. Self-emulsifying drug delivery systems (SEDDS) improve the drug permeability of drugs, especially which have poor oral drug solubility. Moreover, SEDDS have the ability to reduce the degradation of drugs in the GI tract. Currently, drug carrier systems that can shift zeta potential from negative to positive were developed. The benefits of inducing zeta potential changing approach are that negatively charged nanoformulations permeate quickly across the mucus and surface charges reversed to positive at epithelium surface to increase cellular uptake. Among various systems of drug delivery, zeta potential changing SEDDS seem to signify a promising approach as they can promptly diffuse over mucus due to their smaller size and shape distortion ability. Due to such findings, mucus permeation and drug diffusion may improve by the mixture of the zeta potential changing approach and SEDDS.

Designing Functionally Substituted Pyridine-Carbohydrazides for Potent Antibacterial and Devouring Antifungal Effect on Multidrug Resistant (MDR) Strains.

The emergence of multidrug-resistant (MDR) pathogens and the gradual depletion of available antibiotics have exacerbated the need for novel antimicrobial agents with minimal toxicity. Herein, we report functionally substituted pyridine carbohydrazide with remarkable antimicrobial effect on multi-drug resistant strains. In the series, compound 6 had potent activity against four MDR strains of Candida spp., with minimum inhibitory concentration (MIC) values being in the range of 16-24 µg/mL and percentage inhibition up to 92.57%, which was exceptional when compared to broad-spectrum antifungal drug fluconazole (MIC = 20 µg/mL, 81.88% inhibition). Substitution of the octyl chain in 6 with a shorter butyl chain resulted in a significant anti-bacterial effect of 4 against Pseudomonas aeruginosa (ATCC 27853), the MIC value being 2-fold superior to the standard combination of ampicillin/cloxacillin. Time-kill kinetics assays were used to discern the efficacy and pharmacodynamics of the potent compounds. Further, hemolysis tests confirmed that both compounds had better safety profiles than the standard drugs. Besides, molecular docking simulations were used to further explore their mode of interaction with target proteins. Overall results suggest that these compounds have the potential to become promising antimicrobial drugs against MDR strains.

Optimization of metronidazole SR buccal tablet for gingivitis using genetic algorithm.

Gingivitis is a condition that needs sustained concentration of antibiotic locally over extended period of time. The current study aimed to formulate and evaluate the sustained and localized release of metronidazole (MTZ) as mucoadhesive buccal tablet containing hydroxypropylmethyl cellulose (HPMC), Carbopol 940® (CP), carboxymethylcellulose (CMC) and ethyl cellulose (EC) as mucoadhesive polymers. Tablets were directly compressed with proportions of polymeric blends (F1-F16). The results indicated that weight variation (249±2.10mg) and friability (0.21%) were within USP compendial limits. Maximum mucoadhesive strength and time were depicted by F1 and F14 which were 28.47g and 12hr respectively. Formulations, except F4, were within physiological pH limit. Maximum swellability index (261.9%) was exhibited by F16, at 8 hr, containing highest concentration of CP, HPMC and additional CMC. For in vitro release, the pre-set 8 hr complete release were shown by formulations, F15 and F16 which were 100% and 97%, respectively. Genetic algorithm was applied on the attributes to optimize polymeric response in accordance with desirability. The software predicted composition (F17) was tested which revealed that physical characteristics were in accordance with the compendial standards. The release kinetics, evaluated through DDsolver⌖, suggested that release of MTZ followed non-Fickian diffusion type in Korsmeyer-Peppas model. Therefore, MTZ, if delivered as mucoadhesive buccal formulation (F17) containing amounts (mg) of CP (16.4), HPMC (78.7), CMC (8.3) and EC (10.5) will simulate satisfactory release i.e. 96% at 8 hr in simulated buccal fluid.

Aqueous leaching of lithium from simulated pyrometallurgical slag by sodium sulfate roasting.

In the pyrometallurgical treatment for spent lithium-ion batteries (LIBs), lithium is generally present in slag with Al, Ca and Si and is hard to be further treated. In this study, lithium was recovered from a simulated pyrometallurgical slag (pyro-slag) via sodium roasting and water leaching. The thermodynamic process for the reactions between slag and additives such as NaCl, NaNO3 and Na2SO4 were simulated during roasting by the HSC software, where Na2SO4 possessed stronger chemical reactivity. The optimal conditions for roasting were experimentally determined to be 800 °C for 60 min and an Na2SO4/Li molar ratio of 3 : 1, followed by water leaching at 70 °C for 80 min using a liquid-to-solid (L/S) mass ratio of 30 : 1. This yielded a maximum of 93.62% lithium recovery. The mechanism by which insoluble lithium in slag was transformed into soluble lithium by salt roasting was proposed using the analysis of XRD and EDS spectra, in which ion exchange occurred between Na+ and Li+ at a certain temperature.

Electrochemical Properties of Controlled Size Mn3O4 Nanoparticles for Supercapacitor Applications.

A simple and controlled strategy has been used to synthesise Mn3O4 nanoparticles (NPs) via hydrothermal method. The Mn3O4 nanoparticles were further applied for supercapacitor electrode materials. The unique squared-shape Mn3O4 nanoparticles exhibited excellent electrochemical performance due to the small size and porous architecture. After electrochemical testing, the Mn3O4 NPs based electrode showed a large specific capacitance (380 F g-1, 1.0 mAcm-2) and good cycling stability (88.6%) of the initial capacitance after 5000 cycles in 1.0 M Na2SO4 solution. These results may provide useful guidelines for materials selection, synthesis, size and configuration designs for the novel energy storage devices based on transitional metal oxides.

Health assessment using aqua-quality indicators of alpine streams (Khunjerab National Park), Gilgit, Pakistan.

This preliminary research was conducted to evaluate the alpine stream health by using water quality as an indicator in Khunjerab National park of the Karakoram ranges located in Pak-China boarder Pakistan having altitude of 3660 m. This study investigated the stream health in the context of the presence or absence of sensitive species, their diversity, and their taxa richness. The water and macroinvertebrate samples were collected from 17 different locations from upstream and downstream of the river by using random sampling method. Macroinvertebrate samples were obtained using kick net (500-µm mesh size) and hand-picking method (NYSDEC). A total of 710 counts including 41 families of macroinvertebrates were recorded comprising of 7 orders including: Ephemeroptera (46%) being the most dominant group, Plecoptera (33%), Trichoptera (5%), Chironomidae (Diptera) (14%), Heteroptera (1%), and Coleoptera (1%). Ephemeroptera, Trichoptera, and Plecoptera (EPT) were found in abundance at the main source, Qarchanai, Dhee, and Tourqeen Nullah, as compared to the other locations of the stream. The most dominant macroinvertebrate was Ephemeroptera whose relative abundance is Pi = 0.49 by using the Shannon index. However, different statistical tools, including principal component analysis (PCA), cluster analysis (CA), ANOVA, and linear regression model, show a strong correlation between water quality and macroinvertebrates. The overall results of the biological indicators showed better ecological health at downstream compared to upstream. This study will provide basic information and understanding about the macroinvertebrates for future researchers, and the data will be helpful for upcoming research programs on alpine streams for the discovery and occurrences of macroinvertebrates and associated fauna.

Synthesis and electrochemical properties of stannous oxide clinopinacoid as anode material for lithium ion batteries.

Tin monoxide is a significant functional semiconductor material which employed to a wide area of applications especially optical and energy storage devices. Presently, template free hydrothermal technique has been employing to synthesize stannous oxide (SnO) clinopinacoid type controlled morphology using SnCl2 x 2H2O, NH3, and H2O as raw materials. The crystalline phase, morphology, particle size and component were characterized by X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and field-emission scanning electron microscopy (FESEM). FESEM results exhibited the large scale homogeneous growth of clinopinacoid architecture with the obvious size of 5 - 7 micrometers. The XRD results showed that the average crystallite size of the tetragonal phase romarchite SnO was about 29 nm calculated from the FWHM of X-ray diffraction pattern. The dominant Raman active modes A(1g) = 205 cm(-1), B(1g) = 105-107 cm(-1) and about 6 cm(-1) redshift were observed by the Raman spectroscopy, which further confirmed the existence of the nano tetragonal phase SnO. The electrochemical performance of as-synthesized SnO clinopinacoid structure as the anode material for lithium ion batteries was investigated. It was observed that the first discharge capacity of the two samples could reach a very high value of 1502 mA h g(-1) and 1422 mA h g(-1) respectively. The effect of nitrogen concentration on morphology as well as cyclic performance of Li-Ion-batteries was also discussed.

Ultrasound of Musculoskeletal Infections.

Ultrasound (US) can play an important role in differentiating infectious processes from other musculoskeletal diseases. US is the imaging modality of choice to diagnose superficial abscesses. These abscesses may have variable echogenicity and their detection can be facilitated by ultrasonographic dynamic evaluation and color Doppler imaging. Septic arthritis either in a native or prosthetic joint may have devastating complications on the joint function. Early diagnosis requires joint fluid analysis. US is very sensitive in the detection of joint effusions and is helpful to guide the arthrocentesis. US may help in the early diagnosis of osteomyelitis, although one must always remember that a normal US never excludes bone infection. This article also reviews the role of US in the diagnosis of necrotizing fasciitis, tenosynovitis, bursitis, and pyomyositis. After initial radiographs, along with nuclear medicine studies, US should be considered as the next imaging step in the investigation of musculoskeletal infections.