Investigating the Potential of 2-Ethylbutyl-(Phenoxy)phosphoryl-D-Alaninate Against RNA-Dependent RNA Polymerase (RdRp) of SARS-CoV-2.

There was an emergency call globally when COVID-19 was detected in December 2019. The SARS-CoV-2 virus, a modified virus, is what causes this contagious disease. Although research is being conducted throughout the world, the main target is still to find the promising candidate to target RNA-dependent RNA polymerase (RdRp) to provide possible drug against COVID-19. Aim of this work is to find a molecule to inhibit the translational process of viral protein synthesis. Density Functional Theory calculations revealed information about the formation of the desired ligand (RD). Molecular docking of RD with RdRp was performed and compared with some reported molecules and the data revealed that RD had the best docking score with RdRp (-6.7 kcal/mol). Further, molecular dynamics (MD) simulations of RD with RdRp of SARS-CoV-2 revealed the formation of stable complex with a maximum number of seven hydrogen bonds. Root mean square deviations values are in acceptable range and root mean square fluctuations has less fluctuation indicate stable complex formation. Further, based on MM-GBSA calculation, RD formed a stable complex with RdRp of nCoV with ΔG° of -12.28 kcal·mol-1.

Advances in chromone-based copper(ii) Schiff base complexes: synthesis, characterization, and versatile applications in pharmacology and biomimetic catalysis.

Chromones are well known as fundamental structural elements found in numerous natural compounds and medicinal substances. The Schiff bases of chromones have a much wider range of pharmacological applications such as antitumor, antioxidant, anti-HIV, antifungal, anti-inflammatory, and antimicrobial properties. A lot of research has been carried out on chromone-based copper(ii) Schiff-base complexes owing to their role in the organometallic domain and promise as potential bioactive cores. This review article is centered on copper(ii) Schiff-base complexes derived from chromones, highlighting their diverse range of pharmacological applications documented in the past decade, as well as the future research opportunities they offer.

Catharanthus roseus-mediated CuAl2O4 nanocomposites for evaluation of killing kinetics.

The present article portrayed on the killing kinetic of human pathogenic bacteria using bioinspired mesoporous CuAl2O4 nanocomposites (NCs). The NCs was fabricated using leaf extract of medicinal plant Catharanthus roseus (CR) as a green reducer and stabilizer. As bio-fabricated material was calcined at 800 °C and characterized by several analytical techniques like X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR), Ultraviolet-Visible Diffuse Reflectance Spectroscopy (UV-DRS), Energy Dispersive X-Ray Spectroscopy (EDS), X-Ray Photoelectron Spectroscopy (XPS), Raman, Brunauer-Emmett-Teller (BET), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM) to authenticate its structure, phase, chemical bonding, chemical state, size and morphology behaviors. XRD and TEM revealed a reduced crystallite and nanoscale sizes of biosynthesized NCs. Moreover, XRD study exposed a cubic-structure of material, while transmission electron microscopy rendered an average particles size in range 10-15 nm. However, BET profile advocates a mesoporous nature of the particles. An effective biological molecular docking modulation assessed by substituting natural inhibitor by bioinspired NCs, while the protein PDB ID 4Z8D FabH as a receptor site for the present investigation. After assessment of molecular docking examination, the antibacterial activity of bioinspired NCs were performed against Staphylococcus aureus, Bacillus subtillis, Klebsiella pneumoniae and Escherichia coli using agar-well method. The broth culture method was employed on different pathogenic strains by kinetic growth assays and colony forming unit.

Greening up organic reactions with caffeine: applications, recent developments, and future directions.

Numerous studies in the field of alkaloid chemistry have provided researchers with valuable insights into their unique properties as catalysts. Among the diverse natural catalysts, caffeine has emerged as a green, expedient, and biodegradable catalyst with high efficiency and applicability. Interest in using caffeine as a catalyst has burgeoned over the past few years with its role in diverse multicomponent reactions. Preparation of its imidazolium salts and further conversion to Nitrogen Heterocyclic Carbene (NHC) ligands and ionic liquids offers new paradigms. Caffeine has also played a multifaceted role as a support material in influencing the structural properties of nanoparticles. We hope that the chemistry of caffeine and its applications for sustainable organic transformations discussed in this review will stimulate new thinking and open new avenues in this field.

Transition-Metal Catalyzed Synthesis of Pyrimidines: Recent Advances, Mechanism, Scope and Future Perspectives.

Pyrimidine is a pharmacologically important moiety that exhibits diverse biological activities. This review reflects the growing significance of transition metal-catalyzed reactions for the synthesis of pyrimidines (with no discussion being made on the transition metal-catalyzed functionalization of pyrimidines). The effect of different catalysts on the selectivity/yields of pyrimidines and catalyst recyclability (wherever applicable) are described, together with attempts to illustrate the role of the catalyst through mechanisms. Although several methods have been researched for synthesizing this privileged scaffold, there has been a considerable push to expand transition metal-catalyzed, sustainable, efficient and selective synthetic strategies leading to pyrimidines. The aim of the authors with this update (2017-2023) is to drive the designing of new transition metal-mediated protocols for pyrimidine synthesis.

A Study of Pulmonary Function Tests in Patients with Chronic Rhinosinusitis Following Endoscopic Sinus Surgery.

Chronic inflammatory disorders of the upper airways are extremely prevalent and they have a major impact on public health.To assess the change in pulmonary function tests in patients of chronic rhinosinusitis undergoing functional endoscopic sinus surgery pre operatively and post operatively.To evaluate the difference in mean of FEV1, FEV1%, FVC, FVC%, FEV1/FVC in patients of chronic rhinosinusitis undergoing functional endoscopic sinus surgery.Prospective observational study.From July 2019 to September 2020 in Department of ENT and Head & Neck surgery, SMS Medical College, Jaipur.There was a significant improvement in the mean FEV1, FEV1%, FVC, and FVC% values post-surgically (p < 0.05). In our study, there was also a significant improvement in the FEV1/FVC value at one month postoperatively, reflecting the effect of FESS on relieving the symptomatic lower airway obstruction.Our study concludes that following Functional Endoscopic Sinus Surgery there is significant improvement in pulmonary function tests reflecting the improvement of asymptomatic lower airway disease in cases of chronic rhinosinusitis.

2,3-Diaminomaleonitrile: A Multifaceted Synthon in Organic Synthesis.

2,3-Diaminomaleonitrile (DAMN), a tetramer of hydrogen cyanide, displays weakly basic properties and has reactivity comparable to o-phenylenediamine. It has emerged as a versatile, cheap as well as a readily accessible building block towards the synthesis of a variety of organic compounds. The present review focuses on the applications of 2,3-diaminomaleonitrile for the synthesis of Schiff's base, imidazoles, pyrazines, quinoxolines, benzodiazocines, 1,4-diazepines, purines, pyrimidines, pyrazine-tetrazole hybrids, triazoles, thiadiazole, thiazolidines, porphyrazines, formamidines, 1,3,5-triazepines, pyrrolo[3,4-b][1,4]diazepin-6(3H)-ones, triaza[22]annulenes, pyrrolo[3,4-f][1,3,5]triazepines, spiro compounds, pyrazoles and 2,3-dicyano-5,7- bismethylthieno[3,4-b]pyrazine.

Capsaicin has potent anti-oxidative effects in vivo through a mechanism which is non-receptor mediated.

Capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide) is the active ingredient of chilli peppers and is responsible for the characteristic pungency. The ubiquitous human consumption of chilli peppers indicates their influence on human health. The effect of capsaicin through sensory neurons via TRPV1 activation has been well studied, but its non-neuronal effects are still not extensively explored. The purpose of this study was to investigate the in vivo antioxidant effect of capsaicin on erythrocytes of male Wistar rats. Markers of oxidative stress in blood were determined by assessing the plasma total antioxidant potential, activity of plasma membrane redox system, intracellular glutathione (GSH) level, ROS level, protein oxidation and lipid peroxidation. Results of this study suggest a significant protective effect of capsaicin against oxidative stress by enhancing FRAP, GSH level, PMRS activity and ameliorating ROS, MDA, PCO and AOPP.

The changing accuracy of traffic forecasts.

Researchers have improved travel demand forecasting methods in recent decades but invested relatively little to understand their accuracy. A major barrier has been the lack of necessary data. We compiled the largest known database of traffic forecast accuracy, composed of forecast traffic, post-opening counts and project attributes for 1291 road projects in the United States and Europe. We compared measured versus forecast traffic and identified the factors associated with accuracy. We found measured traffic is on average 6% lower than forecast volumes, with a mean absolute deviation of 17% from the forecast. Higher volume roads, higher functional classes, shorter time spans, and the use of travel models all improved accuracy. Unemployment rates also affected accuracy-traffic would be 1% greater than forecast on average, rather than 6% lower, if we adjust for higher unemployment during the post-recession years (2008 to 2014). Forecast accuracy was not consistent over time: more recent forecasts were more accurate, and the mean deviation changed direction. Traffic on projects that opened from the 1980s through early 2000s was higher on average than forecast, while traffic on more recent projects was lower on average than forecast. This research provides insight into the degree of confidence that planners and policy makers can expect from traffic forecasts and suggests that we should view forecasts as a range of possible outcomes rather than a single expected outcome. Supplementary Information: The online version contains supplementary material available at 10.1007/s11116-021-10182-8.

Recent development in the synthesis of heterocycles by 2-naphthol-based multicomponent reactions.

2-Naphthol or ß-naphthol is an important starting material that has drawn great attention in various organic transformations because of its attributes, such as low cost, easy to handle and eco-friendliness. The electron-rich aromatic framework of 2-naphthol with multiple reactive sites allows it to be utilized in several kinds of organic reactions eventuated to several organic molecules with potent biological properties. Multicomponent reaction approach has been tremendously utilized to explore the synthetic utility of 2-naphthol for the construction of diverse N/O-containing heterocyclic framework. In this review, we summarize recent data pertaining to multicomponent reactions, wherein heterocyclic compounds are synthesized utilizing 2-naphthol as one of the starting materials. It is anticipated that this review will stimulate the researchers to design new multicomponent strategies complying with the Green Chemistry principles for the further exploitation of 2-naphthol for the rapid synthesis of versatile biologically relevant heterocycles. This review provides a concise overview of the different 2-naphthol based multicomponent reactions utilized for the construction of diverse bioactive heterocyclic scaffold.

Metformin protects red blood cells against rotenone induced oxidative stress and cytotoxicity.

CONTEXT: The anti-diabetic medicine metformin has been reported as an anti-ageing drug candidate as it mimics the benefits of caloric restriction and reduces ageing-related oxidative stress in various experimental organisms. OBJECTIVE: We investigated the possible anti-oxidative role of metformin against rotenone-induced oxidative stress and cytotoxicity in erythrocytes of Wistar rats. Rotenone is a well-known inducer of oxidative stress which leads to a cellular redox imbalance. MATERIALS AND METHODS: We have co-exposed the experimental rats with rotenone (2.5 mg/kg, i.p.) and metformin (300 mg/kg, orally) for 30 days to investigate the protective effects of metformin on various rotenone-induced impaired oxidative stress biomarkers in rat erythrocytes. RESULTS: We found that a significant alleviation in the levels of rotenone-induced pro-oxidant and anti-oxidant markers following exposure of metformin. DISCUSSION AND CONCLUSIONS: Our findings suggest that metformin supplementation shows a protective role in against rotenone-induced redox imbalance and cytotoxicity in rat erythrocytes.

Cutting the subconjunctival fragment of the XEN gel implant during needling procedure.

PURPOSE: To describe the case and the follow-up of an inadvertently damaged XEN gel implant during needling procedure. METHODS: Case report. RESULTS: A 60-year-old African American patient underwent an uncomplicated combined phacoemulsification with the insertion of a XEN gel implant. Two months postoperatively, a needling procedure was required. During the needling procedure, a fragment of the XEN gel implant was inadvertently damaged. One month postoperatively, the intraocular pressure was still controlled and the bleb was functioning well. CONCLUSION: This case report reveals a previously unreported complication concerning XEN gel implant. It is important for the surgeon to pay attention during needling procedure, especially if there is a subconjunctival hemorrhage impairing the view, to defer the procedure until good visibility exists.

Efficacy of Needling Revision After XEN Gel Stent Implantation: A Prospective Study.

INTRODUCTION: The XEN gel stent is currently the only minimally invasive glaucoma surgical device that targets the subconjunctival outflow pathway through an ab interno placement. It has demonstrated a significant intraocular pressure (IOP)-lowering potential and a favorable safety profile compared with traditional filtering surgery. However, despite a less invasive approach, the presence of a filtering bleb inevitably implies some risk of complications. The most commonly reported bleb-related complication, with rates as high as 45%, is bleb fibrosis associated with raised IOP. To restore filtration in those failing blebs, needling revision is considered the procedure of choice. In this study, we present the results of mitomycin C-augmented needling after XEN implantation. METHODS: This was a prospective, interventional study, conducted at a single tertiary glaucoma center. Fifty-one eyes of 51 patients with raised IOP associated with either a fibrotic or shallow bleb or increased vascularity following XEN gel stent implantation at the investigation site between January 2015 and June 2016 were enrolled in this study. Patients with other identified causes of filtration failure (stent malposition, internal ostium obstruction, retained viscoelastic) were excluded. Included patients who underwent mitomycin C-augmented needling revision, and follow-up examinations were conducted at 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months. The primary outcome was the magnitude of IOP reduction following needling revision at the last follow-up visit. Secondary outcome measures were the number of needling procedures carried out in all patients, the rate of patients requiring further filtering surgery following needling revision, and the rate of intraoperative and postoperative complications associated with needling revisions. RESULTS: The average age was 74.4±9.6 years; 66.7% (n=34) were female individuals. Primary open-angle glaucoma was the most common diagnosis (n=21, 41.2%). A total of 78 needling procedures were performed over the 24-month follow-up. Overall 20 of 51 eyes (39.2%) required >1 needling revision, and 14 eyes (24.5%) eventually required reoperation to maintain IOP within their desired target range. Before XEN implantation, mean preoperative IOP was 22.3±8.2 mm Hg and decreased to 14.1±8.0 mm Hg at day 1 postoperatively (-36.8%). The last measured IOP before the first needling revision was on average 23.6±8.9 mm Hg, which reduced to a mean 12.1±4.2 mm Hg at the first postrevision appointment (-48.7%). At the last follow-up appointment, on average 17.0±7.0 months after the first needling, the mean IOP was 14.3±4.1 mm Hg (-35.9% and -39.4% from preoperative and prerevision baselines, respectively). Complications associated with needling revisions were partial amputation of the XEN implant during needling (n=2, 3.9%), hypotony with choroidal detachment (n=1, 2%), and failure to achieve target IOP requiring subsequent surgery (n=14, 27.5%). No association was found between any of the recorded characteristics and the number of needling revisions performed or their outcomes. DISCUSSION: The present study shows that needling revision following XEN gel stent implantation is a relatively safe and efficient intervention to restore filtration in failing blebs, with a significant and durable IOP-reduction potential.

A Prospective Evaluation of the Repeatability and Reliability of New Steady-state Pattern Electroretinogram Parameters.

PURPOSE: The purpose of this study was to determine the repeatability and reproducibility of a new Pattern Electroretinography (PERG) device in healthy subjects. METHODS: A total of 40 eyes of 20 healthy subjects (45.6±6.8 y, 70% female) were enrolled in this prospective study. Steady-state PERG were recorded using the Diopsys NOVA (Diopsys Inc., NJ) to obtain the Magnitude, MagnitudeD, MagnitudeD/Magnitude Ratio, and Signal to Noise Ratio. Subjects underwent 2 "contrast sensitivity" protocols with the same electrodes and 2 after changing electrodes, by a single examiner. Eyes were stimulated separately using high and low contrast patterns. The same examination was repeated by a different operator following the same protocol 6 months after the baseline measures. Repeatability and reproducibility of the readings were calculated using intraclass correlation coefficient (ICC). A Bland-Altman plot was used to analyze the agreement between measures. RESULTS: ICC of Magnitude, MagnitudeD, MagnitudeD/Magnitude ratio, and SNR were 0.87, 0.81, 0.36, and 0.81, respectively between measures taken with the same electrodes (repeatability). After changing electrodes, ICC of the Magnitude, MagD, MagD/Mag ratio, and SNR were 0.79, 0.85, 0.51, and 0.83, respectively during the same session as baseline measures, and 0.87, 0.85, 0.40, and 0.76 when repeated after 6 months (reproducibility). The variability of MagD/Mag ratio increased with successive test repetitions. CONCLUSIONS: Mag, MagD, and SNR were repeatable and reproducible, whereas the MagD/Mag ratio was less repeatable and reproducible. These results suggest that the former parameters are sufficiently reliable to be used in clinical practice.

Goniotomy Using the Kahook Dual Blade in Severe and Refractory Glaucoma: 6-Month Outcomes.

PURPOSE: The purpose of the study is to describe short-term efficacy and safety of goniotomy with trabecular meshwork excision using the Kahook Dual Blade (KDB, New World Medical Inc., Rancho Cucamonga, CA) in patients with severe or refractory glaucoma. METHOD: Retrospective multicentric case series of 53 eyes with severe or refractory glaucoma as defined by ICD-10 conducted in the United States, Mexico, and Switzerland. Primary efficacy outcome was a ≥20% decrease in intraocular pressure (IOP) from baseline at 6 months. Secondary efficacy outcome measures were probability of achieving an IOP≤14 or 18 mm Hg at 6 months and the mean IOP change from baseline at 6 months. Medication use required to obtain target IOP at last follow up and adverse effects were analyzed. RESULTS: The proportion of eyes achieving an IOP reduction of >20% from preoperative baseline at 6 months was 57.7% (n=30). The mean IOP decreased from 18.4±6.1 mm Hg at baseline to 13.9±3.5 mm Hg at month 6 (23.9% reduction; P<0.001). At 6 months, 63.5% and 92.3% achieved an IOP≤14 and ≤18 mm Hg, respectively, and the mean number of glaucoma medications was reduced by 1.2±1.3 (36.6%) compared with baseline (P<0.001). The most common adverse event was hyphema (n=29, 34.9%) with spontaneous resolution in all cases. No severe complications were reported. One case presented with uncontrolled IOP and required glaucoma drainage device surgery at 1 month. CONCLUSIONS: Goniotomy with trabecular meshwork excision using the KDB could be an alternative surgery for severe or refractory glaucoma, significantly reducing IOP and medication use at 6 months, with a low rate of complications.

Optical Coherence Tomography Angiography Description of Ocular Decompression Retinopathy After Deep Sclerectomy in Traumatic Glaucoma.

PURPOSE: The purpose of this article is to present a case of ocular decompression retinopathy (ODR) occurring after uncomplicated deep sclerectomy with Mitomycin C using optical coherence tomography angiography (OCTA). PATIENT AND METHOD: This is a single case report. RESULTS: A 55-year-old man with traumatic glaucoma in the right eye complained of blurred vision. Visual acuity was 20/25 and intraocular pressure (IOP) was 50 mm Hg. Deep sclerectomy with Mitomycin C was performed. On the first postoperative day, best-corrected visual acuity (BCVA) was light perception and IOP was 6 mm Hg. At 3 months follow-up, BCVA was 20/40 and IOP was 14 mm Hg. Fundoscopy showed multiple diffuse round retinal hemorrhages over the posterior pole, in all quadrants. On OCTA (RTVue XR Avanti; Optovue Inc., Fremont, CA), hemorrhages were present in superficial and deep retinal layers, with a normal vascularization in the en face image. BCVA improved to 20/32 at postoperative month 4 with reduced but persistent retinal hemorrhages. CONCLUSIONS: ODR is a rare complication of filtering surgery. To the best of our knowledge, this is the second reported case of ODR occurring after deep sclerectomy and first description using OCTA. OCTA showed superficial and deep retinal hemorrhages with a normal vascular configuration. High-preoperative IOP seems to be the most important risk factor for this complication.

XEN Gel Implant: a new surgical approach in glaucoma.

INTRODUCTION: Glaucoma is a leading cause of blindness worldwide. Intraocular pressure (IOP) lowering is the only effective treatment strategy. Traditional glaucoma surgeries are generally considered to be unpredictable and associated with a high rate of complications. This has led to the development of a novel XEN Gel Implant, a type of minimally invasive glaucoma surgery (MIGS), lowering the IOP without extensive surgical dissection. AREAS COVERED: A literature search was undertaken on PubMed using the terms XEN glaucoma, gelatin microstent, and MIGS. All the articles and case reports on XEN Gel Implant and selected articles on MIGS were studied and reviewed. We have discussed the results of most studies on XEN Gel Implant related to its efficacy, safety and success. EXPERT COMMENTARY: The XEN Gel Implant effectively lowers IOP and medication use, with a favorable safety profile. Long-term data on its success and cost-effectiveness are lacking. The studies have shown it to be without any serious adverse events and to have good safety profile encouraging future research on this novel implant. There is a need to correctly identify selection criteria for patients, who would benefit the most from the XEN Gel Implant.

Revision of a Leaking Bleb With XEN Gel Stent Replacement.

Minimally invasive glaucoma surgery includes different devices which provide a less invasive and safer means of reducing intraocular pressure. The XEN Gel Stent (Allergan Inc., CA) is an ab interno procedure which creates a subconjunctival drainage pathway. It is a new surgical device and there is a paucity of data on complications and their management. We report a clinical case of a leaking bleb after XEN surgery managed by bleb revision, conjunctival suturing, and XEN replacement.