Comprehensive Computational Screening and Analysis of Natural Compounds Reveals Promising Estrogen Receptor Alpha Inhibitors for Breast Cancer Therapy.

Breast cancer remains a leading cause of death among women, with estrogen receptor alpha (ERα) overexpression playing a pivotal role in tumor growth and progression. This study aimed to identify novel ERα inhibitors from a library of 561 natural compounds using computational techniques, including virtual screening, molecular docking, and molecular dynamics simulations. Four promising candidates-Protopine, Sanguinarine, Pseudocoptisine, and Stylopine-were selected based on their high binding affinities and interactions with key ERα residues. Molecular dynamics simulations conducted over 500 nanoseconds revealed that Protopine and Sanguinarine exhibited more excellent stability with minimal fluctuations, suggesting strong and stable binding. In contrast, Pseudocoptisine and Stylopine showed higher flexibility, indicating less stable interactions. Binding free energy calculations further supported the potential of Protopine and Sanguinarine as ERα inhibitors, though their binding strength was slightly lower than that of the reference compound. These findings highlight Protopine and Sanguinarine as leading candidates for further investigation, and in vitro and in vivo studies are recommended to evaluate their therapeutic potential in breast cancer treatment.

Understanding the stability and dynamics of influenza a H5N1 polymerase PB2 CAP-Binding domain in complex with natural compounds for antiviral drug discovery.

Influenza A virus, particularly the H5N1 strain, poses a significant threat to public health due to its ability to cause severe respiratory illness and its high mortality rate. Traditional antiviral drugs targeting influenza A virus have faced challenges such as drug resistance and limited efficacy. Therefore, new antiviral compounds are needed to be discovered and developed. This study concentrated on examining the stability and behavior of the H5N1 polymerase PB2 CAP-binding domain when interacting with natural compounds, aiming to identify potential candidates for antiviral drug discovery. Through the virtual screening process, four lead compounds, ZINC000096095464, ZINC000044404209, ZINC000001562130, and ZINC000059779788, were selected, and these compounds showed binding energies -9.6, -9.4, -9.3, and -9.2 kcal/mol, respectively. When complexed with PB2, the ligand showed acceptable binding stability due to significant bond formation. However, during the 200ns MD simulation analysis, three (ZINC000096095464, ZINC000044404209, and ZINC000059779788) showed significant stability, which was proven by the trajectory analysis. The Rg-RMSD-based FEL plot showed significant structural stability due to stable conformers. The free-binding energy calculation also validates the stability of these complexes. This study offers valuable insights into the stability and dynamics of the H5N1 polymerase PB2 CAP-binding domain in complexes with natural compounds. These findings highlight the potential of these natural compounds as antiviral agents against the H5N1 influenza virus. Furthermore, this research contributes to the broader field of influenza virus treatment by demonstrating the effectiveness of computational methods in predicting and evaluating the stability and dynamics of potential drug candidates.

Unveiling the Detrimental Effect of Glipizide on Structure and Function of Catalase: Spectroscopic, Thermodynamics and Simulation Studies.

Free radicals, products of oxidative processes, induce cellular damage linked to diseases like Parkinson's and diabetes due to increased reactive oxygen species (ROS) levels. Catalase, crucial for scavenging ROS, emerges as a therapeutic agent against ailments including atherosclerosis and tumor progression. Its primary function involves breaking down hydrogen peroxide into water and oxygen. Research on catalase-drug interactions reveals structural changes under specific conditions, affecting its activity and cellular antioxidant balance, highlighting its pivotal role in defending against oxidative stress-related diseases. Hence, targeting catalase is considered an effective strategy for controlling ROS-induced cellular damage. This study investigates the interaction between bovine liver catalase and glipizide using spectroscopic and computational methods. It also explores glipizide's effect on catalase activity. More than 20% inhibition of catalase enzymatic activity was recorded in the presence of 50 µM glipizide. To investigate the inhibition of catalase activity by glipizide, we performed a series of binding studies. Glipizide was found to form a complex with catalase with moderate affinity and binding constant in the range of 3.822 to 5.063 × 104 M-1. The binding was spontaneous and entropically favourable. The α-helical content of catalase increased from 24.04 to 29.53% upon glipizide complexation. Glipizide binding does not alter the local environment surrounding the tyrosine residues while a notable decrease in polarity around the tryptophan residues of catalase was recorded. Glipizide interacted with numerous active site residues of catalase including His361, Tyr357, Ala332, Asn147, Arg71, and Thr360. Molecular simulations revealed that the catalase-glipizide complex remained relatively stable in an aqueous environment. The binding of glipizide had a negligible effect on the secondary structure of catalase, and hydrogen bonds persisted consistently throughout the trajectory. These results could aid in the development of glipizide as a potent catalase inhibitor, potentially reducing the impact of reactive oxygen species (ROS) in the human body.

An environmentally sustainable approach for the utilization of Erigeron bonariensis as a green inhibitor against weathering steel corrosion in acidic media.

In the realm of corrosion mitigation, the search for sustainable and ecologically accountable inhibitors attracts significant interest from the environmental point of view. This study investigates the intriguing possibilities presented by Erigeron bonariensis (EB) as a green and innovative corrosion inhibitor for weathering steel in 1 M H2SO4. EB, a naturally abundant plant species, holds promise as a green and sustainable inhibitor due to its inherent chemical composition in the environment. The intricate interplay between the phytochemical constituents of the extract and the corrosive environment is meticulously deciphered. Furthermore, the environmentally benign nature of the inhibitor adds an extra layer of significance to its application, aligning with contemporary green chemistry principles. The inhibition effect of Erigeron bonariensis (EB) extract on the corrosion of mild steel in acidic media (H2SO4) was studied using weight loss, absorption studies, phytochemical analysis, electrochemical methods, and scanning electron microscopy. The experimental findings revealed that an increase in inhibitor concentration is correlated with higher inhibition efficiency. The adsorption of inhibitor molecules on the mild steel surface was found to agree with the UV-Vis adsorption spectrum. Additionally, a surface study conducted using scanning electron microscopy indicated notable differences in the presence and absence of inhibitors for weathering steel. At 2000 mg L-1, EB extract has the best inhibitory efficiency for weathering steel in 1 M H2SO4 of 99.50% by the leaf part, followed by 94.35% by the flower part, and 85.22% by the stem part. Overall, this study suggests that EB extract serves as a promising alternative for corrosion prevention, demonstrating significant inhibition efficiency.

Antiglycation potential of metal ions and polyphenolic extract of chickpea on thiol-protease inhibitor: A management for diabetic complications.

Glycation is the non-enzymatic adduct formation between reducing sugars or dicarbonyls with proteins and is a crucial molecular event under hyperglycaemic conditions of diabetes. The accumulation of advanced glycation end products (AGEs) due to glycation of proteins has been implicated in several diseases associated with ageing and diabetes. Thus, investigating the antiglycation potential of some trace metal ions (Manganese; Mn2+, and Zinc; Zn2+) and polyphenolic extract of chickpea seeds (PEC) on the methylglyoxal (MGO) induced glycation of a phytocystatin isolated from chickpea was taken up to find an inexpensive and non-toxic therapeutic means of medicating protein glycation and associated diabetic complications. The current study focused on the comparative analyses of these micronutrients and herbal extracts in inhibiting protein glycation and AGEs formation in a quest to develop nutraceuticals for managing diabetes. The effect of metals (Mn2+, Zn2+) and PEC on protein glycation was assessed by different techniques, i.e., glycation-specific AGE fluorescence and absorbance, thiol protease inhibitory activity assay, and conformational alterations by spectroscopic assays. This study revealed the significant anti-glycation potencies of Mn2+, Zn2+, and PEC against the MGO-induced glycation of CPC, which might pave the way for resolving pathological complications of diabetes by combining higher levels of efficacy, selectivity, and safety in humans. Moreover, characterization and identification of different AGEs formed during the glycation process in diabetics was done to apply the same for determining the onset of glycation at the early stage so that appropriate steps be taken to address the menace of diabetic complications.

Modulation of quorum sensing and biofilm of Gram-negative bacterial pathogens by Cinnamomum zeylanicum L.

The development of antibiotic resistant microbial pathogens has become a global health threat and a major concern in modern medicine. The problem of antimicrobial resistance (AMR) has majorly arisen due to sub-judicious use of antibiotics in health care and livestock industry. A slow progress has been made in last two decades in discovery of new antibiotics. A new strategy in combatting AMR is to modulate or disarm the microbes for their virulence and pathogenicity. Plants are considered as promising source for new drugs against AMR pathogens. In this study, fraction-based screening of the Cinnamomum zeylanicum extract was performed followed by detailed investigation of antiquorum sensing and antibiofilm activities of the most active fraction that is, C. zeylanicum hexane fraction (CZHF). More than 75% reduction in violacein pigment of C. violaceum 12472 was overserved. CZHF successfully modulated the virulence of Pseudomonas aeruginosa PAO1 by 60.46%-78.35%. A similar effect was recorded against Serratia marcescens MTCC 97. A broad-spectrum inhibition of biofilm development was found in presence of sub-MICs of CZHF. The colonization of bacteria onto the glass coverslips was remarkably reduced apart from the reduction in exopolymeric substances. Alkaloids and terpenoids were found in CZHF. GC/MS analysis revealed the presence of cinnamaldehyde dimethyl acetal, 2-propenal, coumarin, and α-copaene as major phytocompounds. This study provides enough evidence to support potency of C. zeylanicum extract in targeting the virulence of Gram -ve pathogenic bacteria. The plant extract or active compounds can be developed as successful drugs after careful in vivo examination to target microbial infections. RESEARCH HIGHLIGHTS: Hexane fraction of Cinnamomum zeylanicum is active against QS and biofilms. The broad-spectrum antibiofilm activity was further confirmed by microscopic analysis. Dimethyl acetal, 2-propenal, coumarin, α-copaene, and so forth are major phytocompounds.

Aggregation and cytotoxicity of food additive dye (Azorubine)-albumin adducts: a multi-spectroscopic, microscopic and computational analysis.

Protein and peptide misfolding is a central factor in the formation of pathological aggregates and fibrils linked to disorders like Alzheimer's and Parkinson's diseases. Therefore, it's essential to understand how food additives, particularly Azorubine, affect protein structures and their ability to induce aggregation. In this study, human serum albumin (HSA) was used as a model protein to investigate the binding and conformational changes caused by azorubine, a common food and drink colorant. The research revealed that azorubine destabilized the conformation of HSA at both physiological (pH 7.4) and acidic (pH 3.5) conditions. The loss of tryptophan fluorescence in HSA suggested significant structural alterations, particularly around aromatic residues. Far UV-CD analysis demonstrated disruptions in HSA's secondary structure, with a notable reduction in α-helical structures at pH 7.4. At pH 3.5, Azorubine induced even more extensive perturbations, resulting in a random coil conformation at higher azorubine concentrations. The study also investigated aggregation phenomena through turbidity measurements, RLS analysis, and TEM imaging. At pH 3.5, larger insoluble aggregates formed, while at pH 7.4, only conformational changes occurred without aggregate formation. Cytotoxicity assessments on neuroblastoma (SH-SY5Y) cells highlighted the concentration-dependent toxicity of albumin aggregates. Molecular dynamics simulations reaffirmed the stable interaction between azorubine and HSA. This research provides valuable insights into the mechanisms by which azorubine influences protein conformations. To further advance our understanding and contribute to the broader knowledge in this area, several future directions can be considered such as exploring other proteins, studying dose-response relationship, gaining mechanistic insights, biological relevance, toxicity assessment, identifying alternative food colorants, and mitigation strategies to prevent adverse effects of azorubine on serum proteins.Communicated by Ramaswamy H. Sarma.

Electrochemical synthesis and antimicrobial evaluation of some N-phenyl α-amino acids.

In the present report, the authors describe a synthetic route for the generation of N-phenyl amino acid derivatives using CO2via a C-C coupling reaction in an undivided cell containing a combination of Mg-Pt electrodes. The reactions were completed in a short time without the formation of any other side product. The final products were purified via a simple recrystallization procedure. The structures of the newly prepared compounds were established using advanced spectroscopic techniques including 1H, 13C NMR, IR, and ESI-MS. All the prepared derivatives show good-to-excellent activity when tested against bacterial and fungal strains. Interestingly, it was observed that the presence of polar groups (capable of forming H-bonds) such as -OH (4d) and -NO2 (4e) at the para position of the phenyl ring show activity equivalent to the standard drugs.

Unravelling the role of microneedles in drug delivery: Principle, perspectives, and practices.

In recent year, the research of transdermal drug delivery systems has got substantial attention towards the development of microneedles (MNs). This shift has occurred due to multifaceted advantages of MNs as they can be utilized to deliver the drug deeper to the skin with minimal invasion, offer successful delivery of drugs and biomolecules that are susceptible to degradation in gastrointestinal tract (GIT), act as biosensors, and help in monitoring the level of biomarkers in the body. These can be fabricated into different types based on their applications as well as material for fabrication. Some of their types include solid MNs, hollow MNs, coated MNs, hydrogel forming MNs, and dissolving MNs. These MNs deliver the therapeutics via microchannels deeper into the skin. The coated and hollow MNs have been found successful. However, they suffer from poor drug loading and blocking of pores. In contrast, dissolving MNs offer high drug loading. These MNs have also been utilized to deliver vaccines and biologicals. They have also been used in cosmetics. The current review covers the different types of MNs, materials used in their fabrication, properties of MNs, and various case studies related to their role in delivering therapeutics, monitoring level of biomarkers/hormones in body such as insulin. Various patents and clinical trials related to MNs are also covered. Covered are the major bottlenecks associated with their clinical translation and potential future perspectives.

Umbelliferone modulates the quorum sensing and biofilm of Gram - ve bacteria: in vitro and in silico investigations.

In last two decades, the world has seen an exponential increase in the antimicrobial resistance (AMR), making the issue a serious threat to human health. The mortality caused by AMR is one of the leading causes of human death worldwide. Till the end of the twentieth century, a tremendous success in the discovery of new antibiotics was seen, but in last two decades, there is negligible progress in this direction. The increase in AMR combined with slow progress of antibiotic drug discovery has created an urgent demand to search for newer methods of intervention to combat infectious diseases. One of such approach is to look for biofilm and quorum sensing (QS) inhibitors. Plants are excellent source of wide class compounds that can be harnessed to look for the compounds with such properties. This study proves a broad-spectrum biofilm and QS inhibitory potential of umbelliferone. More than 85% reduction in violacein production Chromobacterium violaceum 12472 was found. All tested virulent traits of Pseudomonas aeruginosa PAO1 and Serratia marcescens MTCC 97 were remarkably inhibited that ranged from 56.62% to 86.24%. Umbelliferone also successfully prevented the biofilm of test bacteria at least by 67.68%. Umbelliferone interacted at the active site of many proteins of QS circuit, which led to the mitigation of virulent traits. The stable nature of complexes of umbelliferone with proteins further strengthens in vitro results. After examining the toxicological profile and other drug-like properties, umbelliferone could be potentially developed as new drug to target the infections caused by Gram - ve bacteria.Communicated by Ramaswamy H. Sarma.

Exoprotease exploitation and social cheating in a Pseudomonas aeruginosa environmental lysogenic strain with a noncanonical quorum sensing system.

Social cheating is the exploitation of public goods that are costly metabolites, like exoproteases. Exoprotease exploitation in Pseudomonas aeruginosa has been studied in reference strains. Experimental evolution with reference strains during continuous growth in casein has demonstrated that nonexoprotease producers that are lasR mutants are selected while they behave as social cheaters. However, noncanonical quorum-sensing systems exist in P. aeruginosa strains, which are diverse. In this work, the exploitation of exoproteases in the environmental strain ID4365 was evaluated; ID4365 has a nonsense mutation that precludes expression of LasR. ID4365 produces exoproteases under the control of RhlR, and harbors an inducible prophage. As expected, rhlR mutants of ID4365 behave as social cheaters, and exoprotease-deficient individuals accumulate upon continuous growth in casein. Moreover, in all continuous cultures, population collapses occur. However, this also sometimes happens before cheaters dominate. Interestingly, during growth in casein, ID4565's native prophage is induced, suggesting that the metabolic costs imposed by social cheating may increase its induction, promoting population collapses. Accordingly, lysogenization of the PAO1 lasR mutant with this prophage accelerated its collapse. These findings highlight the influence of temperate phages in social cheating.

Expanding Arsenal against Neurodegenerative Diseases Using Quercetin Based Nanoformulations: Breakthroughs and Bottlenecks.

Quercetin (Qu), a dietary flavonoid, is obtained from many fruits and vegetables such as coriander, broccoli, capers, asparagus, onion, figs, radish leaves, cranberry, walnuts, and citrus fruits. It has proven its role as a nutraceutical owing to numerous pharmacological effects against various diseases in preclinical studies. Despite these facts, Qu and its nanoparticles are less explored in clinical research as a nutraceutical. The present review covers various neuroprotective actions of Qu against various neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. A literature search was conducted to systematically review the various mechanistic pathways through which Qu elicits its neuroprotective actions and the challenges associated with raw Qu that compromise therapeutic efficacy. The nanoformulations developed to enhance Qu's therapeutic efficacy are also covered. Various ongoing/completed clinical trials related to Qu in treating various diseases, including NDs, are also tabulated. Despite these many successes, the exploration of research on Qu-loaded nanoformulations is limited mostly to preclinical studies, probably due to poor drug loading and stability of the formulation, time-consuming steps involved in the formulation, and their poor scale-up capacity. Hence, future efforts are required in this area to reach Qu nanoformulations to the clinical level.

Diabetes Health Literacy, Drug Adherence and Factors Associated with Them among Urban Patients in Kerala, India.

Aims: The study aimed to assess diabetes health literacy, adherence to diabetes medication, and its associated factors in Kerala, India, the most advanced Indian state in epidemiological transition with the highest literacy level in India. Materials and methods: We conducted a community-based cross-sectional study among 280 diabetes patients (mean age 62 years, male 42%) selected by multistage cluster sampling. Information on sociodemographic variables was collected using a pretested structured interview schedule. Diabetes health literacy was assessed using the revised Michigan Diabetes Knowledge test. Adherence to diabetes medication was assessed using the Hill-Bone subscale. Binary logistic regression analysis was done to find out the factors associated with diabetes health literacy and medication adherence. Results: Good diabetes health literacy was reported by 35.7% [95% confidence interval (CI): 30.1-41.6] of the patients. Perfect adherence to diabetes medication was reported by 33.2% of patients (CI: 27.7-39.1). Patients who reported regular newspaper reading [adjusted odds ratio (AOR) 3.16; CI: 1.57-6.30], using the internet (AOR 2.23; CI: 1.11-4.50) and insulin use (AOR 2.60; CI: 1.35-5.00) were more likely to report good diabetes health literacy compared to their counterparts. Patients who reported reading health magazines (AOR 2.75; CI: 1.01-7.60) were more likely to report perfect medication adherence compared to those who did not. Conclusion: Why diabetes health literacy and medication adherence were low among diabetes patients in the most literate state needs further investigation. Interventions to enhance diabetes health literacy and medication adherence may be undertaken among diabetes patients encouraging them to read newspapers and health magazines regularly and use the internet.

Resistance against two lytic phage variants attenuates virulence and antibiotic resistance in Pseudomonas aeruginosa.

Background: Bacteriophage therapy is becoming part of mainstream Western medicine since antibiotics of clinical use tend to fail. It involves applying lytic bacteriophages that self-replicate and induce cell lysis, thus killing their hosts. Nevertheless, bacterial killing promotes the selection of resistant clones which sometimes may exhibit a decrease in bacterial virulence or antibiotic resistance. Methods: In this work, we studied the Pseudomonas aeruginosa lytic phage φDCL-PA6 and its variant φDCL-PA6α. Additionally, we characterized and evaluated the production of virulence factors and the virulence in a Galleria mellonella model of resistant mutants against each phage for PA14 and two clinical strains. Results: Phage φDCL-PA6α differs from the original by only two amino acids: one in the baseplate wedge subunit and another in the tail fiber protein. According to genomic data and cross-resistance experiments, these changes may promote the change of the phage receptor from the O-antigen to the core lipopolysaccharide. Interestingly, the host range of the two phages differs as determined against the Pseudomonas aeruginosa reference strains PA14 and PAO1 and against nine multidrug-resistant isolates from ventilator associated pneumonia. Conclusions: We show as well that phage resistance impacts virulence factor production. Specifically, phage resistance led to decreased biofilm formation, swarming, and type III secretion; therefore, the virulence towards Galleria mellonella was dramatically attenuated. Furthermore, antibiotic resistance decreased for one clinical strain. Our study highlights important potential advantages of phage therapy's evolutionary impact that may be exploited to generate robust therapy schemes.

In vitro inhibition of biofilm and virulence factor production in azole-resistant strains of Candida albicans isolated from diabetic foot by Artemisia vulgaris stabilized tin (IV) oxide nanoparticles.

The advent of nanotechnology has been instrumental in the development of new drugs with novel targets. Recently, metallic nanoparticles have emerged as potential candidates to combat the threat of drug-resistant infections. Diabetic foot ulcers (DFUs) are one of the dreadful complications of diabetes mellitus due to the colonization of numerous drug-resistant pathogenic microbes leading to biofilm formation. Biofilms are difficult to treat due to limited penetration and non-specificity of drugs. Therefore, in the current investigation, SnO2 nanoparticles were biosynthesized using Artemisia vulgaris (AvTO-NPs) as a stabilizing agent and were characterized using ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). Furthermore, the efficacy of AvTO-NPs against biofilms and virulence factors of drug-resistant Candida albicans strains isolated from DFUs was assessed. AvTO-NPs displayed minimum inhibitory concentrations (MICs) ranging from 1 mg/mL to 2 mg/mL against four strains of C. albicans. AvTO-NPs significantly inhibited biofilm formation by 54.8%-87%, germ tube formation by 72%-90%, cell surface hydrophobicity by 68.2%-82.8%, and exopolysaccharide (EPS) production by 69%-86.3% in the test strains at respective 1/2xMIC. Biosynthesized NPs were effective in disrupting established mature biofilms of test strains significantly. Elevated levels of reactive oxygen species (ROS) generation in the AvTO-NPs-treated C. albicans could be the possible cause of cell death leading to biofilm inhibition. The useful insights of the present study could be exploited in the current line of treatment to mitigate the threat of biofilm-related persistent DFUs and expedite wound healing.

Incidence of Gastrointestinal Bleeding After Transesophageal Echocardiography Use in Orthotopic Liver Transplantation.

The risk of upper gastrointestinal bleeding (UGIB) after transesophageal echocardiography (TEE) in patients with high grade esophageal varices (EV) that are undergoing Orthotopic Liver transplantation (OLT) is poorly understood. This was a retrospective single-centre cohort study in all patients that underwent OLT at Queen Elizabeth Hospital Birmingham between September 2016 and September 2018. The primary outcome was to determine the incidence of UGIB in patients that have undergone OLT with EV that received TEE. 401 patients were included in the study, of which 320 (80%) received TEE. The incidence of post-operative UGIB in patients that received TEE was 1.6% (5/320) in the entire cohort: 2.7% (4/149) in patients with no evidence of EV and 0.6% (1/171) in patients with EV. UGIB occurred in 1 patient with grade 2 EV and did not occur in patients with grade 1 or 3 EV. The incidence of UGIB in patients that received TEE was not statistically different to patients that did not: 1.6% (5/320) vs. 3.7% (3/81) p = 0.218. In conclusion, in patients that underwent OLT, intra-operative TEE use was associated with low rates of UGIB, even in cohorts with high grade EV. This suggests that TEE is a relatively safe method of haemodynamic monitoring in patients undergoing OLT.

Evaluating Accuracy of Plain Magnetic Resonance Imaging or Arthrogram versus Wrist Arthroscopy in the Diagnosis of Scapholunate Interosseous Ligament Injury.

Introduction Scapholunate interosseous ligament injury (SLIL) is the most common cause of wrist instability and a cause of morbidity in a proportion of patients with wrist injuries. Aim To evaluate the accuracy of plain magnetic resonance imaging (MRI) and MR arthrogram (MRA) in the diagnosis of SLIL injury against the existing gold standard-wrist arthroscopy. Materials and Methods We retrospectively reviewed 108 cases by comparing MRI/MRA reports and their wrist arthroscopy operation notes. Results Overall MRI sensitivity to SLIL injuries was 38.5% (91.0% specificity). When broken down into plain MRI and MRA the results were: plain MRI sensitivity = 19.2% (91.4% specificity) and MRA sensitivity = 57.7% (90.5% specificity). Conclusion Neither MRI nor MRA scanning is sensitive enough compared with the gold standard. Positive predictive value remains too low (62.5 and 88.2%, respectively) to consider bypassing diagnostic arthroscopy and treating surgically. The negative predictive value (60.4 and 63.6%, respectively) is inadequate to confirm exclusion of injury from MRI results alone.

Determinants of COVID-19 Vaccine Acceptance among Dental Professionals: A Multi-Country Survey.

PURPOSE: This study sought to investigate the acceptance rate and associated factors of COVID-19 vaccines among dentists and dental students in seven countries. MATERIAL AND METHODS: A structured questionnaire prepared and guided by the report of the SAGE Working Group on Vaccine Hesitancy was distributed among groups of dentists and dental students in seven countries across four continents. RESULTS: A total of 1527 subjects (850 dentists and 677 dental students) participated in this survey. Although 72.5% of the respondents reported their intention to accept COVID-19 vaccines (dentists: 74.4%, dental students: 70.2%), there was a significant difference in agreement between dentists/dental students across countries; generally, respondents in upper-middle-, and high-income countries (UM-HICs) showed significantly higher acceptance rates compared to those in low- and lower-middle income countries (L-LMICs). Potential predictors of higher vaccine acceptance included being a dentist, being free of comorbidity, being well-informed about COVID-19 vaccines, having better knowledge about COVID-19 complications, having anxiety about COVID-19 infection, having no concerns about the side effects of the produced vaccines and being a resident of an UM-HIC. CONCLUSION: The results of our survey indicate a relatively good acceptance rate of COVID-19 among the surveyed dentists and dental students. However, dentists and dental students in L-LMICs showed significantly lower vaccine acceptance rates and trust in COVID-19 vaccines compared to their counterparts in UM-HICs. Our results provide important information to policymakers, highlighting the need for implementation of country-specific vaccine promotion strategies, with special focus on L-LMICs.

Assessment of Foodborne Bacterial Pathogens in Buffalo Raw Milk Using Polymerase Chain Reaction Based Assay.

Milk is a putrescible commodity that is extremely prone to microbial contamination. Primarily, milk and dairy products are believed to be easily contaminated by pathogenic microorganisms, including Listeria monocytogenes, Salmonella spp., and Staphylococcus aureus. The microbiological quality of raw milk and dairy products regarding foodborne pathogens is of paramount importance due to concern of human health. In this study 400 buffalo raw milk samples were screened for assessing the prevalence of L. monocytogenes, Salmonella spp., and S. aureus. This study implemented uniplex-polymerase chain reaction (u-PCR) and multiplex-polymerase chain reaction (m-PCR) assays for the fast simultaneous detection of these pathogens comparing to the conventional culturing methods. Raw milk samples were found contaminated with the prevalence of 2.2%, 4.0%, and 14.2% for L. monocytogenes, Salmonella spp., and S. aureus, respectively. These pathogens were detected with the optimized polymerase chain reaction assays after 6 h of enrichment. u-PCR and m-PCR demonstrated the limit of detection as 104, 102, and 10 cells/mL after 6, 12, 18, and 24 h for each culture of the pathogens. A high sensitivity (10 colony-forming unit [CFU]/mL) of the m-PCR protocol was noted. The developed protocol is a cost-effective and rapid method for the simultaneous detection of pathogens associated with raw milk and dairy industries.

Silicon Nanoparticle-Induced Regulation of Carbohydrate Metabolism, Photosynthesis, and ROS Homeostasis in Solanum lycopersicum Subjected to Salinity Stress.

Agricultural crops are facing major restraints with the rapid augmentation of global warming, salt being a major factor affecting productivity. Tomato (Solanum lycopersicum) plant has immense nutritional significance; however, it can be negatively influenced by salinity stress. Nanoparticles (NPs) have excellent properties, due to which these particles are used in agriculture to enhance various growth parameters even in the presence of abiotic stresses. The objective of this study was to investigate the effects of silicon NPs (Si-NPs) through root dipping and foliar spray on tomato in the presence/absence of salt stress. Plant root and leaf were used for the measurements of morphological, physiological, and biochemical parameters treated with Si-NPs under salt stress. At 45 days after sowing, the activity of antioxidant enzymes, photosynthesis, mineral concentration, chlorophyll index, and growth attributes of tomato plants were measured. The developmental processes of tomato plants were severely slowed down by salt stress upto 35.8% (shoot dry mass), 44.3% (root dry mass), 51% (shoot length), and 62% (root length), but this reduction was mitigated by the treatment of Si-NPs. Application of Si-NPs significantly increased the growth attributes (height and dry weight), mineral content [magnesium (Mg), potassium (K), copper (Cu), iron (Fe), manganese (Mn), zinc (Zn)], photosynthesis [net photosynthetic rate (P N), stomatal conductance (gs), transpiration rate (E), internal CO2 concentration (Ci)], and activity of antioxidative enzymes including superoxide dismutase and catalase in salt stress. Foliar application of Si-NPs in tomato plants appears to be more effective over root dipping and alleviates the salt stress by increasing the plant's antioxidant enzyme activity.