An insight for the inhibition of anxiolytic and anti-convulsant effects in zebrafish using the curcumins via exploring molecular docking and molecular dynamics simulations.

In the contemporary landscape, anxiety and seizures stand as major areas of concern, prompting researchers to explore potential drugs against them. While numerous drugs have shown the potential to treat these two neurological conditions, certain adverse effects emphasize the need for development of safer alternatives. This study seeks to employ an in silico approach to evaluate natural compounds, particularly curcumins, as potential inhibitors of GABA-AT to mitigate anxiety and seizures. The proposed methodology includes generating a compound library, minimizing energy, conducting molecular docking using AutoDock, molecular dynamics simulations using Amber, and MM-GBSA calculations. Remarkably, CMPD50 and CMPD88 exhibited promising binding affinities of - 9.0 kcal/mol and - 9.1 kcal/mol with chains A and C of GABA-AT, respectively. Further, MM-GBSA calculations revealed binding free energies of - 10.88 kcal/mol and - 10.72 kcal/mol in CMPD50 and CMPD88, respectively. ADME analysis showed that these compounds contain drug-likeness properties and might be considered as potential drug candidates. The findings from this study will have practical applications in the field of drug discovery for the development of safer and effective drugs for treatment of anxiety and seizures. Overall, this study will lay the groundwork for providing valuable insights into the potential therapeutic effects of curcumins in alleviating anxiety and seizures, establishing a computational framework for future experimental validation.

An updated review on 1,2,3-/1,2,4-triazoles: synthesis and diverse range of biological potential.

The synthesis of triazoles has attracted a lot of interest in the field of organic chemistry because of its versatile chemical characteristics and possible biological uses. This review offers an extensive overview of the different pathways used in the production of triazoles. A detailed analysis of recent research indicates that triazole compounds have a potential range of pharmacological activities, including the ability to inhibit enzymes, and have antibacterial, anticancer, and antifungal activities. The integration of computational and experimental methods provides a thorough understanding of the structure-activity connection, promoting sensible drug design and optimization. By including triazoles as essential components in drug discovery, researchers can further explore and innovate in the synthesis, biological assessment, and computational studies of triazoles as drugs, exploring the potential therapeutic significance of triazoles.

Molecular Docking and Molecular Dynamics Simulations of Synthesized Thiazole-Isatin-1,2,3-triazole Hybrids as Promising Inhibitors for DNA Gyrase and 14α-Sterol Demethylase.

In the present work, a new class of thiazole-isatin-1,2,3-triazole hybrids (5a-5p) and precursor alkyne hybrids (6a-6d) has been reported with their in-silico studies. After structural identifications using different spectroscopic technique such as FTIR, 1H and 13C NMR and HRMS, the synthesized hybrids were explored for their biological potential using molecular docking and molecular dynamics calculations. Molecular docking results revealed that compound 5j showed maximum binding energy i.e. -10.3 and -12.6 kcal/mol against antibacterial and antifungal enzymes; 1KZN (E. coli) and 5TZ1 (C. albicans), respectively.Top of FormBottom of Form Molecular dynamics simulations for the best molecule (100 ns) followed by PBSA calculations  suggested a stable complex of 5j with 5TZ1 with binding energy of -118.760 kJ/mol as compared to 1KZN (-94.593 kJ/mol). The mean RMSD values for the 1KZN with 5j complex remained approximately 0.175 nm throughout all the time span of 100 ns in the production stages and is in the acceptable range.  Whereas, 5TZ1 with 5j complex, RMSD values exhibited variability within the range of 0.15 to 0.25 nm.

An Updated Review on Functionalized Graphene as Sensitive Materials in Sensing of Pesticides.

Numerous chemical pesticides were employed for a long time to manage pests, but their uncontrolled application harmed the health and the environment. Accurately quantifying pesticide residues is essential for risk evaluation and regulatory purposes. Numerous analytical methods have been developed and utilized to achieve sensitive and specific detection of pesticides in intricate sampl es like water, soil, food, and air. Electrochemical sensors based on amperometry, potentiometry, or impedance spectroscopy offer portable, rapid, and sensitive detection suitable for on-site analysis. This study examines the potential of electrochemical sensors for the accurate evaluation of various effects of pesticides. Emphasizing the use of Graphene (GR), Graphene Oxide (GO), Reduced Graphene Oxide (rGO), and Graphdiyne composites, the study highlights their enhanced performance in pesticide sensing by stating the account of many actual sensors that have been made for specific pesticides. Computational studies provide valuable insights into the adsorption kinetics, binding energies, and electronic properties of pesticide-graphene complexes, guiding the design and optimization of graphene-based sensors with improved performance. Furthermore, the discussion extends to the emerging field of biopesticides. While the GR/GO/rGO based sensors hold immense future prospects, and their existing limitations have also been discussed, which need to be solved with future research.

Analytic and In Silico Methods to Understand the Interactions between Dinotefuran and Haemoglobin.

This work lies in the growing concern over the potential impacts of pesticides on human health and the environment. Pesticides are extensively used to protect crops and control pests, but their interaction with essential biomolecules like haemoglobin (Hb) remains poorly understood. Spectrofluorometric, electrochemical, and in silico investigations have been chosen as potential methods to delve into this issue, as they offer valuable insights into the molecular-level interactions between pesticides and haemoglobin. The research aims to address the gaps in knowledge and contribute to developing safer and more sustainable pesticide practices. The interaction was studied by spectroscopic techniques (UV-Visible & Fluorescence), in silico studies (molecular docking & molecular dynamics simulations) and electrochemical techniques (cyclic voltammetry and tafel). The studies showed effective binding of dinotefuran with the Hb which will cause toxicity to human. The formation of a stable molecular complex between ofloxacin and Haemoglobin was shown via molecular docking and the binding energy was found to be -5.37 kcal/mol. Further, molecular dynamics simulations provide an insight for the stability of the complex (Hb-dinotefuran) for a span of 250 ns with a binding free energy of -53.627 kJ/mol. Further, cyclic voltammetry and tafel studies show the interaction of dinotefuran with Hb effectively.

Comparison of neuraxial acoustic target window of the spine among rider sitting, cross leg, hamstring stretch, and classical sitting position: An observational study.

Background and Aims: To compare ultra-sonographic dimensions of acoustic target window of the spine in the participants at four different sitting positions namely cross leg sitting (CLP), hamstring stretch (HSP), classical sitting (CSP) and riders sitting position (RSP). The primary objective of this study was to measure the neuraxial acoustic target window (defined as interlaminar distance between L3-L4 lamina). The secondary objective was to compare ultra-sonographic measurements of the depth of ligamentum flavum from the skin, and to compare the diameter of intrathecal space and comfort score in the four different sitting positions. Material and Methods: This study is a prospective observational study. Eighty participants were included and positioned in four different sitting positions to perform an ultra-sonographic scan and measure various parameters of the acoustic neuraxial window. The interlaminar distance, the distance of skin from the ligamentum flavum, and the diameter of the spinal canal or intrathecal space was measured in the L3-L4 intervertebral space in different positions. Results: The mean value of interlaminar distance among four sitting positions was ranging from 1.40 cm to 1.44 cm (P value 0.725.) The distance of ligamentum flavum from skin and diameter of intrathecal space was also comparable in all the groups. The comfort score in CSP was significantly better when compared to other groups with a median score of 4 (P value < 0.001). Conclusions: There is no statistically significant difference in interlaminar distance in various sitting positions. All four positions are equally effective and can be used as an alternative to spinal/epidural intervention, but the CSP came out to be the most comfortable and more emphasis should be given to the comfort as it increases the chance of success rate of the procedure.

Synthesis, antimicrobial, antibiofilm and computational studies of isatin-semicarbazone tethered 1,2,3-triazoles.

In present era, heterocyclic compounds containing two or three nitrogen atoms play a vital role in drug discovery. In this context, a new class of isatin-semicarbazone tethered 1,2,3-triazole hybrids was synthesized via Cu(I)-mediated azide alkyne cycloaddition reaction. Structural characteristics of the newly derived compounds were identified by various spectral techniques like FTIR, 1H NMR, 13C NMR, HRMS and single crystal X-ray crystallography. Synthesized derivatives were also screened for in vitro antimicrobial and antibiofilm activity against different microbial species. Triazole hybrid 7e showed significant efficacy towards E. coli having MIC of 0.0063 µmol/mL, whereas 6a, 6b, 7a, 7c, 7e, and 7f showed highest percentage of biofilm inhibition against P. aeruginosa. Bioassay results suggested that these triazole hybrids could act as biomaterial for antimicrobial and antibiofilm applications and may constitute a new promising class of antimicrobial and antibiofilm agents. These results were further supported by in silico docking, DFT calculations and ADME studies.

Perioperative anesthesia challenges and outcomes of patients with Rhino-Orbito-Cerebral Mucormycosis during the second wave of COVID-19 pandemic: An observational study.

Background and Aims: A rapid surge in rhino-orbito-cerebral mucormycosis (ROCM) cases was reported during the second wave of COVID, especially in India, needing extensive surgical debridement along with medical management. The present study was planned to observe perioperative anesthesia challenges and outcomes of patients with ROCM during the second wave of the COVID-19 pandemic. The primary objective was to observe intraoperative anesthesia challenges and the secondary objectives were to observe postoperative challenges and outcomes of patients. Material and Methods: This was a single-centered, bidirectional (retrospective and prospective) observational study, conducted at a tertiary care center. We enrolled 218 adult patients scheduled for surgical debridement of ROCM under general anesthesia. Demographics, COVID status, comorbid illness, intraoperative challenges (difficult airway, hemodynamic instability, blood loss), and postoperative outcome (postoperative mechanical ventilation, and mortality rate) were noted. Results: The majority of the patients were males (71%) and had diabetes mellitus (54%). COVID-associated mucormycosis was seen in 67% and 41% of them received steroids. Post-induction hypotension was noted in 20.6% of patients, and 14.2% had intraoperative hypotension out of which 5.5% required vasopressor support. Difficult mask ventilation and difficult intubation were reported in 7.3% and 6.4% of patients, respectively. No significant difference was found among intraoperative challenges when COVID mucormycosis was compared to non-COVID mucormycosis. Postoperative mechanical ventilation and ICU care were required in 41.3%, whereas mortality was seen in 11.5% of patients. The mortality was significantly more (P = 0.041) in patients with COVID mucormycosis (13%) compared to that with non-COVID mucormycosis (4.2%). Conclusion: Diabetic male patients who received steroids during COVID illness are at the highest risk of developing ROCM. Difficult airway and hemodynamic instability, are significant perioperative challenges encountered by anesthesiologists. Postoperative ICU management is crucial for decreasing postoperative morbidity and mortality.

Hunting the main protease of SARS-CoV-2 by plitidepsin: Molecular docking and temperature-dependent molecular dynamics simulations.

COVID-19 has shaken all the countries across the globe and researchers are trying to find promising antiviral to cure the patients suffering from infection and can decrease the death. Even, different nations are using repurposing drugs to cure the symptoms and these repurposing drugs are hydroxychloroquine, remdesivir, and lopinavir, and recently, India has recently given the approval for the 2-deoxy-D-glucose for emergency purpose to cure the patients suffering from the COVID-19. Plitidepsin is a popular molecule and can be used in treatment of myeloma. Plitidepsin was explored by scientists experimentally against the COVID-19 and was given to the patient. It is found to be more a promising repurposing drug against the COVID-19 than the remdesivir. Therefore, there is a need to understand the interaction of plitidepsin with the main protease of SARS-CoV-2. Molecular docking of the plitidepsin against Mpro of SARS-CoV-2 was performed and the binding energy was found to be - 137.992 kcal/mol. Furthermore, authors have performed the molecular dynamics simulations of the main protease of SARS-CoV-2 in presence of plitidepsin at 300 and 325 K. It was found that the plitidepsin binds effectively with the main protease of SARS-CoV-2 at 300 K.

Intravenous cannula for percutaneous rescue needle gastrostomy in a neonate with tracheoesophageal fistula-A case report.

Tracheoesophageal fistula offers concrete difficulties for anesthesiologists, which comprise associated congenital anomalies and more importantly the problems concerning ventilation and oxygenation. Among all the types of tracheoesophageal fistula, ventilatory problems are frequently encountered with type C fistula. Effective ventilation can be a challenge in such cases where the endotracheal tube invariably ventilates the fistula causing stomach inflation and respiratory compromise. Thorough knowledge and experience are of utmost importance when it comes to the successful airway management and better survival of neonates undergoing tracheoesophageal fistula repair. We report a case of a 3-day-old neonate, diagnosed with type C tracheoesophageal fistula and esophageal atresia posted for thoracoscopic repair. We want to highlight our experience of percutaneous needle gastrostomy done using an intravenous cannula, as a rescue measure for stomach decompression, to manage life-threatening hypoxia.

L-amino-acids as immunity booster against COVID-19: DFT, molecular docking and MD simulations.

There is great interest to explore the importance of different amino-acids on immunity of human. Immunity helps to protect us from the pathogenic infections. The amino-acids are being use to give energy and is also used as an important basic molecule for the making of cells, protecting cell and others. Still, a little information is known for their importance in the inhibition of main protease of SARS-CoV-2. As known, tens of billions of humans are infected due to the SARS-CoV-2 and about a million of deaths are reported due to it or COVID. As of now, no promising drug is available in the market to cure the patients from this infection. Even, the medicines beings used for the partial cure may have some side effects. Therefore, the focus is to explore the natural amino-acids against the Mpro of SARS-CoV-2 as using of amino-acids is not toxic to humans. In the present work, authors have studied the amino-acids using DFT calculations and then they were explored for their promising role in the inhibition of main protease of SARS-CoV-2 using molecular docking and molecular dynamics simulations. Out of the 20 amino-acids, arginine found to best against the main protease of SARS-CoV-2 using the molecular docking and the binding energy was -0.94 kcal/ mol. Further, molecular dynamics simulations for the main protease of SARS-CoV-2 with and without arginine was performed using the Amber and different thermodynamic parameters like ΔH and TΔS to get ΔG, comes out to be 2.74 kcal/mol. It is expected that arginine can boost the immunity.

Psychosocial impact and coping strategies of frontline healthcare workers in Western Rajasthan during COVID-19 pandemic.

Background and Aims: Coronavirus disease-2019 (COVID-19) pandemic-related stress is an important but under-rated issue needing attention. Stress and causative factors vary between the regions and individuals depending on the availability of resources, socio-cultural differences, and individual perceptions. We aimed to study the psychosocial impact and coping strategies among the healthcare workers (HCWs) in Western Rajasthan during COVID-19 pandemic. Material and Methods: This questionnaire-based observational study, consisting of 59 questions in 6 sections, was conducted to identify stress, causative factors, coping strategies, and experiences of HCWs working in personal protective equipment (PPE). Chi-square test was used to compare the responses between different subgroups. Results: Majority of the HCWs felt responsible for treating COVID-19 patients (98.8%), but also felt that it was affecting their safety (81.4%). On subgroup analysis, doctors were found to be more stressed than nursing staff (P = 0.004). Major stressors included concerns about infecting family members and lack of specific treatment for COVID-19 (87.5%). Family support was found to be a major stress-relieving factor (97.3%). Most HCWs suggested that comfortable quarantine stay, adequate supply of PPE, and equipments would help in reducing stress. Conclusion: Frontline HCWs in Western Rajasthan were under significant stress during COVID-19 pandemic. We found that stress-causing factors and coping strategies varied between different subgroups based on profession, gender, and age. We recommend conducting such studies in different regions of the world to develop relevant and region-specific strategies to help HCWs cope with stress more efficiently, thereby, strengthening the healthcare system to deal with future pandemics.

Gastric emptying time of two different quantities of clear fluids in children: A double-blinded randomized controlled study.

BACKGROUND: Perioperative pulmonary aspiration risk increases with increased preoperative gastric volume; hence traditionally, healthy children are kept fasted overnight before surgery. Current guidelines recommend 2-h clear fluids fasting prior to anesthesia. However, emerging evidence favors allowing 3 ml/kg clear fluids up to 1-h before anesthesia. We compared the gastric volume and gastric emptying time after ingestion of 3 ml/kg and 5 ml/kg of clear fluids. METHODS: The present study enrolled 44 children, aged between 6 and 14 years. On the day of surgery, baseline gastric volume was estimated using ultrasound and patients were randomly allocated into two groups of equal number, that is, Group 3 and Group 5 (patients received 3 ml/kg and 5 ml/kg 5% Dextrose respectively). Repeated gastric ultrasound was performed at every 5 min until the gastric volume reached baseline levels. The primary objective of the study was to compare gastric emptying time. Secondary objectives included comparison of antral cross-sectional area and gastric volume. RESULTS: The demographic profile, preoperative fasting duration for clear fluids, and baseline gastric volume were comparable between groups. In both groups, compared to baseline the antral cross-sectional area and gastric volume increased significantly following fluid ingestion and then decreased exponentially to reach baseline within 1-h. The median (IQR) (range) gastric emptying time (minutes) [35.0 (28.8, 40.0) (20.0-45.0) in group 3 and 40.0 (28.8, 45.0) (20.0-50.0) in group 5] and emptying half-time (minutes) [17.0 (15.7, 21.5) (14.4-24.0) in group 3 and 18.6 (16.0, 22.0) (15.1-23.8) in group 5] were comparable [median difference -5 (95% CI -7.8 to 2.1) and -1.5 (95% CI -2.3 to 1.0), respectively] (p = .16 and p = .44, respectively). CONCLUSION: As the gastric volume returned to baseline within 1-h even after ingesting 5 ml/kg clear fluids, the preoperative fasting time can be reduced to 1-h and healthy children undergoing elective procedure can be safely allowed to drink up to 5 ml/kg clear fluids.

Effect of dexmedetomidine on attenuation of hemodynamic response to intubation, skin incision, and sternotomy in coronary artery bypass graft patients: A double-blind randomized control trial.

BACKGROUND AND AIMS: Coronary artery bypass grafting (CABG) surgery involves various noxious stimuli resulting in stress response, which in turn increases the risk of perioperative myocardial ischemia. The present study was conducted to evaluate the effect of dexmedetomidine on the attenuation of hemodynamic response to intubation, skin incision, and sternotomy in CABG surgery. MATERIAL AND METHODS: Sixty patients were randomized into two groups of 30 each. Group D patients received dexmedetomidine 1 µg/kg as loading dose over 10 min, followed by continuous infusion of 0.5 µg/kg/h. In group P, normal saline was infused as loading and maintenance dose at similar rate. Hemodynamic parameters, total induction dose of thiopentone, and adverse effects were recorded. Statistical analysis was performed using SPSS version 20.0. Chi-square test and ANNOVA test were used and P < 0.05 was considered significant. RESULTS: The percentage increase in heart rate was significantly lesser in group D than group P after intubation (7.04% v/s 15.08%), skin incision (5.91% v/s 10.11%), and sternotomy (5.33% v/s 11.65%). Similarly increase in systolic, diastolic, and mean blood pressure were significantly lesser in group D than group P after intubation, skin incision, and sternotomy. There was a significant reduction of mean total of thiopentone in group D in comparison to group P. (1.16 mg/kg v/s 2.44 mg/kg) (P<0.001). CONCLUSION: Dexmedetomidine resulted in significant attenuation of hemodynamic response to intubation, skin incision, and sternotomy in CABG surgery without significant adverse effects. It also significantly reduced the dose of thiopentone required for induction.

Quality of recovery and analgesia after total abdominal hysterectomy under general anesthesia: A randomized controlled trial of TAP block vs epidural analgesia vs parenteral medications.

BACKGROUND AND AIMS: Parenteral analgesics and epidural analgesia are two standard options to treat postoperative pain after total abdominal hysterectomy (TAH). Fascial plane blocks such as transversus abdominis plane (TAP) block have gained popularity recently. However, effect of these analgesic regimens on quality of postoperative recovery (QoR) has not been studied. Hence we aimed to assess and compare the QoR with three different postoperative analgesic regimens---parenteral analgesia, epidural analgesia, and TAP block in patients undergoing TAH under general anesthesia. MATERIAL AND METHODS: Sixty female patients undergoing TAH were randomized into three groups of 20 each for postoperative analgesia. Epidural group received boluses of 0.125% bupivacaine for 24 h, parenteral group received injection diclofenac and injection tramadol alternately every 6 h for 24 h, and TAP group received bilateral TAP block with 0.25% bupivacaine at end of operation. QoR was assessed postoperatively by 40-item questionnaire-QOR-40 and pain was assessed by numerical rating scale (NRS). RESULTS: QOR-40 score was comparable across the three groups at 24, 48, and 72 h postoperatively. TAP block prolonged the time to first rescue analgesic (P = 0.02) and reduced the total 24-h postoperative morphine consumption by 2.4 (95% CI: 1.0, 3.8) mg (P = 0.002) and 7.8 (95% CI: 6.4, 9.1) mg (P < 0.001) when compared with epidural and parenteral groups, respectively. CONCLUSION: The QoR after abdominal hysterectomy is similar with either intravenous analgesics or epidural analgesia or TAP block when used with rescue analgesia to manage postoperative pain. TAP block provides superior analgesia and reduces 24-h morphine consumption when compared with parenteral and epidural analgesia.

Postoperative nausea and vomiting in neurosurgical patients: Current concepts and management.

Postoperative nausea and vomiting (PONV) is a significant complication for neurosurgical patients. PONV affects patient satisfaction, prolongs hospital stay, and increases the economic burden and morbidity. In addition to these problems, there are certain consequences of PONV specific to the craniotomy, including increased intracranial pressure and increased risk of tumor bed hematoma formation. Expert panels have suggested that, if the consequences of PONV are deleterious to the patients, then prophylaxis should be instituted. This article describes the pathophysiology, risk factors, prevention, and management of PONV in neurosurgery patients as per the recent guidelines.