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 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.

A rare case of huge frontoethmoidal encephalocele projecting through mouth, with cleft palate.

Frontoethmoidal encephalocele represents protrusion of meninges and brain in a sac through a defect in the anterior skull base, mostly as swelling over the nose. Rarely it is associated with facial dysmorphism and palatal cleft. There are various perioperative concerns like airway difficulties, leaking from the swelling causing fluid and electrolyte disturbances, risk of infection, compression of the swelling causing a rise in intracranial pressure, bleeding, hypothermia, etc., In neonates, these challenges rise exponentially because of the inherent difficulties in dealing with this group of patients. Frontoethmoidal encephaloceles are common in low socioeconomic strata and are often missed in the antenatal period. We are reporting a rare case of frontoethmoidal encephalocele, with a huge swelling protruding through the cleft palate and occupying more than 50% of the face and oral cavity, making mask ventilation impossible.

A Prospective Study to Evaluate the Role of Combined Diagnostic Laparoscopy and Hysteroscopy in the Management of Female Infertility.

Introduction Infertility affects approximately 10-15% of couples worldwide. Hysteroscopy and laparoscopy are two newer modalities available for the evaluation of infertility and are complementary rather than mutually exclusive. Each provides useful information that the other may not have and each has its advantages. Materials and methods A total of 75 patients of female infertility (study group) in the age group of 18-40 years from the Outpatient Department (OPD) were recruited. Infertility was defined as one year of unprotected intercourse without pregnancy. Hysteroscopy and laparoscopy were carried out in each patient at the follicular phase of the menstrual cycle. Hysteroscopic findings were compared with laparoscopic findings for uterine and tubal pathology. Hysteroscopy as a procedure was also compared with laparoscopy as a one-step procedure for diagnostic accuracy in investigating a case of female infertility. The data was analyzed by Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 29.0, Armonk, NY). Observations and results In our study, out of a total of 75 cases evaluated for infertility, primary infertility patients were 48 (64%) and secondary infertility patients were 27 (36%). In our study, both tubes were patent on chromopertubation in primary infertility (PI) vs secondary infertility (SI) in 49.33% vs 21.33% of total cases. Both tubes were blocked in PI vs SI in 9.33% vs 8% of total cases. In our study, 20 patients (26.66%) underwent hysteroscopic intervention. Adhesiolysis was the commonest procedure required in seven (9.33%) followed by hysteroscopic cannulation in six (8%). In our study, a total of 30 procedures were performed in 20 patients during laparoscopy. The most common procedure required was ovarian drilling in 22.66% (17/75) followed by surgery for endometriosis in 10.66% (8/75). Adhesiolysis was required in 5/75 (6.66%). Both laparoscopy and hysteroscopy were normal in 44/75 cases for uterine findings. Conclusion Thus, hysterolaparoscopy as "one step" had various advantages in our study, more accuracy in the findings and therapeutic intervention in the same sitting reducing the cost. The addition of hysteroscopy to laparoscopy is invaluable in the infertility workup as it has a definite edge in the detection of uterine pathology, as well as being therapeutic at the same time. More accuracy in the diagnostic findings and therapeutic intervention in the same setting will help in reducing the time and cost of treatment.

Comparison of procedural time with two different ultrasound-guided approaches for dorsalis pedis artery cannulation in adult patients: A randomized trial.

BACKGROUND: In adult patients, there has never been an evaluation of short-axis out-of-plane versus long-axis in-plane approaches of ultrasound-guided dorsalis pedis artery cannulation. This research was conducted to compare these two techniques to cannulate the dorsal pedis artery. METHODS: In this trial, 128 adult patients undergoing surgery and necessitating arterial cannulation were examined. Dorsalis pedis artery cannulation was performed utilizing an ultrasound by long-axis in-plane approach (group L) or short-axis out-of-plane (group S) techniques. RESULTS: Group S had a higher first attempt success rate than group L (46.9% vs 28.6%, p = 0.039). The S group had a lower assessment time than the L group (11.48 ± 3.07 vs 19.68 ± 2.79 s; p = 0.000). Cannulation time was higher in the S group (18.91 ± 1.92 s) compared to the L group (12.48 ± 1.61 s; p = 0.000). Nevertheless, the total procedure time was comparable between the L group and the S group (32.16 ± 2.95 vs 30.42 ± 4.07 s; p = 0.107). CONCLUSIONS: In adults, both views of ultrasonography can be used to guide DPA cannulation. The cannulation time for the DPA in L group was less than the S group, whereas the assessment time was less in S group. The total procedure time, however, was similar between both the groups.

Imidazolium-Based Ionic Liquid-Assisted Silver Nanoparticles and Their Antibacterial Activity: Experimental and Density Functional Theory Studies.

The exclusive properties of ionic liquids (ILs) offer various opportunities to develop advanced materials with appreciable therapeutic applications. Imidazolium-based ILs have been frequently used as reaction media and stabilizers for the development and surface functionalization of noble metal nanoparticles (NPs). This study reports the citrate-mediated reduction of silver ions in three different ILs, that is, 1-ethyl-3-methylimidazolium methyl sulfate ([EMIM][MS]), 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIM][OTf]), and 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([BMIM][TFSI]). The resulting Ag-ILs NPs were characterized using many analytical techniques, including UV-visible spectroscopy, dynamic light scattering (DLS), scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction (XRD). DLS and XRD characterization revealed the negatively charged Ag-[EMIM][MS] NPs, Ag-[BMIM][OTf] NPs, and Ag-[BMIM][TFSI] NPs with mean hydrodynamic sizes of 278, 316, and 279 nm, respectively, and a face-centered cubic structure. These hybrid nanomaterials were subjected to in vitro antibacterial screening against three bacterial strains. The Ag-[BMIM][OTf] NPs exhibited significant activities against Escherichia coli, Staphylococcus aureus, and Enterobacter cloacae. The lowest inhibition concentration of 62.5 µg/mL was recorded against E. coli using Ag-[EMIM][MS] and Ag-[BMIM][OTf] NPs. Further, the density functional theory calculations carried out on the computed Ag-ILs in the gas phase and water showed relatively stable systems. Ag-[BMIM][TFSI] exhibited the lowest Gibbs free energy change of -34.41 kcal/mol. The value of the global electrophilicity index (ω = 0.1865 eV) for the Ag-[BMIM][OTf] correlated with its good antibacterial activity.

Comparison of Caudal Dexmedetomidine and Midazolam as an Adjuvant to Ropivacaine for Postoperative Pain Relief in Children Undergoing Infra-Umbilical Surgeries: A Randomized Controlled Trial.

BACKGROUND: We explored the analgesic efficacy of two non-opioid adjuvants (midazolam and dexmedetomidine) with ropivacaine in children undergoing infraumbilical surgeries. METHODS: In this parallel group randomized controlled trial, 135 children aged between 2 and 8 years were recruited. Children were randomly allocated to one of three groups: RD received 1 mL/kg of ropivacaine (0.2%) with dexmedetomidine 1 µg/kg, RM received 1 mL/kg of ropivacaine (0.2%) with midazolam 30 µg/kg, and R received 1 mL/kg of ropivacaine (0.2%) with 1 mL normal saline. The primary outcome of the present study was to determine the duration of postoperative analgesia. Secondary outcomes were assessing postoperative face, leg, activity, cry, consolability (FLACC) pain score, rescue analgesics, hemodynamics, sedation scores, and adverse effects. RESULTS: The analgesia duration was significantly prolonged in the RD and RM group (600.0 [480.0-720.0] minutes and 600.0 [480.0-720.0] minutes, respectively) compared to the R group 360.0 (300.0-480.0) minutes (P < 0.001). The FLACC score was comparatively higher in the R group compared to the RD and RM groups postoperatively. Time for the first rescue analgesia was more prolonged in RD and RM groups when compared with the R group. Postoperative sedation was higher in the RM group up to 120 minutes postoperatively compared to the RD and R groups. CONCLUSION: The combination of dexmedetomidine or midazolam with local anesthetics significantly increases the analgesia duration while minimizing adverse effects.

Antimicrobial, antibiofilm, docking, DFT and molecular dynamics studies on click-derived isatin-thiosemicarbazone-1,2,3-triazoles.

In an effort to develop new antimicrobial and antibiofilm agents, we have designed and synthesized a novel class of isatin-thiosemicarbazone-1,2,3-triazoles through the CuAAC approach. All the synthesized hybrids were characterized by several spectral techniques such as FTIR, 1H NMR, 13C NMR, 2D NMR and HRMS. All the derivatives were evaluated for their antimicrobial and antibiofilm efficacy towards various microbial species. Triazole hybrid 8d exhibited the highest efficacy towards E. coli (MIC = 0.0067 µmol/mL) and S. aureus (MIC = 0.0067 µmol/mL), whereas, compounds 8b, 8c, 8d, 8e, 9a and terminal alkyne (10) significantly inhibited biofilm formation against S. aureus, B. subtilis and E. coli. To find out the structure-activity relationship and binding interactions of synthesized hybrids with enzymes 1KZN and 5TZ1, molecular docking for all the synthesized hybrids was carried out. DFT calculations for all hybrids and the molecular dynamics studies for compounds 9e and 9f were also performed to support the biological behavior of these hybrids.Communicated by Ramaswamy H. Sarma.

Click synthesis, antimicrobial, DNA photocleavage and computational studies of oxindole-tethered 1H-1,2,3-triazoles.

Aim: To obtain new hybrids derived from isatin and triazole. Materials & methods: A series of oxindole-1-H-1,2,3-triazole hybrids (4a-l) were synthesized from 3-sulfenylated N-propargylated oxindoles and organic azides employing Cu(I)-catalyzed azide-alkyne cycloaddition. These compounds were evaluated in vitro for antimicrobial activity by the standard serial dilution method and DNA photocleavage activity. Results: Antimicrobial assay revealed that compounds 4l and 4f exhibited promising efficacy against Candida albicans and Rhizopus oryzae, respectively, with a minimum inhibitory concentration value of 0.0008 µmol/mL. Compounds 4h and 4k completely degraded plasmid DNA. Further molecular docking of compounds with 1KZN (4j and 4k) and 5TZ1 (4h and 4l) revealed good binding interactions. Conclusion: Results of the current research can help in the development of new antimicrobial agents with high efficacy.

Cavity architecture based modulation of ligand binding tunnels in plant START domains.

The Steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain represents an evolutionarily conserved superfamily of lipid transfer proteins widely distributed across the tree of life. Despite significant expansion in plants, knowledge about this domain remains inadequate in plants. In this work, we explore the role of cavity architectural modulations in START protein evolution and functional diversity. We use deep-learning approaches to generate plant START domain models, followed by surface accessibility studies and a comprehensive structural investigation of the rice START family. We validate 28 rice START domain models, delineate binding cavities, measure pocket volumes, and compare these with mammalian counterparts to understand evolution of binding preferences. Overall, plant START domains retain the ancestral α/ß helix-grip signature, but we find subtle variation in cavity architectures, resulting in significantly smaller ligand-binding tunnels in the plant kingdom. We identify cavity lining residues (CLRs) responsible for reduction in ancestral tunnel space, and these appear to be class specific, and unique to plants, providing a mechanism for the observed shift in domain function. For instance, mammalian cavity lining residues A135, G181 and A192 have evolved to larger CLRs across the plant kingdom, contributing to smaller sizes, minimal STARTs being the largest, while members of type-IV HD-Zip family show almost complete obliteration of lipid binding cavities, consistent with their present-day DNA binding functions. In summary, this work quantifies plant START structural & functional divergence, bridging current knowledge gaps.

In silico study on antidiabetic and antioxidant activity of bioactive compounds in Ficus carica L.

Hyperglycemia is one of the diagnostic issues in diabetes mellitus and is considered as a complex metabolic condition. It has been one of the most prevalent illnesses of the twenty-first century and still rising at an alarming rate across the globe and expected to impact 693 million individuals by 2045. Therefore, it is mandatory to develop more effective and safer treatments to manage diabetes. One of the ways to manage hyperglycemia is through inhibiting carbohydrate digestion and thereby lowering the glucose formation in the human body. The enzyme salivary amylase and pancreatic amylase is responsible for cleaving α-1,4-glucoside bond. Amylase inhibitors can lower blood glucose in diabetics by slowing digestion. Ficus carica is commonly known for its medicinal properties due to its various phytochemicals. In the present study, 10 phytochemicals present in F. carica compounds named, ß-carotene, lutein, cyanidin-3-glucoside, gallic acid, luteolin, catechin, kaempferol, vanillic acid, peonidin-3-glucoside, and quercetin hydrate were taken to study their inhibition potential against pancreatic amylase and salivary amylase through molecular docking and molecular dynamics simulations. Further, density functional theory calculations are used to investigate the delocalization of electron density on the molecule as well as study ADME properties of the molecules take. A QSAR model has been developed using the binding energy obtained using molecular docking and thermodynamic parameters from DFT calculations.Communicated by Ramaswamy H. Sarma.

Comparison of ultrasound-guided dynamic needle tip positioning and acoustic shadowing technique with palpation technique for radial arterial cannulation by experienced clinicians: A randomized controlled trial.

BACKGROUND: Radial artery cannulation is usually done for monitoring invasive blood pressure during intraoperative period. The dynamic needle tip positioning approach allows continuous visualization of the needle tip during ultrasound-guided cannulation. The acoustic shadowing technique, using two lines on the ultrasound probe, might be used to facilitate radial artery puncture. We aimed to compare these two ultrasound-guided techniques of radial artery cannulation with the traditional palpation method in adult patients. METHODS: In this trial, 180 adult patients requiring arterial cannulation were randomized into three groups (Traditional palpation (TP), Dynamic needle tip positioning (DNTP), and acoustic shadow technique (AST)). All cannulations were carried out by experienced anesthetists. Data was analyzed for the success rate of arterial cannulation in the first attempt, total number of attempts in 5 min, time taken to cannulate, number of cannulas used, and complications related to the procedure. RESULTS: The first attempt success rates among TP, DNTP, and AST were 66.7%, 66.7%, and 71.7%, respectively (p = 0.794). The median time taken for cannulation was 60.5 (37.0, 129.5) s, 71.0 (50.0, 170.0) s, and 108.0 (58.0, 181.0) s, respectively (p = 0.066) and the median number of cannulation attempts was 1, in all the three groups (p = 0.684). There was also no difference in the total number of cannulas used, the overall success rate of cannulation, and complications related to the procedure in the three groups. CONCLUSION: The TP, DNTP, and AST technique for radial artery cannulation had comparable first attempt success rate, the time taken for cannulation, the number of cannulas used, and overall complications. We conclude that radial arterial cannulation by palpation, as well as ultrasound-guided DNTP and AST techniques performed by experienced clinicians in hemodynamically stable adult patients are equally advantageous.

Management of airway obstruction following lidocaine nebulization in a case of tracheal stenosis: case report

Abstract Stenting for lower tracheal stenosis is a tricky situation and for the safe conduct of anesthesia, it is imperative to maintain spontaneous respiration. Airway topicalization is routinely recommended for anticipated difficult airway. We report a case of upper airway obstruction following lidocaine nebulization in a patient to be taken for tracheal stenting for lower tracheal stenosis. We would like to highlight that close monitoring of the patient is advisable during airway topicalization to detect any airway obstruction at the earliest and how fiberoptic intubation can play a pivotal role to secure the airway in an emergency scenario.

Mucous Extractor for Tumor Tissue Sampling in Neurosurgery.

Objective Collection of sample for histopathological analysis is highly important during any surgical procedure. The histopathology report helps determine the diagnosis, prognosis further management, and follow-up plan. The use of a reliable sample collection technique is doubly important in neurosurgical procedures because lesions are often deep-seated and difficult to access. Materials and Methods Conventional techniques of sample collection, such as use of tumor-grasping forceps and collection of material from the ultrasonic aspirator device suffer from limitations of access and unreliability. We propose a novel technique of sample collection using readily available mucous aspirator device. Results This device is economical, sterile, and disposable. It can be used even in low-resource settings because it is easily available. It can also be connected to suction cannula and the negative pressure settings can be adjusted as required. Conclusion The use of this device for neurosurgical procedures has been tried in the transcranial and transnasal neurosurgical procedures and found to be effective. The sample collected in the canister of the mucous aspirator can be directly sent to the laboratory for histopathological analysis.

Comparison of the effects of intravenous lignocaine and ketamine on postoperative pain after lower abdominal surgeries under general anaesthesia.

Background and Aims: As a component of multimodal analgesia, the administration of systemic lignocaine and ketamine is a well-known technique. This study was designed to compare the effect of intravenous lignocaine and ketamine on postoperative pain in the patients undergoing lower abdominal surgeries under general anaesthesia. Methods: Total 126 patients, aged between18 to 60 years, American Society of Anesthesiologists (ASA) physical status I and II, were randomly allocated into lignocaine (Group L), ketamine (Group K), or control (Group C). We assessed the mean fentanyl consumption 24 hours postoperatively, visual analogue score (VAS), time to first rescue analgesia, haemodynamic parameters, postoperative complications patient satisfaction score, and duration of hospital stay among three groups. Results: The mean fentanyl consumption in first 24 hours postoperatively was higher in group C (194.65 ± 48.48 µg) compared to group L (139.69 ± 46.96 µg) and group K (161.37 ± 46.31 µg) (P < 0.05). The VAS pain scores were lower in group L and group K compared to group C (P < 0.05). The time to first rescue analgesia was prolonged in group L and group K as compared to group C (P < 0.05). The patients were more satisfied in group L and group K as compared to group C (P < 0.05). Conclusion: The mean fentanyl consumption in 24 hours postoperatively and pain intensity were less with intraoperative lignocaine and ketamine infusion with improved patient satisfaction in patients undergoing lower abdominal surgery under general anaesthesia.

Comparison of Binaural Tone Music vs Patient Choice Music vs Midazolam on Perioperative Anxiety in Patients Posted for Surgery Under Spinal Anaesthesia: a Randomized Control Trial.

Background Perioperative anxiety affects patients' hemodynamics by increasing stress levels, leading to delayed recovery. In this study, we compared the anxiety-reducing effect of music (patient choice and binaural tone music) with midazolam for perioperative anxiolysis in patients undergoing surgery under spinal anaesthesia. Methods After obtaining institutional ethical clearance and informed written consent, a total of 225 patients classified as ASA grades 1 and 2 (American Society of Anesthesiologists) were enrolled and randomised into three groups of 75 patients per group. Group A patients received research-selected music (binaural tone) via noise-cancelling headphones, Group B received intravenous midazolam (minimum of 1 mg to 2 mg maximum) as per clinical judgement, and Group C participants provided patient-preferred music via noise-cancelling headphones. The patient's perioperative anxiety was assessed using a visual analogue anxiety scale at regular time intervals. Results Anxiety scores were significantly reduced in the patient's choice music group (Group C) and binaural tone music group (Group A) as compared to the midazolam group (Group B). Postoperative pain scores were statistically significantly lower in Group C, followed by Group A and Group B. On comparing patient satisfaction scores, using numerical rating scores, 96% of patients in Group C achieved excellent scores with a p-value of 0.007. Conclusion Binaural tone music and patient choice music can be suitable alternatives to pharmacological therapies for perioperative anxiolysis.

Comparison of novel anteroposterior short-axis in-plane technique with conventional short-axis out-of-plane technique for ultrasound-guided internal jugular vein cannulation: A randomized-controlled trial.

OBJECTIVES: Various ultrasound (US)-guided probe positioning and needle procedures have been described in the literature for cannulation of the internal jugular vein (IJV). In the present study, we compared the conventional short-axis out-of-plane (SAX-OOP) method with a novel anteroposterior short-axis in-plane (APSAX-IP) technique for IJV cannulation under US guidance. The APSAX-IP method of IJV cannulation has not been compared to other IJV cannulation techniques. METHODS: A total of 104 patients above 18-year-old were randomly allocated to one of two groups - APSAX-IP or SAX-OOP and evaluated for US-guided IJV cannulation in either the operating room or critical care unit. The primary outcome of this research was the access time for IJV cannulation using both approaches. The secondary outcomes were the number of attempts of needle insertion, success rate, and complications of IJV cannulation. RESULTS: The access time for IJV cannulation was 13.0 (12.0-15.0) sec in the APSAX-IP group and 13.0 (12.0-14.0) sec in the SAX-OOP group; P = 0.947. The number of successful 1st attempts was 90.91%, and the 2nd attempts were 9.09% in the APSAX-IP group and 85.19% and 14.81% in the SAX-OOP group, respectively. Both techniques did not have any complications. CONCLUSIONS: We conclude that the US-guided APSAX-IP IJV cannulation method has comparable access time to the SAX-OOP technique.