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Background The normal ability to distinguish two points from one is known as the two-point discriminative (2PD) sense. This forms an extremely important assessment in patient with injuries to the nerves distributed to the upper extremity.

Objective The aim of this study is to create clinical normative data for ulnar length in the pediatric population and to demonstrate the usefulness of such data.

Abstract Cyprinid herpesvirus is a causative agent of a destructive disease in common and koi carp (Cyprinus carpio), which leads to substantial global financial losses in aquaculture industries. Among the strains of C. herpesvirus, C. herpesvirus 1 (CyHV-1) and C. herpesvirus 3 (CyHV-3) are known as highly pathogenic to carp fishes in Europe, Asia, and Africa. To date, no effective vaccine has been developed to combat these viruses. This study aimed to develop unique multi-epitope subunit vaccines targeting the CyHV-1 and CyHV-3 using a reverse vaccinology approach. The study began with a comprehensive literature review to identify the most critical proteins, which were then subjected to in silico analyses to predict highly antigenic epitopes. These analyses involved assessing antigenicity, transmembrane topology screening, allergenecity, toxicity, and molecular docking approaches. We constructed two multi-epitope-based vaccines incorporating a suitable adjuvant and appropriate linkers. It revealed that both the vaccines are non-toxic and immunogenic. The tertiary structures of the vaccine proteins were generated, refined, and validated to ensure their suitability. The binding affinity between the vaccine constructs and TLR3 and TLR5 receptors were assessed by molecular docking studies. Molecular dynamics simulations indicated that vaccine construct V1 exhibited greater stability with both TLR3 and TLR5 based on RMSD analysis. Hydrogen bond analysis revealed a stronger binding affinity between the vaccine constructs and TLR5 compared to TLR3. Furthermore, MM-PBSA analysis suggested that both vaccine constructs exhibited a better affinity for TLR5. Considering all aspects, the results suggest that in silico development of CyHV vaccines incorporating multiple epitopes holds promise for management of diseases caused by CyHV-1 and CyHV-3. However, further in vivo trials are highly recommended to validate the efficacies of these vaccines.

In the previous study, the synthesis and characterization of 4-(3-fluorophenyl)-3-thiosemicarbazide and benzaldehyde derivatives based thiosemicarbazone ligands and their Co(II), Ni(II), Cu(II), Zn(II) complexes were carried out to evaluate their malarial and oxidant and inflammatory inhibition abilities, demonstrating that these compounds have robust efficacy for these ailments. In the present research, to find out a combating agent against breast cancer, tuberculosis, bacterial and fungal ailments, the compounds were tested through MTT, microplate alamar blue and serial dilution protocols. ADMET and DFT investigation were analyzed against highly bioactive compounds (2, 7–10) to give a new insight about compound's reactivity, stability and drug likeness properties. Furthermore, activity results shows that the ligand (2) and its complexes demonstrate greater efficacy compared to ligand (1) and its complexes. The Cu(II) (9) and Zn(II) (10) complexes were observed as highly efficient for breast cancer (MCF-7 cell line), TB (H37Rv strain), bacterial and fungal ailments in comparison of standard drugs with 0.029 ± 0.001 μM IC50 value for (9) in anticancer activity and 0.0034 ± 0.0017 μmol/mL MIC value for (10) in anti-tuberculosis activity. In the molecular docking investigation, the various kind of binding interactions and lowest binding affinity of (9) (against 4RJ3 (−10.0 kcal/mol), 2VCJ (−7.9 kcal/mol)) and (10) (−7.8 and −8.3 kcal/mol for 5V3Y and 3PTY protein) support their bioactivity. This research highlights the pharmaceutical importance of transition metal complexes having thiosemicarbazones, presenting a significant approach for the discovery of potent anti-infectious agent.

The Hindu Kush Himalaya (HKH) is one of the most flood-prone regions in the world, yet heavy cloud cover and limited in situ observations have hampered efforts to monitor the impact of heavy rainfall, flooding, and inundation during severe weather events. This paper introduces HydroSAR, a Sentinel-1 SAR-based hazard monitoring service which was co-developed with in-region partners to provide year-round, low-latency weather hazard information across the HKH. This paper describes the end user-focused concept and overall design of the HydroSAR service. It introduces the main processing algorithms behind HydroSAR’s broad product portfolio, which includes qualitative visual layers as well as quantitative products measuring the surface water extent and water depth. We summarize the cloud-based implementation of the developed service, which provides the capability to scale automatically with the event size. A performance assessment of our quantitative algorithms is described, demonstrating the capabilities to map the flood extent and water depth with an accuracy of >90% and

Flooding poses a significant threat as a prevalent natural disaster. To mitigate its impact, identifying flood-prone areas through susceptibility mapping is essential for effective flood risk management. This study conducted flood susceptibility mapping (FSM) in Chandrapur district, Maharashtra, India, using geographic information system (GIS)-based frequency ratio (FR) and Shannon’s entropy index (SEI) models. Seven flood-contributing factors were considered, and historical flood data were utilized for model training and testing. Model performance was evaluated using the area under the curve (AUC) metric. The AUC values of 0.982 for the SEI model and 0.966 for the FR model in the test dataset underscore the robust performance of both models. The results revealed that 5.4% and 8.1% (FR model) and 3.8% and 7.6% (SEI model) of the study area face very high and high risks of flooding, respectively. Comparative analysis indicated the superiority of the SEI model. The key limitations of the models are discussed. This study attempted to simplify the process for the easy and straightforward implementation of FR and SEI statistical flood susceptibility models along with key insights into the flood vulnerability of the study region.

Abstract While aqueous organic redox flow batteries (RFBs) represent potential solutions to large-scale grid storage, their electrolytes suffer from short lifetimes due to rapid degradation. We show how an understanding of these degradation processes can be used to dramatically improve performance, as illustrated here via a detailed study of the redox-active biomolecule, flavin mononucleotide (FMN), a molecule readily derived from vitamin B2. Via in-situ nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) we identify FMN hydrolysis products and show that these give rise to the additional plateau seen during charging of an FMN-cyanoferrate battery. The redox reactions of the hydrolysis product are not reversible, but we demonstrate that capacity is still retained even after substantial hydrolysis, albeit with reduced voltaic efficiency, FMN acting as a redox mediator. Critically, we demonstrate that degradation is mitigated and battery efficiency is substantially improved by lowering the pH to 11. Furthermore, the addition of cheap electrolyte salts to tune the pH results in a dramatic increase in solubility (above 1 M), this systematic improvement of the flavin-based system bringing RFBs one step closer to commercial viability.

Abstract Human Respiratory Syncytial Virus (RSV) is one of the leading causes of lower respiratory tract infections (LRTI), responsible for infecting people from all age groups—a majority of which comprises infants and children. Primarily, severe RSV infections are accountable for multitudes of deaths worldwide, predominantly of children, every year. Despite several efforts to develop a vaccine against RSV as a potential countermeasure, there has been no approved or licensed vaccine available yet, to control the RSV infection effectively. Therefore, through the utilization of immunoinformatics tools, a computational approach was taken in this study, to design a multi-epitope polyvalent vaccine against two major antigenic subtypes of RSV, RSV-A and RSV-B. Potential predictions of the T-cell and B-cell epitopes were followed by extensive tests of antigenicity, allergenicity, toxicity, conservancy, homology to human proteome, transmembrane topology, and cytokine-inducing ability. The peptide vaccine was modeled, refined, and validated. Molecular docking analysis with specific Toll-like receptors (TLRs) revealed excellent interactions with suitable global binding energies. Additionally, molecular dynamics (MD) simulation ensured the stability of the docking interactions between the vaccine and TLRs. Mechanistic approaches to imitate and predict the potential immune response generated by the administration of vaccines were determined through immune simulations. Subsequent mass production of the vaccine peptide was evaluated; however, there remains a necessity for further in vitro and in vivo experiments to validate its efficacy against RSV infections.

Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and treatment strategies are needed. This study utilized a reverse vaccinology approach to retrieve conserved epitopes for monkeypox virus and construct a vaccine that could provide cross-protection against related viruses with similar antigenic properties. The selected virulent proteins of monkeypox virus, MPXVgp165, and Virion core protein P4a, were subjected to epitope mapping for vaccine construction. Two vaccines were constructed using selected T cell epitopes and B cell epitopes with PADRE and human beta-defensins adjuvants conjugated in the vaccine sequence. Both constructs were found to be highly antigenic, non-allergenic, nontoxic, and soluble, suggesting their potential to generate an adequate immune response and be safe for humans. Vaccine construct 1 was selected for molecular dynamic simulation studies. The simulation studies revealed that the TLR8-vaccine complex was more stable than the TLR3-vaccine complex. The lower RMSD and RMSF values of the TLR8 bound vaccine compared to the TLR3 bound vaccine suggested better stability and consistency of hydrogen bonds. The Rg values of the vaccine chain bound to TLR8 indicated overall stability, whereas the vaccine chain bound to TLR3 showed deviations throughout the simulation. These results suggest that the constructed vaccine could be a potential preventive measure against monkeypox and related viruses however, further experimental validation is required to confirm these findings.

Rice blast disease, caused by the fungus Magnaporthe oryzae, poses a severe threat to rice production, particularly in Asia where rice is a staple food. Concerns over fungicide resistance and environmental impact have sparked interest in exploring natural fungicides as potential alternatives. This study aimed to identify highly potent natural fungicides against M. oryzae to combat rice blast disease, using advanced molecular dynamics techniques. Four key proteins (CATALASE PEROXIDASES 2, HYBRID PKS-NRPS SYNTHETASE TAS1, MANGANESE LIPOXYGENASE, and PRE-MRNA-SPLICING FACTOR CEF1) involved in M. oryzae's infection process were identified. A list of 30 plant metabolites with documented antifungal properties was compiled for evaluation as potential fungicides. Molecular docking studies revealed that 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin exhibited superior binding affinities compared to reference fungicides (Azoxystrobin and Tricyclazole). High throughput molecular dynamics simulations were performed, analyzing parameters like RMSD, RMSF, Rg, SASA, hydrogen bonds, contact analysis, Gibbs free energy, and cluster analysis. The results revealed stable interactions between the selected metabolites and the target proteins, involving important hydrogen bonds and contacts. The SwissADME server analysis indicated that the metabolites possess fungicide properties, making them effective and safe fungicides with low toxicity to the environment and living beings. Additionally, bioactivity assays confirmed their biological activity as nuclear receptor ligands and enzyme inhibitors. Overall, this study offers valuable insights into potential natural fungicides for combating rice blast disease, with 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin standing out as promising and environmentally friendly alternatives to conventional fungicides. These findings have significant implications for developing crop protection strategies and enhancing global food security, particularly in rice-dependent regions.

Type 2 diabetes is a major health concern contributing to most of diabetic cases worldwide. Mangiferin and its congeners are known for their diverse pharmacological properties. This study sought to investigate the inhibitory property of naturally occurring mangiferin congeners on sodium-glucose co-transporter 2 protein (SGLT-2) using comprehensive computational methods. The naturally occurring mangiferin congeners were subjected to molecular docking, molecular dynamics (MDs) simulation (100 ns), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy, density functional theory calculations (B3LYP 6-31G basis set), and ADMET approaches to identify potential SGLT-2 inhibitor. The molecular docking studies revealed neomangiferin (−9.0 kcal/mol) as the hit molecule compared with dapagliflozin (−8.3 kcal/mol). Root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) plots from the MD simulations established that neomangiferin stabilizes SGLT-2 better than the dapagliflozin, a standard drug. The MM-PBSA binding free energy calculations showed that neomangiferin (−26.05 kcal/mol) elicited better binding affinity than dapagliflozin (−17.42 kcal/mol). The electronic studies showed that neomangiferin (3.48 eV) elicited high electrophilicity index compared with mangiferin (3.31 eV) and dapagliflozin (2.11 eV). Also, the ADMET properties showed that the hit molecule is safe when administered to diabetic subjects. The current in silico studies suggest that neomangiferin could emerge as a promising lead molecule as a SGLT-2 inhibitor.

Introduction: Allogenic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for hematologic malignancies. Nowadays, usually, haploidentical stem cell transplant is performed across the ABO blood group barrier; however, the effect of ABO incompatibility on haploidentical hematopoietic stem-cell transplantation is still uncertain. Methodology: Retrospective analysis of data of patients who underwent haploidentical hematopoietic stem-cell transplantation at our hospital was performed. The patient cohort was classified in to two arms: ABO compatible and ABO-incompatible haploidentical stem cell transplantation. ABO-incompatible was further categorized as major mismatch, minor mismatch and bidirectional mismatch. The average follow-up period was 6 months posttransplant for which the following parameters were studied: (a) engraftment kinetics for white blood cell (WBC) and platelets, (b) graft rejection, (c) overall graft survival, (d) graft-versus-host disease (GVHD), and (e) clinical variation in outcome for patients receiving peripheral blood stem cell/bone marrow harvest (BMH) as the source of stem cells. Results: The median age of recipients for both ABO compatible and ABO incompatible was 24 years and most of them were parent-offspring transplants. A total of 39 patients underwent haploidentical stem cell transplantation during the study period. Our cohort consisted of 23 ABO-compatible patients and 17 ABO incompatible patients. Out of these 17, 6 were major mismatch, 11 were minor mismatch and none were bidirectional mismatch. Of these 39 patients, 82% (32/39) engrafted within the normal expected time frame. The average days to WBC and platelet engraftment in these subgroups were noted to be as follows: Major – 12 and 18 days, compatible – 9 and 17 days, and minor – 10 and 17 days, respectively. Graft failure was observed in 20% (8/39) of patients, of which 4 patients had undergone ABO-compatible transplants while 4 patients had undergone minor ABO incompatible transplants. In this study, we observed that major ABO incompatibility had severe risk of GVHD (17%) compared to compatible (39%) and minor (27%) blood group mismatch. The overall survival rate in 6 months was equal (70%) in both arms. 5/39 patients, i.e., 12% received BMH as the source of stem cells, of these 80% are alive. Conclusion: Haploidentical transplants done in patients with ABO-incompatible donors had outcomes comparable to the ABO-compatible group. The risk of severe GVHD did not increased in the ABO mismatch group. Recipient of BMH had a marginally better graft survival.

Candida auris is a serious health concern of the current world that possesses a serious global health threat and is emerging at a high rate. Available antifungal drugs are failing to combat this pathogen as they are growing resistant to those drugs and some strains have already shown resistance to all three available antifungal drugs in the market. Hence, finding alternative therapies is essential for saving lives from this enemy. To make the development of new treatments easier, we conducted some in silico study of this pathogen to discover possible targets for drug design and also recommended some possible metabolites to test in vivo circumstances. The complete proteome of the representative strain was retrieved, and the duplicate, non-essential, human homologous, non-metabolic, and druggable proteins were then eliminated. As a result, out of a total of 5441 C. auris proteins, we were able to isolate three proteins (XP 028890156.1, XP 028891672.1, and XP 028891858.1) that are crucial for the pathogen's survival as well as host-non-homolog, metabolic, and unrelated proteins to the human microbiome. Their subcellular locations and interactions with a large number of proteins (10 proteins) further point to them being good candidates for therapeutic targets. Following in silico docking of 29 putative antifungals of plant origin against the three proteins we chose, Caledonixanthone E, Viniferin, Glaucine, and Jatrorrhizine were discovered to be the most effective means of inhibiting those proteins since they displayed higher binding affinities (ranging from −28.97 kcal/mol to −51.99 kcal/mol) than the control fluconazole (which ranged between −28.84 kcal/mol and −41.15 kcal/mol). According to the results of MD simulations and MM-PBSA calculations, Viniferin and Caledonixanthone E are the most effective ligands for the proteins XP 028890156.1, XP 028891672.1, and XP 028891858.1. Furthermore, they were predicted to be safe and also showed proper ADME properties.

Emotion recognition using Electroencephalography (EEG) is a convenient and reliable technique. EEG based emotion detection study can find its application in various fields such as defense, aerospace, medical, and many more. This analysis helps to understand the emotional state of mind. There are two approaches to study EEG analysis known as subject dependent and independent. In this paper, Modified Differential Entropy (MD-DE) feature extractor is proposed to detect nonlinearity and non-Gaussianity of the EEG signal. The paper adopts both approaches by conducting an EEG analysis on own generated database named as ‘IDEA- Intellect Database for Emotion Analysis’ on 14 subjects. In this work, bidirectional long short-term memory (BiLSTM) network and multilayer perceptron (MLP) network is used to classify emotional state of mind of the subjects. On the ‘IDEA’ database, subject dependent average accuracy achieved is in the order of 98.5% and for subject independent, 88.57%. To reaffirm the improvement in accuracy level, a new approach of Modified Differential Entropy and BiLSTM network is applied on the openly available SEED and DEAP database as well. This experiment established that the average accuracy of emotion detection using MD-DE and BiLSTM network is better than the established methods.

Background and Objectives: PON1 is a multi-functional antioxidant protein that hydrolyzes a variety of endogenous and exogenous substrates in the human system. Growing evidence suggests that the Leu55Met and Gln192Arg substitutions alter PON1 activity and are linked with a variety of oxidative-stress-related diseases. Materials and Methods: We implemented structural modeling and molecular dynamics (MD) simulation along with essential dynamics of PON1 and molecular docking with their endogenous (n = 4) and exogenous (n = 6) substrates to gain insights into conformational changes and binding affinity in order to characterize the specific functional ramifications of PON1 variants. Results: The Leu55Met variation had a higher root mean square deviation (0.249 nm) than the wild type (0.216 nm) and Gln192Arg (0.202 nm), implying increased protein flexibility. Furthermore, the essential dynamics analysis confirms the structural change in PON1 with Leu55Met vs. Gln192Arg and wild type. Additionally, PON1 with Leu55Met causes local conformational alterations at the substrate binding site, leading to changes in binding affinity with their substrates. Conclusions: Our findings highlight the structural consequences of the variants, which would increase understanding of the role of PON1 in the pathogenesis of oxidative-stress-related diseases, as well as the management of endogenous and exogenous chemicals in the treatment of diseases.

Introduction: While donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been implicated in graft rejection in solid organ transplantation, their role in hematopoietic stem-cell transplantation (HSCT) remains unclear. Aim: The aim of this study is to study the role of DSA for proper donor selection and its effect in the setting of allogeneic HSCT. Methodology: HLA A, B, C, DRB1, and DQB1 high-resolution typing, and DSA cross match (XM) of patients (n = 73) and their prospective donors (n = 74) were assessed. A case–control study was designed retrospectively to evaluate the effect of pre- existing DSAs on engraftment. Thirty-five cases with 5/10 HLA alleles mismatches and 38 cases with full HLA matched, these two controls were selected for comparison. These were matched for disease, graft type, conditioning regimen, age, gender, blood group, and sensitizing events. DSAs were tested with solid-phase assay (Luminex 100/200 platform). Results: DSAs were detected in six of 35 patients (17%); however, donors selected for transplantation were all negative for DSA crossmatch. These six patients who underwent haploidentical (HI) transplants had antibodies against Class I and II. One patient carried antibodies against both classes. A patient who experienced primary graft failure had a second HI transplant. No other known factors that could negatively influence engraftment were associated with the development of graft failure in this patient. Conclusions: DSAs are not associated with graft rejection in patients undergoing HI stem-cell transplantation. Anti-HLA sensitization should be evaluated routinely in HSCT with HLA mismatched donors for a better outcome.

Purpose To study the demography, incidence, symptoms, histopathology, postoperative complications and recovery in operated patients of spinal tumor. Overview of Literature Primary spinal cord tumors (SCT) are an uncommon entity. According to their location, spinal tumors are conveniently classified as extradural (ED) and intradural (ID), although some can be both inside and outside the dura. ID tumors can be intradural extramedullary (IDEM) or intramedullary SCT (IMSCT). Methods This is a retrospective study of 122 patients with spinal tumors who were surgically treated at the department of neurosurgery from 2014 to 2019 over a period of 5 years. Study Design This is a retrospective study. Results Out of 122 patients, there were 19 patients with ED tumor, 73 had IDEM, and 30 had IMSCT. As many as 73 patients were males and the rest of the 49 patients were females. Mean age at time of surgery was 40.79 years. The thoracic region of spinal canal was most frequently involved (64; 52.4%). The common clinical symptom was motor weakness (90 cases; 73.77%). Majority of the patients had symptoms for duration of 6 to 12 months. Schwannomas were the most common tumor among IDEM and extradural location. Ependymomas were the most common type in IMSCT. We observed significant improvement in most of our cases. Four patients deteriorated at 3 months follow- up. Conclusions There was a higher male:female ratio for all spinal cord tumors except meningiomas. There was also a higher proportion of nerve sheath tumors, and a lower proportion of meningiomas and neuroepithelial tumors. These results are similar to other studies from Asian countries.

Background: Nowadays, brand-name drugs are becoming an out-of-pocket expense which comprises 80% of total health-care expenditures. However, generic drugs are less expensive than brand-name drugs with the same therapeutic effect, but many doctors hold negative views of generics and resist prescribing. This study was designed to assess the knowledge, attitude, and practice of doctors toward generic medicines. Methods: This was a questionnaire-based cross-sectional study conducted in a multispecialty private hospital. The study participants were doctors who were practising in a hospital during the study period (January 2017 to July 2017). The questionnaire comprises 35 questions related to demographics, knowledge, attitude, and practice evaluation of generic medicines. Descriptive statistics was applied to represent participant characteristics and response rates. Results: A total of 86 questionnaires were distributed to the doctors and the response rate was 37%. The majority of doctors who participated in this survey perceived that generic medicine is effective, safe, and has same active component, dose, and bioequivalent as the brand medicines. Majority of the doctors (72%) believe that generic drugs were manufactured by poor techniques. However, more than three-quarter of doctors (78%) routinely prescribed generic drugs. Conclusion: Most of the doctors had an honest angle about the efficacy and safety of generic medicine. However, a high proportion of physicians believe that the generic drugs are of poorer quality. To have a better understanding of the generic drug, the doctor must be well informed about the generics products during their academic career that will significantly impact health-care budgets.

Human T-lymphotropic virus (HTLV), a group of retroviruses belonging to the oncovirus family, has long been associated with various inflammatory and immunosuppressive disorders. At present, there is no approved vaccine capable of effectively combating all the highly pathogenic strains of HTLV that makes this group of viruses a potential threat to human health. To combat the devastating impact of any potential future outbreak caused by this virus group, our study employed a reverse vaccinology approach to design a novel polyvalent vaccine targeting the highly virulent subtypes of HTLV. Moreover, we comprehensively analyzed the molecular interactions between the designed vaccine and corresponding Toll-like receptors (TLRs), providing valuable insights for future research on preventing and managing HTLV-related diseases and any possible outbreaks. The vaccine was designed by focusing on the envelope glycoprotein gp62, a crucial protein involved in the infectious process and immune mechanisms of HTLV inside the human body. Epitope mapping identified T cell and B cell epitopes with low binding energies, ensuring their immunogenicity and safety. Linkers and adjuvants were incorporated to enhance the vaccine's stability, antigenicity, and immunogenicity. Initially, two vaccine constructs were formulated, and among them, vaccine construct-2 exhibited superior solubility and structural stability. Molecular docking analyses also revealed strong binding affinity between the vaccine construct-2 and both targeted TLR2 and TLR4. Molecular dynamics simulations demonstrated enhanced stability, compactness, and consistent hydrogen bonding within TLR-vaccine complexes, suggesting a strong binding affinity. The stability of the complexes was further corroborated by contact, free energy, structure, and MM-PBSA analyses. Consequently, our research proposes a vaccine targeting multiple HTLV subtypes, offering valuable insights into the molecular interactions between the vaccine and TLRs. These findings should contribute to developing effective preventive and treatment approaches against HTLV-related diseases and preventing possible outbreaks. However, future research should focus on in-depth validation through experimental studies to confirm the interactions identified in silico and to evaluate the vaccine's efficacy in relevant animal models and, eventually, in clinical trials.

ABSTRACT Epstein-Barr virus (EBV) is a lymphotropic virus responsible for numerous epithelial and lymphoid cell malignancies, including gastric carcinoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma, and Burkitt lymphoma. Hundreds of thousands of people worldwide get infected with this virus, and in most cases, this viral infection leads to cancer. Although researchers are trying to develop potential vaccines and drug therapeutics, there is still no effective vaccine to combat this virus. In this study, the immunoinformatics approach was utilized to develop a potential multiepitope subunit vaccine against the two most common subtypes of EBV, targeting three of their virulent envelope glycoproteins. Eleven cytotoxic T lymphocyte (CTL) epitopes, 11 helper T lymphocyte (HTL) epitopes, and 10 B-cell lymphocyte (BCL) epitopes were predicted to be antigenic, nonallergenic, nontoxic, and fully conserved among the two subtypes, and nonhuman homologs were used for constructing the vaccine after much analysis. Later, further validation experiments, including molecular docking with different immune receptors (e.g., Toll-like receptors [TLRs]), molecular dynamics simulation analyses (including root means square deviation [RMSD], root mean square fluctuation [RMSF], radius of gyration [Rg], principal-component analysis [PCA], dynamic cross-correlation [DCC], definition of the secondary structure of proteins [DSSP], and Molecular Mechanics Poisson-Boltzmann Surface Area [MM-PBSA]), and immune simulation analyses generated promising results, ensuring the safe and stable response of the vaccine with specific immune receptors after potential administration within the human body. The vaccine’s high binding affinity with TLRs was revealed in the docking study, and a very stable interaction throughout the simulation proved the potential high efficacy of the proposed vaccine. Further, in silico cloning was also conducted to design an efficient mass production strategy for future bulk industrial vaccine production. IMPORTANCE Epstein-Barr virus (EBV) vaccines have been developing for over 30 years, but polyphyletic and therapeutic vaccines have failed to get licensed. Our vaccine surpasses the limitations of many such vaccines and remains very promising, which is crucial because the infection rate is higher than most viral infections, affecting a whopping 90% of the adult population. One of the major identifications covers a holistic analysis of populations worldwide, giving us crucial information about its effectiveness for everyone’s unique immunological system. We targeted three glycoproteins that enhance the virulence of the virus to design an epitope-based polyvalent vaccine against two different strains of EBV, type 1 and 2. Our methodology in this study is nonconventional yet swift to show effective results while designing vaccines.

The human ABCB1 (P-glycoprotein, Pgp) protein is an active exporter expressed in the plasma membrane of cells forming biological barriers. In accordance with its broad substrate spectrum and tissue expression pattern, it affects the pharmacokinetics of numerous chemotherapeutic drugs and it is involved in unwanted drug–drug interactions leading to side effects or toxicities. When expressed in tumor tissues, it contributes to the development of chemotherapy resistance in malignancies. Therefore, the understanding of the molecular details of the ligand–ABCB1 interactions is of crucial importance. In a previous study, we found that quercetin (QUR) hampers both the transport and ATPase activity of ABCB1, while cyandin-3O-sophroside (C3S) stimulates the ATPase activity and causes only a weak inhibition of substrate transport. In the current study, when QUR and C3S were applied together, both a stronger ATPase inhibition and a robust decrease in substrate transport were observed, supporting their synergistic ABCB1 inhibitory effect. Similar to cyclosporine A, a potent ABCB1 inhibitor, co-treatment with QUR and C3S shifted the conformational equilibrium to the “inward-facing” conformer of ABCB1, as it was detected by the conformation-selective UIC2 mAb. To gain deeper insight into the molecular details of ligand–ABCB1 interactions, molecular docking experiments and MD simulations were also carried out. Our in silico studies support that QUR and C3S can bind simultaneously to ABCB1. The most favourable ligand–ABCB1 interaction is obtained when C3S binds to the central substrate binding site and QUR occupies the “access tunnel”. Our results also highlight that the strong ABCB1 inhibitory effect of the combined treatment with QUR and C3S may be exploited in chemotherapy protocols for the treatment of multidrug-resistant tumors or for improving drug delivery through pharmacological barriers.

Inflammatory bowel disease, comprising Crohn’s disease (CD) and ulcerative colitis (UC), is often debilitating. The disease etiology is multifactorial, involving genetic susceptibility, microbial dysregulation, abnormal immune activation, and environmental factors. Currently, available drug therapies are associated with adverse effects when used long-term. Therefore, the search for new drug candidates to treat IBD is imperative. The peroxisome proliferator-activated receptor-γ (PPARγ) is highly expressed in the colon. PPARγ plays a vital role in regulating colonic inflammation. 1,8-cineole, also known as eucalyptol, is a monoterpene oxide present in various aromatic plants which possess potent anti-inflammatory activity. Molecular docking and dynamics studies revealed that 1,8-cineole binds to PPARγ and if it were an agonist, that would explain the anti-inflammatory effects of 1,8-cineole. Therefore, we investigated the role of 1,8-cineole in colonic inflammation, using both in vivo and in vitro experimental approaches. Dextran sodium sulfate (DSS)-induced colitis was used as the in vivo model, and tumor necrosis factor-α (TNFα)-stimulated HT-29 cells as the in vitro model. 1,8-cineole treatment significantly decreased the inflammatory response in DSS-induced colitis mice. 1,8-cineole treatment also increased nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into the nucleus to induce potent antioxidant effects. 1,8-cineole also increased colonic PPARγ protein expression. Similarly, 1,8-cineole decreased proinflammatory chemokine production and increased PPARγ protein expression in TNFα-stimulated HT-29 cells. 1,8-cineole also increased PPARγ promoter activity time-dependently. Because of its potent anti-inflammatory effects, 1,8-cineole may be valuable in treating IBD.

Background: Apomorphine is an option for continuous dopaminergic therapy in Parkinson's disease (PD). However, its effects in varied populations are limited due to its availability. Objective: To assess the efficacy and outcomes of apomorphine in Indian patients. Materials and Methods: Retrospective analysis of PD patients who underwent apomorphine response test (ART), along with the subset, who went on to apomorphine pumps. Results: Twenty-nine confirmed PD patients underwent ART and all PD patients showed good clinical response. 19 subjects developed adverse events which included: nausea (n-15, 51.7%), vomiting (n-10, 34.4%), sleepiness (n-08; 27.5%), yawning (n-07, 24.1%), postural hypotension (n-03, 10.3%), dizziness (n-03, 10.3%), and profuse sweating (n-01, 3.4%). Apomorphine pumps were initiated in six subjects, with significant clinical improvement. Adverse events on pump included subcutaneous nodules, nausea, hypersexuality. Two among them subsequently discontinued the pump primarily due to financial constraints. Conclusions: Apomorphine adds up to the armamentarium for treatment of PD patients in India with good clinical responses.

The incidence and prevalence of inflammatory bowel disease (IBD, Crohn’s disease, and ulcerative colitis) are increasing worldwide. The etiology of IBD is multifactorial, including genetic predisposition, dysregulated immune response, microbial dysbiosis, and environmental factors. However, many of the existing therapies are associated with marked side effects. Therefore, the development of new drugs for IBD treatment is an important area of investigation. Here, we investigated the anti-inflammatory effects of α-bisabolol, a naturally occurring monocyclic sesquiterpene alcohol present in many aromatic plants, in colonic inflammation. To address this, we used molecular docking and dynamic studies to understand how α-bisabolol interacts with PPAR-γ, which is highly expressed in the colonic epithelium: in vivo (mice) and in vitro (RAW264.7 macrophages and HT-29 colonic adenocarcinoma cells) models. The molecular docking and dynamic analysis revealed that α-bisabolol interacts with PPAR-γ, a nuclear receptor protein that is highly expressed in the colon epithelium. Treatment with α-bisabolol in DSS-administered mice significantly reduced Disease Activity Index (DAI), myeloperoxidase (MPO) activity, and colonic length and protected the microarchitecture of the colon. α-Bisabolol treatment also reduced the expression of proinflammatory cytokines (IL-6, IL1β, TNF-α, and IL-17A) at the protein and mRNA levels. The expression of COX-2 and iNOS inflammatory mediators were reduced along with tissue nitrite levels. Furthermore, α-bisabolol decreased the phosphorylation of activated mitogen-activated protein kinase (MAPK) signaling and nuclear factor kappa B (NFκB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. However, the PPAR-α and β/δ expression was not altered, indicating α-bisabolol is a specific stimulator of PPAR-γ. α-Bisabolol also increased the PPAR-γ transcription factor expression but not PPAR-α and β/δ in pretreated in LPS-stimulated RAW264.7 macrophages. α-Bisabolol significantly decreased the expression of proinflammatory chemokines (CXCL-1 and IL-8) mRNA in HT-29 cells treated with TNF-α and HT-29 PPAR-γ promoter activity. These results demonstrate that α-bisabolol mitigates colonic inflammation by inhibiting MAPK signaling and stimulating PPAR-γ expression.

Hepatocellular carcinoma (HCC) is the most common malignant condition of the liver that occurs as a result of uncontrolled cellular proliferation after a series of disruptions at cell cycle regulatory checkpoints in the normal cell. Due to the lack of appropriate therapeutics or remedial treatment methods, new treatment strategies against HCC need to be developed. Cyclin dependent kinases (CDKs) are required to control the cell cycle and apoptosis, but their overexpressionis critical in the progression of cancer and is often expressed in HCC. Thus, CDKs are considered a promising class of target-defined therapy for HCC. Milciclib is a potential candidate for HCC which exhibits inhibitory activity against CDK2 leading to cell cycle arrest and apoptosis of tumor cells. Herein, we have halogenated the parent drug milciclib to improve its efficacy against CDK2. The primary structure of milciclib (D) was modified with F, Cl and,CF3 groups. The frontier molecular orbital features, binding affinity, non-bonded interaction and the pharmacokinetic parameters were analyzed for milciclib and its derivatives. We also performed molecular docking and extended molecular dynamics simulation studies to study the binding interactions and binding affinity more closely. Our computational investigation showed the derivatives D-F and D-CF3 have significant chemical reactivity, the best binding affinity, nonbonding interactions, and improved pharmacokinetic properties compared to the parent drug milciclib. Molecular dynamics analysis and MM-PBSA calculations indicated that D-Cl had a slightly more stable conformation and higher binding affinity compared to D-CF3.

The detection of antibodies before transplantation is an important step in assessment of patient immunological risk and exclusion of incompatible donors. Many centers have now implemented donor-specific antibody (DSA) along with complement-dependent cytotoxicity crossmatch (CDC XM) for renal transplant cases. A 34-year-old male with end-stage kidney disease was referred for an ABO-compatible transplant from his mother. The CDC XM done 30 days before transplant was negative. DSA XM was negative for Class I (median fluorescence intensity [MFI] 189) and positive for Class II (MFI 1671). Since CDC and DSA Class I were negative, the nephrologists went ahead with the transplantation. On day 6 posttransplant, serum creatinine showed a rising trend (up to 2.13 mg/dl), and therefore, renal biopsy was done which showed mild acute tubular necrosis with positive C4d staining. DSA XM performed on day 15 posttransplant showed negative Class I (MFI 148) and positive Class II (MFI 9987) confirming antibody-mediated rejection (AMR). The patient was started on steroids, and intravenous immunoglobulin and serial plasma exchanges were performed. Then, DSA Class II levels came down to 1602. DSA levels have been monitored periodically and Class II MFI values have been ranging from 2000 to 4000. The patient is maintained on routine immunosuppression, and a graft is intact with serum creatinine level between 1.7 and 1.8 mg/dl 8 months posttransplant. DSA-isolated Class II positivity in renal transplant recipients correlates strongly with AMR and should be considered clinically significant.

A false-positive complement-dependent cytotoxicity cross-match (CDC XM) has a negative impact in donor selection process obliterating healthy, donor compatible population. A 47-year-old male with chronic kidney disease was planned for ABO-compatible renal transplantation from his sister. CDC and donor-specific antibody (DSA) lysate XM were negative 10 days before transplant. The pretransplant CDC XM showed 40% positivity. DSA lysate XM and HLA antibody screen were negative. Patient's Indirect antiglobulin test (IAT) was positive and anti-M antibody (IgG + IgM) was identified. Therapeutic plasma exchange, intravenous immunoglobulin, and rituximab were used for desensitization. Decrease in positivity of CDC XM and anti-M titer was seen. The transplant was performed successfully. Red cell alloantibody should be considered in differential diagnosis of a positive CDC XM. The utility of DSA lysate XM as a pretransplant monitoring tool is immense in such situations. Institutional policies regarding plan of action in the event of positive CDC XM and negative DSA lysate XM and vice versa should be formed.

Background: Since December 2019, SARS-CoV-2 had been a significant threat globally, which has accounted for about two million deaths. Several types of research are undergoing and have reported the significant role of repurposing existing drugs and natural lead in the treatment of COVID-19. The plant Phyllanthus emblica (Synonym-Emblica officinalis) (Euphorbiaceae) is a rich source of vitamin C, and its use as an antiviral agent has been well established. Purpose: The present study was undertaken to investigate the potency of the several components of Phyllanthus emblica against three protein targets of 2019-nCoV viz. NSP15 endoribonuclease, main protease, and receptor binding domain of prefusion spike protein using molecular docking and dynamics studies. Methods: The docking simulation studies were carried out using Schrödinger maestro 2018-1 MM share version, while dynamics studies were conducted to understand the binding mechanism and the complexes' stability studies. Results: Out of sixty-six tested compounds, Chlorogenic acid, Quercitrin, and Myricetin were most effective in showing the highest binding energy against selected protein targets of SARS-CoV-2. The network pharmacology analysis study confirmed these compounds' role in modulating the immune response, inflammatory cascade, and cytokine storm through different signaling pathways. Conclusion: Current pharmacoinformatic approach shows possible role of Phyllanthus emblica in the treatment and management of COVID-19.

Aim and Objective: The prospective study was conducted to assess the role of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in healing of soft tissue after the surgical extraction of mandibular-impacted third molars. The main objective of the study was to compare clinical parameters and especially the postoperative pain, swelling, interincisal distance, wound dehiscence, dry socket, soft tissue healing, and infection. Materials and Methods: 300 patients having impacted mandibular third molar were included in this study. They were selected on the OPD basis at the Department of Oral and Maxillofacial Surgery. Patients were divided into Group A treated with PRP and Group B treated with PRF. Result and Conclusion: The study indicates faster healing with no untoward reaction on PRP and PRF group. Platelet concentrates especially PRF in extracted third molar socket give excellent enhancement in wound healing with lesser postoperative complication.

Objectives: Endovascular revascularisation is the mainstay of the treatment of lower extremity peripheral arterial disease. Improvement in perfusion after treatment is often quantified by a corresponding increment in ankle or toe brachial indices. These measurements are difficult to obtain in patients with foot wounds, and have to be performed at a separate time and setting after revascularisation. This preliminary study aimed to evaluate the use of parametric colour coding and analysis of time attenuation curves as a real time quantitative measure of perfusion after endovascular revascularisation. Methods: Forty-seven consecutive patients with critical limb ischaemia were retrospectively enrolled and analysed. Parametric colour coding and generation of time attenuation curves in the main pedal vessel was performed for pre- and post-intervention digital subtraction angiograms of each patient. The change in time attenuation curve parameters was compared with the change in ankle or toe brachial indices before and after intervention. Results: Comparing before and after lower extremity endovascular intervention, there were significant changes in the washout parameters derived from the time attenuation curve. The percentage of contrast decay 4 seconds after peak (I4s) demonstrated the strongest correlation (R = .482) with the change in ankle or toe brachial indices. Conclusions: Parametric colour coding and time attenuation curve analysis might be a helpful tool that can provide real time intra-procedural quantitative data on pedal perfusion which can improve clinical outcomes. Keywords: Endovascular, Perfusion, Revascularisation

Flow cytometry-based testing approaches have no longer remained restricted to the research laboratories. With widening of its horizons in the field of diagnostics in oncology and transplantation medicine, the flow cytometer-based testing approach is now relevant to many aspects of the field of transfusion medicine. Two of the most important applications of flow cytometry in transfusion medicine are the enumeration of CD34-positive cells in the peripheral blood and stem cell product and the enumeration of residual white blood cell counts in blood product as a quality control measure. The flow cytometer-based crossmatch for detection of donor-specific anti-human leukocyte antigen antibodies is also gaining popularity in the field of histocompatibility and immunogenetics. The utility of this platform in the field of immunohematology is also increasing and looks promising for clinical decision-making in the near future.

Introduction: The presence of red blood cell (RBC) auto and/or alloantibodies can pose a serious challenge of finding transfusion support for such patients. Aim and Objectives: The aim of this study was to assess the frequency and type of unexpected RBC antibodies in the patient population of a tertiary care super specialty hospital and analyze the transfusion support and its effectiveness in these patients. Methodology: This was a retrospective cross sectional study based on data contained in all blood requests, received over a period of 39 months inclusive of demographic,laboratory and clinical variables. Results: Among the 25,338 patients screened, 122 (0.48%) had alloantibodies and 19 (0.07%) had autoantibodies. Of the 141 patients with atypical antibodies, 109 (77.30%) were female and 32 (22.69%) were male. Antibodies directed against the antigens from various blood group systems were as follows: Rh – 54.5%, MNS – 21.8%, and Lewis – 13.6%. Anti-D (32.8%), Anti-M (16.4%), and Anti-E (10.9%) were the most prevalent. Multiple alloantibodies were seen in 2 (1.41%) cases and autoantibodies coexisting with an alloantibody in 9 (6.38%) cases. Discussion: RBC alloimmunization rate is lower (0.41%) in our hospital in comparison with published reports. Higher alloimmunization in female patients in the age group of 20–40 years mainly associated with a history of pregnancy and comparatively lower rate in males and strongly associated with a history of transfusion in the age group of 40–60 years has been reported in literature. Conclusion: RBC alloimmunization rate (0.55%) in general patients treated in our hospital is lower as compared to other reported rates in our country. The provision of RBC phenotype-matched (Rh and Kell) blood for patients likely to get multiple transfusions right from the beginning may reduce the alloimmunization rates further.

Diabetes mellitus is a life-threatening non-communicable disease that affects all age groups. Despite the increased attention it has received in recent years, the number of diabetic patients has grown exponentially. These increased cases are attributed to essential enzymes involved in blood glucose regulation. In this study, we attempt to reveal the aldose reductase inhibitory potential of xanthones isolated from African medicinal plants. Ensemble docking, molecular dynamics simulation, density functional theory (DFT), and ADMET methods were employed to identify drug candidates as aldose reductase inhibitors. The ensemble docking results identified mangostenone B, bangangxanthone A, smeathxanthone B, mangostenone A, and allanxanthone B as potent inhibitors against the aldose reductase enzyme. Molecular dynamics studies showed the xanthones established better binding mode and affinities against the enzyme. Moreover, the electronic properties of the xanthones explained their good pharmacological potentials. Therefore, our findings suggest that the hit molecules be investigated in vitro and in vivo for drug development against aldose reductase.

Introduction: Aorto-oesophageal fistula is a rare but life threatening cause of upper gastrointestinal haemorrhage. Severity of presentation and complexity of subsequent management depends on the size of the defect on both the aortic side and oesophagus. Report: The patient was a 67 year old Chinese man, who presented initially with a Stanford type A dissection with caudal extension to the right common iliac artery. The patient underwent replacement of the ascending aorta and proximal arch with debranching of the right innominate artery and aortic valve replacement. A follow up computed tomography (CT) aortogram done in the post-operative period showed a stable appearance of the caudal extension of the aortic dissection. The patient was discharged with a plan for future stenting of the thoracic aorta. Three weeks later the patient re-presented with an upper gastrointestinal bleed from an aorto-oesophageal fistula. The patient underwent endovascular stenting of the descending aorta for management of the fistula. Repeat oesophagogastroduodenoscopy showed a small erosion 35 cm from the incisors where the previous bleeding site had been. No further bleeding was seen. Discussion: The patient recovered uneventfully after the procedure. Follow up CT aortogram done at 6 weeks demonstrated thrombosis of the false lumen of the descending thoracic aorta. Aorto-oesophageal fistula related to chronic type B aortic dissection is an extremely rare clinical entity and presents a challenge to the treating surgeon. This case demonstrates that selected cases can be judiciously managed by thoracic endovascular aneurysm repair alone. Keywords: Aorto-oesophageal fistula, Haematemesis, Nipple sign, Thoracic aortic dissection, Thoracic aortic endovascular stenting

Background: The aim of this study was to evaluate the hypoglycemic, hypolipidemic, and anti-inflammatory potentials of ethanolic extract of leaves of Amaranthus paniculatus linn. (EEAP) on alloxan-induced diabetic rats scientifically. Hyperglycemia induces the generation of free radicals which can affect antioxidant defenses, thus leading to the disruption of beta cellular functions, oxidative damage to membranes, leading to the release of C-reactive protein and altered lipid metabolism. Methods: Diabetes was induced by intraperitoneal injection of ice-cold aqueous alloxan monohydrate at the dose of 150 mg/kg body weight. Results: After a daily single oral administration of the EEAP for 28 days starting from the study protocol, the blood glucose, serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), total cholesterol (TC), triglyceride (TG), and C-reactive protein (CRP) levels were assessed. The results obtained from the study administration of daily dose of EEAP significantly reduced the blood glucose, SGPT, SGOT, TC, TG, and CRP in a dose-dependent manner. The results obtained were comparable to those of glibenclamide. The serum levels of TC, TG, and CRP were significantly altered in the diabetic control group, but it was significantly decreased in the extract-treated group and standard glibenclamide-treated group, except at a dose of 100 mg/kg where there was no significant effect on the TG level. The finding obtained suggests that EEAP acts through molecular level, modifying the altered pathways in diabetes and associated complications. Conclusion: The results obtained suggest that EEAP possesses a potential for the management of diabetes and associated complications in experimentally-induced diabetic rats.

Coenzyme Q10 (CoQ10) is a lipid soluble, endogenous antioxidant present at highest levels in the heart followed by the kidney and liver. The reduced CoQ10 ubiquinol is well known for its chemical instability and low bioavailability. The present study was designed to synthesize ubiquinol acetate, which is more stable and biologically active, and further evaluate its safety and genotoxic potential. Synthesized ubiquinol acetate showed better stability than that of ubiquinol at the end of 3 months. In vitro genotoxicity studies (AMES test, in vitro micronucleus and chromosomal aberration) showed ubiquinol acetate as nongenotoxic with no clastogenic or aneugenic effects at high dose of 5000 and 62.5 μg/mL, respectively. In subchronic toxicity study, ubiquinol acetate was administered orally to Sprague Dawley rats at 150, 300, and 600 mg/kg/day for 90 days. No treatment related adverse effects were observed in males at 600 mg/kg/day; however, females showed treatment related increase in AST and ALT with small focal irregular white-yellow spots in liver on gross necropsy examination. Histopathological evaluation revealed hepatocellular necrosis in high dose females which was considered as adverse. Based on the results, the No-Observed-Adverse-Effect Level (NOAEL) of ubiquinol acetate in males and females was determined as 600 and 300 mg/kg/day, respectively.

Visceral leishmaniasis (VL) is a deadly vector-borne disease. Approximately 90% of Indian VL cases occur in Bihar, where the sand fly, Phlebotomus argentipes, is the principal vector. Sand fly control in Bihar consists of indoor residual spraying (IRS), the practice of spraying the inner walls of village dwellings with insecticides. Prior researchers have evaluated success of IRS-control by estimating vector abundance in village houses, but the number of sampling periods (n = 2-3) were minimal, and outdoor-resting P. argentipes were neglected. We describe a large-scale field study, performed in 24 villages within two Bihari districts, during which P. argentipes were collected biweekly over 47-weeks, in cattle enclosures, houses, and outdoors in peri-domestic vegetation. The objectives of this study were to provide updated P. argentipes ecological field data, and determine if program-initiated IRS-treatment had led to noticeable differences in vector abundance.P. argentipes (n = 126,901) relative abundance was greatest during the summer months (June-August) when minimum temperatures were highest. P. argentipes were most frequently collected from cattle enclosures (~46% total; ~56% blood fed). Many sand flies were found to have taken blood from multiple sources, with ~81% having blood fed on humans and ~60% blood feeding on bovines. Nonparametric statistical tests were determined most appropriate for evaluating IRS-treatment. Differences in P. argentipes abundance in houses, cattle enclosures and vegetation were detected between IRS-treated and untreated villages in only ~9% of evaluation periods occurring during the peak period of human-vector exposure (June-August) and in ~8% of the total observations. No significant differences were detected between the numbers of P. argentipes collected in vegetation close to the experimental villages.The results of this study provide updated data regarding P. argentipes seasonal abundance, spatial distribution, and host preferances, and suggest vector abundance has not significantly declined in IRS-treated villages. We suggest that IRS be supplemented with vector control strategies targeting exophagic, exophilic P. argentipes, and that disease surveillance be accompanied by rigorous vector population monitoring.

Adenomatoid odontogenic tumor (AOT) is a slowly growing benign tumor of the oral cavity. It accounts of 3-7% of all odontogenic tumors. It is seen to occur commonly in the anterior maxilla. The tumor is usually associated with an impacted tooth with maxillary canine being the most common tooth. AOT is seen in a younger group, especially below 20 years with a female preponderance. AOT occurs in two main variants: Central or intraosseous which is more common and second is peripheral which is rare. Radiologically, it represents as a radiolucent lesion with radiopaque foci usually an impacted or a supernumerary tooth. With a close clinical and radiographic resemblance to dentigerous cyst correct diagnosis and treatment is necessary. AOT being benign in nature requires a conservative management with enucleation. This is a case report of a 13-year-old girl with an AOT occurring in the anterior maxillary region.

Objective: To analyze the surgical outcome and safety of posterior quadrant disconnection in medically refractory epilepsy arising from the posterior head region from a level IV tertiary care center over a period of three years. Materials and Methods: Seven consecutive patients who underwent posterior quadrant disconnection for refractory epilepsy were analyzed. Results: We analyzed the data of seven (n = 7) consecutive posterior quadrant epilepsy patients who underwent posterior quadrant disconnection with a mean age of 8.5 years over the last three years of which 4 were male and 3 females. All patients underwent extensive pre-surgical evaluation including detailed history, examination, prolonged video EEG recordings, neuropsychological testing, MRI brain, DTI, PET scan (n = 6), fMRI (n = 4), WADA test (n = 1) and invasive recording (n = 1), Of seven patients four had left sided pathology and three had right sided pathology. All patients except one underwent pure disconnection and one underwent partial resection. Conclusion: Posterior quadrant disconnection is effective surgical procedure for medically refractory epilepsy arising from the posterior quadrant in carefully selected patients without morbidity or functional disability across various age groups especially in children. In our series, all seven patient had good seizure outcome and none had functional disabilities.