Assessing the gas sensing capability of undoped and doped aluminum nitride nanotubes.

CONTEXT: CO2 and CO gas sensors are very important to recognize the insulation situation of electrical tools. ToCO explore the application of noble metal doped of aluminum nitride nanotubes for gas sensors, DFT computations according to the first principal theory were applied to study sensitivity, adsorption attributes, and electronic manner. In this investigation, platinum-doped aluminum nitride nanotubes were offered for the first time to analyze the adsorption towards CO2 and CO gases. Firm construction of platinum-doped aluminum nitride nanotubes (Pt-AlNNT) was investigated in four feasible places, and the binding energy of firm construction is 1.314 eV. Respectively, the adsorption energy between the CO2 and Pt-AlNNT systems was - 2.107 eV, while for instance of CO, the adsorption energy was - 3.258 eV. The mentioned analysis and computations are considerable for studying Pt-AlNNT as a new CO2 and CO gas sensor for electrical tools insulation. The current study revealed that the Pt-AlNNT possesses high selectivity and sensitivity towards CO2 and CO. METHODS: In this research, Pt-doped AlNNT (Pt-AlNNT) has been studied as sensing materials of CO and CO2 for the first time. The adsorption process of Pt-AlNNT has been computed and analyzed through the DFT approach. DFT computations by using B3LYP functional and 6-31 + G* basis sets have been applied in the GAMESS code for sensing attributes, which contribute to potential applications.

Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

Predictive insights into plant-based compounds as fibroblast growth factor receptor 1 inhibitors: a combined molecular docking and dynamics simulation study.

The discovery of novel therapeutic agents with potent anticancer activity remains a critical challenge in drug development. Natural products, particularly bioactive phytoconstituents derived from plants, have emerged as promising sources for anticancer drug discovery. In this study, we used virtual screening techniques to explore the potential of bioactive phytoconstituents as inhibitors of fibroblast growth factor receptor 1 (FGFR1), a key signaling protein implicated in cancer progression. We used virtual screening techniques to analyze phytoconstituents extracted from the IMPPAT 2.0 database. Our primary objective was to discover promising inhibitors of FGFR1. To ensure the selection of promising candidates, we initially filtered the molecules based on their physicochemical properties. Subsequently, we performed binding affinity calculations, PAINS, ADMET, and PASS filters to identify nontoxic and highly effective hits. Through this screening process, one phytocompound, namely Mundulone, emerged as a potential lead. This compound demonstrated an appreciable affinity for FGFR1 and exhibited specific interactions with the ATP-binding site residues. To gain further insights into the conformational dynamics of Mundulone and the reference FGFR1 inhibitor, Lenvatinib, we conducted time-evolution analyses employing 200 ns molecular dynamics simulations (MDS) and essential dynamics. These analyses provided valuable information regarding the dynamic behavior and stability of the compounds in complexes with FGFR1. Overall, the findings indicate that Mundulone exhibits promising binding affinity, specific interactions, and favorable drug profiles, making it a promising lead candidate. Further experimental analysis will be necessary to confirm its effectiveness and safety profiles for therapeutic advancement in the cancer field.Communicated by Ramaswamy H. Sarma.

Hematopoietic cell kinase as a nexus for drug repurposing: implications for cancer and HIV therapy.

Hematopoietic cell kinase (HCK) has emerged as a potential target for therapeutic intervention in cancer and HIV infection because of its critical role in critical signaling pathways. Repurposing FDA-approved drugs offers an efficient strategy to identify new treatment options. Here, we address the need for novel therapies in cancer and HIV by investigating the potential of repurposed drugs against HCK. Our goal was to identify promising drug candidates with high binding affinities and specific interactions within the HCK binding pocket. We employed an integrated computational approach combining molecular docking and extensive molecular dynamics (MD) simulations. Initially, we analyzed the binding affinities and interaction patterns of a library of FDA-approved drugs sourced from DrugBank. After careful analysis, we focused on two compounds, Nilotinib and Radotinib, which exhibit exceptional binding affinities and specificity to the HCK binding pocket, including the active site. Additionally, we assessed the pharmacological properties of Nilotinib and Radotinib, making them attractive candidates for further drug development. Extensive all-atom MD simulations spanning 200 nanoseconds (ns) elucidated the conformational dynamics and stability of the HCK-Nilotinib and HCK-Radotinib complexes. These simulations demonstrate the robustness of these complexes over extended timescales. Our findings highlighted the potential of Nilotinib and Radotinib as promising candidates against HCK that offer valuable insights into their binding mechanisms. This computational approach provides a comprehensive understanding of drug interactions with HCK and sets the stage for future experimental validation and drug development endeavors.Communicated by Ramaswamy H. Sarma.

Computational exploration of the genomic assignments, molecular structure, and dynamics of the ccdABXn2 toxin-antitoxin homolog with its bacterial target, the DNA gyrase, in the entomopathogen Xenorhabdus nematophila.

Toxin-antitoxin (TA) modules, initially discovered on bacterial plasmids and subsequently identified within chromosomal contexts, hold a pivotal role in the realm of bacterial physiology. Among these, the pioneering TA system, ccd (Control of Cell Death), primarily localized on the F-plasmid, is known for its orchestration of plasmid replication with cellular division. Nonetheless, the precise functions of such systems within bacterial chromosomal settings remain a compelling subject that demands deeper investigation. To bridge this knowledge gap, our study focuses on exploring ccdABXn2, a chromosomally encoded TA module originating from the entomopathogenic bacterium Xenorhabdus nematophila. We meticulously delved into the system's genomic assignments, structural attributes, and functional interplay. Our findings uncovered intriguing patterns-CcdB toxin homologs exhibited higher conservation levels compared to their CcdA antitoxin counterparts. Moreover, we constructed secondary as well as tertiary models for both the CcdB toxin and CcdA antitoxin using threading techniques and subsequently validated their structural integrity. Our exploration extended to the identification of key interactions, including the peptide interaction with gyrase for the CcdB homolog and CcdB toxin interactions for the CcdA homolog, highlighting the intricate TA interaction network. Through docking and simulation analyses, we unequivocally demonstrated the inhibition of replication via binding the CcdB toxin to its target, DNA gyrase. These insights provide valuable knowledge about the metabolic and physiological roles of the chromosomally encoded ccdABXn2 TA module within the context of X. nematophila, significantly enhancing our comprehension of its functional significance within the intricate ecosystem of the bacterial host.Communicated by Ramaswamy H. Sarma.

Machine Learning Enabled Photoacoustic Spectroscopy for Noninvasive Assessment of Breast Tumor Progression In Vivo: A Preclinical Study.

Breast cancer is a dreaded disease affecting women the most in cancer-related deaths over other cancers. However, early diagnosis of the disease can help increase survival rates. The existing breast cancer diagnosis tools do not support the early diagnosis of the disease. Therefore, there is a great need to develop early diagnostic tools for this cancer. Photoacoustic spectroscopy (PAS), being very sensitive to biochemical changes, can be relied upon for its application in detecting breast tumors in vivo. With this motivation, in the current study, an aseptic chamber integrated photoacoustic (PA) probe was designed and developed to monitor breast tumor progression in vivo, established in nude mice. The device served the dual purpose of transporting tumor-bearing animals to the laboratory from the animal house and performing PA experiments in the same chamber, maintaining sterility. In the current study, breast tumor was induced in the nude mice by MCF-7 cells injection and the corresponding PA spectra at different time points (day 0, 5, 10, 15, and 20) of tumor progression in vivo in the same animals. The recorded photoacoustic spectra were subsequently preprocessed, wavelet-transformed, and subjected to filter-based feature selection algorithm. The selected top 20 features, by minimum redundancy maximum relevance (mRMR) algorithm, were then used to build an input feature matrix for machine learning (ML)-based classification of the data. The performance of classification models demonstrated 100% specificity, whereas the sensitivity of 95, 100, 92.5, and 85% for the time points, day 5, 10, 15, and 20, respectively. These results suggest the potential of PA signal-based classification of breast tumor progression in a preclinical model. The PA signal contains information on the biochemical changes associated with disease progression, emphasizing its translational strength toward early disease diagnosis.

In silico screening of chalcone derivatives as promising EGFR-TK inhibitors for the clinical treatment of cancer.

Epidermal growth factor receptor (EGFR) promotes tumorigenic characteristics and activates cancer-associated signaling pathways such as Wnt/-catenin, transforming growth factor (TGF-ß), and phosphoinositide-3-kinase (PI3K). Several inhibitors have been reported to suppress the activity of EGFR and are being used in cancer treatment. However, patients in the malignant stage of cancer show resistance to those inhibitors, opening a wide space for research to discover novel inhibitors. Therefore, we carried out machine learning and virtual screening to discover novel inhibitors with high affinity against EGFR-TK. Initially, a library of 2640 chalcones were screened out using a machine-learning model developed based on the random forest algorithm, exhibiting high sensitivity and a Receiver Operating Characteristic curve (ROC area) of 0.99. Furthermore, out of the initial 2640 screened compounds, 412 compounds exhibiting potential activity are subjected to evaluation for drug-likeness properties through different filters: Blood-brain barrier penetration, Lipinski's rule, CMC-50 like rule, Veber rule, and Ghose filter, alongside Cell Line Cytotoxicity Prediction. A total of 30 compounds that successfully pass through all these filters are selected for molecular docking. Of these, 6 compounds display substantial binding affinity and closer interaction with the conserved catalytic residues of the target EGFR-TK compared to the reference molecule (erlotinib). Furthermore, molecular dynamics simulation studies were conducted on four compounds (CID-375861, CID-375862, CID-23636403, and CID-259166) to confirm the stability of the docked complexes over a 100 ns simulation trajectory. Additionally, the binding free energy calculations by MMPBSA reveal that these four chalcone compounds exhibit strong affinity towards the EGFR-TK enzyme, with binding free energies of - 65.421 kJ/mol, - 94.266 kJ/mol, - 80.044 kJ/mol, and - 79.734 kJ/mol, respectively. The findings from this investigation highlight a set of promising chalcone compounds that have the potential to be developed into effective drugs for the treatment of various cancers. Further research and development on these compounds could pave the way for novel therapeutic interventions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03858-8.

Estimation of SARS-CoV-2 IgG Antibodies in Healthcare Worker-Administered Covishield and Covaxin Vaccines at a Tertiary Care Hospital in Jharkhand, India.

Introduction To mitigate the impact of the COVID-19 pandemic caused by the SARS-CoV-2 virus, global distribution of vaccines such as Covishield and Covaxin has been undertaken. This research aimed to assess the responses and potential differences between these vaccines by examining the presence and levels of SARS-CoV-2 IgG antibodies in healthcare professionals who received them. Methodology A comprehensive cross-sectional study was conducted at a tertiary care facility in Ranchi involving 227 healthcare professionals who had completed both doses of either Covishield or Covaxin. Blood samples were collected and subjected to chemiluminescence immunoassay analysis to measure IgG antibodies. Demographic data, immunization records, and previous COVID-19 infections were recorded. Statistical analyses, including analysis of variance (ANOVA), linear regression, and independent sample t-tests were performed. Results Antibody titers exhibited variability, potentially influenced by factors. There was no difference in antibody titers between recipients of Covishield and Covaxin vaccines. Linear regression analysis revealed a correlation between antibody levels and the number of days after vaccination. Factors such as age, gender, blood group, and prior COVID-19 infections did not significantly impact antibody titers. Conclusions This study contributes to responses elicited by Covishield and Covaxin vaccines among healthcare workers. The results highlight that Covishield showed a higher mean titer value than Covaxin, which is not statistically significant. The overall model showed statistically significant results indicating age, type of vaccine, number of days after vaccination, blood group, and previous history of COVID-19 infection collectively influenced the CoV-2 IgG titer values. The findings indicate that age, number of days after vaccination, and prior history of COVID-19 infection have substantial relationships with the CoV-2 IgG titer, but sex, vaccine type, and blood group show lesser, nonsignificant associations.

Screening of potential inhibitors of Leishmania major N-myristoyltransferase from Azadirachta indica phytochemicals for leishmaniasis drug discovery by molecular docking, molecular dynamics simulation and density functional theory methods.

Leishmaniasis is one of the most neglected parasitic diseases worldwide. The toxicity of current drugs used for its treatment is a major obstacle to their effectiveness, necessitating the discovery and development of new therapeutic agents for better disease control. In Leishmania parasites, N-Myristoyltransferase (NMT) has been identified as a promising target for drug development. Thus, exploring well-known medicinal plants such as Azadirachta indica and their phytochemicals can offer a diverse range of treatment options, potentially leading to disease prevention and control. To assess the therapeutic potential of these compounds, their ADMET prediction and drug-likeness properties were analyzed. The top 4 compounds were selected which had better and significantly low binding energy than the reference molecule QMI. Based on the binding energy score of the top compounds, the results show that Isonimocinolide has the highest binding affinity (-9.8 kcal/mol). In addition, a 100 ns MD simulation of the four best compounds showed that Isonimocinolide and Nimbolide have good stability with LmNMT. These compounds were then subjected to MMPBSA (last 30 ns) calculation to analyze protein-ligand stability and dynamic behavior. Nimbolide and Meldenin showed lowest binding free energy i.e. -84.301 kJ/mol and -91.937 kJ/mol respectively. DFT was employed to calculate the HOMO-LUMO energy gap, global reactivity parameters, and molecular electrostatic potential of all hit molecules. The promising results obtained from MD simulations and MMPBSA analyses provide compelling evidence for the potential use of these compounds in future drug development efforts for the treatment of leishmaniasis.Communicated by Ramaswamy H. Sarma.

Increased vitamin B12 levels in patients with oral cancer.

Background: Oral cancer (OC), which happens to be one of the leading causes of death in the Indian population, is caused primarily by tobacco use, although other factors are also responsible. Serum vitamin B12 is important in maintaining the immune system and also repairing the damaged deoxyribonucleic acid (DNA) of cells. The aim of our study was to evaluate the serum B12 levels in patients with OC and look for any association between the two. Methods: One hundred subjects were selected for the study and divided into two groups: group A having OC (including cases of oral squamous cell carcinoma (OSCC), verrucous carcinoma and oropharyngeal carcinoma; 50 patients) and group B had age- and gender-matched healthy controls (50 healthy volunteers). Patients diagnosed clinically and histopathologically confirmed as OC were selected for the study. All the patients were subjected to haematological investigation to assess serum vitamin B12. Results: Males subjects in the 4th and 5th decades of life were predominantly affected. Serum vitamin B12 was significantly increased in OC patients when compared with controls, which was statistically significant. The mean serum vitamin B12 was slightly higher in males than in females, which was statistically non-significant. Conclusion: Our study found increased vitamin B12 levels in OC patients, and it was statistically significant.

Measurement of radon concentration in soil gas and radon exhalation rate from soil samples along and across the Main Central Thrust of Garhwal Himalaya, India.

The present study focuses on measuring radon concentrations in soil gas at various depths, radon exhalation rate (surface and mass) from soil samples, and gamma dose rate along and across the Main Central Thrust of Garhwal Himalaya, India. Radon concentration in soil gas, surface, and mass exhalation rates was measured using a portable SMART radon monitor (RnDuo). Furthermore, the gamma dose rate was measured using a pocket radiation monitor. The soil gas radon concentration varied from 15 ± 4 to 579 ± 82 Bq m-3 at a depth of 25 cm, 10 ± 2 to 533 ± 75 Bq m-3 at a depth of 30 cm, and 9 ± 1 to 680 ± 95 Bq m-3 at a depth of 35 cm. The surface and mass exhalation rates were found 3 ± 0.7 to 98 ± 3 Bq m-2 h-1 (with AM ± SD = 36 ± 28 Bq m-2 h-1) and 1 ± 0.2 to 95 ± 2 mBq kg-1 h-1 (with AM ± SD = 30 ± 22 mBq kg-1 h-1), respectively. The gamma dose rate for the present study area varies from 0.11 ± 0.05 to 0.28 ± 0.05 µSv h-1 with a mean value of 0.17 ± 0.05 µSv h-1. The correlation analysis between the exhalation rates (mass and surface) and radon concentration of soil gas at various depths was carried out in the current study.

Incidence of Canine Impaction in Tribal Population of Jharkhand.

Introduction: The position of the canine has a key role in facial harmony, dental aesthetics, functional occlusion, and health of temperomandibular joint. Maxillary canine impaction is the second most common tooth after third molars impaction. Maxillary canines are more prone to impaction due to longer path of eruption. Settings and Design: All the patients were examined in the Dental Chair light and referred to the department of Oral Radiology for Orthopantomogram. Yamamoto's classification was used to classify maxillary canine impaction. Position of mandibular canine from cement-enamel junction was used for mandibular canine impaction. Materials and Methods: The study was performed on 2300 patients who consulted the orthodontic department from January 2018 to July 2022. Orthopantomogram of each patient was examined for canine impaction, retained deciduous teeth, cyst, and other anomalies. The incidence and pattern of canine impaction was assessed. Statistical Analysis: The data was then statistically analyzed using Graph Pad Prism software. The incidence of impacted canine was evaluated. The effect of gender was evaluated using a t-test. Results: A total of 2300 subjects were examined out of which 52 individuals were diagnosed with canine impaction. The incidence of canine impaction among orthodontic patients is 2.26%. The amount of canine impaction in females (60%) is higher than males (40%). The ratio of canine impaction of the maxilla and mandible is 2.5. Conclusion: The incidence of canine impaction was found to be 2.26 percent in the tribal dominant population of Jharkhand. Type II (50%) pattern in the maxilla and Level A (57%) impaction in the mandible was found to be the highest.

Potent multi-target natural inhibitors against SARS-CoV-2 from medicinal plants of the Himalaya: a discovery from hybrid machine learning, chemoinformatics, and simulation assisted screening.

The emergence and immune evasion ability of SARS-CoV-2 Omicron strains, mainly BA.5.2 and BF.7 and other variants of concern have raised global apprehensions. With this context, the discovery of multitarget inhibitors may be proven more comprehensive paradigm than its one-drug-to-one target counterpart. In the current study, a library of 271 phytochemicals from 25 medicinal plants from the Indian Himalayan Region has been virtually screened against SARS-CoV-2 by targeting nine virus proteins, viz., papain-like protease, main protease, nsp12, helicase, nsp14, nsp15, nsp16, envelope, and nucleocapsid for screening of a multi-target inhibitor against the viral replication. Initially, 94 phytochemicals were screened by a hybrid machine learning model constructed by combining 6 confirmatory bioassays against SARS-CoV-2 replication using an instance-based learner lazy k-nearest neighbour classifier. Further, 25 screened compounds with excellent drug-like properties were subjected to molecular docking. The phytochemical Cepharadione A from the plant Piper longum showed binding potential against four proteins with the highest binding energy of -10.90 kcal/mol. The compound has acceptable absorption, distribution, metabolism, excretion, and toxicity properties and exhibits stable binding behaviour in terms of root mean square deviation (0.068 ± 0.05 nm), root-mean-square fluctuation, hydrogen bonds, solvent accessible surface area (83.88-161.89 nm2), and molecular mechanics Poisson-Boltzmann surface area during molecular dynamics simulation of 200 ns with selected target proteins. Concerning the utility of natural compounds in the therapeutics formulation, Cepharadione A could be further investigated as a remarkable lead candidate for the development of therapeutic drugs against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Prevalence of Oral Submucous Fibrosis, Its Correlation of Clinical Grading to Various Habit Factors among Patients of Bihar: A Cross Sectional Study.

Aim: To find out the prevalence of OSMF and its Co-relation of clinical grading to various habit factors (time span of habit practiced in years, repetition of habit practiced per day, time of habit practiced in minutes per use). Method: This descriptive, cross-sectional survey was carried out and close ended questionnaire was used for data collection. Demographic details like gender & age and different tissue exploiting habits like, chewing gutkha, chewing areca nut, chewing panmasala with or without tobacco, plain tobacco, mawa, smoking, alcohol was recorded. Also, duration of habit in years, repetition of habit per day, time of habit per use & site of involvement was recorded. Results: Among 5297 patients examined at OPD, 120 were diagnosed with OSMF. The present study found no statistical relation between age, gender & OSMF. The present study concluded that majority 83 (69.17%) of the OSMF patients are guthka user and buccal mucosa was most affected site. OSMF was more prevalent in patients who practiced the habit for more than 15 years. Conclusion: Among the OSMF patients, guthka was most commonly practiced & buccal mucosa was most commonly involved. Duration and frequency of consumption were significantly associated with severity of OSMF.

Theoretical study on efficient HF gas sensing by functionalized, decorated, and doped nanocone strategy.

Hydrogen fluoride (HF) is a highly dangerous and corrosive gas that can cause severe burns and respiratory damage. The density functional theory method (DFT) used to study the interaction between the HF gas and the surface of a carbon nanocone (CNC) doped with gallium atom as a chemical sensor. The results showed that CNC wasn't a good candidate to sense the HF gas and consequently its electrical properties are changed insignificant. To improve the properties of the CNC, several strategies were tried: functionalizing by pyridinol (Pyr) and pyridinol oxide (PyrO), decorated with metals (M = B, Al, and Ga), and doped with element of third group (M = B, Al, and Ga). The obtained data demonstrated that the promising results were obtained by doping the CNC with Ga atom. After full optimization, we achieved one stable configuration between the HF gas and CNC-Ga structure (S15 configuration) with Eads = -19.86 kcal/mol. The electronic properties of the CNC-Ga structure is sensible changed after the HF molecule is adsorbed. According to calculated the energy gap between HOMO and LUMO orbitals of S15 configuration are increased which could be applied a chemical signal. Eventually, one could propose that the CNC-Ga has the ability to act as a Φ-type sensor based on its physical adsorption energy and quick recovery time and doped with gallium atom is a promising strategy.

Comparison of recovery profiles in target-controlled infusions (TCI) versus manually controlled infusions for total intravenous anesthesia (TIVA) in laparoscopic surgeries. A randomized controlled trial.

Background and Aims: Considerable importance has been attached to early recovery and discharge readiness after surgeries. Many centers use total intravenous anesthesia (TIVA) as their anesthesia technique of choice. Target-controlled infusions (TCI) have been proposed as a method to precisely deliver continuous infusions of propofol and opioids as compared to the traditionally used manual-controlled infusion (MCI) methods. However, TCI has also been shown to result in the administration of larger doses of propofol which could cause delayed emergence and recovery from anesthesia. Studies involving TCI have focused mainly on its effects on anesthesia induction but not much literature is available on recovery profiles of patients on TCI. This study was designed to compare the effect of conventionally used MCI methods versus the target-controlled infusion (TCI) method of administering TIVA on recovery characteristics in patients undergoing laparoscopic surgery. Material and Methods: This was a prospective randomized interventional study on 54 patients. Our primary objective was to compare the rates of recovery from anesthesia as judged by four parameters. Time to return of spontaneous ventilation, time to respond to verbal commands, time to extubation, and time to shift patient out of the operating room after stoppage of propofol infusion. As secondary objectives, intraoperative average bispectral index (BIS) values and total anesthetic drugs (propofol and fentanyl) consumption were also compared. Results: We noted that for laparoscopic surgeries lasting less than 4 hours, both MCI and TCI techniques of TIVA have comparable rates of recovery after the stoppage of propofol infusion. Total consumption of propofol and fentanyl was also similar; however, with the use of the TCI method of TIVA, better depth of anesthesia as evidenced by lower average BIS levels was noted. Conclusion: Recovery rates after TIVA using a target-controlled infusion (TCI) system are similar to BIS-guided MCIs in patients undergoing laparoscopic surgery lasting less than 4 hours. TCI resulted in better depths of anesthesia though per kg/min consumption of propofol was found to be more.

Evaluation of the Prevalence of White Spot Lesions During Fixed Orthodontic Treatment Among Patients Reporting for Correction of Malocclusion: A Prevalence Study.

BACKGROUND: Despite recent breakthroughs in caries preventive measures, one of the biggest issues clinicians confront is preventing demineralization while undergoing orthodontic therapy. The buildup of plaques around orthodontic brackets over time causes white spot lesions (WSLs). The goal of the present research was to assess the prevalence of WSLs in patients undergoing orthodontic treatment before starting therapy and at six and 12 months into therapy, adopting the visual examination approach. MATERIALS AND METHODS: We looked for WSLs on tooth surfaces gingival to an archwire because this is the area most likely to experience enamel demineralization during orthodontic treatment. The visual assessment was conducted using the following scale at baseline, six months, and 12 months for orthodontic patients: score 0: no demineralization or noticeable white patches on the surface; score 1: mild demineralization with a visible white spot but no surface disruption; score 2: moderate demineralization with a noticeable WSL that has a roughened surface but does not need repair; and score 3: severe demineralization with a noticeable WSL that needs repair. Fisher's exact test was used after a chi-square analysis to determine whether there were any differences between all three categories (six months, 12 months, and control). RESULTS: The frequency of WSL in patients at 12 months of orthodontic treatment was 46.57%, while it was 11.86% in patients who just started orthodontic treatment. The difference was statistically significant (p = 0.01), showing that the frequency was greater in patients at 12 months of orthodontic treatment as compared to patients who had just started undergoing orthodontic treatment. The frequency of WSL in patients at six months of orthodontic treatment was 37.34%, while it was 11.86% in patients who just started orthodontic treatment. The difference was statistically significant (p = 0.03), showing that the frequency was greater in patients at six months of orthodontic treatment as compared to patients who had just started undergoing orthodontic treatment. The frequency of WSL in patients at six months of orthodontic treatment was 37.34%, while it was 46.57% in patients at 12 months of orthodontic treatment. The frequency was greater in patients at 12 months of orthodontic treatment as compared to patients at six months of orthodontic treatment; however, the difference was non-significant statistically (p = 0.76). CONCLUSION: This clinical investigation revealed that the number of WSLs increased significantly during the first six months of treatment and then increased gradually until the final 12 months. During the first few months of treatment, doctors should assess the patients' dental hygiene habits and, if necessary, take further precautions to prevent demineralization.

State of Dental Health and Management Needs of Young Hemophilic Patients: A Case-control Study.

Background: In particular, when it comes to systemic diseases like hemophilia, good dental health is crucial to a person's overall health and wellness. Through the means of this study, we aim to assess the prevalence of various dental anomalies in children suffering from hemophilia in comparison to healthy children and assess their treatment needs. Materials and methods: This was a descriptive, case-control study with 400 subjects, 200 each in the study (hemophilic) and control (nonhemophilic) groups. The subjects' ages ranged from 5 to 15 years. Utilizing the oral hygiene index-simplified (OHI-S), the state of oral hygiene was documented (OHI-S). Using decaying extracted filled tooth (DEFT) and decayed, missing, and filled tooth (DMFT) for the primary and permanent dentition, respectively, teeth afflicted by dental caries and teeth restored/extracted as a result of dental caries were assessed. Statistical Package for the Social Sciences (SPSS) software (version 27.0) was used for statistical analysis. Results: Hemophilic people had a considerably greater incidence of dental caries. Furthermore, even though their DMFT/DEFT and OHI-S scores were barely poorer than those of healthy people, children with hemophilia had a significantly larger percentage of dental treatment needs across all age categories than the other group. Conclusion: The percentage of hemophilic children who needed dental treatment across different age groups was significantly higher than the other group, which supports our observations that the dental health status of hemophilic children was poor and treatment requirement was high among them as well. This is true even though the DMFT/DEFT scores and OHI-S scores in hemophilic children were only slightly worse than in healthy individuals. How to cite this article: Sharma S, Shahi AK, Chandra S, et al. State of Dental Health and Management needs of Young Hemophilic Patients: A Case-control Study. Int J Clin Pediatr Dent 2023;16(2):380-387.

Network pharmacology, molecular docking, and molecular dynamics simulation to elucidate the mechanism of anti-aging action of Tinospora cordifolia.

Scientific research has demonstrated that Tinospora cordifolia acts as an anti-aging agent in several experimental models, generating global interest in its underlying molecular mechanisms of this activity. The aim of the study was to identify the possible phytochemical compounds of T. cordifolia that might combat age-related illness through integrating network pharmacology, molecular docking techniques, and molecular dynamics (MD) study to explore their potential mechanisms of action. To carry out this study, several databases were used, including PubChem, KNApSAcK family database, PubMed, SwissADME, Molsoft, SwissTargetPrediction, GeneCards, and OMIM database. For network development and GO enrichment analysis KEGG, ShinyGo 0.77, and the STRING database were used. For better analysis, the networks were also constructed using Cytoscape 3.9.1. The Cytoscape network analyzer tool was used for data analysis, and molecular docking was done via Vina-GPU-2.0. The best compounds and AKT1 were finally subjected to MD simulation for 100 ns. The CytoHubba plugin of Cytoscape identified ten key targets, commonly called hub genes, including AKT1, GAPDH, and TP53, and so on. GO and KEGG pathway enrichment analysis revealed the relevant biological processes, cellular components, and molecular functions involved in treating aging-related disorders. KEGG pathway analysis involved neuroactive ligand-receptor interactions, lipid and atherosclerosis, and cAMP signaling. The docking of 100 T. cordifolia compounds with AKT1 demonstrated good binding affinity, particularly for Amritoside, Sitagliptin, Berberine, and Piperine. Finally, the relative stability of four-hit phytochemicals was validated by MD simulation, which may be the most crucial compound for anti-aging activity. In conclusion, this study used network pharmacology, molecular docking, and MD simulation to identify the compounds in T. cordifolia and proposed a potential mechanism for anti-aging activity. These results suggest future directions for the prevention and treatment of age-related diseases.

The restriction of calcium influx in metaphase and post-metaphase stages of cell division revealed by imaging secondary ion mass spectrometry (SIMS).

A secondary ion mass spectrometry (SIMS)-based isotopic imaging technique of ion microscopy was used for observing calcium influx in single renal epithelial LLC-PK1 cells. The CAMECA IMS-3f SIMS instrument, used in the study, is capable of producing isotopic images of single cells at 500 nm spatial resolution. Due to the high-vacuum requirements of the instrument the cells were prepared cryogenically with a freeze-fracture method and frozen freeze-dried cells were used for SIMS analysis. The influx of calcium was imaged directly by exposure of cells to 44 Ca stable isotope in the extracellular buffer for 10 min. The 44 Ca influx was measured at mass 44 and the distribution of endogenous calcium at mass 40 (40 Ca) in the same cell. A direct comparison of interphase cells to cells undergoing division revealed that calcium influx is restricted in metaphase and post-metaphase stages of cell division. This restriction is lifted in late cytokinesis. The net influx of 44 Ca in 10 min was approximately half under calcium influx restriction in comparison to interphase cells. Under calcium influx restriction the 44 Ca concentration was the same between the mitotic chromosome and the cytoplasm. These observations indicate that the endoplasmic reticulum (ER) calcium uptake is compromised under calcium influx restriction in cells undergoing division.