Design, synthesis, molecular docking, and biological evaluation of coumarin-thymidine analogs as potent anti-TB agents.

With the intent to discover new antituberculosis (TB) compounds, coumarin-thymidine analogs were synthesized using second-order nucleophilic substitution reactions of bromomethyl coumarin with thymidine. The newly synthesized coumarin-thymidine conjugates (1a-l) were characterized using IR, NMR, GC-MS, and CHN elemental analysis. The novel conjugates were found to exhibit potent anti-TB activity against the Mycobacterium tuberculosis H37 Rv strain, with minimum inhibitory concentrations (MIC) of the active compounds ranging between 0.012 and 0.482 µM. Compound 1k was established as the most active candidate with a MIC of 0.012 µM. The toxicity study on HEK cells confirmed the nontoxic nature of compounds 1e, 1h, 1i, 1j, and 1k. Also, the most active compounds (1k, 1j, and 1e) were stable in the pH range from 2.5 to 10, indicating compatibility with the biophysical environment. Based on the pKa studies, compounds 1k, 1j, and 1e are capable of crossing lipid-membrane barriers and acting on target cells. Molecular docking studies on the M. tuberculosis ß-oxidation trifunctional enzyme (PDB ID: 7O4V) were conducted to investigate the mechanisms of anti-TB activity. All compounds showed excellent hydrogen binding interactions and exceptional docking scores against M. tuberculosis, which was in accordance with the results. Compounds 1a-l possessed excellent affinity to proteins, with binding energies ranging from -7.4 to -8.7 kcal/mol.

Drug re-engineering and repurposing: A significant and rapid approach to tuberculosis drug discovery.

The prevalence of tuberculosis (TB) remains the leading cause of death from a single infectious agent, ranking it above all other contagious diseases. The problem to tackle this disease seems to become even worse due to the outbreak of SARS-CoV-2. Further, the complications related to drug-resistant TB, prolonged treatment regimens, and synergy between TB and HIV are significant drawbacks. There are several drugs to treat TB, but there is still no rapid and accurate treatment available. Intensive research is, therefore, necessary to discover newer molecular analogs that can probably eliminate this disease within a short span. An increase in efficacy can be achieved through re-engineering old TB-drug families and repurposing known drugs. These two approaches have led to the production of newer classes of compounds with novel mechanisms to treat multidrug-resistant strains. With respect to this context, we discuss structural aspects of developing new anti-TB drugs as well as examine advances in TB drug discovery. It was found that the fluoroquinolone, oxazolidinone, and nitroimidazole classes of compounds have greater potential to be further explored for TB drug development. Most of the TB drug candidates in the clinical phase are modified versions of these classes of compounds. Therefore, here we anticipate that modification or repurposing of these classes of compounds has a higher probability to reach the clinical phase of drug development. The information provided will pave the way for researchers to design and identify newer molecular analogs for TB drug development and also broaden the scope of exploring future-generation potent, yet safer anti-TB drugs.

Efficacy of contrast enhanced grey scale ultrasound in characterisation of hepatic focal lesions: A pilot study.

BACKGROUND: Contrast enhanced ultrasound (CEUS) has recently gained widespread acceptance as an adjunct to conventional grey scale ultrasound. The present pilot study was undertaken to evaluate the efficacy of this technique in characterisation of hepatic focal lesions. METHODS: Adult patients who had at least one focal liver lesion underwent ultrasound evaluation in regular and contrast mode before and after intravenous administration of sulphur hexafluoride. The diagnoses were confirmed by comparison with a reference standard (multidetector CT), response to treatment or pathological correlation. RESULTS: The rate of correct diagnosis for unenhanced ultrasound was 54%, CEUS was 72% and multidetector CT (MDCT) was 92%. A comparison of unenhanced ultrasound versus CEUS using the McNemar test yielded a p value of 0.0704 (>0.05). However, comparison of CEUS versus MDCT using the McNemar test yielded a p value of 0.0265 (<0.05). Additionally, comparison of unenhanced ultrasound versus MDCT using the McNemar test yielded a p value of <0.0001. CONCLUSION: CEUS increases diagnostic efficacy over unenhanced ultrasound but does not have any significant advantages over MDCT. Currently it may be used as a problem solving tool in atypical haemangiomas, echogenic focal liver lesions, contrast sensitivity and to avoid multiple studies utilising ionising radiation.

From Campus to Crisis: Psychological Effect of the COVID-19 Pandemic on Indian Management Students.

BACKGROUND: The COVID-19 pandemic has adversely affected students pursuing higher education, but limited studies highlight student's psychological experiences, especially from Western India. OBJECTIVE: The present study aimed to understand psychological experiences, coping behaviors, and the perceived role of tele-counseling services among final-year students of Masters of Business Administration from leading business schools (B-schools) in Western India. DESIGN: A qualitative research design was adopted for the study. A semi-structured interview guide was utilized to conduct in-depth interviews with 35 students. Students were reached via personal networks and social media, and data was gathered after the second wave of the COVID-19 pandemic. A thematic analysis technique was employed to analyze the data. RESULTS: The findings showed that management students had upsetting psychological experiences. Key stressors that emerged in the study were job concerns, lifestyle changes, concerns about their own and parents' health and safety, uncertainty about the future, and social isolation. They expressed the need for mental health help; however, they were reluctant to utilize tele-counseling services. The authors present an integrated psychological well-being model for promoting positive mental health among students in higher education institutions. CONCLUSION: The study explains the psychological toll on management students. Enhancing mental health literacy through awareness sessions and other innovative means would be critical to addressing myths around mental health and mental healthcare-seeking behavior in higher education institutions. An integrated approach to promoting positive mental health and well-being is needed.

The Influence of Nickel-Titanium (Ni-Ti) Rotary Instrument Systems on Debris and Smear Layer Formation in Endodontic Procedures: An In Vitro Scanning Electron Microscopy Study.

Background Successful endodontic treatment relies on the effective removal of debris and the prevention of smear layer formation within the root canals. The choice of nickel-titanium (Ni-Ti) rotary instrument systems can significantly impact these outcomes. Aim This study aims to evaluate and compare the debris and smear layer formation in root canals of extracted mandibular second premolar teeth following instrumentation with the ProTaper Universal (Dentsply Sirona, Charlotte, NC) (Group II), Twisted File (Kerr Endodontics, Gilbert, AZ) (Group III), and XP Endo (FKG Dentaire, La Chaux-de-Fonds, Switzerland) (Group IV) Ni-Ti rotary instrument systems. Methods In this in vitro study, 60 extracted mandibular second premolar teeth were randomly divided into four groups, each containing 15 teeth. Group I served as the control with no instrumentation. Groups II, III, and IV were instrumented with the ProTaper Universal rotary file, the Twisted File, and the XP Endo file systems, respectively. Debris and smear layer formation were evaluated through scanning electron microscopy (SEM), and photomicrographs were scored using a standardized index. Results Group II (ProTaper) exhibited the highest mean debris and smear layer scores, with values of 3.50 and 2.70, respectively. Group IV (XP Endo) demonstrated the least debris and smear layer formation, with mean scores of 2.65 and 2.08, respectively. Statistical analysis confirmed significant differences among the groups for both debris and smear layer formation. Conclusion The results highlight the practical importance of selecting appropriate Ni-Ti rotary instrument systems to minimize debris and smear layer formation during endodontic procedures. The XP Endo file system showed promise as a favorable choice in this regard, but further clinical research is needed to validate these findings.

Lesions Misdiagnosed as Endodontic Pathosis: A Narrative Review.

In daily practice, clinicians come across certain radiographic abnormalities which may or may not be asymptomatic. This abstract discusses radiographic abnormalities encountered by clinicians in daily practice, some of which resemble endodontic lesions. Prompt attention is crucial as these lesions can be benign or malignant. The article emphasizes the importance of differential diagnosis for accurate identification of periapical pathosis.

Periapical Cemento-Osseous Dysplasia: A Journey from Diagnostic Dilemma to Accurate Diagnosis with Use of 3D Imaging.

Cemento-osseous dysplasia is a subgroup of fibro-osseous dysplasia commonly invading the tooth-bearing regions of the mandible quite often. These bony pathologies are asymptomatic and are seen on radiographs as an incidental finding. Accurate diagnosis of periapical cemento-osseous dysplasia is very crucial as it will help in the proper management of the patient as the incorrect diagnosis can lead to the unnecessary endodontic treatment of the concerned teeth as it may be misdiagnosed as a periapical pathology. We describe a case of periapical cemento-osseous dysplasia in which a 52-year-old woman had been experiencing discomfort in the right mental area of her mandible for the previous 6 months and had finally sought help at the outpatient department. This case study aims to highlight the significance of making an accurate diagnosis of cemento-osseous dysplasias in the tooth-bearing area.

Primary extranodal lymphomas: five-year experience from a tertiary care center of North India.

BACKGROUND: Primary extranodal lymphomas (pENL) are lymphomas with minimal nodal involvement and dominant extranodal disease. We aimed to study the prevalence and clinicopathological characteristics of pENL presenting at our center over 5 years from January 2015 to January 2020. METHODS: This is a cross-sectional study of pENL patients in which relevant clinical and laboratory data was collected including demography, site, stage, international prognostic index-revised, imaging findings, hematological, and biochemical parameters and comorbidities including underlying immunodeficiency. The paraffin blocks were subjected to routine hematoxylin and eosin stain and immunohistochemistry with standard lymphoma panel. RESULTS: Of 341 lymphomas, 73 (21.4%) were pENL with commonest site being gastrointestinal tract (31.5%) followed by head and neck (23.2%) and soft tissues (9.6%). Diffuse large B-cell lymphoma (DLBCL) (39.7%) was the commonest histological type (germinal center type-48%, nongerminal center-52%) followed by marginal zone lymphomas (MZL) (23.3%) and primary CNS lymphoma (8.2%). Primary breast lymphoma, primary bone marrow lymphoma, and follicular lymphoma constituted 4.1, 5.4, and 4.1% of pENL, respectively. There was a case of high grade B cell lymphoma of ileum with features intermediate between DLBCL and Burkitt. Other unusual pENL were anaplastic DLBCL of tonsils, DLBCLs of bone marrow with M band, MZL of base of tongue, Richter's transformation of tonsillar small lymphocytic lymphoma, and follicular lymphoma presenting as pericardial mass. Of 12 cases of T-non-Hodgkin lymphoma, commonest were mycosis fungoides (4/12) followed by mediastinal T-lymphoblastic lymphoma (2/12) and peripheral T-cell lymphoma (2/12). CONCLUSION: pENL has unique clinical presentation depending on the location with site-specific distribution of histological subtypes.

ON donor tethered copper (II) and vanadium (V) complexes as efficacious anti-TB and anti-fungal agents with spectroscopic approached HSA interactions.

Antimicrobial drug resistance poses a significant threat worldwide, hence triggering an urgent situation for developing feasible drugs. 3D-transition metal coordination complexes being multifaceted, offer tremendous potency as drug candidates. However, there are fewer reports on non-toxic and safe transition metal complexes; therefore, we hereby attempted to develop novel copper and vanadium-based therapeutic agents. We have synthesised six metal complexes viz., [VVO2(Quibal-INH)] (1), [CuII(Quibal-INH)2] (2), [VVO(Quibal-INH) (cat)] (3), [CuII(Quibal-INH) (cat)] (4), [VVO(Quibal-INH) (bha)] (5) and [CuII(Quibal-INH) (bha)] (6). Quibal-INH (L) is an ON bidentate donor ligand synthesized from Schiff base reaction between 4-(2-(7-chloroquinolin-3-yl)vinyl)benzaldehyde (Quibal) and Isoniazid (INH). The synthesized compounds were characterized using analytical techniques involving ATR-IR, UV-Vis, EPR, 1H NMR, 13C NMR, and 51V NMR. Ligand (L) and compound 3 exhibited moderate growth inhibitory activity towards Candida albicans and Cryptococcus neoformans fungal species. Compound 6 has been identified as active against the above fungal species with no toxicity and hemolysis activity on the healthy cells. Compound 5 exhibited significant activity against the Mycobacterium tuberculosis H 37 R v strain. Further, compounds 4, 5 and 6 exhibited excellent free radical scavenging activity. All the developed compounds were found to exhibit stability over a wide range of pH conditions. The complexes were additionally studied for their interaction with human serum albumin (HSA) with the UV-vis spectroscopic technique.

A Comparative Study to Evaluate the Anesthetic Efficacy of Buffered Versus Non-buffered 2% Lidocaine During Inferior Alveolar Nerve Block.

BACKGROUND: The study aimed to compare the clinical efficacy, safety, and acceptability of buffered lidocaine (8.4% sodium bicarbonate and 2% lidocaine with 1:80,000 adrenaline) versus non-buffered lidocaine (2% lidocaine with 1:80,000 adrenaline) during inferior alveolar nerve block. MATERIALS AND METHODS: Fifty patients who required bilateral extractions in a single arch were included in this study. One hundred extractions were carried out, and all of the patients had nerve blocks during the procedure. We also took note of the patient's pain level as measured on a visual analog scale, as well as the start of the action, duration of postoperative analgesia, and occurrence of any problems. The duration of anesthesia was assessed by the feeling of numbness and the first sign of pain. RESULT: All the patients in both study groups reported subjective numbness of the lips and tongue. The depth of anesthesia was evaluated by pain and comfort during the procedure with a visual analog scale and showed no significant difference between the two groups. The onset of action for the pterygomandibular nerve block was 1.240.31 minutes (buffered) and 1.710.51 minutes (non-buffered). When compared, the duration of anesthesia was 327.18102.98 minutes (buffered) and 129.0826.85 minutes (non-buffered). CONCLUSION: This study concludes that the buffered solution has a faster onset of action than the non-buffered solution. Both solutions exhibit similar intraoperative efficacy. The duration of postoperative anesthesia was prolonged with buffering. Buffering also reduced pain scores during the early postoperative period.

Cytological Correlates of Axillary Nodal Involvement in Invasive Ductal Carcinoma of Breast.

CONTEXT: Fine needle aspiration cytology (FNAC) plays an important role in the diagnosis of breast carcinoma. However, its role as a prognostic tool needs to be explored. This can be achieved by studying its correlation with an established prognostic marker such as axillary nodal metastasis. AIMS: This study was undertaken to correlate the cytological features of invasive ductal carcinoma (IDC) of breast with axillary lymph node status. SETTINGS AND DESIGN: Tertiary care hospital, retrospective analytical study. MATERIALS AND METHODS: The study group included 150 cases of IDC of breast diagnosed on FNAC, who had subsequently undergone modified radical mastectomy. Cytologic grades were assigned as per Robinson's grading system. Histopathological sections of axillary lymph nodes were assessed for metastasis. STATISTICAL ANALYSIS USED: The cytologic grade and each feature of the cytologic grade were correlated with the lymph node metastasis using χ2 test. Values of P < 0.05 were considered significant. RESULT: A statistically significant correlation was noted between cytologic grade of tumor and axillary lymph node metastasis (P < 0.05). In addition, a positive correlation was found between two of the individual features of cytologic grade, namely, nuclear size and cell uniformity with axillary lymph node metastasis (P < 0.05). CONCLUSION: Robinson's cytologic grade of breast carcinoma correlates well with the presence of axillary lymph node metastasis and hence can be used as a prognostic tool. As there is an increasing trend toward conservative approach to management of breast carcinoma, patients receive preoperative neoadjuvant therapy which may alter the nodal status on the resected specimen. Hence, a high cytological grade of primary tumor, as assessed on FNAC before initiation of therapy, should alert the treating team of the possibility of axillary lymph nodal metastasis.

Correlative Study of Cytological Features in Grading of Invasive Breast Carcinoma.

CONTEXT: Fine-needle aspiration cytology (FNAC) is a proven diagnostic technique for establishing the benign or malignant character of breast lesions. Several cytological grading systems have been proposed for grading of carcinoma breast, with results similar to histologic grades. AIMS: This study sought to evaluate the prognostic value of FNAC in invasive ductal carcinoma of breast by correlating it with histological grade. SETTINGS AND DESIGN: Tertiary care hospital, retrospective analytical study. PATIENTS AND METHODS: One hundred and fifty cases of breast carcinoma that underwent modified radical mastectomy consequent to an FNAC diagnosis were included in the study. Robinson's grading system and Elston-Ellis modification of Scarff-Bloom-Richardson grading system were used to assign cytologic and histologic grades, respectively. STATISTICAL ANALYSIS: The cytological grades were correlated with the histological grades using χ2-test and Spearman's rank correlation coefficient. The individual features of the cytological grades were correlated with the histological grades using Kappa coefficient and χ2-test. Values were considered significant at P < 0.05. RESULTS: A statistically significant association was observed between cytologic and histologic grades (r = 0.97; P < 0.01) with sensitivity and specificity, respectively, of 100% and 93.95% for cytological grade 1, 100% and 100% for cytological grade 2 and 100% and 100% for cytological grade 3. Also, a positive correlation was found between each feature of the cytologic grade and the histologic grade (P < 0.05). Among these, a better correlation was demonstrated by cytological features like cell uniformity (Kappa coefficient = 0.50) and appearance of nucleoli (Kappa coefficient = 0.52). CONCLUSIONS: Robinson's cytologic grading system is a reliable grading method on FNAC smears of cases of carcinoma breast. It correlates well with Elston-Ellis modification of Scarff-Bloom-Richardson grade in invasive ductal carcinoma of breast.