Increased taxes and regulation of Indian cigarillos (bidi) industry: Effects on revenue and years of life lost.

INTRODUCTION: Indian cigarillos (bidi) are low-cost alternatives to cigarettes with only 22% imposed taxes, and turnover of upto INR 4 million per annum exempted from taxation. This paper estimates revenue implications and potential loss of life years (YLLs) averted, if bidi industry is subjected to increased regulations and taxation. METHODS: Revenue estimated at 10% increased regulation and 100% regulation were calculated, followed by estimates at taxes equivalent to cigarettes and World Health Organization - Framework Convention on Tobacco Control (WHO-FCTC) recommendation. Price elasticity was considered to assess demand. Price change in separate fractions (previously regulated and unregulated) were calculated to obtain potential YLLs averted. RESULTS: Current revenue of USD 59.25 million is projected to increase to USD 179.25 million with 695,159 averted YLLs at cigarette equivalent taxes and 10% increased regulation; USD 639.38 million with 4,527,597 averted YLLs with 100% regulation; USD 54.75 million, at WHO recommended taxes with 2,233,740 YLLs averted at 10% increased regulation, and 10,486,192 YLLs at 100% regulation. CONCLUSION: Proposed estimates are inline with WHO recommendations as they consider price elasticity and suggest substantial increase in revenue, while averting YLLs. A national action is needed to drive the policy decisions towards increased regulation and taxation and revision of India's tobacco control legislation. IMPLICATIONS: Our study presented empirical evidence of how the currently underutilized tool of taxation, as proposed in the WHO-FCTC, can be utilized to decrease bidi smoking prevalence and save measurable life years while generating government revenue simultaneously. While the revenue statistics counter the misleading tobacco industry narratives, the projected reduction in mortality will be seen as an irrefutable driving force for policy reforms, targeted at strategic increase in regulation and taxation of the traditional Indian cigarillos industry.

Electronic-PRO Measures for adverse events Of Treatment In ONcology (E-PROMOTION).

PURPOSE: Cancer patients struggle with the trauma of the disease and its treatment. PRO-CTCAE was developed to improve the recording of underreported symptomatic toxicities. We evaluated the improvement and ease in reporting symptomatic adverse events through add-on PRO-CTCAE (via a mobile application) compared to standard clinician-reported outcomes in routine clinical practice. We also evaluated changes in the health-related quality of life (HRQoL). METHODS: 110 cancer patients were studied for three weeks between their first and second chemotherapy session. HRQoL was assessed using EORTC QLQ-c30. RESULTS: Fifty-three patients self-reported their symptomatic adverse events on the day 7th & day 14th after the first cycle of chemotherapy. For the other fifty-seven patients, recording of adverse events was done by standard clinician-reported outcomes. All the patients in the study group reported adverse events compared to only 21 % in the standard reporting group. All 15 domains of adverse events were reported in the self-reporting group compared to only 5 in the standard reporting group. The self-reporting group had a significantly better overall quality of life. CONCLUSIONS: Self-reporting of adverse events using mobile app-based PRO-CTCAE helps patients and clinicians with better documentation of symptomatic toxicities of chemotherapy, reducing the burden on physicians and improving patient satisfaction. Mobile app-based self-reporting empowers cancer patients undergoing treatment, improves their quality of life, and should be implemented in routine clinical practice. Wider implementation can lead to further optimised solutions.

Estimating the weight of consumed tobacco product waste in various Indian states: a novel method to assess the potential burden of tobacco product waste.

INTRODUCTION: The direct morbidity and mortality caused by tobacco are well documented, but such products also contribute to a range of environmental pollutants resulting from tobacco product waste. No previous studies have yet quantified tobacco product waste in a low-income and middle-income country (LMIC). This study estimates the potential annual waste generated due to consumption of smoked and smokeless tobacco products in India and its states. METHODOLOGY: We systematically collected samples of smoked and smokeless tobacco products from 33 districts of 17 Indian states/union territories. Stratified weights of plastic, paper, foil and filter packaging components, and gross empty package weights were recorded. Prevalence of smoking and smokeless tobacco use at national and state-level estimates was derived from the Global Adult Tobacco Survey (2016-2017) to quantify waste potentially generated by tobacco products. RESULTS: We included 222 brands of tobacco products (70 cigarette, 94 bidi and 58 smokeless tobacco brands) in the final analysis. A total of 170 331 (±29 332) tonnes of waste was estimated to be generated annually, out of which 43.2% was plastic, 3.6% was foil and 0.8% was filter. Two-thirds of the overall waste was contributed by smokeless products alone. Maximum waste was generated in Uttar Pradesh (20.9%; 35 723.7±6151.6 tonnes), Maharashtra (8.9%; 15 116.84±2603.12 tonnes) and West Bengal (8.6%; 14 636.32±2520.37 tonnes). CONCLUSION: This study provides first of its kind national-level evidence on the types (plastic, paper, foil and filter) and quantity of waste potentially generated by use of tobacco products in India. Similar studies from other LMICs can serve to raise consciousness about many negative environmental impacts of tobacco products and need for policies to address them.

Effects of Sudarshan KriyaYoga and Advanced Meditation Program on Genetic Expression of Pro-inflammatory and Antioxidants Genes.

Background Stress leads to immune system dysregulation and dyshomeostasis at the gene level. Mind-body practices are known to influence genomic expression, leading to better health and quality of life. Objective To assess the effect of Advanced Meditation Program (AMP) on the mRNA expression of pro-inflammatory and antioxidative genes among those already practicing Sudarshan Kriya Yoga (SKY). Methods A total of 97 healthy volunteers participated in the study, distributed into two groups. The Group I SKY practitioners attended a four-day AMP (50 participants with an average age of 38.8 ± 11.9 consisting of 37 females and 13 males); they are first-time participants of the AMP. Group II SKY practitioners, on the other hand, consisted of 47 participants with an average age of 36.4 ± 9.3 with 43 females and four males. At day 0, day 5, and day 90, the mRNA expression of pro-inflammatory genes, namely interleukin (IL) 1ß, IL6, and the tumor necrosis factor (TNF), and the expression of antioxidative genes, namely superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) was observed. The data were analysed in two phases due to the emergence of coronavirus disease 2019 (COVID-19): (i) pre-COVID-19 and (ii) during COVID-19. Results In the pre-COVID-19 data set, IL1ß, IL6, and TNF were found to have decreased in both groups. There is a significant increase in the expression of SOD and catalase in Group I and a decrease in Group II by day 90. During COVID-19, pro-inflammatory genes increased in Group I and had no significant change in Group II. All three antioxidant genes had decreased expression by day 90 in Group I; SOD decreased in Group II. Interpretation and conclusions Reduced expression of pro-inflammatory genes and increase in the expression of antioxidative genes during the pre-COVID-19 time suggest that the practice of SKY and added AMP may enhance antioxidative defense and may reduce the chance of getting diseases related to inflammation in the body.

Death, Disability, and Premature Life Years Lost Due to Cigarettes, Bidis, and Smokeless Tobacco in India: A Comparative Assessment.

Background: Due to the staggering number of tobacco users in India, it is important to determine the exact mortality and morbidity rates due to tobacco use. This study aimed to estimate deaths, disability-adjusted life years (DALYs), and years of life lost (YLLs) attributable to cigarettes, bidis, and smokeless tobacco (SLT) in India. Methods: Data pooling and meta-analysis were done using case-control studies available on the three types of tobacco products. Health burden was estimated by applying the population attributable fraction (PAF) value to the total disease burden. Findings: A total of 33 studies were included. PAF was calculated for oral and lung cancer as well as ischemic heart disease (IHD) due to cigarettes, oral and lung cancer, IHD, and chronic obstructive pulmonary disease due to bidi, and oral and stomach cancer and IHD due to SLT. Cigarettes resulted in 8.4 million DALYs, 8.26 million YLLs, and 341 deaths; bidis led to 11.7 million DALYs, 10.7 million YLLs, and 478 thousand deaths, and SLTs accounted for 4.38 million DALYs, 4.3 million YLLs, and 171 thousand deaths annually. Conclusion: Evidence of measurable health burden and methodology for calculation for individual states was provided in the study. The generated evidence could be utilized for policy recommendations and revision of the existing taxation norms.

Apremilast Add-On Benefits Over Conventional Drugs (ABCD) in Unstable Non-segmental Vitiligo: A 12-Week Single-Center Randomized Controlled Trial.

Background Apremilast is an oral phosphodiesterase-4 enzyme inhibitor that modulates the immune system by increasing intracellular cyclic adenosine monophosphate levels and inhibiting inflammatory cytokines synthesis. We aimed to compare the efficacy and safety of add-on apremilast in combination therapy with standard treatment in patients with unstable, non-segmental vitiligo. Methods The study was a 12-week randomized, controlled, parallel-group, open-labeled trial. The control group received standard treatment (n=15), and the intervention group received 30 mg apremilast twice daily in addition to standard treatment (n= 16). Time to the first sign of re-pigmentation, halt in progression, and change in vitiligo area scoring index (VASI) score is the primary outcomes. Normality was assessed, and appropriate parametric and nonparametric tests were undertaken. Results Thirty-seven participants were randomized into two groups, and analysis was done on thirty-one participants. Over the treatment duration of 12 weeks, the median time to observe the first sign of re-pigmentation was four weeks in the add-on apremilast group compared to seven weeks in the control group (p=0.018). The halt in progression was observed more in the add-on Apremilast group (93.75%) compared to the control group (66.66%) (p=0.08). The VASI score decreased by 1.24 in the add-on apremilast group and 0.05 in the control group (p= 0.754). Parameters including body surface area, dermatology life quality index, and body mass index reduced significantly, while the visual analog scale increased significantly in the add-on apremilast group. However, results were comparable between groups. Conclusions Treatment with add-on apremilast accelerated clinical improvement. It also reduced disease progression and improved the disease index among participants. However, add-on apremilast had a lower tolerability profile than the control group.

Relationship between biochemical parameters of mineral bone disease and static bone histomorphometry in chronic kidney disease patients on hemodialysis: An Indian cross-section study.

AIM: We estimated the relationship between routine biochemical laboratory parameters with static bone histomorphometric parameters and their high and low bone turnover capacity predictability in hemodialysis patients. METHOD: It was a single-center cross-sectional study, included 28 hemodialysis patients. The routine biochemical parameters measured including calcium, phosphorous, alkaline phosphatase, intact PTH, and 25-hydroxycholecalciferol. The histomorphometric parameters assessed were osteoblasts perimeter, osteoclast perimeter, eroded perimeter, osteoid perimeter, bone fibrosis and bone volume. RESULT: Total 28 hemodialysis patients underwent bone biopsy. Seventy percent were male, with a mean age was 33.07±10.42 yrs; serum alkaline phosphatase was 219.10±311.3IU/ml; vitamin D was 18.18±9.56ng/ml, and intact PTH was 650.7±466.0pg/ml. Intact PTH had a significant positive association with osteoblast, osteoclast, eroded surface, and osteoid perimeter. Serum alkaline phosphatase had a significant relationship with bone fibrosis (r=0.525, p-value=0.004). Intact PTH was significantly higher in females than males (1078.75±533.04 vs. 479.6±309.83; p-value=0.004). The osteoid surface was significantly high in females compared to males (p=0.038). Age had a significant impact on osteoblast and eroded surface (p=0.008 and p=0.031, respectively). Intact PTH is a reliable biomarkers for bone turnover compare to ALP (p<0.001 and p=0.554, respectively). CONCLUSION: Intact PTH strongly associated with bone formation, bone resorption parameters. Gender and age had significant impact on static histomorphometric parameters in our study.

Computational study of novel inhibitory molecule, 1-(4-((2S,3S)-3-amino-2-hydroxy-4-phenylbutyl)piperazin-1-yl)-3-phenylurea, with high potential to competitively block ATP binding to the RNA dependent RNA polymerase of SARS-CoV-2 virus.

For coronaviruses, RNA-dependent RNA polymerase (RdRp) is an essential enzyme that catalyses the replication from RNA template and therefore remains an attractive therapeutic target for anti-COVID drug discovery. In the present study, we performed a comprehensive in silico screening for 16,776 potential molecules from recently established drug libraries based on two important pharmacophores (3-amino-4-phenylbutan-2-ol and piperazine). Based on initial assessment, 4042 molecules were obtained suitable as drug candidates, which were following Lipinski's rule. Molecular docking implemented for the analysis of molecular interactions narrowed this number of compounds down to 19. Subsequent to screening filtering criteria and considering the critical parameters viz. docking score and MM-GBSA binding free energy, 1-(4-((2S,3S)-3-amino-2-hydroxy-4-phenylbutyl)piperazin-1-yl)-3-phenylurea (compound 1) was accomplished to score highest in comparison to the remaining 18 shortlisted drug candidates. Notably, compound 1 displayed higher docking score (-8.069 kcal/mol) and MM-GBSA binding free energy (-49.56 kcal/mol) than the control drug, remdesivir triphosphate, the active form of remdesivir as well as adenosine triphosphate. Furthermore, a molecular dynamics simulation was carried out (100 ns), which substantiated the candidacy of compound 1 as better inhibitor. Overall, our systematic in silico study predicts the potential of compound 1 to exhibit a more favourable specific activity than remdesivir triphosphate. Hence, we suggest compound 1 as a novel potential drug candidate, which should be considered for further exploration and validation of its potential against SARS-CoV-2 in wet lab experimental studies.Communicated by Ramasawamy H. Sarma.

Detection of nerve fibers in the eutopic endometrium of women with endometriosis, uterine fibroids and adenomyosis.

OBJECTIVE: The primary objective of this study was to establish the presence of nerve fibers in the eutopic endometrium of women with endometriosis and to determine whether these nerve fibers are exclusive to endometriosis or are also found in other pelvic pathologies associated with dysmenorrhea. METHODS: Endometrial tissue was obtained by aspiration (Pipelle), endometrial curettage, or following hysterectomy in women with endometriosis confirmed through histopathological examination, leiomyomas, and adenomyosis. The eutopic endometrium was subjected to immunohistochemical staining to detect PGP 9.5, which is a highly specific pan-neuronal marker. The nerve fiber density was correlated with the patient's pain score, as indicated by the Visual Analog Scale. A control group was formed by staining the endometrium of women presenting with dysmenorrhea but without the above-mentioned disorders. RESULTS: Nerve fibers were observed in sections of the endo-myometrium (in the deep endometrium) in 68% of patients with endometriosis who underwent hysterectomy or a deep endometrial biopsy. Nerve fibers were not observed in the aspirated endometrium of women with endometriosis. Only 13.7% of women with adenomyosis and 3.3% of women with fibroids had nerve fibers in their endometrium. Nerve fiber density was correlated with pain score in women with endometriosis. CONCLUSION: Nerve fibers were found in the functional layer of eutopic endometrium in women with endometriosis; hence, we concluded that the presence of nerve fibers in the eutopic endometrium could diagnose endometriosis with a fairly good specificity of 92.7%. However, the absence of nerve fibers does not always exclude the disease.

Synthesis of alkynylated 1,2,4-oxadiazole/1,2,3-1H-triazole glycoconjugates: Discovering new compounds for use in chemotherapy against lung carcinoma and Mycobacterium tuberculosis.

A total of forty-three compounds were synthesized, including thirty-two new ones. Among those compounds, seventeen were selected and tested on human tumor cell lines: PC-3 (prostate adenocarcinoma), HCT-116 (colorectal tumor), NCIH-460 (lung carcinoma), SKMEL-103 (melanoma) and AGP-01 (gastric tumor). Alkynylated 1,2,4-oxadiazoles 2m, 3g and 3k exhibited antiproliferative activities against NCIH-460 in culture. Alkynylated N-cyclohexyl-1,2,4-oxadiazoles 3a-m and bis-heterocycle glucoglycero-1,2,3-triazole-N-cyclohexyl-1,2,4-oxadiazole derivatives 5a-k and 6-11 were evaluated for their in vitro efficacy towards Mycobacterium tuberculosis (Mtb) H37Ra and H37Rv strains. In general, glycerosugars conjugated to 1,2,4-oxadiazole via a 1,2,3-triazole linkage (5a, 5e, 5j, 5k, and 7) showed in vitro inhibitory activity against Mtb (H37Rv). The largest molecules bis-triazoles 10 and 11, proved inactive against TB. Probably, the absence of the N-cyclohexyl group in compound 8 and 1,2,4-oxadiazole nucleus in compound 9 were responsible for its low activity. Glucoglycero-triazole-oxadiazole derivatives 5e (10 µM) and 7 (23.9 µM) were the most promising antitubercular compounds, showing a better selective index than when tested against RAW 264.7 and HepG2 cells. Vero cell were used to investigate cytotoxicity of compounds 5a, 5h, 5j, 5k, and these compounds showed good cell viability. Further, in silico studies were performed for most active compounds (5e and 7) with potential drug targets, DprE1 and InhA of Mtb to understand possible interactions aided with molecular dynamic simulation (100ns).

Vascular patterns on narrow band imaging (NBI) video bronchoscopy of lung cancer patients and its relationship with histology: an analytical cross-sectional study.

INTRODUCTION: Narrow band imaging (NBI) video bronchoscopy provides better visualisation of submucosal vascular patterns in malignant airway lesions compared to white light bronchoscopy. This analytical cross-sectional study was aimed to look for any relationship between these NBI vascular patterns and the histologic type of lung cancer. MATERIAL AND METHODS: After screening 78 patients with suspected lung cancer, 53 subjects underwent video bronchoscopy. Thirty-two patients showing abnormal bronchial mucosa or endobronchial growth with any of the NBI vascular patterns on bronchoscopy were enrolled in the study. These abnormal areas were then biopsied and sent for histologic examination. RESULTS: NBI bronchoscopy revealed a dilated tortuous vascular pattern in 54.8% of the patients, a non-specific pattern in 32%, a dotted pattern in 9.7% and an abrupt ending vessels pattern in 3.2% of the patients. We did not find any statistically significant relationship between a dilated tortuous pattern and squamous-cell carcinoma (p = 0.48), adenocarcinoma (p = 0.667) or small-cell carcinoma (p = 1); between a dotted pattern and squamous-cell carcinoma (p = 1), adenocarcinoma (p = 0.54) or small-cell carcinoma (p = 1), and between an abrupt ending capillary pattern and squamous-cell carcinoma (p = 1), adenocarcinoma (p = 1) or small-cell carcinoma (p =1). CONCLUSION: No relationship exists between NBI vascular patterns and the histology of lung cancer. Endobronchial lesions showing any vascular pattern on NBI needs to be adequately sampled for proper histologic and molecular studies in lung cancer patients.

In silico identification of potential inhibitor for TP53-induced glycolysis and apoptosis regulator in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the six most common cancer globally and most common cancer in men in India. The metabolic regulation is highly altered and is considered as a hall mark of HNSCC. TP53-induced glycolysis and apoptosis regulator (TIGAR) plays very important role in the development and progression of HNSCC. The aim of our study is to identify a novel FDA approved anticancer inhibitor against mutated TP53-induced glycolysis and apoptosis regulator (TIGAR) through drug repurposing approach. A library of 105 FDA approved anticancer compounds were screened using molecular docking approach against TIGAR (PDB: 3DCY) both Wild-Type (WT) and mutated (Mut). Specific mutations in TIGAR were identified using cBioPortal, a cancer genomics database and mutated structure was modelled using SWISS-MODEL. Out of 510 sequenced cases/patients samples, 17(3%) patients showed alteration in TIGAR [TIGARWT and TIGARMut (R88W)]. The virtual drug screening showed 45 drugs out of 105 high binding affinity with TIGAR, Trabectedin showed highest binding affinity with both TIGARWT (- 13.3 kcal/mol) as well as TIGARMut (R88W) (- 13.8 kcal/mol). The molecular docking studies were validated using molecular dynamics simulation (MD Simulation) of protein-ligand complex of TIGAR and Trabectedin for 100 ns. The MD Simulation of Trabectedin complex showed more stable with TIGARMut (R88W) compared to TIGARWT. Moreover, the string analysis revealed that metabolic-related genes, HK2, PFKFB1, PFKM, PFKP, PFKL, FBP1 are closely associated with TIGAR in HNSCC. Our findings suggest that Trabectedin can be proposed as an inhibitor for [TIGARMut (R88W)] which can be used to target metabolic signalings in HNSCC. However, further investigation and in vitro and in vivo validation our findings required to understand the molecular mechanisms of regulation of Trabectedin in HNSCC.

Tobacco, alcohol use and other risk factors for developing symptomatic COVID-19 vs asymptomatic SARS-CoV-2 infection: a case-control study from western Rajasthan, India.

BACKGROUND: Understanding risk factors of symptomatic coronavirus disease 2019 (COVID-19) vis-à-vis asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severe disease and death is important. METHODS: An unmatched case-control study was conducted through telephonic interviews among individuals who tested positive for SARS-CoV-2 in Jodhpur, India from 23 March to 20 July 2020. Contact history, comorbidities and tobacco and alcohol use were elicited using standard tools. RESULTS: Among 911 SARS-CoV-2-infected individuals, 47.5% were symptomatic, 14.1% had severe COVID-19 and 41 (4.5%) died. Older age, working outside the home, cardiac and respiratory comorbidity and alcohol use were found to increase the risk of symptomatic disease as compared with asymptomatic infection. Current tobacco smoking (odds ratio [OR] 0.46 [95% confidence interval {CI} 0.26 to 0.78]) but not smokeless tobacco use (OR 0.81 [95% CI 0.55 to 1.19]) appeared to reduce the risk of symptomatic disease. Age ≥60 y and renal comorbidity were significantly associated with severe COVID-19. Age ≥60 y and respiratory and cardiac comorbidity were found to predispose to mortality. CONCLUSIONS: The apparent reduced risk of symptomatic COVID-19 among tobacco smokers could be due to residual confounding owing to unknown factors, while acknowledging the limitation of recall bias. Cross-protection afforded by frequent upper respiratory tract infection among tobacco smokers could explain why a similar association was not found for smokeless tobacco use, thereby being more plausible than the 'nicotinic hypothesis'. Those with comorbidities and age ≥60 y should be prioritized for hospital admission.

Blood lead levels in antenatal women and its association with iron deficiency anemia and adverse pregnancy outcomes.

OBJECTIVES: Lead is one of the most toxic heavy metal prevalent in the environment, which affects almost all major organs including heart, brain, intestines, kidneys as well as reproductive organs. It has been known that serum iron deficiency is associated with increased serum lead levels as lead is a particularly pernicious element to iron metabolism. Lead is also known to freely cross the placenta too; hence, this study was planned to determine any association between antenatal iron deficiency anemia (IDA), raised blood lead levels (BPb), and adverse pregnancy outcomes. MATERIALS AND METHODS: This was an observational study done on 99 antenatal women with IDA and 41 nonanemic antenatal women. Lead levels were assessed in these 140 antenatal women and they were followed for adverse pregnancy outcomes. Chi-square test was used to find a difference in quantitative variables and Pearson's correlation test was used to assess association between BPb and hemoglobin levels. RESULTS: We found that in 11 out of 99 (11.11%) women with IDA, BPb levels were high as compared to high BPb levels in only 1 out of 41 (2.4%) women without IDA and the high BPb levels ranged from 4 µg/dl-16.9 µg/dl with a mean BPb of 8.1 µg/dl. The difference in BPb among anemic and nonanemic antenatal women was significant (P < 0.05) and there was a negative dose effect relationship between BPb levels and hemoglobin levels. This difference in antenatal outcomes among women with and without high BPb levels was also significant with increased incidence of pre-eclampsia, FGR, and preterm deliveries in women with raised BPb levels. The incidence of NICU admission was also higher in the neonates of mothers with high BPb levels. CONCLUSIONS: We propose screening of high-risk women based on their social, occupational, environmental, and personal factors, with serum lead levels in the preconception period itself. All public and personal measures must be taken to reduce lead consumption and exposure in the preconception and antenatal period.

Discovery of New Hydroxyethylamine Analogs against 3CLpro Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies.

The novel coronavirus, SARS-CoV-2, has caused a recent pandemic called COVID-19 and a severe health threat around the world. In the current situation, the virus is rapidly spreading worldwide, and the discovery of a vaccine and potential therapeutics are critically essential. The crystal structure for the main protease (Mpro) of SARS-CoV-2, 3-chymotrypsin-like cysteine protease (3CLpro), was recently made available and is considerably similar to the previously reported SARS-CoV. Due to its essentiality in viral replication, it represents a potential drug target. Herein, a computer-aided drug design (CADD) approach was implemented for the initial screening of 13 approved antiviral drugs. Molecular docking of 13 antivirals against the 3-chymotrypsin-like cysteine protease (3CLpro) enzyme was accomplished, and indinavir was described as a lead drug with a docking score of -8.824 and a XP Gscore of -9.466 kcal/mol. Indinavir possesses an important pharmacophore, hydroxyethylamine (HEA), and thus, a new library of HEA compounds (>2500) was subjected to virtual screening that led to 25 hits with a docking score more than indinavir. Exclusively, compound 16 with a docking score of -8.955 adhered to drug-like parameters, and the structure-activity relationship (SAR) analysis was demonstrated to highlight the importance of chemical scaffolds therein. Molecular dynamics (MD) simulation analysis performed at 100 ns supported the stability of 16 within the binding pocket. Largely, our results supported that this novel compound 16 binds with domains I and II, and the domain II-III linker of the 3CLpro protein, suggesting its suitability as a strong candidate for therapeutic discovery against COVID-19.

Impact of Oral Submucous Fibrosis on Quality of Life: A Multifactorial Assessment.

BACKGROUND: Oral submucous fibrosis (OSMF) has been extensively researched for its etiopathogenesis, malignant potential, and various available treatment modalities, but its effect on different domains of patient's life has not been thoroughly investigated. The present study aimed to clearly construe the effects of OSMF like severity and demographic variables on different domains of quality of life in OSMF patients. METHODS: A cross-sectional study was conducted in the Department of Dentistry, AIIMS Jodhpur, India. A total of 200 patients (after informed consent) were selected and detailed proforma filled including patient's demographics, habits, clinical features, and quality of life using a World Health Organization Quality of life-BREF tool (WHOQOL-BREF questionnaire). Thereafter, interpretation and statistics were done by a separate trained examiner minimizing the risk of assessment bias. RESULT: Quality of life (QOL) scores differed significantly according to age, site affected, habit duration, and severity of OSMF. It, however, did not differ according to gender. CONCLUSION: In this study, there has been a statistically significant deterioration of quality of life in OSMF patients in all the domains. Realization of this would increase our chance to bring the focus of the society and its policy makers to confront the growing menace of OSMF.

Impact of Oral Submucous Fibrosis on Quality of Life: A Cross-Sectional Study.

BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic disease of the oral cavity which presents clinically with burning sensation, leathery consistency of oral mucosa with palpable fibrous bands leading to reduced mouth opening. Though the evaluation of quality of life (QOL) in health care is gaining importance, researches regarding the evaluation of QOL in OSMF individuals are very sparse. AIM: The aim of the present study is to evaluate the QOL assessment in OSMF patients through WHOQOL-BREF questionnaire. METHODOLOGY: The study includes a total of 300 participants recruited from the outpatient department. The quality of life was assessed using the WHOQOL-BREF questionnaire. The raw scores for the physical health, psychological health, social relationships and environmental health domains were done on 4-20 scale suggested by the WHOQOL procedural manual. The analysis of variance (ANOVA) was used for the simultaneous comparison of mean scores for the four domains, and independent t test was used for the comparison of two means of domain scores. RESULTS: The participants with OSMF have a significant negative impact on the quality of life when compared with the participants without OSMF (P = 0.002). The environmental factors in the WHOQOL-BREF have shown a significant difference in the QOL of participants with OSMF than without OSMF (P = 0.001). CONCLUSION: The oral submucous fibrosis has a negative impact on the quality of life in participants with OSMF specifically in social and environmental domains of the WHOQOL-BREF questionnaire.