Volumetric Analysis of Hand and Rotary Instrumentation, Root Canal Filling Techniques, and Obturation Materials in Primary Teeth Using Spiral CT.

AIM AND BACKGROUND: To compare the root canal volume in primary teeth using hand and rotary instruments and to evaluate root canal filling techniques and flow of root canal obturation materials in the postinstrumented root canal volume using spiral computed tomography (SCT). MATERIALS AND METHODS: Freshly extracted 16 primary molars were randomly divided into two groups and subjected to SCT analysis before and after instrumentation. For the manual technique (group I) with eight teeth were prepared using K files, and rotary (group II) eight teeth preparation was performed with ProTaper files. The filled volume in each canal was measured using SCT, and the percentage of obturated volume was calculated. The data were statistically analyzed using the Mann-Whitney U test. RESULTS: There was a statistically significant difference in both groups' volume of root canals enlarged. Even though both K files and the ProTaper system brought about enlarged canals after instrumentation, there was a statistically significant increase in volume after using K files in two canals. In three canals, there was a statistically significant increase in volume after using ProTaper. Irrespective of the obturation technique and materials used, there is no statistically significant difference in the volume after obturation. CONCLUSION: From the results of this study, the ProTaper file system shows suitable volumetric enlargement up to an optimum level, which is needed in primary root canal walls, and is better in canal shaping, as evidenced by good postobturation volume. CLINICAL SIGNIFICANCE: The traditional method of cleaning and shaping the root canals in permanent teeth using manual stainless-steel files can lead to undesirable curvatures in root canal morphology, making correctly filling the root canals difficult. It is also time-consuming and sometimes leads to iatrogenic errors. Rotary nickel-titanium (Ni-Ti) instrumentation techniques have been developed to overcome these problems. How to cite this article: Yadav DBUC, Varma RB, Kumar JS, et al. Volumetric Analysis of Hand and Rotary Instrumentation, Root Canal Filling Techniques, and Obturation Materials in Primary Teeth Using Spiral CT. J Contemp Dent Pract 2024;25(3):250-259.

Pleural effusion guidelines from ICS and NCCP Section 1: Basic principles, laboratory tests and pleural procedures.

Pleural effusion is a common problem in our country, and most of these patients need invasive tests as they can't be evaluated by blood tests alone. The simplest of them is diagnostic pleural aspiration, and diagnostic techniques such as medical thoracoscopy are being performed more frequently than ever before. However, most physicians in India treat pleural effusion empirically, leading to delays in diagnosis, misdiagnosis and complications from wrong treatments. This situation must change, and the adoption of evidence-based protocols is urgently needed. Furthermore, the spectrum of pleural disease in India is different from that in the West, and yet Western guidelines and algorithms are used by Indian physicians. Therefore, India-specific consensus guidelines are needed. To fulfil this need, the Indian Chest Society and the National College of Chest Physicians; the premier societies for pulmonary physicians came together to create this National guideline. This document aims to provide evidence based recommendations on basic principles, initial assessment, diagnostic modalities and management of pleural effusions.

Genome-wide CRISPR screens in spheroid culture reveal that the tumor suppressor LKB1 inhibits growth via the PIKFYVE lipid kinase.

The tumor suppressor LKB1 is a serine/threonine protein kinase that is frequently mutated in human lung adenocarcinoma (LUAD). LKB1 regulates a complex signaling network that is known to control cell polarity and metabolism; however, the pathways that mediate the tumor-suppressive activity of LKB1 are incompletely defined. To identify mechanisms of LKB1-mediated growth suppression, we developed a spheroid-based cell culture assay to study LKB1-dependent growth. We then performed genome-wide CRISPR screens in spheroidal culture and found that LKB1 suppresses growth, in part, by activating the PIKFYVE lipid kinase. Finally, we used chemical inhibitors and a pH-sensitive reporter to determine that LKB1 impairs growth by promoting the internalization of wild-type EGFR in a PIKFYVE-dependent manner.

Evaluation of the surface characteristics and antibacterial properties of Titanium dioxide nanotube and methacryloyloxyethylphosphorylcholine (MPC) coated orthodontic brackets-a comparative invitro study.

OBJECTIVES: White spot lesions are the most common iatrogenic effect observed during orthodontic treatment. This study aimed to compare the surface characteristics and antibacterial action of uncoated and coated orthodontic brackets. MATERIALS AND METHODS: Sixty commercially available stainless steel brackets were coated with TiO2 nanotubes and methacryloyloxyethylphosphorylcholine. The sample was divided into Group 1: uncoated orthodontic brackets, Group 2: Stainless steel brackets with TiO2 nanotubes coating, Group 3: Stainless steel brackets with methacryloyloxyethylphosphorylcholine coating, and Group 4: Stainless steel brackets with TiO2 nanotubes combined with methacryloyloxyethylphosphorylcholine coating. Surface characterization was assessed using atomic force microscopy and scanning electron microscopy. Streptococcus mutans was selected to test the antibacterial ability of the orthodontic brackets, total bacterial adhesion and bacterial viability were assessed. The brackets were subjected to scanning electron microscopy to detect the presence of biofilm. RESULTS: The surface roughness was the greatest in Group 1 and least in Group 2 followed by Group 4 and Group 3 coated brackets. The optical density values were highest in Group 1 and lowest in Group 4. Comparison of colony counts revealed high counts in Group 1 and low counts in Group 4. A positive correlation between surface roughness and colony counts was obtained, however, was not statistically significant. CONCLUSIONS: The coated orthodontic brackets exhibited less surface roughness than the uncoated orthodontic brackets. Group 4 coated orthodontic brackets showed the best antibacterial properties. CLINICAL RELEVANCE: Coated orthodontic brackets prevent adhesion of streptococcus mutans and reduces plaque accumulation around the brackets thereby preventing formation of white spot lesions during orthodontic treatment.

Is Percentage Improvement in Anteroposterior Pelvic Diameter a Valuable Marker for Successful Drainage Postpyeloplasty in Isolated Pediatric Pelvi-ureteric Junction Obstruction.

Context: Pelvic-ureteric junction obstruction (PUJO) causes urine stasis in the renal pelvis and progressive kidney damage. Postpyeloplasty improvement of renal function and urinary drainage is assessed by diuretic isotope renogram and ultrasonography. Renograms are expensive and have radiation exposure. This study explores whether ultrasound parameters such as percentage improvement in anteroposterior pelvic diameter (PI-APD) is a valuable markers for successful pediatric pyeloplasties. Aims: The aim of this study was to identify patients who would benefit from ultrasound monitoring of PI-APD alone instead of diuretic isotope renal scan for postoperative follow-up of pyeloplasty. Settings and Design: This was a retrospective descriptive study. Subjects and Methods: We analyzed 127 pediatric pyeloplasties performed and under follow-up between June 2016 and May 2021. We recorded the postoperative ultrasound and isotope renogram parameters. PI-APD (preoperative AP diameter - postoperative AP diameter)/preoperative AP diameter × 100) was compared with improvement in renogram parameters (differential renal function, Tmax, curve pattern, and retention) to look for a correlation between them. Statistical Analysis Used: SPSS version 20.5, Chi-square and paired t-test were used for statistical analysis. Results: About 73.2% of patients were males, with most cases detected antenatally (76.4%). The majority was left-sided PUJO (67.7%). The mean age at surgery was 30.8 months. We identified a statistically significant correlation between the ultrasound parameter PI-APD and the renogram parameter Tmax. There is no significant correlation between PI-APD and other renogram parameters. Conclusions: In patients whose ultrasound parameter PI-APD is >40% and renal parenchymal thickness has increased, isotope renograms can be avoided for follow-up of postpyeloplasty patients.

Medication Adherence in Cancer Patients: A Comprehensive Review.

Cancer is a complex disease that can affect different parts of the body. The rates of cancer have shown an increasing trend in the past decade. A majority of cancers are detected late, therefore becoming untreatable and resulting in significant mortality. Additionally, the lack of awareness about cancers, their risk factors, diagnostic modalities, and preventive measures contributes to increased burden among people. Despite significant developments in the therapeutic and comprehensive management of cancers, the cause for concern is the lack of medication adherence. This is majorly attributed to the adverse effects of the medication, the cost of the drugs, and other reasons. This review comprehensively discusses various aspects of cancer medication adherence that include therapeutic modalities for treating cancers, factors influencing medication adherence, barriers, and facilitators to medication adherence.

Vertical pathway inhibition of receptor tyrosine kinases and BAD with synergistic efficacy in triple negative breast cancer.

Aberrant activation of the PI3K/AKT signaling axis along with the sustained phosphorylation of downstream BAD is associated with a poor outcome of TNBC. Herein, the phosphorylated to non-phosphorylated ratio of BAD, an effector of PI3K/AKT promoting cell survival, was observed to be correlated with worse clinicopathologic indicators of outcome, including higher grade, higher proliferative index and lymph node metastasis. The structural optimization of a previously reported inhibitor of BAD-Ser99 phosphorylation was therefore achieved to generate a small molecule inhibiting the phosphorylation of BAD at Ser99 with enhanced potency and improved oral bioavailability. The molecule 2-((4-(2,3-dichlorophenyl)piperazin-1-yl)(pyridin-3-yl)methyl) phenol (NCK) displayed no toxicity at supra-therapeutic doses and was therefore assessed for utility in TNBC. NCK promoted apoptosis and G0/G1 cell cycle arrest of TNBC cell lines in vitro, concordant with gene expression analyses, and reduced in vivo xenograft growth and metastatic burden, demonstrating efficacy as a single agent. Additionally, combinatorial oncology compound library screening demonstrated that NCK synergized with tyrosine kinase inhibitors (TKIs), specifically OSI-930 or Crizotinib in reducing cell viability and promoting apoptosis of TNBC cells. The synergistic effects of NCK and TKIs were also observed in vivo with complete regression of a percentage of TNBC cell line derived xenografts and prevention of metastatic spread. In patient-derived TNBC xenograft models, NCK prolonged survival times of host animals, and in combination with TKIs generated superior survival outcomes to single agent treatment. Hence, this study provides proof of concept to further develop rational and mechanistic based therapeutic strategies to ameliorate the outcome of TNBC.

Atezolizumab plus bevacizumab as a downstaging therapy for liver transplantation in hepatocellular carcinoma with portal vein thrombosis: The first report.

Atezolizumab plus bevacizumab is the preferred first-line treatment regimen for patients with advanced hepatocellular carcinoma. Limited data have shown promising results with the use of immune checkpoint inhibitors like nivolumab to downstage these patients for liver transplantation (LT). Here, we describe the first case of successful downstaging with atezolizumab plus bevacizumab in a patient with multifocal hepatocellular carcinoma and main portal vein tumoral thrombosis, followed by ABO-incompatible live donor LT. This illustrated case highlights that atezolizumab plus bevacizumab therapy may be a potential bridging tool for curative LT.

Risk Factors for Unfavorable Glycemic Control Trajectory in Type-2 Diabetes Mellitus: A Community-based Longitudinal Study in Urbanslums of Central India.

BACKGROUND: Diabetes mellitus (DM) is a chronic disease, which requires optimal glycemic control to prevent its ensuing vascular complications. Pathway to optimal glycemic control in T2DM has a complex socio-behavioral construct, especially in vulnerable populations, like slum dwellers, who have reduced health-care access and lower prioritization of health needs. OBJECTIVE: The study aimed to map trajectories of glycemic control amongst individuals with T2DM living in urban slums and identify key determinants associated with unfavourable glycaemic trajectory. METHODS: This study was a community-based longitudinal study conducted in an urban slum of Bhopal in Central India. Adult patients diagnosed with T2DM and on treatment for more than one year were included. All 326 eligible participants underwent a baseline interview, which captured sociodemographic, personal behavior, medication adherence, morbidity profile, treatment modality, anthropometric and biochemical measurements (HbA1c). Another 6-month follow-up interview was conducted to record anthropometric measurements, HbA1c and treatment modality. Four mixed effect logistic regression models (through theory-driven variable selections) were created with glycemic status as dependent variable and usage of insulin was considered as random effect. RESULTS: A total of 231 (70.9%) individuals had unfavorable glycemic control trajectory (UGCT), and only 95 (29.1%) had a favorable trajectory. Individuals with UGCT were more likely to be women, with lower educational status, non-vegetarian food preference, consumed tobacco, had poor drug adherence, and were on insulin. The most parsimonious model identified female gender (2.44,1.33-4.37), tobacco use (3.80,1.92 to 7.54), and non-vegetarian food preference (2.29,1.27 to 4.13) to be associated with UGCT. Individuals with good medication adherence (0.35,0.13 to 0.95) and higher education status (0.37,0.16 to 0.86) were found to be protective in nature. CONCLUSION: Unfavorable glycemic control trajectory seems to be an inescapable consequence in vulnerable settings. The identified predictors through this longitudinal study may offer a cue for recognizing a rational response at societal level and adopting strategy formulation thereof.

Vetting of New 2,5-Bis (2,2,2-trifluoroethoxy) Phenyl-Linked 1,3-Thiazolidine-4-one Derivatives as AURKA and VEGFR-2 Inhibitor Antiglioma Agents Assisted with In Vitro and In Silico Studies.

The bioactivity of 1,3-thiazolidin-4-one derivatives with a 2,5-bis (2,2,2-trifluoroethoxy) phenyl moiety was computationally developed and evaluated. All of the synthesized thiazolidin-4-one derivatives have their chemical structures characterized using a variety of methods, including nuclear magnetic resonance (NMR) (1H and 13C), high-resolution mass spectrometry (HRMS), and Fourier transform infrared (FTIR) radiation. A human glioblastoma cancer cell line (LN229) was used to investigate the purified derivatives' antiglioma cancer efficacy. By using the MTT, colony formation, and tunnel tests, respectively, the in vitro cytotoxic and apoptotic effects of these compounds were assessed. Thiazolidin-4-one derivatives 5b, 5c, and 5e were discovered to have the best efficacy against glioblastoma cells out of all of these compounds. The derivatives 5b, 5c, and 5e were determined to have respective IC50 values of 9.48, 12.16, and 6.43 g/mL. Computation results showed that the bioactivity evaluations of the compounds were quite significant. The bridging -NH group forms a hydrogen bond with Glu 260 of synthesized derivatives 5b, 5c, 5d, 5e, and 5h. The vast majority of freshly developed compounds obeyed Lipinski's rule of five, which is in line with the results that the ADMET model predicted. Additionally, molecular docking evaluation and molecular dynamics simulation investigations against the proteins AURKA and VEGFR-2 were conducted for the synthesized compounds to incorporate both in silico and in vitro data. The findings revealed that almost all of the compounds had considerable binding to AURKA and VEGFR-2 residues, with binding affinities ranging from -9.8 to -7.9 kcal/mol. Consequently, the results of the biological investigations and the docking scores demonstrated that thiazolidinone molecule 5e containing 4-chlorophenyl substituent may be considered as a potential moiety for glioblastoma cancer treatments.

Disability Certification for Parkinson's Disease in India: Challenges and the Way Forward.

Disability certification is mandatory for people with Parkinson's disease to avail any schemes and benefits in India. The process of certification of the extent of disability in a complex disorder like Parkinson's needs to be made less cumbersome and streamlined to ensure that people for whom the benefits are meant are able to avail them.

LKB1 suppresses growth and promotes the internalization of EGFR through the PIKFYVE lipid kinase.

The tumor suppressor LKB1 is a serine/threonine protein kinase that is frequently mutated in human lung adenocarcinoma (LUAD). LKB1 regulates a complex signaling network that is known to control cell polarity and metabolism; however, the pathways that mediate the tumor suppressive activity of LKB1 are incompletely defined. To identify mechanisms of LKB1- mediated growth suppression we developed a spheroid-based cell culture assay to study LKB1- dependent growth. Using this assay, along with genome-wide CRISPR screens and validation with orthogonal methods, we discovered that LKB1 suppresses growth, in part, by activating the PIKFYVE lipid kinase, which promotes the internalization of wild-type EGFR. Our findings reveal a new mechanism of regulation of EGFR, which may have implications for the treatment of LKB1 -mutant LUAD.

Assessment of potential predictors affecting preoperative anxiety in Indian children- A prospective observational study.

Background and Aims: Preoperative anxiety is a common problem among children undergoing surgery. The aim of the study was to assess the incidence and identify various predictors of preoperative anxiety in Indian children. Material and Methods: A prospective, observational study was conducted on 60 children of the American Society of Anesthesiologists Physical status 1/2, aged 2-6 years and scheduled for elective surgery under general anesthesia in a tertiary care teaching hospital. Preoperative parental anxiety was assessed using the State-Trait Anxiety Inventory questionnaire. The children's anxiety was assessed in the preoperative room, at the time of parental separation, and at the induction of anesthesia using modified Yale Preoperative Anxiety Scale (mYPAS) scoring by an anesthesiologist and a psychologist. Sedative premedication was employed prior to parental separation. Logistic regression analysis was carried out to identify the possible predictors of anxiety. Results: The incidence of high preoperative anxiety among the studied children was 76% in the preoperative room, 93% during parental separation, and 96% during anesthetic induction. Among the nine possible predictors identified on univariate regression, the presence of siblings was found to be a significant independent predictor on multivariate regression analysis (P = 0.04). The inter-rater agreement was excellent for the assessment of preoperative anxiety using mYPAS by the anesthesiologist and psychologist (weighted Kappa, k = 0.79). Conclusion: The incidence of preoperative anxiety in Indian children in the age group of 2-6 years is very high. The preop anxiety escalates progressively at parental separation and induction of anesthesia despite sedative premedication. The presence of siblings is a significant predictor of preoperative anxiety.

Incidence and Comparison of Suicide in Various Phases of the Menstrual Cycle: a Systematic Review and Meta-analysis.

Background: Suicide is a global health concern. There are reproductive health-related factors that are responsible for increasing the risk of female suicide. There are a number of studies examining the association between suicide and the menstrual cycle, but still, there are no conclusive findings. Aim: We aimed to pool data from all the studies reporting data on suicides and the menstrual cycle phase to report the following outcomes: incidence of suicidal deaths in the menstrual, secretory, and proliferative phases, and to find out whether the burden of suicide in the menstrual phase in particular, was more at a young age (18-35 years) or middle age (36-50years). Methods: The PubMed database was extensively searched from inception till 12th April 2022. The data for the number of events occurring for each outcome were pooled using random-effects model and forest plots were created. Results: Five articles were shortlisted for inclusion in our analysis. Incidence of suicide in the secretory phase was highest at 45.2% [95% CI, 0.367-0.537]. The incidence of suicide, when occurring in the menstrual phase, was reported to be 68.4% (95 CI, 0.317-1.052) and 31.6% (95 CI, -0.052.3-0.68) for young-aged and middle-aged victims, respectively. Conclusion: Our results demonstrate that the menstrual phase has a lower risk of mortality due to suicide when compared to the other two phases of the menstrual cycle. Nevertheless, when suicide occurred in the menstrual phase, the incidence of suicide among the younger age-group was higher than for those in the middle age-group.

Viewpoints from the National Consultation on Addressing Acute Malnutrition on Mainstreaming Community-Based Program for Management of Acute Malnutrition in India.

High burden of acute malnutrition among children less than 5 years is a major public health problem in India. A "Two-days National Consultation on Addressing Acute Malnutrition" was organized to gather experiences and evidence from 13 states of India on prevention and management of acute malnutrition among children and documenting viewpoints from experts and government counterparts on the same. The consultation centered around five key themes of addressing acute malnutrition; 1) capacity building, 2) strengthening screening, 3) nutritional care of wasting, 4) tracking progress, and 5) scale-up. The paper highlights the experiences and key recommendations around the above key themes. It emerged that there is a need to further accelerate the efforts toward strengthening existing platforms and services to address acute malnutrition among children. Regular trainings of the frontline workers, increased convergence, regular monitoring, and continued service delivery during the pandemic should be undertaken for better outcomes.

Esophageal luminal temperature monitoring using a multi-sensor probe lowers the risk of esophageal injury in cryo and radiofrequency catheter ablation for atrial fibrillation.

BACKGROUND: Esophageal luminal temperature monitoring is a commonly used strategy to reduce esophageal thermal injury in catheter ablation for atrial fibrillation (AFib). OBJECTIVES: We sought to compare the incidence of endoscopically detected esophageal lesions (EDEL) between two commonly used esophageal luminal temperature probes. METHODS: Consecutive patients undergoing ablation with esophageal luminal temperature monitoring and upper endoscopy within 24 h after ablation were included. RESULTS: Four hundred forty-five patients (64 ± 10 years, 44% female) were included. Esophageal temperature monitoring was done with a single-sensor probe in 213 (48%) and multi-sensor probe in 232 (52%). Cryoballoon (CB) ablation was performed in 118 (27%) and radiofrequency (RF) ablation in 327 (73%) of patients. EDEL was present in 94 (22.9%) of which 85 were mild, 8 were moderate, and 1 was severe, and none progressed to atrial-esophageal fistula. The use of the multi-sensor probe during CB ablation was associated with a reduction in EDEL compared to single sensor (6.8% vs 24.3%; P = 0.016). Similarly, in the RF ablation group, EDEL was present in 19.5% of the multi-sensor group vs 32.8% in the single-sensor group (P = 0.001). Logistic regression showed that multi-sensor probe use was associated with reduction in EDEL with an odds ratio of 0.23 in CB ablation (P = 0.024) and 0.44 for RF ablation (P = 0.001). CONCLUSIONS: Esophageal luminal temperature monitoring during AFib ablation using a multi-sensor probe was associated with a significant reduction in EDEL compared to a single-sensor probe.

Accelerometer-based portable navigation, a faster guide compared to computer-assisted navigation in bilateral total knee arthroplasty-a randomized controlled study.

PURPOSE: There are limited studies in the literature comparing the alignment accuracy of  the large console, imageless, computer-assisted navigation (CAN) and portable, hand-held, accelerometer-based navigation (ABN) in total knee arthroplasty (TKA).  This study was aimed to compare the operative time, blood loss, radiological, clinical and functional outcomes between CAN- and ABN-guided bilateral TKA. METHODS: From Jan 2016 to Dec 2017, 50 patients who underwent bilateral TKA were randomized to undergo either CAN-guided or ABN-guided TKA. Tourniquet time and blood loss were recorded, and intra-op complications were noted. Post-op radiological outcomes at 2 weeks were compared between the groups. The clinical and functional outcomes using the American Knee Society Scores (KSS) and Oxford Knee Score (OKS) were recorded pre-operatively and post-operatively at 3, 6, 12 months and at the end of the study with a minimum follow-up of 48 months. RESULTS: Both groups were well-matched in terms of patient demographic parameters. The mean surgical time per knee was significantly lower in the ABN group (54.5 ± 5.6 min) compared to the CAN group (61.7 ± 13.7 min; p < 0.01). Mean blood loss per knee in the ABN group was 592.1 ± 245.3 mL compared to 682.8 ± 322.0 in the CAN group (p = 0.11). In the ABN group, the mean post-op mechanical axis was 1.2 ± 3.2° (vs 1.5 ± 2.2° in the CAN group, p 0.6), the frontal femoral angle was 88.8 ± 2.3° (vs 88.8 ± 1.8° in the CAN group, p 1.0) and frontal tibial angle was 90.1 ± 1.6° (vs 89.7 ± 1.1° in the CAN group, p 0.14). At 48 month follow-up, the mean functional KSS in the ABN group was 89.0 ± 5.7 (vs 88.1 ± 4.5 in the CAN group, p 0.37) and the mean OKS was 40.5 ± 2.8 (vs 39.6 ± 3.2 in the CAN group, p 0.12). CONCLUSION: Portable, hand-held ABN offers alignment accuracy and functional outcomes in TKA similar to that with CAN, with a reduced duration of surgery. There was no advantage of either of the techniques in terms of clinical or functional outcomes at 48 month follow-up. LEVEL OF EVIDENCE 1.

A study of disability and socio-economic impact of mental morbidities from the state of Madhya Pradesh, India.

Background: Disability associated with mental illness has a disproportionate impact on the work, social, and family responsibilities of an individual toward society. The evidence for disability in mental illnesses would help the clinician, caregivers, policymakers, and various stakeholders to come up with sustainable solutions not only to help fill the existing gaps in care but also to develop new avenues as per the specific needs of the population of Madhya Pradesh (MP). Aim: To estimate the burden of disability related to mental illnesses in the state of MP. Materials and Methods: A multi-site cross-sectional study was conducted in 2015-16 as part of National Mental Health Survey among adults above 18 years of age. Samples were selected using multi-stage, stratified, random cluster sampling based on probability proportionate to size. Six tehsils with one urban metro out of four districts from a total of 50 districts were selected in the state of MP. The Sheehan Disability Scale and socio-economic impact of illness (from selected questions from WHO-Disability Assessment Schedule-2.0) were used to assess mental morbidity and the subjective reporting of disability. Results: The weighted prevalence of disability (n = 1011) was found as 10.2%, 13.1%, and 13.9%, respectively, in work/school, social life, and family/home domains. The weighted prevalence of moderate to extreme disability in the same domains was, respectively, 5.1%, 6.7%, and 7.3%. The presence of common mental disorders (CMDs) increases the odds of self-reported disability in work [odds ratio (OR) 2.48, 95% CI 1.35 to 4.59], social life (OR 2.74, 95% CI 1.50 to 5.07), and family domains (OR 3.03, 95% CI1.62 to 5.74). When combined with common mental disorders, tobacco use disorder further escalates the odds of self-reported disability in all three domains [OR 7.10, confidence interval (CI) 3.15 to 16.37; 4.93, CI 2.19 to 11.28; and 7.10, CI 2.78 to 19.25]. Currently, non-working persons had a higher disability in social life and family life domains (P = 0.003 and P = 0.021), respectively. Conclusion: We report a substantial magnitude of disability in social, work, and family life domains. Participants having CMDs, female gender, and those non-working had more disabilities and would require targeted interventions.

2,5-Bis(2,2,2-trifluoroethoxy)phenyl-tethered 1,3,4-Oxadiazoles Derivatives: Synthesis, In Silico Studies, and Biological Assessment as Potential Candidates for Anti-Cancer and Anti-Diabetic Agent.

In the present work, a series of new 1-{5-[2,5-bis(2,2,2-trifluoroethoxy)phenyl]-1,3,4-oxadiazol-3-acetyl-2-aryl-2H/methyl derivatives were synthesized through a multistep reaction sequence. The compounds were synthesized by the condensation of various aldehydes and acetophenones with the laboratory-synthesized acid hydrazide, which afforded the Schiff's bases. Cyclization of the Schiff bases yielded 1,3,4-oxadiazole derivatives. By spectral analysis, the structures of the newly synthesized compounds were elucidated, and further, their anti-cancer and anti-diabetic properties were investigated. To examine the dynamic behavior of the candidates at the binding site of the protein, molecular docking experiments on the synthesized compounds were performed, followed by a molecular dynamic simulation. ADMET (chemical absorption, distribution, metabolism, excretion, and toxicity) prediction revealed that most of the synthesized compounds follow Lipinski's rule of 5. The results were further correlated with biological studies. Using a cytotoxic assay, the newly synthesized 1,3,4-Oxadiazoles were screened for their in vitro cytotoxic efficacy against the LN229 Glioblastoma cell line. From the cytotoxic assay, the compounds 5b, 5d, and 5m were taken for colony formation assay and tunnel assay have shown significant cell apoptosis by damaging the DNA of cancer cells. The in vivo studies using a genetically modified diabetic model, Drosophila melanogaster, indicated that compounds 5d and 5f have better anti-diabetic activity among the different synthesized compounds. These compounds lowered the glucose levels significantly in the tested model.