Efficient synthesis of indole-chalcones based glycohybrids and their anticancer activity.

Indole based glycosides belong to the class of pharmacologically active molecules and found in diverse natural compounds. Herein, we report the synthesis of 1,2,3-triazole bridged chirally enriched diverse indole-chalcones based glycohybrids. Three series of glycohybrids were designed and efficiently synthesized using d-glucose, d-galactose and d-mannose derived 1-azido glycosides. The reactions sequence involved were, the synthesis of indole derived chalcones which were formed via Claisen-Schmidt condensation reaction and subsequently N-propargylation which leads to the production of N-propargylated indole-chalcones. The N-propargylated indole-chalcones get transformed into 1,2,3-triazole bridged indole-chalcone based glycohybrids by reacting with 1-azido sugar glycosides under click-chemistry reaction conditions. Further, the biological activity of synthesized glycohybrids (n = 27) was assessed in-vitro against MDA-MB231, MCF-7, MDA-MB453 cancer, and MCF-10A normal cell lines. The selected compounds showed potent anti-oncogenic properties against MCF-7 and MDA-MB231 breast cancer cell line with IC50 values of 1.05 µM and 11.40 µM respectively, with very good selectivity index (SI > 161). The active compounds show better binding affinity as compared to co-crystallized inhibitor 1-(tert-butyl)-3-(p-tolyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP1) with HCK (PTKs) proteins in molecular docking studies.

Post-campaign coverage evaluation of a measles and rubella supplementary immunization activity in five districts in India, 2019-2020.

BACKGROUND: In alignment with the Measles and Rubella (MR) Strategic Elimination plan, India conducted a mass measles and rubella vaccination campaign across the country between 2017 and 2020 to provide a dose of MR containing vaccine to all children aged 9 months to 15 years. We estimated campaign vaccination coverage in five districts in India and assessed campaign awareness and factors associated with vaccination during the campaign to better understand reasons for not receiving the dose. METHODS AND FINDINGS: Community-based cross-sectional serosurveys were conducted in five districts of India among children aged 9 months to 15 years after the vaccination campaign. Campaign coverage was estimated based on home-based immunization record or caregiver recall. Campaign coverage was stratified by child- and household-level risk factors and descriptive analyses were performed to assess reasons for not receiving the campaign dose. Three thousand three hundred and fifty-seven children aged 9 months to 15 years at the time of the campaign were enrolled. Campaign coverage among children aged 9 months to 5 years documented or by recall ranged from 74.2% in Kanpur Nagar District to 90.4% in Dibrugarh District, Assam. Similar coverage was observed for older children. Caregiver awareness of the campaign varied from 88.3% in Hoshiarpur District, Punjab to 97.6% in Dibrugarh District, Assam, although 8% of children whose caregivers were aware of the campaign were not vaccinated during the campaign. Failure to receive the campaign dose was associated with urban settings, low maternal education, and lack of school attendance although the associations varied by district. CONCLUSION: Awareness of the MR vaccination campaign was high; however, campaign coverage varied by district and did not reach the elimination target of 95% coverage in any of the districts studied. Areas with lower coverage among younger children must be prioritized by strengthening the routine immunization programme and implementing strategies to identify and reach under-vaccinated children.

Evaluating the effect of measles and rubella mass vaccination campaigns on seroprevalence in India: a before-and-after cross-sectional household serosurvey in four districts, 2018-2020.

BACKGROUND: India did phased measles-rubella supplementary immunisation activities (MR-SIAs; ie, mass-immunisation campaigns) targeting children aged 9 months to less than 15 years. We estimated measles-rubella seroprevalence before and after the MR-SIAs to quantify the effect on population immunity and identify remaining immunity gaps. METHODS: Between March 9, 2018 and March 19, 2020 we did community-based, cross-sectional serosurveys in four districts in India before and after MR-SIAs. 30 villages or wards were selected within each district, and one census enumeration block from each was selected as the survey cluster. Households were enumerated and 13 children in the younger age group (9 months to <5 years) and 13 children in the older ager group (5 to <15 years) were randomly selected by use of computer-generated random numbers. Serum samples were tested for IgG antibodies to measles and rubella viruses by enzyme immunoassay. FINDINGS: Specimens were collected from 2570 children before the MR-SIA and from 2619 children afterwards. The weighted MR-SIA coverage ranged from 73·7% to 90·5% in younger children and from 73·6% to 93·6% in older children. Before the MR-SIA, district-level measles seroprevalence was between 80·7% and 88·5% among younger children in all districts, and between 63·4% and 84·5% among older children. After the MR-SIA, measles seroprevalence among younger children increased to more than 90% (range 91·5 to 96·0) in all districts except Kanpur Nagar, in which it remained unchanged 80·4%. Among older children, measles seroprevalence increased to more than 90·0% (range 93·7% to 96·5%) in all districts except Hoshiarpur (88·7%). A significant increase in rubella seroprevalence was observed in all districts in both age groups, with the largest effect in Dibrugarh, where rubella seroprevalence increased from 10·6% to 96·5% among younger children. INTERPRETATION: Measles-rubella seroprevalence increased substantially after the MR-SIAs but the serosurvey also identified remaining gaps in population immunity. FUNDING: The Bill & Melinda Gates Foundation and Indian Council of Medical Research.

Resonance Frequency Analysis to Evaluate the Effect of Different Drilling Techniques on Implant Stability at Different Time Intervals: A Randomized Clinical Trial.

PURPOSE: To evaluate the effect of different drilling techniques on implant stability at different time intervals. MATERIALS AND METHODS: Patients were randomly allotted into three groups based on drilling technique for osteotomy: conventional drilling technique; simplified drilling technique; or modified conventional drilling technique. In 30 patients (n = 10 each group), a total of 44 implants were placed. In the conventional drilling technique, drills with increasing diameters were used. In the simplified drilling technique, only pilot and final-diameter drills were used. In the modified conventional drilling technique, all the drills were used in sequential order in the clockwise direction except the last drill, which was used in the counterclockwise direction. Implant stability quotient was recorded immediately after placing implants and at 1 and 3 months. Statistical analysis was performed with two-way analysis of variance (ANOVA) and Student t test. RESULTS: Two-way ANOVA showed that drilling technique (P < .001) and time (P = .002) did have a statistically significant effect on implant stability quotient. The modified conventional drilling technique showed a drop in secondary implant stability at 1 month that was negligible compared to the other techniques. After 1 month, there was a significant increase in implant stability quotient with the modified conventional drilling technique compared to the conventional drilling technique (P = .001). The least crestal bone loss during 3 months of follow-up was with the modified conventional drilling technique (0.37 ± 0.06). CONCLUSION: Secondary stability increased with the modified conventional drilling technique in 3 months and showed a negligible drop at 1 month. This novel drilling technique had an early shift from a decrease to an increase in stability pattern, along with the least crestal bone loss at 3 months.

Diagnostic Accuracy and Optimal Cut-off of Controlled Attenuation Parameter for the Detection of Hepatic Steatosis in Indian Population.

Background and aims: Ultrasound of the liver is not good to pick up mild steatosis. Controlled attenuation parameter (CAP) evaluated in transient elastography (FibroScan) is widely available in India. However, data regarding the diagnostic accuracy and optimal cut-off values of CAP for diagnosing hepatic steatosis are scarce in Indian population. MRI-PDFF is an accurate technique for quantifying hepatic steatosis. Thus, this study examined the diagnostic accuracy and optimal cut-off values of CAP for diagnosing steatosis with MRI-PDFF as reference standard. Methods: A total of 137 adults underwent CAP and MRI-PDFF measurements prospectively. A subset of participants (n = 23) underwent liver biopsy as part of liver transplantation evaluation. The optimal cut-off values, area under the receiver operating characteristic (AUROC) curves, sensitivity, and specificity for CAP in detecting MRI-PDFF ≥5% and ≥10% were assessed. Results: The mean age and body mass index (BMI) were 44.2 ±10.4 years and 28.3 ±3.9 kg/m2, respectively. The mean hepatic steatosis was 13.0 ±7.7% by MRI-PDFF and 303 ±54 dB/m by CAP. The AUROC of CAP for detecting hepatic steatosis (MRI-PDFF ≥5%) was 0.93 (95% CI, 0.88-0.98) at the cut-off of 262 dB/m, and of MRI-PDFF ≥10% was 0.89 (95% CI, 0.84-0.94) at the cut-off of 295 dB/m. The CAP of 262 dB/m had 90% sensitivity and 91% specificity for detecting MRI-PDFF ≥5%, while the CAP of 295 dB/m had 86% sensitivity and 77% specificity for detecting MRI-PDFF ≥10%. Conclusions: The optimal cut-off of CAP for the presence of liver steatosis (MRI-PDFF ≥5%) was 262 dB/m in Indian individuals. This CAP cut-off was associated with good sensitivity and specificity to pick up mild steatosis.

Platform-Switching Concept in Dental Implants: A Systematic Review and Meta-analysis of Randomized Controlled Trials with a Minimum Follow-up of 3 Years.

PURPOSE: To evaluate studies with a minimum follow-up of 3 years to find the peri-implant marginal bone loss (MBL) and rate of implant failure with platform-switching (PS) and platform-matching (PM) implant-abutment connections. MATERIALS AND METHODS: A systematic review and meta-analysis was done based on the preferred reporting items for systematic reviews and meta-analyses guidelines, with a focused question on population, intervention, comparison, and outcome. The Cochrane Collaboration's Risk of Bias tool was used to assess bias. Randomized controlled trials (RCTs) comparing peri-implant MBL and implant failure in patients receiving PS implants and PM implants only were included. The risk ratio (RR) of the implant-abutment connection and implant failure was calculated, and peri-implant MBL was expressed in mean differences (MD) at 95% confidence intervals (CIs). RESULTS: Three hundred eighty-one articles were obtained after an initial literature search. Finally, nine articles were included in the study that fulfilled the inclusion criteria. Four hundred twenty-six PS and 411 PM implants were placed with 16 implant failures (8 PS and 8 PM). The implant survival rate was 98.12% for the PS group, and 98.05% for the PM group, with no statistically significant difference (P = .97). The mean peri-implant MBL with the PS implant was lower (0.33 ± 0.41 mm) compared with the PM implant (0.66 ± 0.42 mm). A significant effect of PS implants was found in reducing peri-implant MBL (MD: -0.70, 95% CI: -1.25,-0.15; P = .01) compared with PM implants. The MD of peri-implant MBL between the PS and PM implants decreases with increased follow-up: MD of 0.69 (P = .15) with follow-up of ≥ 3 years but < 5 years, and MD of 0.62 (P = .04) with follow-up of ≥ 5 years. CONCLUSION: Reduced peri-implant MBL was found with the PS concept. The peri-implant MBL decreases with an increased mismatch between the abutment and implant platform. The difference in peri-implant MBL in PS and PM implants in the maxilla was greater and favored the PS concept. Bone-level implants with single crowns or splinted prostheses better preserved the peri-implant marginal bone with the PS concept.

Rehabilitation of Severe Atrophic Ridges with Zygomatic Implant and/or All-on-4 Treatment Concepts-A Case Series.

Rehabilitation of completely edentulous patients with implant-supported prosthesis (ISP) is the need of the day, but in many patients, the routine ISP is not possible due to the severe atrophic residual ridges. The present case series describes three cases with atrophic ridges rehabilitated using zygomatic implants and/or All-on-4 treatment concepts. In case 1 and case 3, in maxillary arch, there was not enough bone in Zone 3 to rehabilitate the patient with routine protocol followed for the All-on-4 treatment concept, so in these two cases, zygomatic implants were placed. Case 1 and case 2 were rehabilitated with Malo Bridge and case 3 with acrylic teeth-hybrid prosthesis using a computerized milling procedure to obtain improved fit, function, esthetics, and ease of retrievability whenever required.

Cardenolide and pregnatriene compounds from the roots of Nerium oleander.

Cardenolide and pregnatriene compounds were isolated from the chloroform fraction of the 95% aqueous ethanolic extract of dried roots of Nerium oleander. The stereochemical structure of the cardenolide and pregnatriene compounds was determined to be 3ß-O-(D-diginosyl)-14ß-hydroxy card-20(22)-enolide and 12ß-hydroxy pregna-4,6,16-triene-3,20-dione using spectroscopic methods including IR, HRMS and NMR spectroscopy.

Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial).

AIMS/HYPOTHESIS: Liraglutide, a daily injectable glucagon-like peptide-1 receptor (GLP-1r) agonist, has been shown to reduce liver fat content (LFC) in humans. Data regarding the effect of dulaglutide, a once-weekly GLP-1r agonist, on human LFC are scarce. This study examined the effect of dulaglutide on LFC in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). METHODS: Effect of dulaglutide on liver fat (D-LIFT) was a 24 week, open-label, parallel-group, randomised controlled trial to determine the effect of dulaglutide on liver fat at a tertiary care centre in India. Adults (n = 64), who had type 2 diabetes and MRI-derived proton density fat fraction-assessed LFC of ≥6.0% at baseline, were randomly assigned to receive dulaglutide weekly for 24 weeks (add-on to usual care) or usual care, based on a predefined computer-generated number with a 1:1 allocation that was concealed using serially numbered, opaque, sealed envelopes. The primary endpoint was the difference of the change in LFC from 0 (baseline) to 24 weeks between groups. The secondary outcome measures included the difference of the change in pancreatic fat content (PFC), change in liver stiffness measurement (LSM in kPa) measured by vibration-controlled transient elastography, and change in liver enzymes. RESULTS: Eighty-eight patients were screened; 32 were randomly assigned to the dulaglutide group and 32 to the control group. Overall, 52 participants were included for per-protocol analysis: those who had MRI-PDFF data at baseline and week 24. Dulaglutide treatment resulted in a control-corrected absolute change in LFC of -3.5% (95% CI -6.6, -0.4; p = 0.025) and relative change of -26.4% (-44.2, -8.6; p = 0.004), corresponding to a 2.6-fold greater reduction. Dulaglutide-treated participants also showed a significant reduction in γ-glutamyl transpeptidase (GGT) levels (mean between-group difference -13.1 U/l [95% CI -24.4, -1.8]; p = 0.025) and non-significant reductions in aspartate aminotransferase (AST) (-9.3 U/l [-19.5, 1.0]; p = 0.075) and alanine aminotransferase (ALT) levels (-13.1 U/l [-24.4, 2.5]; p = 0.10). Absolute changes in PFC (-1.4% [-3.2, 0.3]; p = 0.106) and LSM (-1.31 kPa [-2.99, 0.37]; p = 0.123) were not significant when comparing the two groups. There were no serious drug-related adverse events. CONCLUSIONS/INTERPRETATION: When included in the standard treatment for type 2 diabetes, dulaglutide significantly reduces LFC and improves GGT levels in participants with NAFLD. There were non-significant reductions in PFC, liver stiffness, serum AST and serum ALT levels. Dulaglutide could be considered for the early treatment of NAFLD in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03590626 FUNDING: The current study was supported by an investigator-initiated study grant from Medanta-The Medicity's departmental research fund and a grant from the Endocrine and Diabetes Foundation (EDF), India. Graphical abstract.

Patient's oral health-related quality of life and satisfaction with implant supported overdentures -a systematic review.

PURPOSE: This systematic review was done to find the patients oral health-related quality of life (OHRQoL) and satisfaction with implant supported overdentures (IODs) when compared to conventional complete dentures (CCDs). MATERIALS AND METHODS: To identify suitable literature, an electronic search was performed using Medline/PubMed and Cochrane databases. Manual search of Prosthodontics, Gerodontology and journals related to dental implants were also done. Articles published in English and articles whose abstract is available in English were included. The search was focused on patient's oral health-related quality of life and satisfaction with IODs when compared to CCDs.Titles and abstracts were screened, and literature that fulfilled the inclusion criteria was selected for a full-text reading. RESULTS: Initial literature search resulted in 1803 papers, 1779 were excluded after screenings of the abstracts by the reviewers which resulted in 24 studies. 5 studies were further excluded due to not fulfilling the inclusion criteria, 2 additional articles included after hand searching, resulting in total 21 articles in systematic review. The result suggests that mandibular CCDs had less retention as compared to maxillary conventional dentures CCDs, which improved drastically with IODs and provides a better oral health-related quality of life and satisfaction to the patients. CONCLUSION: Retention, stability, comfort, speech and chewing efficiency improved drastically with IODs, with enhanced patient's satisfaction and a better OHRQoL. Patients reported more satisfaction and OHRQoL with mandibular IOD when compared CCDs.

Antioxidant, antimicrobial and cytotoxic potential of silver nanoparticles synthesized using flavonoid rich alcoholic leaves extract of Reinwardtia indica.

The present work discusses the establishment of a green route for the rapid synthesis of silver nanoparticles (AgNPs) using an alcoholic extract of Reinwardtia indica (AERI) leaves which act as a reducing as well as a capping agent. The change in color from yellowish green to dark brown confirmed the synthesis of AgNPs. A characteristic surface plasmon resonance (SPR) band at 436 nm advocated the presence of AgNPs. The synthesis process was optimized using one factor at a time approach where 1.0 mM AgNO3 concentration, 5 mL 0.4% (v/v) of AER inoculum dose and 30 min of sunlight exposure were found to be the optimum conditions. The synthesized AgNPs was characterized by several characterizing techniques such as HR- TEM, SAED, HR-SEM, EDX, XRD, FTIR and AFM analysis. For evaluation and comparison of AgNPs with AERI used human pathogen E. coli, P. aeurogenosa, S. aeurus and C. albicans for antimicrobial, for cytotoxicity study SiHa cell line at concentration of (10, 50, 100, 250 and 500 µg mL-1) and for enzymatic assay superoxide dismutase, catalase, malondialdehyde and glutathione peroxidase method were used. The size of nanoparticle in the range of 3-15 nm was confirmed TEM, spherical shape by SEM and crystal lattice nature by XRD. AFM results revealed the 2 D and 3 D pattern of particle scatter nature on the surface. This protocol as simple, rapid, one step, eco-friendly, nontoxic and AgNPs showed strong antimicrobial activity as well as cytotoxic potential in comparison to AERI.

Pharmacological evaluation of the efficacy of Dysoxylum binectariferum stem bark and its active constituent rohitukine in regulation of dyslipidemia in rats.

The antidyslipidemic effect of the ethanolic extract of Dysoxylum binectariferum stem bark and its major active constituent rohitukine was evaluated in a high fat diet (HFD)-fed dyslipidemic rat model. Chronic feeding of ethanolic extract (200 mg/kg) in HFD-fed rats showed significant lipid lowering activity. The bioassay guided fractionation of ethanolic extract resulted in the identification of known alkaloid rohitukine as major active constituent. Rohitukine (50 mg/kg) significantly decreased the plasma levels of total cholesterol (24 %), phospholipids (25 %), triglycerides (27 %), very low density lipoprotein (27 %) and low density lipoprotein (32 %) accompanied with an increase in high density lipoprotein (21 %). The present study demonstrated that ethanolic extract of Dysoxylum binectariferum stem bark and its major constituent rohitukine both have antidyslipidemic as well as antioxidant potentials. The antidyslipidemic activity of rohitukine can be correlated to its effect on enzymes involved in lipid metabolism.

Pharmacokinetic and metabolism studies of rohitukine in rats by high performance liquid-chromatography with tandem mass spectrometry.

A sensitive, selective, and rapid high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the quantification of rohitukine in rat plasma. HPLC was performed using a Symmetry-Shield C18 (5 µ, 4.6 × 150 mm) column, and isocratic elution with ammonium acetate buffer (pH4; 10 mM):methanol (08:92, v/v) at a flow rate of 0.6 mL/min. Sample clean-up involved solid phase extraction (SPE) of analyte and internal standard (phenacetin) from 100 µL plasma. The parent→product ion transitions (MRM) for analyte and IS were 306.1→245.1 m/z and 180.1→138.1 m/z respectively, and were monitored on a triple quadrupole mass spectrometer, operating in positive ion mode. The method was validated across the dynamic concentration range of 5-500 ng/mL for rohitukine, with a fast run time of 4.5 min. The analytical method measured concentrations of rohitukine with accuracy (% bias) of <±10% and precision (% RSD) of <±12%. Rohitukine was stable during the battery of stability studies viz., bench-top, auto-sampler, freeze/thaw cycles and 30 days of storage in a freezer at -70±10°C. Finally, the applicability of this assay has been successfully demonstrated in vivo pharmacokinetic and in vitro metabolism studies in Sprague-Dawley rat. This method will therefore be highly useful for future preclinical and clinical pharmacokinetic studies of rohitukine.

Antidyslipidemic effect and antioxidant activity of anthraquinone derivatives from Rheum emodi rhizomes in dyslipidemic rats.

The aim of the present study was to evaluate the antidyslipidemic effect of ethanolic extract of Rheum emodi rhizomes and its constituents in Triton-WR-1339 and high-fat diet (HFD)-induced dyslipidemic rats. In preliminary screening, the ethanolic extract showed significant activity in Triton-treated rats. Bioassay-guided fractionation of the ethanolic extract resulted in the identification of four anthraquinone derivatives, viz. chrysophanol, emodin, chrysophanol 8-O-ß-D-glucopyranoside and emodin 8-O-ß-D-glucopyranoside as active constituents. All these compounds significantly reduced plasma lipid levels. The most active compound emodin showed significant lipid-lowering activity in the HFD-fed model. In addition, these compounds showed significant antioxidant activity. The effect of emodin on enzymes modulating lipid metabolism confirms and supports the efficiency of emodin as a potent antidyslipidemic agent.

Evaluation of binding property of mucilage from Litsea glutinosa wall.

BACKGROUND: Litsea glitinosa is an evergreen tree of medium size which grows to a height of about 20 to 30 feet. It belongs to family Lauraceae. In India it is found mainly in North Eastern region. The leaves and the mucilage from the bark of plant is utilized in the gum for poultices. METHODS: Mucilage of Litsea glutinosa was isolated from powdered bark by continuous hot extraction technique using water and precipitation by absolute alcohol (38% w/w yield). The mucilage was evaluated for binding properties in tablets and granules, using paracetamol as a model drug. The granules were prepared using 4 different concentrations of mucilage (4%, 6%, 8%, and 10%) and evaluated for percentage of fines, average particle size, total porosity, compressibility index, and flow properties. The prepared tablets were evaluated for content uniformity, hardness, friability, disintegration time, and in vitro dissolution profiles. RESULTS: The results obtained with the lower concentrations of mucilage, that is, less than 6% were not so encouraging. The tablets prepared by using 10% mucilage of L. glutinosa as binder exhibited more hardness as compared with the starch. CONCLUSION: It may be concluded that the concentration ranging from 6% to 8% of L. glutinosa mucilage may be considered as better option as a binding agent for the preparation of tablets as compared to the starch (10%).