Synthesis, crystal structure and Hirshfeld surface analysis of 4-{(1E)-1-[(car-bamo-thioyl-amino)-imino]-eth-yl}phenyl propano-ate.

The title compound, C12H15N3O2S, adopts an E configuration with respect to the C=N bond. The propionate group adopts an anti-periplanar (ap) conformation. There are short intra-molecular N-H⋯N and C-H⋯O contacts, forming S(5) and S(6) ring motifs, respectively. In the crystal, mol-ecules are connected into ribbons extending parallel to [010] by pairs of N-H⋯S inter-actions, forming rings with R 2 2(8) graph-set motifs, and by pairs of C-H⋯S inter-actions, where rings with the graph-set motif R 2 1(7) are observed. The O atom of the carbonyl group is disordered over two positions, with a refined occupancy ratio of 0.27 (2):0.73 (2). The studied crystal consisted of two domains.

Knowledge of undergraduate and postgraduate dental students about managing traumatic dental injuries based on the 2020 International Association of Dental Traumatology guidelines: A online survey of 10 dental schools from 10 countries.

BACKGROUND/AIM: The knowledge of dental students about managing traumatic dental injuries (TDIs) may not be uniform, depending on global location and dental education. The aim of this study was to evaluate the level of knowledge of undergraduate and postgraduate students specializing in endodontics and pediatric dentistry at 10 dental schools in 10 countries about the 2020 International Association of Dental Traumatology (IADT) guidelines regarding the management of TDIs. MATERIALS & METHODS: A previously published questionnaire was used in the current survey. It was an online survey with 12 questions regarding the management of TDIs and some additional questions regarding sociodemographic and professional profiles of the participants were added. The survey was distributed to final-year undergraduate students and postgraduate students in pediatric dentistry and endodontics from 10 dental schools. Simple frequency distributions and descriptive statistics were predominantly used to describe the data. Differences in the median percentage scores among the student categories were assessed using the Kruskal-Wallis test followed by Dwass-Steel-Critchlow-Fligner pairwise comparisons. RESULTS: A total of 347 undergraduates, 126 postgraduates in endodontics, and 72 postgraduates in pediatric dentistry from 10 dental schools participated in this survey. The postgraduates had a significantly higher percentage score for correct responses compared with the undergraduates. No significant difference was observed between the endodontic and pediatric dentistry postgraduates. CONCLUSION: The knowledge possessed by undergraduate and postgraduate students concerning the IADT-recommended management of TDIs varied across the globe and some aspects were found to be deficient. This study emphasizes the critical importance of reassessing the teaching and learning activities pertaining to the management of TDIs.

Customised enriched coconut oil as panacea for oral biofilm mediated diseases - A prospective study.

Aims: To evaluate a customised enriched formulation of coconut (CEC) oil with Arimedadi Tailam (AT) and 0.2% chlorhexidine mouth rinse (CHX) for their plaque control and potential anticaries effects using the oratest in healthy volunteers. Settings and Design: Parallel, double-blinded (outcome assessor and statistician), randomised controlled institution-based pilot study. Methods and Materials: 60 adults (18-22 years) having DMFT score of 2-11, gingival and plaque index as zero, no history of antibiotics for one month or fluoride application in 2 weeks were randomly divided (computer-generated list) and allocated into 3 groups (A-CHX, B-CEC, C-AT) of 20 subjects each based on the intervention. Oratest at baseline, days 15 and 30 were recorded. Statistical Analysis Used: Due to 5 dropouts on day 30, data were analysed based on the intention-to-treat (ITT) approach. The difference in oratest scores (baseline vs. day 15 and 30) were found to be normally distributed (Shapiro-Wilk test and Levene's test). One way ANOVA followed by Tukey's post hoc test was used to determine the statistically significant difference (P < 0.05) between groups. Results: Plaque and gingival index was zero throughout the study period. Difference in oratest scores was highest with CEC oil, followed by CHX and AT though there was no statistically significant differences between groups at baseline vs day 15 (P = 0.203) and baseline vs day 30 (P = 0.085) and between oils from baseline vs day 30 (P = 0.068). Conclusions: Within the limitations of the pilot study, both oils are comparable to CHX for their antiplaque and anticaries potential. Clinically, CEC was better than AT though statistical difference was not there.

Methodological assessment and overall confidence in the results of systematic reviews with meta-analyses focusing on traumatic dental injuries: A cross-sectional study.

BACKGROUND/AIMS: High methodological quality is required to interpret results of systematic reviews (SRs) in a reliable and accurate manner. The primary aim of this study was to appraise the methodologic quality of SRs with meta-analysis within the field of traumatic dental injuries using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 tool and assess overall confidence in their results. A secondary aim was to identify potential predictive factors associated with methodological quality. MATERIALS AND METHODS: SRs with meta-analyses published in English in the field of traumatic dental injuries from inception to March 2023 were identified. The methodological quality of the included reviews was assessed using the AMSTAR 2 checklist. Two independent evaluators scored each AMSTAR 2 item as "yes" if it was adequately addressed, "partial yes" if it was partially addressed, and "no" if it was not addressed. The overall confidence in the results of each review was classified as "High," "Moderate," "Low," or "Critically low." Using multiple regression, the relationship between five predictor variables (journal impact factor, year of publication, number of authors, journal adherence to Preferred Reporting Items for Systematic reviews and Meta-analyses [PRISMA] guidelines and a priori protocol registration) and the total AMSTAR 2 scores was analyzed. The p-value was 5%. RESULTS: Forty-one SRs were included. The overall confidence in the results of 13 reviews was categorized as "Critically low," 18 as "Low," 3 as "Moderate" and 7 as "High." Among the five predictor variables analyzed statistically, impact factor of the journal and year of publication significantly influenced the total AMSTAR 2 scores. The number of authors, adherence to PRISMA guidelines, and a priori protocol registration had no significant impact on AMSTAR 2 scores. CONCLUSION: The overall confidence in the results of SRs with meta-analysis within the field of traumatic dental injuries was "Low" or "Critically Low" in the vast majority of studies (31 of 41). SRs with meta-analyses published in journals with higher impact factors and more recent publications had significantly higher methodological quality.

White spot lesions, plaque accumulation and salivary caries-associated bacteria in clear aligners compared to fixed orthodontic treatment. A systematic review and meta- analysis.

OBJECTIVE: To analyse the available evidence regarding the incidence and severity of white spot lesions (WSLs), plaque accumulation and salivary caries-associated bacteria(SCB) in clear aligners (CA) verses conventional fixed (CF) orthodontic appliances. METHODS: Electronic searches of MEDLINE, Scopus, Embase, Google Scholar, Clinical trial registry, OpenGrey and ProQuest were done for all relevant studies. Eligibility criteria were; Randomized Controlled Trials and Non-Randomized Studies that compared the incidence and severity of WSLs, plaque accumulation and SCB between CA and CF appliances in patients undergoing orthodontic treatment. The risk of bias(ROB) and certainty of evidence was assessed independently by two reviewers using Cochrane's ROB and GRADEpro, respectively. Standardized mean difference (SMD) was used to estimate the effect size using STATA 17 software. RESULTS: A total of 14 studies met the eligibility criteria, and eight were suitable for meta-analysis. The qualitative results showed lower incidence and severity of WSLs, plaque accumulation, and SCB in CA group compared to CF appliances. The pooled results showed significantly lower plaque accumulation(SMD - 1.58;95%CI:-2.57,0.58;p = 0.002) in CA compared to CF appliances. CONCLUSIONS: A moderate-quality evidence reveals less plaque accumulation and less SCB in CA, which might be related to the reduced incidence and severity of WSLs associated with CA when compared with CF appliances. However, the results of the present study should be interpreted with caution given the high ROB among some of the included studies as well as the marked heterogeneity across the studies. CLINICAL RELEVANCE: For patients who can be treated with either CA or CF appliances, CA may be a better choice concerning oral health. REGISTRATION: Open Science Framework (DOI: https://doi.org/10.17605/osf.io/kcpvb ).

Phthalate exposure in the neonatal intensive care unit is associated with development of bronchopulmonary dysplasia.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is a serious yet common morbidity of preterm birth. Although prior work suggests a possible role for phthalate exposure in the development of BPD, no study has rigorously evaluated this. Our objective was to determine whether hospital-based phthalate exposure is associated with the development of BPD and to identify developmental windows sensitive to exposure. STUDY DESIGN: This is a prospective multicenter cohort study of 360 preterm infants born at 23-33 weeks gestation participating in the Developmental Impact of NICU Exposures (DINE) cohort. 939 urine specimens collected during the NICU stay were analyzed for biomarkers of phthalate exposure by liquid chromatography with tandem mass spectrometry. The modified Shennan definition was used to diagnose bronchopulmonary dysplasia. Reverse distributed-lag modeling identified developmental windows sensitive to specific phthalate exposure, controlling for relevant covariates including sex and respiratory support. RESULTS: Thirty-five percent of participants were diagnosed with BPD. Exposure to specific phthalate mixtures at susceptible points in preterm infant development are associated with later diagnosis of BPD in models adjusted for use of respiratory support. The weighted influence of specific phthalate metabolites in the mixtures varied by sex. Metabolites of di(2-ethylhexyl) phthalate, a phthalate previously linked to neonatal respiratory support equipment, drove this association, particularly among female infants, at 26- to 30-weeks post-menstrual age. CONCLUSIONS: This is the largest and only multi-site study of NICU-based phthalate exposure and clinical impact yet reported. In well-constructed models accounting for infant sex and respiratory support, we found a significant positive association between ultimate diagnosis of BPD and prior exposure to phthalate mixtures with DEHP predominance at 26- to 30-weeks PMA or 34-36-weeks PMA. This information is critically important as it identifies a previously unrecognized and modifiable contributing factor to BPD.

An International Investigation of Molar Incisor Hypomineralisation (iMIH) and Its Association with Dental Anomalies: Development of a Protocol.

BACKGROUND: Molar incisor hypomineralisation (MIH) is a common disorder of tooth development, which has recently been found to be associated with a higher prevalence of hypodontia. The aim of this international multicentre study is to determine the association between MIH and other developmental anomalies in different populations. METHODS: Investigators were trained and calibrated for the assessment of MIH and dental anomalies and ethical approvals obtained in each participating country. The study aimed to recruit 584 children with MIH and 584 children without MIH. Patients aged 7-16 years who attend specialist clinics will be invited to participate. Children will undergo a clinical examination to determine the presence and severity of MIH, using an established index. The presence of any other anomalies, affecting tooth number, morphology, or position, will be documented. Panoramic radiographs will be assessed for dental anomalies and the presence of third permanent molars. Statistical analysis, using a chi squared test and regression analysis, will be performed to determine any differences in dental anomaly prevalence between the MIH and non-MIH group and to determine any association between dental anomalies and patient characteristics. CONCLUSION: This large-scale study has the potential to improve understanding about MIH with benefits for patient management.

Efficiency of Immediate and Controlled release of Aceclofenac on Post-instrumentation Pain in Root Canal Treatment - A Triple Blind Randomized Controlled Trial.

OBJECTIVE: Patients with moderate to severe preoperative pain have a high incidence of postoperative pain. The objective of this trial was to evaluate the efficiency of oral premedication with Aceclofenac (immediate release and controlled release) in the management of post-instrumentation pain in root canal treatment, in patients with moderate to severe preoperative pain. METHODS: Three-arm parallel, triple blinded randomized controlled trial was planned. Patients with moderate to severe endodontic pain, requiring primary endodontic treatment were enrolled. Aceclofenac 100mg- immediate release (Aceclofenac-IR), Aceclofenac 200mg- controlled release (Aceclofenac-CR), and Ibuprofen 400mg were compared. The tablets were given one hour before the root canal treatment. Postoperatively, patients rated their pain at various time points. The duration of pain relief (primary outcome), the intensity of post-instrumentation pain, and the need for additional medicine were calculated. Statistical analysis was done using Kruskal-Wallis followed by Dunn post-hoc, Chi-square tests, and Binominal logistic regression. RESULTS: Aceclofenac-CR had a statistically significant longest duration of pain relief when compared to Ibuprofen (p=0.037) and Aceclofenac-IR (p=0.026). The intensity of post-instrumentation pain was lowest in Aceclofenac-CR, followed by Aceclofenac-IR and Ibuprofen. Additional medicine was required for only 8% of patients in Aceclofenac-CR group; whereas for 32% in each of Aceclofenac-IR and Ibuprofen groups. The odds of taking additional medicine were reduced to 0.16 in Aceclofenac-CR; increased to 1.05 with age. CONCLUSION: Aceclofenac-CR had the longest duration of pain relief compared to Aceclofenac-IR and Ibuprofen. (EEJ-2022-03-037).

Reporting quality of systematic reviews with network meta-analyses in Endodontics.

OBJECTIVES: To evaluate the reporting quality of systematic reviews with network meta-analyses (NMAs) in Endodontics using the the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) for NMA checklist. METHODS: The current investigation extends a recently published study in the International Endodontic Journal (Nagendrababu V, Faggion Jr CM, Pulikkotil SJ, Alatta A, Dummer PM Methodological assessment and overall confidence in the results of systematic reviews with network meta-analyses in Endodontics. International Endodontic Journal 2022;55:393-404) that assessed the methodological quality of systematic reviews with NMAs in Endodontics using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) tool. In the present study, the PRISMA for NMA checklist with 32 items was used to assess the reporting quality of the systematic reviews with NMAs (n = 12). Two independent assessors assigned '1' when an item was completely addressed, '0.5' when it was partially addressed, and '0' when it was not addressed. Disagreements were resolved through reviewer discussion until consensus was reached. If conflicts persisted, a third reviewer made the final decision. The PRISMA for NMA scores were shared with the relevant authors of the individual reviews to reduce the likelihood of misinterpretation and verify the scores assigned. The results for each individual item of the PRISMA-NMA items were calculated by summing the individual scores awarded; the maximum score for each item was 12. RESULTS: All the systematic reviews with NMAs adequately reported the following items: Title, Introduction section (Objectives), Methods section (Eligibility criteria and Information sources), Results section (Study selection, Study characteristics and Risk of bias within studies), and Discussion section (Summary of evidence). The items that were reported least often were the "geometry of the network" and "the summary of network geometry" with only 2 manuscripts (17%) including these items. CONCLUSION: A number of the items in the PRISMA-NMA checklist were adequately addressed in the NMAs; however, none adequately reported all the PRISMA-NMA items. The inadequacies of published NMAs that have been identified should be taken into consideration by authors of NMAs in Endodontics and by editors when managing the peer review process. In future, researchers who are writing systematic reviews with NMAs should comply with the PRISMA-NMA checklist. CLINICAL RELEVANCE: None of the included systematic reviews with NMA adequately reported all the PRISMA-NMA items. Inadequate reporting of a systematic review with NMA increases the possibility that it will provide invalid results. Therefore, authors should follow the PRISMA-NMA guidelines when reporting systematic reviews with NMA in Endodontics.

Exposure to perfluoroalkyl substances and women's fertility outcomes in a Singaporean population-based preconception cohort.

OBJECTIVES: Experimental models have demonstrated a link between exposure to perfluoroalkyl substances (PFAS) and decreased fertility and fecundability; however, human studies are scarce. We assessed the associations between preconception plasma PFAS concentrations and fertility outcomes in women. METHODS: In a case-control study nested within the population-based Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO), we measured PFAS in plasma collected in 2015-2017 from 382 women of reproductive age trying to conceive. Using Cox proportional hazards regression (fecundability ratios [FRs]) and logistic regression (odds ratios [ORs]) models, we assessed the associations of individual PFAS with time-to-pregnancy (TTP), and the likelihoods of clinical pregnancy and live birth, respectively, over one year of follow-up, adjusting for analytical batch, age, education, ethnicity, and parity. We used Bayesian weighted quantile sum (BWQS) regression to assess the associations of the PFAS mixture with fertility outcomes. RESULTS: We found a 5-10 % reduction in fecundability per quartile increase of exposure to individual PFAS (FRs [95 % CIs] for clinical pregnancy = 0.90 [0.82, 0.98] for PFDA; 0.88 [0.79, 0.99] for PFOS; 0.95 [0.86, 1.06] for PFOA; 0.92 [0.84, 1.00] for PFHpA). We observed similar decreased odds of clinical pregnancy (ORs [95 % CIs] = 0.74 [0.56, 0.98] for PFDA; 0.76 [0.53, 1.09] for PFOS; 0.83 [0.59, 1.17] for PFOA; 0.92 [0.70, 1.22] for PFHpA) and live birth per quartile increases of individual PFAS and the PFAS mixture (ORs [95 % CIs] = 0.61 [0.37, 1.02] for clinical pregnancy, and 0.66 [0.40, 1.07] for live birth). Within the PFAS mixture, PFDA followed by PFOS, PFOA, and PFHpA were the biggest contributors to these associations. We found no evidence of association for PFHxS, PFNA, and PFHpS and the fertility outcomes examined. CONCLUSIONS: Higher PFAS exposures may be associated with decreased fertility in women. The potential impact of ubiquitous PFAS exposures on infertility mechanisms requires further investigation.

Cross-sectional associations of maternal PFAS exposure on SARS-CoV-2 IgG antibody levels during pregnancy.

BACKGROUND: Perfluoroalkylated substances (PFAS) are man-made, persistent organic compounds with immune-modulating potentials. Given that pregnancy itself represents an altered state of immunity, PFAS exposure-related immunotoxicity is an important environmental factor to consider in SARS-CoV-2 infection during pregnancy as it may further affect humoral immune responses. AIM: To investigate the relationship between maternal plasma PFAS concentrations and SARS-CoV-2 antibody levels in a NYC-based pregnancy cohort. METHODS: Maternal plasma was collected from 72 SARS-CoV-2 IgG + participants of the Generation C Study, a birth cohort established at the beginning of the COVID-19 pandemic in New York City. Maternal SARS-CoV-2 anti-spike IgG antibody levels were measured using ELISA. A panel of 16 PFAS congeners were measured in maternal plasma using a targeted UHPLC-MS/MS-based assay. Spearman correlations and linear regressions were employed to explore associations between maternal IgG antibody levels and plasma PFAS concentrations. Weighted quantile sum (WQS) regression was also used to evaluate mixture effects of PFAS. Models were adjusted for maternal age, gestational age at which SARS-CoV-2 IgG titer was measured, COVID-19 vaccination status prior to IgG titer measurement, maternal race/ethnicity, parity, type of insurance and pre-pregnancy BMI. RESULTS: Our study population is ethnically diverse with an average maternal age of 32 years. Of the 16 PFAS congeners measured, nine were detected in more than 60% samples. Importantly, all nine congeners were negatively correlated with SARS-CoV-2 anti-spike IgG antibody levels; n-PFOA and PFHxS, PFHpS, and PFHxA reached statistical significance (p < 0.05) in multivariable analyses. When we examined the mixture effects using WQS, a quartile increase in the PFAS mixture-index was significantly associated with lower maternal IgG antibody titers (beta [95% CI] = -0.35 [-0.52, -0.17]). PFHxA was the top contributor to the overall mixture effect. CONCLUSIONS: Our study results support the notion that PFAS, including short-chain emerging PFAS, act as immunosuppressants during pregnancy. Whether such compromised immune activity leads to downstream health effects, such as the severity of COVID-19 symptoms, adverse obstetric outcomes or neonatal immune responses remains to be investigated.

Application of growth modeling to assess the impact of hospital-based phthalate exposure on preterm infant growth parameters during the neonatal intensive care unit hospitalization.

In this study, we use advanced growth modeling techniques and the rich biospecimen and data repositories of the NICU Hospital Exposures and Long-Term Health (NICU-HEALTH) study to assess the impact of NICU-based phthalate exposure on extrauterine growth trajectories between birth and NICU discharge. Repeated holdout weighed quantile sum (WQS) regression was used to assess the effect of phthalate mixtures on the latency to first growth spurt and on the rate of first growth spurt. Further, we assessed sex as an effect modifier of the relationship between a phthalate mixture and both outcomes. Nine phthalate metabolites, mono-ethyl phthalate (MEP), mono-benzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-(3-carboxypropyl) phthalate (MCPP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) were measured in weekly urine specimens from 101 NICU-HEALTH participants between birth and the first growth spurt. Phthalate levels varied by species but not by infant sex, and decreased over the course of the NICU hospitalization as presented in detail in Stroustrup et al., 2018. There was evidence of nonlinearity when assessing the effect of phthalates on latency to first growth spurt. Above a threshold level, a higher phthalate mixture with dominant contributors MCPP, MBzP, and MEP predicted a shorter latency to the first inflection point, or an earlier growth spurt. A higher phthalate mixture with dominant contributors MECPP, MEHHP, and MEOHP was associated with an increased rate of growth. Results of both models were clearly different for boys and girls, consistent with other studies showing the sexually dimorphic impact of early life phthalate exposure. These results suggest that growth curve modeling facilitates evaluation of discrete periods of rapid growth during the NICU hospitalization and exposure to specific phthalates during the NICU hospitalization may both alter the timing of the first growth spurt and result in more rapid growth in a sexually dimorphic manner.

Prevalence of dens invaginatus and its association with periapical lesions in a Western Indian population-a study using cone-beam computed tomography.

OBJECTIVES: This study aimed to assess the prevalence of dens invaginatus (DI) and its association with periapical lesions (PLs) in a Western Indian population by means of cone-beam computed tomography (CBCT). MATERIALS AND METHODS: CBCT volumes of 5201 subjects were evaluated. Associations among gender, tooth type, DI type (Oehler's classification), and presence of PL were investigated. PL was codified using Estrela's Cone Beam Computed Tomography Periapical Index (CBCTPAI). Chi-square tests and descriptive statistics were used at p = 0.05. RESULTS: Overall, 7048 CBCTs were assessed, containing 19,798 maxillary and mandibular anteriors, of which 77 maxillary teeth demonstrated DI (0.39% of all anteriors). Of all 5201 subjects, 57 had DI (1.1%). Bilateral DI was more common in females than in males (p = 0.046). DI type distribution was as follows: type I (22.1%), type II (61.03%), type IIIa (10.4%), and type IIIb (6.5%), which was significantly different (p < 0.001). Maxillary lateral incisors were the most associated with PL (p < 0.001). Type I was frequently associated with CBCTPAI scores 1 and 2 (absence of PL), whereas types II, IIIa, and IIIb were associated with CBCTPAI scores 3, 4, and 5 (presence of PL). CONCLUSIONS: A prevalence of 1.1% identifies DI as a common developmental tooth anomaly in a Western Indian subpopulation. The percentage of maxillary anteriors affected by DI and associated PLs should be considered before diagnosis and treatment planning. CLINICAL RELEVANCE: Knowledge about the prevalence of DI and its subtypes, and their association with/without periapical pathosis may aid clinicians in treatment planning and execution to improve patient outcomes.

Thyroid-Stimulating Hormone Favors Runx2-Mediated Matrix Mineralization in HOS and SaOS2 Cells: An In Vitro and In Silico Approach.

Osteoporosis is a skeletal disease that is both systemic and silent characterized by an unbalanced activity of bone remodeling leading to bone loss. Rising evidences demonstrate that thyroid stimulating hormone (TSH) has an important role in the regulation on the metabolism of bone. However, TSH regulation on human osteoblast essential transcriptional factors has not been identified. Current study examined the role of TSH on human osteoblastic Runx2 expression and their functional genes by in vitro and in slico analysis. Human osteoblast like (HOS and SaoS-2) cells were cultured with DMEM and treated with hTSH at the concentration of 0.01 ng/mL and 10 ng/mL. After treatment, osteoblastic Runx2 and IGF-1R beta expression were studied using RT-PCR and western blot analysis. TSH treatment induced osteoblastic essential transcriptional factor, Runx2 in HOS and SaOS2 cells on 48 h duration and elevated the expression of IGF-IR ß gene and Protein in SaoS-2 cells. TSH also promotes Runx2 responsive genes such as ALP, Collagen and osteocalcin in SaOS2 cells on day 2 to day 14 of 10 ng/mL of treatment and favors' matrix mineralization matrix in these cells. In addition, TSH facilitated human osteoblastic cells to mineralize their matrix confirmed by day 21 of alizarin red calcium staining. In silico study was performed to check CREB and ELK1 interaction with Runx2. Results of in silico analysis showed that TSH mediated signalling molecules such as CREB and ELK1 showed interaction with Runx2 which involve in osteobalstic gene expression and differentiation. Present findings confirm that TSH promotes Runx2 expression, osteoblastic responsive genes and bone matrix formation.

Secondary metabolites from spice and herbs as potential multitarget inhibitors of SARS-CoV-2 proteins.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the current global pandemic that has caused a death toll of >1.12 million worldwide and number continues to climb in several countries. Currently, there are neither specific antiviral drugs nor vaccines for the treatment and prevention of COVID-19. We screened in silico, a group of natural spice and herbal secondary metabolites (SMs) for their inhibition efficacy against multiple target proteins of SARS-CoV-2 as well as the human angiotensin-converting enzyme 2 protein. Docking and simulation results indicated that epicatechin, embelin, hesperidin, cafestol, murrayanine and murrayaquinone-A have higher inhibition efficacy over at least one of the known antiviral drugs such as Hydroxychloroquine, Remdesivir and Ribavirin. Combination of these potentially effective SMs from their respective plant sources was analysed, and its absorption and acute oral toxicity were examined in Wistar rats and classified as category 5 as per the Globally Harmonized System. The identified SMs may be useful in the development of preventive nutraceuticals, food supplements and antiviral drugs.Communicated by Ramaswamy H. Sarma.

Effect of precooling injection site and cold anesthetic administration on injection pain, onset, and anesthetic efficacy in maxillary molars with symptomatic irreversible pulpitis: a randomized controlled trial.

OBJECTIVE: This randomized controlled clinical trial assessed the analgesic and anesthetic effects of precooling the injection site and administration of refrigerated 2% lignocaine HCl with 1:100,000 epinephrine (LE) in maxillary molars with symptomatic irreversible pulpitis (SIP). MATERIALS AND METHODS: Sixty patients diagnosed with SIP (preoperative pain score ≥ 85 mm) in maxillary first molars were randomly allocated to two groups. In group I (control), topical gel was applied for a minute followed by conventional LE infiltration, whereas in group II (experimental), topical ice application for 15 s and refrigerated (4-6 °C) LE administration was done prior to endodontic treatment. The primary outcome measure was anesthetic efficacy that was defined as none to weak pain (≤ 36 mm) as measured on Heft Parker visual analog scale (HP-VAS) following access cavity preparation. Pain on injection and onset constituted the secondary outcome measures. The pain on injection was measured using HP-VAS, whereas the onset of anesthesia was assessed using an electric pulp tester (EPT) which was applied on the experimental tooth every minute until no response was elicited. Mann-Whitney U test was performed to analyze the data (p < 0.01). RESULTS: Experimental group reported a success rate of 86.6% when compared to control group (26.6%) and a statistically significant reduction on injection pain (20.0 mm vs 54.5 mm) (p < 0.01). The onset of anesthesia for experimental group was 2.4 min which was also significantly lower than control group (4.5 min) (p < 0.01). CONCLUSIONS: Cryotherapy can serve as an effective alternative to conventional anesthesia for achieving success, reduced pain, and faster onset during endodontic treatment of maxillary molars with SIP. CLINICAL RELEVANCE: Precooling the injection site and cold LE administration can result in effective pulpal anesthesia during endodontic management of maxillary molars in SIP patients.

Use of A Hydroalcoholic Extract of Moringa oleifera Leaves for the Green Synthesis of Bismuth Nanoparticles and Evaluation of Their Anti-Microbial and Antioxidant Activities.

The employment of plant extracts in the synthesis of metal nanoparticles is a very attractive approach in the field of green synthesis. To benefit from the potential synergy between the biological activities of the Moringa oleifera and metallic bismuth, our study aimed to achieve a green synthesis of phytochemical encapsulated bismuth nanoparticles using a hydroalcoholic extract of M. oleifera leaves. The total phenolic content in the M. oleifera leaves extract used was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. The physical properties of the synthesized bismuth nanoparticles were characterized using UV-Vis spectrophotometer, FT-IR spectrometer, TEM, SEM, and XRD. The size of the synthesized bismuth nanoparticles is in the range of 40.4-57.8 nm with amorphous morphology. Using DPPH and phosphomolybdate assays, our findings revealed that the M. oleifera leaves extract and the synthesized bismuth nanoparticles possess antioxidant properties. Using resazurin microtiter assay, we also demonstrate that the M. oleifera leaves extract and the synthesized bismuth nanoparticles exert potent anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis (estimated MIC values for the extract: 500, 250, 250, and 250 µg/mL; estimated MIC values for the bismuth nanoparticles: 500, 500, 500, and 250 µg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized bismuth nanoparticles display relatively stronger anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (estimated MIC values for the extract: 62.5, 62.5, 125, and 250 µg/mL; estimated MIC values for the bismuth nanoparticles: 250, 250, 62.5, and 62.5 µg/mL, respectively). Thus, green synthesis of bismuth nanoparticles using M. oleifera leaves extract was successful, showing a positive antioxidant, anti-bacterial, and anti-fungal activity. Therefore, the synthesized bismuth nanoparticles can potentially be employed in the alleviation of symptoms associated with oxidative stress and in the topic treatment of Candida infections.

Green Synthesis of Encapsulated Copper Nanoparticles Using a Hydroalcoholic Extract of Moringa oleifera Leaves and Assessment of Their Antioxidant and Antimicrobial Activities.

: The synthesis of metal nanoparticles using plant extracts is a very promising method in green synthesis. The medicinal value of Moringa oleifera leaves and the antimicrobial activity of metallic copper were combined in the present study to synthesize copper nanoparticles having a desirable added-value inorganic material. The use of a hydroalcoholic extract of M. oleifera leaves for the green synthesis of copper nanoparticles is an attractive method as it leads to the production of harmless chemicals and reduces waste. The total phenolic content in the M. oleifera leaves extract was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. The M. oleifera leaves extract was treated with a copper sulphate solution. A color change from brown to black indicates the formation of copper nanoparticles. Characterization of the synthesized copper nanoparticles was performed using ultraviolet-visible light (UV-Vis) spectrophotometry, Fourier-transform infrared (FTIR) spectrometry, high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The synthesized copper nanoparticles have an amorphous nature and particle size of 35.8-49.2 nm. We demonstrate that the M. oleifera leaves extract and the synthesized copper nanoparticles display considerable antioxidant activity. Moreover, the M. oleifera leaves extract and the synthesized copper nanoparticles exert considerable anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 µg/mL; MIC values for the copper nanoparticles: 500, 500, 500, and 250 µg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized copper nanoparticles exert relatively stronger anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 µg/mL; MIC values for the copper nanoparticles: 125, 125, 62.5, and 31.2 µg/mL, respectively). Our study reveals that the green synthesis of copper nanoparticles using a hydroalcoholic extract of M. oleifera leaves was successful. In addition, the synthesized copper nanoparticles can be potentially employed in the treatment of various microbial infections due to their reported antioxidant, anti-bacterial, and anti-fungal activities.

5-Azacytidine incorporated polycaprolactone-gelatin nanoscaffold as a potential material for cardiomyocyte differentiation.

India has an alarming rate of growth of cardiovascular diseases (CVD). Similar to cancer there is a significant role for epigenetic factors in the increasing prevalence of CVD. Targeting the epigenetic mechanism, viz., the DNA methylation processes, histone modifications, and RNA based arrangements is today considered as a potential therapeutic approach to CVD management. 5-Azacytidine is an epigenetic treatment drug that is involved in the demethylation of DNA. 5-Azacytidine is an FDA approved drug for myelodysplastic syndrome. However, the usage of 5-Azacytidine for CVD has not been found acceptable because of its poor stability in neutral solutions and shorter half-live which makes it toxic to the cells. A significant breakthrough in the use of 5-azacytidine for cell therapy and tissue engineering for CVD treatment has been gained based on its ability to differentiate mesenchymal stem cells into cardiomyocytes. This work addresses the further need for a sustained release of this drug, to reduce its toxicity to the stem cells. Electrospun PCL-gelatin fibres that are well aligned to provide a mat-like structure with sufficient porosity for differentiated cells to move forward have been synthesized. The crystalline character, porosity, fibre width, thermal behavior hydrophilicity of these scaffolds are in tune with those reported in the literature as ideal for cell proliferation and adhesion. FTIR measurements confirm the entrapment of 5-azacytidine on to the scaffold. The adsorption of the drug did not alter the characteristic features of the scaffold. Primary results on cell viability and cell morphology, as well as cardiomyocyte differentiation, have shown that PCL-gelatin scaffolds carrying 5-azacytidine developed in this work could serve as an ideal platform for mesenchymal stem cell differentiation into cardiomyocytes.

Gingival Crevicular Fluid Levels of RANKL and OPG After Placement of Collagen Membrane With Simvastatin in the Treatment of Intrabony Defects in Chronic Periodontitis.

PURPOSE: The aim of this study was to estimate the Receptor activator of nuclear factor kappa-B ligand (RANKL) and Osteoprotegrin (OPG) levels in gingival crevicular fluid (GCF) after placement of collagen membrane with simvastatin in intrabony defects. MATERIALS AND METHODS: Sixty subjects were grouped according to the treatment plan as Group I and Group II. Group I included patients with intrabony defects treated with collagen membrane. Group II included patients with intrabony defects treated with simvastatin of 1.5 mg concentration incorporated into the collagen membrane. A split-mouth design was planned, in which two contralateral sites with >5 mm probing pocket depth and radiographic evidence of bone loss at baseline were chosen. Probing pocket depth was standardized with acrylic stent in all the selected areas. GCF samples were collected at baseline and 21 days. The amount of RANKL and OPG in the samples was determined by commercial ELISA kits (Biomedica Medizinprodukte, Austria). RESULTS: When comparing both the groups, Group II had more statistically significant (P < 0.001**) decrease in the levels of RANKL than Group I. In contrast to RANKL, the OPG levels were significantly increased in patients (Group II) having intrabony defects treated with collagen membrane along with simvastatin. CONCLUSION: Simvastatin-loaded collagen membrane expressed increased OPG and decreased RANKL levels, which could have a potential role in periodontal regeneration.