Associations between per- and poly-fluoroalkyl substance (PFAS) exposure and immune responses among women in the California Teachers study: A cross-sectional evaluation.

INTRODUCTION: Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants that have been linked to a number of health outcomes, including those related to immune dysfunction. However, there are limited numbers of epidemiological-based studies that directly examine the association between PFAS exposure and immune responses. METHODS: In this cross-sectional study nested in the California Teachers Study cohort, we measured nine PFAS analytes in serum. Of the 9 analytes, we further evaluated four (PFHxS [perfluorohexane sulfonate], PFNA [perfluorononanoic acid], PFOA [perfluorooctanoic acid], PFOS [perfluorooctanesulfonic acid]) that had detection levels of > 80 %, in relation to 16 systemic inflammatory/immune markers and corresponding immune pathways (Th1 [pro-inflammatory/macrophage activation], B-cell activation, and T-cell activation). Study participants (n = 722) were female, completed a questionnaire regarding various health measures and behaviors, and donated a blood sample between 2013-2016. The association between PFAS analytes and individual immune markers and pathways were evaluated by calculating odds ratios (OR) and 95 % confidence intervals (CI) in a logistic regression model. PFAS analytes were evaluated both as a dichotomous exposure (above or below the respective median) and as a continuous variable (per 1 unit increase [ng/mL]). RESULTS: The prevalence of detecting any PFAS analyte rose with increasing age, with the highest PFAS prevalence observed among those aged 75 + years and the lowest PFAS prevalence observed among those aged 40-49 years (study participant age range: 40-95 years). Significant associations with BAFF (B-cell activating factor) levels above the median were observed among participants with elevated (defined as above the median) levels of PFHxS (OR=1.53), PFOA (OR=1.43), and PFOS (OR=1.40). Similarly, there were statistically significant associations between elevated levels of PFHxS and TNFRII (tumor necrosis factor receptor 2) levels (OR=1.78) and IL2Rα (interleukin 2 receptor subunit alpha) levels (OR=1.48). We also observed significant inverse associations between elevated PFNA and sCD14 (soluble cluster of differentiation 14) (OR=0.73). No significant associations were observed between elevated PFNA and any immune marker. Evaluation of PFAS exposures as continuous exposures in association with dichotomized cytokines were generally consistent with the dichotomized associations. CONCLUSIONS: PFAS exposure was associated with altered levels of circulating inflammatory/immune markers; the associations were specific to PFAS analyte and immune marker. If validated, our results may suggest potential immune mechanisms underlying associations between the different PFAS analytes and adverse health outcomes.

Methodological quality of umbrella reviews in endodontics: A cross-sectional study.

INTRODUCTION: In endodontics, the number of umbrella reviews has increased significantly over the last few years, but there is no evidence that they were methodologically sound. The aim of the current study was to appraise the methodological quality of umbrella reviews in endodontics, and to identify possible predictive factors associated with methodological quality. METHODS: Umbrella reviews published in the discipline of endodontics until December 2023 were included. The methodological quality of the reviews was evaluated using a checklist consisting of 11 items. Each item in the checklist was evaluated by two independent assessors who assigned a score of '1' if it was fully addressed, '0.5' if it was partially ddressed, and '0' if it was not addressed. Bootstrapped multiple linear regression analysis was used to examine the association between the total scores awarded and five predictor variables (a priori protocol registration, year of publication, number of authors, journal impact factor (IF) and continent of the corresponding author). The statistical significance level was set as 5%. RESULTS: A total of 27 reviews were included. Ninety-six per cent of the reviews adequately reported: eligibility criteria for selecting the reviews, details of the reviews, techniques for assessing the risk of bias or methodological quality of the individual systematic reviews they included. Only 30% of the reviews adequately managed overlapping primary studies within individual systematic reviews. Among the five predictors analysed, a priori protocol registration and journals with IFs were associated with significantly greater total methodological quality scores. DISCUSSION: Several methodological shortcomings in the umbrella reviews published within the field of endodontics were revealed. Umbrella reviews published in journals with IFs and those with protocols registered a priori had significantly superior methodological quality scores. CONCLUSION: In endodontics, authors intending to publish umbrella reviews should consider the limitations revealed in this study and follow the appropriate rules to ensure their reviews comply with the highest standards and provide accurate and dependable information and conclusions.

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.

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.

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.

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 ).

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.

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.