Structural and functional studies reveal the molecular basis of substrate promiscuity of a glycosyltransferase originating from a major agricultural pest.

The two-spotted spider mite, Tetranychus urticae, is a major cosmopolitan pest that feeds on more than 1100 plant species. Its genome contains an unprecedentedly large number of genes involved in detoxifying and transporting xenobiotics, including 80 genes that code for UDP glycosyltransferases (UGTs). These enzymes were acquired via horizontal gene transfer from bacteria after loss in the Chelicerata lineage. UGTs are well-known for their role in phase II metabolism; however, their contribution to host adaptation and acaricide resistance in arthropods, such as T. urticae, is not yet resolved. TuUGT202A2 (Tetur22g00270) has been linked to the ability of this pest to adapt to tomato plants. Moreover, it was shown that this enzyme can glycosylate a wide range of flavonoids. To understand this relationship at the molecular level, structural, functional, and computational studies were performed. Structural studies provided specific snapshots of the enzyme in different catalytically relevant stages. The crystal structure of TuUGT202A2 in complex with UDP-glucose was obtained and site-directed mutagenesis paired with molecular dynamic simulations revealed a novel lid-like mechanism involved in the binding of the activated sugar donor. Two additional TuUGT202A2 crystal complexes, UDP-(S)-naringenin and UDP-naringin, demonstrated that this enzyme has a highly plastic and open-ended acceptor-binding site. Overall, this work reveals the molecular basis of substrate promiscuity of TuUGT202A2 and provides novel insights into the structural mechanism of UGTs catalysis.

Community-Based Diabetes Awareness Strategy With Detection and Intervention: The Mobile Diabetes Education Center.

To prevent diabetes and increase equitable access to health care screenings, Touro University California has created and implemented a community outreach program called the Mobile Diabetes Education Center (MOBEC). This program is a joint effort that also involves Sutter Health, the California Department of Public Health, Kaiser Permanente, the Solano County Department of Public Health, and community-based organizations, focusing on advancing health equity in Solano County's at-risk populations. This article reports on the services and initial successes of MOBEC. With its strong community collaboration, MOBEC has helped to raise awareness of diabetes and ensure access to much-needed health screenings and education. This model can potentially be used as a blueprint for similar efforts nationwide to address the health care needs of medically underserved communities.

Neuronal pentraxin 2 correlates with neurodegeneration but not cognition in idiopathic normal pressure hydrocephalus (iNPH).

AIM OF THE STUDY: Neuronal pentraxin-2 (NPTX2) is a synaptic protein responsible for modulating plasticity at excitatory synapses. While the role of NPTX2 as a novel synaptic biomarker in cognitive disorders has been elucidated recently, its role in idiopathic normal pressure hydrocephalus (iNPH) is not yet understood. CLINICAL RATIONALE FOR STUDY: To determine if NPTX2 predicts cognition in patients with iNPH, and whether it could serve as a predictive marker for shunt outcomes. MATERIAL AND METHODS: 354 iNPH patients underwent cerebrospinal fluid drainage (CSF) as part of the tap test or extended lumbar drainage. Demographic and clinical measures including age, Evans Index (EI), Montreal Cognitive Assessment (MoCA) score, Functional Activities Questionnaire (FAQ) score, and baseline and post-shunt surgery Timed Up and Go (TUG) test scores were ascertained. CSF NPTX2 concentrations were measured using an ELISA. CSF ß-amyloid 1-40 (Aß1-40), ß-amyloid 1-42 (Aß1-42), and phosphorylated tau-181 (pTau-181) were measured by chemiluminescent assays. Spearman's correlation was used to determine the correlation between CSF NPTX2 concentrations and age, EI, MoCA and FAQ, TUG, Aß1-40/Aß1-42 ratio, and pTau-181 concentrations. Logistic regression was used to determine if CSF NPTX2 values were a predictor of short-term improvement post-CSF drainage or long-term improvement post-shunt surgery. RESULTS: There were 225 males and 129 females with a mean age of 77.7 years (± 7.06). Average CSF NPTX2 level in all iNPH patients was 559.97 pg/mL (± 432.87). CSF NPTX2 level in those selected for shunt surgery was 505.61 pg/mL (± 322.38). NPTX2 showed modest correlations with pTau-181 (r = 0.44, p < 0.001) with a trend for Aß42/Aß40 ratio (r = -0.1, p = 0.053). NPTX2 concentrations did not correlate with age (r = -0.012, p = 0.83) or MoCA score (r = 0.001, p = 0.87), but correlated negatively with FAQ (r = -0.15, p = 0.019). CONCLUSIONS: While CSF NPTX2 values correlate with neurodegeneration, they do not correlate with cognitive or functional measures in iNPH. CSF NPTX2 cannot serve as a predictor of either short-term or long-term improvement after CSF drainage. CLINICAL IMPLICATIONS: These results suggest that synaptic degeneration is not a core feature of iNPH pathophysiology.

Development of fluorophore labeled or biotinylated anticancer small molecule NSC243928.

Small molecule NSC243928 binds with LY6K, a potential target for the treatment of triple-negative breast cancer, and induces cancer cell death with an unclear mechanism. We have developed chemical tools to identify the molecular mechanisms of NSC243928-LY6K interaction. Herein, we report on the development and synthesis of biotinylated and fluorophore-tethered derivatives of NSC243928 guided by docking studies and molecular dynamics. Surface plasmon resonance assay indicates that these derivatives retained a direct binding with LY6K protein. Confocal analysis revealed that nitrobenzoxadiazole (NBD) fluorophore tagged NSC243928 is retained in LY6K expressing cancer cells. These novel modified compounds will be employed in future in vitro and in vivo studies to understand the molecular mechanisms of NSC243928 mediated cancer cell death. These studies will pave the path for developing novel targeted therapeutics and understanding any potential side-effects of these treatments for hard-to-treat cancers such as triple-negative breast cancer or other cancers with high expression of LY6K.

Safety, antiviral activity and pharmacokinetics of JNJ-64530440, a novel capsid assembly modulator, as 4 week monotherapy in treatment-naive patients with chronic hepatitis B virus infection.

OBJECTIVES: We investigated JNJ-64530440 (a hepatitis B virus capsid assembly modulator) safety, antiviral activity and pharmacokinetics in patients with chronic hepatitis B (CHB) (Phase 1b, NCT03439488). METHODS: Twenty treatment-naive, HBeAg-positive or -negative CHB patients were randomized 4|:|1 to JNJ-64530440 750 mg once or twice daily, or placebo for 28 days. RESULTS: All patients (mean age 43.8 years; 85% male; 70% White; 20% HBeAg positive) completed dosing/28 day follow-up. Mild-to-moderate treatment-emergent adverse events occurred in 3/4 (placebo), 6/8 (once-daily) and 4/8 (twice-daily) patients; mostly fatigue, increased alanine aminotransferase, decreased neutrophil count, and headache. Hepatitis B virus (HBV) DNA was substantially reduced; mean (range) changes from baseline at day 29 were: -3.2 (-2.4 to -3.9) (once-daily) and -3.3 (-2.6 to -4.1) (twice-daily) log10 IU/mL; placebo 0.1 (0.7 to -0.6) log10 IU/mL. HBV DNA levels were below the lower limit of quantification (LLOQ) in 5/8 (once-daily) and 3/8 (twice-daily) patients. For patients with detectable baseline HBV RNA, mean (SE) changes versus baseline in HBV RNA at day 29 were: -2.65 (0.81) (once-daily) and -2.94 (0.33) (twice-daily) log10 copies/mL. HBV RNA levels were 'target not detected' in 4/6 (once-daily) and 3/7 (twice-daily) patients. JNJ-64530440 pharmacokinetics in CHB patients were comparable with those in healthy volunteers. CONCLUSIONS: JNJ-64530440 750 mg once-daily or twice-daily for 28 days was well tolerated and achieved potent antiviral activity in CHB patients.

Severity of Illness Impacts Outcomes More than Admitting Service for Isolated Hip Fracture Patients.

INTRODUCTION: Isolated hip fractures (IHF) are common injuries in the elderly. Controversy exists about which hospital service is best suited to manage these patients. We hypothesize that baseline patient severity of illness (SOI) score drives patient outcomes, not the hospital service managing these patients. METHODS: Retrospective review of all IHF patients from 2014 to 2018 at our Level 1 trauma center. Basic demographics were obtained. Patients were divided into service line they were admitted; surgical vs non-surgical. Primary outcomes included hospital length of stay (HLOS), time to OR, time to VTE prophylaxis, complication rate (defined by the Trauma Quality Improvement Program), 30-day mortality, and readmissions. SOI score (which is DRG-based) was controlled to see if any differences in primary outcomes occurred between cohorts. Chi-square was used for categorical variables and regression analysis for continuous variables. Significance was p < 0.05. RESULTS: A total of 366 total patients were analyzed with the same ISS. A total of 102 were admitted to a surgical service and 264 to a non-surgical service. Average overall age was 80 year, 66.9% were female, and 86% were Caucasian. There was no statistical difference between outcomes when comparing admitting services. Controlling for SOI score, there was no difference between admitting service for outcomes as well. SOI score was a significant predictor for increased HLOS and complication occurrence (p < 0.001) via regression analysis, with a 6.06-fold increase in complication rate from mild to moderate SOI score (p = 0.001). CONCLUSION: There is no difference in outcomes based on admitting service and process measures. However, the SOI score is perhaps a better predictor of outcomes for isolated hip fracture patients.

Total laparoscopic hysterectomy in combination with dilation and evacuation of an 18-week-sized uterus with gestational trophoblastic neoplasia: a novel treatment approach.

Gestational trophoblastic disease is a spectrum that includes complete and partial hydatidiform moles, invasive mole, choriocarcinoma, and placental site trophoblastic tumor. Although most cases of gestational trophoblastic neoplasia occur after a molar pregnancy, it can develop after any pregnancy. Suction curettage remains the standard first-line management in a molar pregnancy in patients desiring fertility. However, hysterectomy is a reasonable option in patients that do not desire to preserve fertility. Hysterectomy for gestational trophoblastic neoplasia can be difficult because of the enlarged uterus and prominent uterine vasculature. Traditionally, hysterectomy for gestational trophoblastic neoplasia is usually performed via laparotomy. In this article and accompanying video, we describe and illustrate a minimally invasive technique that demonstrates a safe and feasible laparoscopic removal of an enlarged uterus and illustrates alternative extraction techniques to avoid laparotomy in hysterectomy for gestational trophoblastic disease. In this case, a combination of laparoscopic transection of the vascular pedicles followed by dilation and evacuation was used before colpotomy. The addition of dilation and evacuation allowed us to reduce the overall size of the uterus and remove it intact through the vagina with minimal bleeding, avoiding unnecessary laparotomy. This allowed the patient to have an improved postsurgical recovery experience with minimal blood loss compared with standard laparotomy for gestational trophoblastic neoplasia.

Clinical Performance and Parental Satisfaction with Composite Strip Crown and Prefabricated Zirconia Crown for Primary Anterior Teeth: A Randomized Clinical Trial.

AIM: To compare clinical performance and parental satisfaction with composite strip crown and prefabricated zirconia crown for primary anterior teeth. MATERIALS AND METHODS: The study compares clinical evaluation and parental satisfaction of two different crowns for primary anterior teeth. A total of 102 teeth in each group selected between ages 3 and 6 years, who met the inclusion criteria, were randomly allocated into two groups for further evaluation. Group A for strip crowns (55 teeth) and group B for zirconia crowns (47 teeth). The crowns were evaluated clinically with various criteria like-color match, crown retention, gingival health, crown contour, opposing tooth wear, marginal integrity, and recurrent caries. The samples were also evaluated for parental satisfaction based on 5-point Likert scale and child liking was also recorded with Smiley face Likert scale at baseline, 3 and 9 months. Statistical analysis was done using Chi-square test (p <0.05). RESULTS: Zirconia crowns showed better color match, crown retention, crown contour, and gingival health. Strip crowns showed more discoloration and chipping of material over a period of time. None of the samples showed opposing tooth wear, open margins, and recurrent caries in strip and zirconia crown group. Parents and children both were highly satisfied with zirconia crowns. CONCLUSION: Clinically zirconia crowns showed higher success rate as compared to strip crowns and parental overall satisfaction was higher for zirconia crowns. CLINICAL SIGNIFICANCE: Zirconia crowns exhibited a higher clinical performance and parental satisfaction; hence, if affordability is out weighted, zirconia crown stands better with esthetics of the child.

Determination of accuracy of polycythemia vera diagnoses and use of the JAK2V617F test in the diagnostic scheme.

In 2005, three independent research groups described the presence of a specific mutation in the JAK2 gene, JAK2V617F, in patients with a Philadelphia chromosome-negative myeloproliferative neoplasm (MPN). The percentage of patients with the mutation varied according to specific disease with >98 % of polycythemia vera (PV) patients having the mutation. In 2008, the World Health Organization issued new diagnostic criteria for PV including use of the JAK2V617F test as a major diagnostic criterion. The goal of the present study is to determine the accuracy of diagnosing PV in a community practice and reporting of PV to cancer registries, as well as assessing the integration of molecular testing into diagnostic paradigms. Using Geisinger Medical Center's electronic medical records (EMR), patients with a PV diagnosis being seen by a hematologist/oncologist during 2004-2009 were identified. Records were reviewed by a single hematologist/oncologist to determine accuracy of the treating physician's diagnosis and use of the molecular test for the JAK2V617F mutation. There was a diagnosis of PV from the treating physicians in 121 of the 204 evaluable patients (59 %) and another MPN in 21 (10 %). However, we confirmed a PV diagnosis in only 90 patients (44 %). Of the 90 confirmed PV patients, 64 were JAK2V617F-mutation positive while 24 were not tested. While JAK2V617F testing has made a major impact in facilitating the successful delineation of the type of polycythemia (PV versus secondary polycythemia) in patients evaluated in a large, community-based Hematology/Oncology practice, physician usage of other critical tests is inconsistent leading to errors in diagnosis. JAK2V617F mutation testing in combination with other diagnostic criteria may help reduce diagnostic errors.

Effect of Curing Light with Different Intensities on the Penetration of Silver and Fluoride Ions and Dentin Hardness in Primary Carious Molars Following Silver Diamine Fluoride Application: A Comparative Microscopic Ex Vivo Study.

Background: A paradigm shift from surgical to medical approach for caries management has popularized silver diamine fluoride (SDF) as a preventive and interim caries arrest medicament. Few studies conducted have explored the effect of curing light on SDF's microbial property, its penetration, and effect on dentin. However, there is a research gap regarding the effect of different intensities of curing light on SDF performance. Aim: To determine the effect of different curing light intensities on SDF penetration depth and dentin hardness in carious lesions of primary molars. Materials and methods: Silver diamine fluoride was applied on 30 extracted carious primary molars. Teeth were randomly allocated into three groups-(1) control group, no light curing after application of SDF; (2) light curing of SDF with low intensity (1000 mW/cm2); and (3) light curing of SDF with high intensity (2500 mW/cm2). A scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) analysis was performed to check ion penetration after 1 week, and a Vickers hardness test was used to assess dentin hardness of both infected and affected dentin layers at 1-week and 1-month intervals. Based on the distribution of data, parametric and nonparametric tests were applied. Statistical Package for the Social Sciences (SPSS) version 26 was used for statistical analysis. The level of significance was set at 5%. Results: Silver diamine fluoride penetrated beyond the carious lesion in all three groups. The mean silver ion precipitation in infected dentin in group III (16.90 ± 0.68) was maximum, whereas it was found to be minimum in group II (7.31 ± 0.63). The mean fluoride ion precipitation in affected dentin in group III (4.06 ± 0.41) was highest and least in group II (3.09 ± 0.58). A considerable increase in mean dentin hardness of infected dentin was observed in all three groups (214.00 ± 89.06, 218.00 ± 75.17, 231.00 ± 98.86, respectively; p < 0.001) after 1 month. Conclusion: Applying SDF to carious lesions using a high-intensity dental curing light induced more silver ion precipitation in infected dentin and increased its hardness. How to cite this article: Bhatt R, Patel M, Thakkar A, et al. Effect of Curing Light with Different Intensities on the Penetration of Silver and Fluoride Ions and Dentin Hardness in Primary Carious Molars Following Silver Diamine Fluoride Application: A Comparative Microscopic Ex Vivo Study. Int J Clin Pediatr Dent 2024;17(7):766-772.

Clinical Assessment of Preemptive Analgesia on Success of Pulpal Anesthesia and Postendodontic Pain in Children with Irreversible Pulpitis: A Randomized Comparative Study.

Introduction: Optimal pain management of symptomatic pulpitis in formative years goes a long way in developing a positive dental attitude. Efforts should be made to increase the success of anesthesia, thus diminishing negative dental experiences. The aim of the study was to assess the efficacy of preemptive analgesia on the success of pulpal anesthesia following inferior alveolar nerve block (IANB) in children with symptomatic irreversible pulpitis and on reducing postendodontic pain. Materials and methods: The research design was an in vivo, three-group, parallel, quadruple-blind study. A total of 75 patients were randomly allocated to one of the three groups-group I: ibuprofen, group II: combination of ibuprofen and paracetamol, and group III: multivitamin (placebo). Premedication was given 45 minutes before treatment, and patients received IANB in a standardized manner. Pain during pulpectomy was recorded using the face, legs, activity, cry, consolability (FLACC) scale and postoperatively using Wong-Baker's pain rating scale (WBPRS) at 4, 12, and 24 hours. Success was measured if the pain felt was of no or mild intensity. Results: Success of IANB was 64% for ibuprofen, 72% for the combination group, and 40% for the placebo group, with no statistically significant difference between all groups (p = 0.06) on the FLACC scale. At 4 hours postoperatively, a significant difference (p = 0.02) was found among groups with more children experiencing no or mild pain in groups I and II and the highest number of rescue medications taken by the placebo group. Conclusion: Ibuprofen and a combination of ibuprofen and acetaminophen as preemptive analgesics had no significant effect on the success rate of IANB, although it was effective in reducing pain at 4 hours postoperatively. How to cite this article: Gori NA, Patel MC, Bhatt RK, et al. Clinical Assessment of Preemptive Analgesia on Success of Pulpal Anesthesia and Postendodontic Pain in Children with Irreversible Pulpitis: A Randomized Comparative Study. Int J Clin Pediatr Dent 2024;17(1):72-78.

Anterior-Segment Optical Coherence Tomography-Based Evaluation of the Journey of a Bleb in the Early Postoperative Period.

Introduction In the early postoperative period following trabeculectomy, monitoring the journey of bleb formation is crucial for assessing surgical success. Anterior-segment optical coherence tomography (AS-OCT) emerges as a powerful tool in this pursuit, offering high-resolution imaging of bleb morphology and dynamics. This study aims to evaluate the internal structure of blebs through their maturation phases using AS-OCT. Methods Fifty-five eyes undergoing trabeculectomy were enrolled in a prospective observational study. Serial AS-OCT examinations were done on day 1, week 1, week 3, and week 6 postoperatively; bleb parameters were calculated and correlated with intraocular pressure (IOP). Results IOP control was seen in 45 eyes six months of post-trabeculectomy. Multiform bleb wall reflectivity (BWR) statistically correlates with the success of trabeculectomy. Blebs were successful if BWR showed no change from day 1 to week 6. BWR remained the same on all follow-ups if week 1 bleb wall thickness (BWT) was less than 129.5 microns with 82.6% sensitivity and 83.3% specificity. The cumulative hazard of change in BWR is estimated to be approximately 5.6%, 15.7%, and 17.9% at week 1, week 3, and week 6 follow-ups, respectively. Conclusions Successful blebs showed consistent BWR from day 1 to week 6 of follow-up. Serial AS-OCT examination for changes in BWR in early stages can be done to predict the fate of bleb. The maximum change in BWR occurs between the week 1 and week 3 follow-up periods requiring close follow-up.

Impact of Pharmacist Integration Into Primary Care on Reimbursement for Hospital Follow-Up Visits.

BACKGROUND: The financial and clinical impact of transitional care management (TCM) outcomes through pharmacist integration within primary care is not well described. OBJECTIVES: The primary objective of this study was to determine the financial impact of pharmacist conducted post-discharge phone calls. The secondary objectives included readmission rates and number of interventions. METHODS: A computer-generated list identified patients discharged from St. Joseph's/Candler Health System (SJ/C) with a listed primary care provider within the SJ/C Primary Care Medical Group at Eisenhower from November 1, 2019 to April 30, 2020. Eligible patients who received a post-discharge phone call from a pharmacist were compared to those who received a call by another staff member. Data was collected regarding the financial impact of pharmacist conducted post-discharge phone calls. Readmission rates and medication related interventions were also assessed. RESULTS: There were 104 patients discharged meeting criteria. Twenty-four patients were contacted by a pharmacist resulting in 20 subsequent hospital follow up appointments scheduled with the provider. Total amount billed for those appointments was $4220 (average of $211 per visit). Twenty-five calls were made by non-pharmacist staff with 23 appointments scheduled. Total amount billed for those appointments was $2445 (average of $106 per visit). Increased reimbursement was generated by a qualifying 2-way communication by the pharmacist as outlined by Center for Medicaid and Medicare Services enabling providers to bill for a TCM visit versus standard office visit. Pharmacists made 33 clinical interventions including medication reconciliation, medication procurement, referrals, lab orders, and education. One intervention was made by non-pharmacist staff. The 30-day readmission rate for pharmacist contacted patients was 8% versus 12% for non-pharmacist contacted patients. CONCLUSIONS: Pharmacist involvement in TCM while integrated into a primary care office is previously not well described. This data highlights an opportunity for pharmacists to demonstrate sustainability and improved outcomes related to TCM.

Novel fully automated prototype assays for specific detection of phosphorylated and non-phosphorylated Hepatitis B core antigens.

BACKGROUND: Hepatitis B core antigen (HBcAg) has been proposed as a surrogate marker to reflect transcriptional activity of HBV covalently closed circular DNA (cccDNA) during active infections and may be a valuable tool to monitor the efficacy of antiviral therapies. However, HBcAg-specific immunoassays are unavailable, and current assays that measure hepatitis B core-related antigen (HBcrAg) cannot distinguish between HBcAg, HBeAg, and precore (PreC) proteins. OBJECTIVE: Two fully automated assays were developed to specifically detect phosphorylated HBcAg (P-HBcAg, representing non-HBV DNA-containing particles) and non-phosphorylated HBcAg (representing HBV DNA-containing particles) circulating in HBV infected patients. STUDY DESIGN: P-HBcAg and HBcAg levels were analyzed in 124 single timepoint patients with active infections, in three longitudinal specimens from patients with acute HBV infections, and in four chronic hepatitis B (CHB) patients on-therapy (TDF - tenofovir disoproxil fumarate, pegIFN - pegylated interferon, NAPs - nucleic acids polymers). RESULTS: Analyzing acute infections revealed that P-HBcAg and HBcAg levels correlate more closely than HBcrAg to HBV DNA. During antiviral treatment of CHB patients, HBcAg correlates well with HBV DNA and indicates a therapeutic response to the treatment at the beginning of the therapy. In contrast, P-HBcAg tracks more closely to HBV RNA. Importantly, P-HBcAg is detectable several months after HBcAg became undetectable indicating that cccDNA is still transcriptionally active in hepatocytes. CONCLUSIONS: Overall, the ability to specifically distinguish between the various states of HBcAg (phosphorylated and non-phosphorylated) can provide additional insights for disease staging, drug development, and management of HBV therapies.

A comparative assessment of efficacy and preference between needleless device INJEX and insulin syringe for anesthetizing primary maxillary teeth in children aged 4-9 years: A split-mouth crossover randomized clinical study.

insulin syringe for anesthetizing primary maxillary teeth in children aged 4-9 years. Materials and Methods: This randomized clinical study included 46 children aged 4-9 years. The patients were digitally allotted to receive 4% articaine for extractions of primary maxillary teeth, either using needleless device INJEX or insulin syringe on each side of the maxillary arch, in two different appointments after a 1-week washout period. Pain perception was measured by the subjective (Faces Pain Scale-Revised [FPS-R]) and objective pain scores (Face, Legs, Activity, Cry, and Consolability [FLACC]) and hemodynamic parameters (heart rate and oxygen saturation) during LA administration and during extractions. After the second appointment, children were asked about their preference between needleless device INJEX and insulin syringe. Results: On evaluating subjective pain scores with FPS-R, intergroup differences between the INJEX and insulin syringe groups were found statistically insignificant, both during LA administration (P = 0.101) and extraction (P = 0.080). However, on assessing pain objectively during extraction using FLACC, the mean pain score was less with insulin syringe (2.78) as compared to INJEX (4.72) and the difference was statistically significant (P = 0.000). There was no significant difference in patient preference between the two methods. Conclusion: Pain perception was minimal during local anesthesia administration using needleless device INJEX; however, its clinical efficacy during extractions was reported to be lower than insulin syringe. Background: Managing pain in children is the most challenging task as it forms the foundation for instilling positive behavior toward dental treatment. Adequate local anesthesia (LA) is the cornerstone of pain management. However, the fear of needles, particularly in young children, can result in complete avoidance and refusal of treatment. Aim: This study aimed to evaluate and compare the efficacy and preference between needleless device INJEX and.

pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery.

Over the past several decades, there has been significant growth in the design and development of more efficient and advanced biomaterials based on non-cellulosic biological macromolecules. In this context, hydrogels based on stimuli-responsive non-cellulosic biological macromolecules have garnered significant attention because of their intrinsic physicochemical properties, biological characteristics, and sustainability. Due to their capacity to adapt to physiological pHs with rapid and reversible changes, several researchers have investigated pH-responsive-based non-cellulosic polymers from various materials. pH-responsive hydrogels release therapeutic substances in response to pH changes, providing tailored administration, fewer side effects, and improved treatment efficacy while reducing tissue damage. Because of these qualities, they have been shown to be useful in a wide variety of applications, including the administration of chemotherapeutic drugs, biological material, and natural components. The pH-sensitive biopolymers that are utilized most frequently include chitosan, alginate, hyaluronic acid, guar gum, and dextran. In this review article, the emphasis is placed on pH stimuli-responsive materials that are based on biological macromolecules for the purposes of drug administration.

A comparative evaluation of light cure calcium silicate and resin-modified glass ionomer as indirect pulp capping agent in primary molars: A randomized clinical trial.

Background: Minimally invasive techniques should be employed to maintain pulp vitality without affecting physiological tooth resorption for pediatric patients. This study aims to evaluate clinical and radiographic success of light cure calcium silicate and resin-modified glass ionomer (RMGI) as indirect pulp-capping agent in primary molars in children between 5 and 9 years. Materials and Methods: In this randomized clinical trial study, 40 primary molars with the International Caries Detection and Assessment System criteria 4-6 score were divided randomly into two groups after computerized randomization method. After caries excavation by minimally invasive dentistry principle, affected dentin was lined by either light cure calcium silicate (Group I) or RMGI (Group II) liner followed by composite restoration. Clinical success was determined with the absence of symptoms and bitewing radiographs were taken at baseline, 3, and 6 months' interval to measure increase in dentin increment using ImageJ software. Statistical analysis for intergroup comparison was done using Paired t-test, and Independent t-test was used for intragroup comparison. The level of statistical significance was set at P < 0.05. Results: Change in dentin increment seen from baseline to 6 months in Group I was 0.19 mm and in Group II was 0.20 mm (P = 0.924). Intragroup increment was statistically significant during all follow-up intervals for both the groups (Group I - P ≤ 0.001, Group II - P = 0.009). For baseline remaining dentin thickness >1.5 mm, statistically significant increase was observed in the dentin increment at 3 months' interval between both the groups. Conclusion: Both TheraCal LC and Vitrebond show acceptable clinical and radiographic results when used in primary molars as indirect pulp treatment agents. Both the liners are equivalent to each other in terms of feasibility and cost-effectiveness but TheraCal LC can be preferred due to better handling and avoiding the manipulation step thereby reducing treatment time.

Clinical and Radiographic Evaluation of Different Glass Ionomer Restorative Materials in Primary Molars: A Comparative Randomized Clinical Trial.

Aim: The study aimed to evaluate and compare the clinical and radiographic success rate of Ketac Universal (3M), GC 9 EXTRA (GC), and Cention N (Ivoclar) restorative materials in primary molars. Materials and methods: The study was conducted as randomized clinical trial in children aged 3-8 years old, out of which a total of 75 primary molars were selected in 43 patients who met the inclusion criteria. The sample size was further divided into three groups of restorative materials, which included group I-Ketac Universal (n = 25), group II-GC 9 EXTRA (n = 25), and group III-Cention N (n = 25). Class I restorations were placed randomly according to the computerized randomization in primary molars and evaluated at baseline (1 week), 6 months, and 12 months according to modified United States Public Health Service (USPHS) criteria and bitewing radiographs. Results: On intercomparison of three groups at 12 months, there was no significant difference found, while on pairwise comparison of Ketac Universal and Cention N, there was a significant difference in relation to surface texture (p = 0.04*) and anatomic contour (p = 0.04*) at 12 months. Conclusion: Newly introduced restorative material Cention N exhibited improved physical and mechanical properties and can be recommended as a cost-effective restorative and easy-to-use material in posterior load-bearing primary molars. Clinical significance: Restoration of primary teeth continues to be an important aspect of restorative dentistry. The longevity of restorations in primary teeth is significantly different for all materials compared to permanent dentition. This makes the assessment of these restorations as a separate group meaningful. How to cite this article: Kataria VG, Patel MC, Bhatt R, et al. Clinical and Radiographic Evaluation of Different Glass Ionomer Restorative Materials in Primary Molars: A Comparative Randomized Clinical Trial. Int J Clin Pediatr Dent 2023;16(6):829-836.

Exploratory Assessment of Proteomic Network Changes in Cerebrospinal Fluid of Mild Cognitive Impairment Patients: A Pilot Study.

(1) Background: Despite the existence of well-established, CSF-based biomarkers such as amyloid-ß and phosphorylated-tau, the pathways involved in the pathophysiology of Alzheimer's disease (AD) remain an active area of research. (2) Methods: We measured 3072 proteins in CSF samples of AD-biomarker positive mild cognitive impairment (MCI) participants (n = 38) and controls (n = 48), using the Explore panel of the Olink proximity extension assay (PEA). We performed group comparisons, association studies with diagnosis, age, and APOE ε4 status, overrepresentation analysis (ORA), and gene set enrichment analysis (GSEA) to determine differentially expressed proteins and dysregulated pathways. (3) Results: GSEA results demonstrated an enrichment of granulocyte-related and chemotactic pathways (core enrichment proteins: ITGB2, ITGAM, ICAM1, SELL, SELP, C5, IL1A). Moreover, some of the well-replicated, differentially expressed proteins in CSF included: ITGAM, ITGB2, C1QA, TREM2, GFAP, NEFL, MMP-10, and a novel tau-related marker, SCRN1. (4) Conclusion: Our results highlight the upregulation of neuroinflammatory pathways, especially chemotactic and granulocyte recruitment in CSF of early AD patients.

Lymphocyte antigen 6K signaling to aurora kinase promotes advancement of the cell cycle and the growth of cancer cells, which is inhibited by LY6K-NSC243928 interaction.

Lymphocyte antigen 6K (LY6K) is a small GPI-linked protein that is normally expressed in testes. Increased expression of LY6K is significantly associated with poor survival outcomes in many solid cancers, including cancers of the breast, ovary, gastrointestinal tract, head and neck, brain, bladder, and lung. LY6K is required for ERK-AKT and TGF-ß pathways in cancer cells and is required for in vivo tumor growth. In this report, we describe a novel role for LY6K in mitosis and cytokinesis through aurora B kinase and its substrate histone H3 signaling axis. Further, we describe the structural basis of the molecular interaction of small molecule NSC243928 with LY6K protein and the disruption of LY6K-aurora B signaling in cell cycle progression due to LY6K-NSC243928 interaction. Overall, disruption of LY6K function via NSC243928 led to failed cytokinesis, multinucleated cells, DNA damage, senescence, and apoptosis of cancer cells. LY6K is not required for vital organ function, thus inhibition of LY6K signaling is an ideal therapeutic approach for hard-to-treat cancers that lack targeted therapy such as triple-negative breast cancer.