The Impact of Polymers on Enzalutamide Solid Self-Nanoemulsifying Drug Delivery System and Improved Bioavailability.

Enzalutamide (ENZ), marketed under the brand name Xtandi® as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ's low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development.

Systemic Corticosteroid Uses in Endodontics-Part 2: Enhancing the Success of Local Anesthesia.

INTRODUCTION: Chronic inflammation in irreversible pulpitis leads to heightened sensitivity of nociceptive receptors, resulting in persistent hyperalgesia. This poses significant challenges in achieving effective anesthesia for patients with irreversible pulpitis. Various anesthetic techniques and pharmacological approaches have been employed to enhance the success of local anesthesia. Recently, the preemptive use of anti-inflammatory agents, specifically corticosteroids, has gained attention and shown promising results in randomized controlled trials. This systemic review and meta-analysis aimed to evaluate the impact of systemically administered corticosteroids on enhancing anesthetic success in patients undergoing endodontic treatment. METHODS: A comprehensive search was conducted across multiple databases including PubMed, Cochrane Library, Embase, Scopus, Dentistry & Oral Science, and ProQuest. Additionally, the references of primary studies and related systematic reviews were manually searched for additional relevant publications. The primary outcome assessed was the success of anesthesia, and the effect measure was risk ratio using the random-effects inverse variance method. Statistical significance was set at P < .05. The certainty of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Twelve studies involving 917 participants were analyzed to determine the frequency of successful anesthesia. The corticosteroid group demonstrated a significantly higher number of patients achieving successful anesthesia (risk ratio = 1.66; 95% confidence interval, 1.34-2.06;P < .00001). However, heterogeneity within the pooled data analysis was observed (I2 = 57%, P = .007). CONCLUSIONS: Moderate certainty evidence indicates that preemptive use of systemic corticosteroids enhances the success of local anesthesia, specifically inferior alveolar nerve block, in cases of irreversible pulpitis.

Systemic Corticosteroid Uses in Endodontics-Part 1: Managing Postoperative Pain.

INTRODUCTION: This study aimed to systematically search and review all available literature regarding systemic (oral or locally injected) corticosteroids in endodontics to assess their effect on postoperative pain. METHODS: A search was conducted using PubMed, Cochrane Library, Embase, Scopus, Dentistry & Oral Science, and ProQuest. Randomized controlled trials enrolling participants undergoing endodontic treatment and assessing the presence of pain and pain scores at 6, 12, and 24 hours postoperatively were included. We synthesize the effect measures using risk ratios (RRs), standardized mean differences (SMDs), and their corresponding 95% confidence intervals (CIs). Meta-analysis was performed using the random-effects inverse variance method. The level of significance was set at P < .05. The certainty of the evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: A total of 2303 participants from 29 trials were included. Patients who received corticosteroids were significantly less likely to report pain at 6 hours (RR = 2.5; 95% CI, 1.74-3.61; P < .00001), 12 hours (RR = 2.10; 95% CI, 1.53-2.90; P < .00001), and 24 hours (RR = 1.77; 95% CI, 1.38-2.28; P < .00001) postoperatively. Furthermore, they reported lower pain intensity at 6 hours (SMD = - 0.82; 95% CI, -1.17 to -0.48; P < .00001), 12 hours (SMD = - 0.63; 95% CI, -0.75 to -0.51; P < .00001), and 24 hours (SMD = - 0.68; 95% CI, -0.90 to -0.46; P < .00001) postoperatively. CONCLUSIONS: Moderate certainty evidence indicates that the use of systemic corticosteroids likely results in a moderate to large reduction in postoperative endodontic pain.

Intentional Replantation: No Longer a Last Resort for Saving a Natural Tooth.

Intentional replantation (IR) is the intentional extraction of a tooth followed by its replacement back into its socket for the purpose of performing a root-end surgery or other necessary repairs. The procedure may be considered a favorable alternative to conventional microsurgery, especially when surgical access is restricted due to specific anatomical challenges. With advancements in magnification, bioceramics, and instrumentation, IR has become a well-established, scientifically supported treatment modality and is cost-effective when compared to single-implant placement. This article discusses the rationale and indications for IR, describes treatment protocols, and reports on its outcomes.

Case report: Intrathecal baclofen therapy improved gait pattern in a stroke patient with spastic dystonia.

Background: Intrathecal baclofen (ITB) therapy, a viable alternative for unsuitable candidates of conventional spasticity medications, is a preferred method of administration over the oral route. Owing to its enhanced bioavailability, ITB ensures a more effective delivery at the target site. Objective: There is a lack of conclusive evidence regarding the use of ITB treatment in managing ambulatory patients with spastic dystonia. Before ITB pump implantation, patients commonly undergo an ITB bolus injection trial to rule out potential adverse reactions and verify the therapeutic effects on hypertonic issues. In this report, we highlight a case of spastic dystonia, particularly focusing on an ambulatory patient who demonstrated significant improvement in both the modified Ashworth scale (MAS) score and gait pattern following the ITB injection trial. Case report: This case report outlines the medical history of a 67-year-old male diagnosed with left-side hemiplegia and spastic dystonia, resulting from his second episode of intracranial hemorrhage in the right thalamus. An ITB injection trial was initiated because the patient was not suitable for continued botulinum toxin injections and oral medications. This was due to the persistent occurrence of spastic dystonia in both the upper and lower extremities. The patient underwent a four-day ITB injection trial with progressively increasing doses, resulting in improved MAS scores and gait parameters, including cadence, step length, step time, stride length, and stride time were increased. Particularly, kinematic gait analysis demonstrates a substantial improvement of increased knee flexion in the swing phase in stiff knee gait pattern. These findings indicated a gradual reduction in spasticity-related symptoms, signifying the positive effect of the ITB injection trial. The patient eventually received an ITB pump implantation. Conclusion: In this post-stroke patient with spastic dystonia, ITB therapy has demonstrated effective and substantial management of spasticity, along with improvement in gait patterns.

Adsorption of antibiotics onto low-grade charcoal in the presence of organic matter: Batch and column tests.

Antibiotics contaminate diverse ecosystems and threaten human health. In ecosystems including water, sediment, and soil, the amount of antibiotics present is tiny compared to the amount of natural organic matter. However, most studies have ignored the co-presence of natural organic matter in the adsorption of target antibiotics. In this study, we quantitatively evaluated the effect of co-presenting natural organic matter on the adsorption of sulfamethazine (SMZ) through batch and column experiments using low-grade charcoal, an industrial by-product. SMZ was used as a model antibiotic compound and humic acid (HA) was used to represent natural organic matter. The co-presence of 2000 mg/L HA (400 times the concentration of SMZ) lowered the adsorption rate of SMZ from 0.023 g/mg·min to 0.007 g/mg·min, and the maximum adsorption capacity from 39.8 mg/g to 15.6 mg/g. HA blocked the charcoal's pores and covered its surface adsorption sites, which dramatically lowered its capacity to adsorb SMZ. Similar results were obtained in the flow-through column experiments, where the co-presence of natural organic matter shortened the lifetime of the charcoal. As a result, the co-presence of a relatively high concentration of natural organic matter can inhibit the adsorption of SMZ and likely other antibiotic compounds, and thus the presence of natural organic matter should be accounted for in the design of adsorption processes to treat antibiotics in water.

Characterization of gastric cancer-stimulated signaling pathways and function of CTGF in cancer-associated fibroblasts.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that play an important role in cancer progression. Although the mechanism by which CAFs promote tumorigenesis has been well investigated, the underlying mechanism of CAFs activation by neighboring cancer cells remains elusive. In this study, we aim to investigate the signaling pathways involved in CAFs activation by gastric cancer cells (GC) and to provide insights into the therapeutic targeting of CAFs for overcoming GC. METHODS: Alteration of receptor tyrosine kinase (RTK) activity in CAFs was analyzed using phospho-RTK array. The expression of CAFs effector genes was determined by RT-qPCR or ELISA. The migration and invasion of GC cells co-cultured with CAFs were examined by transwell migration/invasion assay. RESULTS: We found that conditioned media (CM) from GC cells could activate multiple receptor tyrosine kinase signaling pathways, including ERK, AKT, and STAT3. Phospho-RTK array analysis showed that CM from GC cells activated PDGFR tyrosine phosphorylation, but only AKT activation was PDGFR-dependent. Furthermore, we found that connective tissue growth factor (CTGF), a member of the CCN family, was the most pronouncedly induced CAFs effector gene by GC cells. Knockdown of CTGF impaired the ability of CAFs to promote GC cell migration and invasion. Although the PDGFR-AKT pathway was pronouncedly activated in CAFs stimulated by GC cells, its pharmacological inhibition affected neither CTGF induction nor CAFs-induced GC cell migration. Unexpectedly, the knockdown of SRC and SRC-family kinase inhibitors, dasatinib and saracatinib, significantly impaired CTGF induction in activated CAFs and the migration of GC cells co-cultured with CAFs. SRC inhibitors restored the reduced expression of epithelial markers, E-cadherin and Zonula Occludens-1 (ZO-1), in GC cells co-cultured with CAFs, as well as CAFs-induced aggregate formation in a 3D tumor spheroid model. CONCLUSIONS: This study provides a characterization of the signaling pathways and effector genes involved in CAFs activation, and strategies that could effectively inhibit it in the context of GC. Video Abstract.

Enhanced Stability and Improved Oral Absorption of Enzalutamide with Self-Nanoemulsifying Drug Delivery System.

The purpose of this study is to develop and evaluate a self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral absorption of poorly water-soluble enzalutamide (ENZ). Considering the rapid recrystallization of the drug, based on solubility and crystallization tests in various oils, surfactants and co-surfactants, Labrafac PG 10%, Solutol HS15 80%, and Transcutol P 10%, which showed the most stable particle size and polydispersity index (PDI) without drug precipitation, were selected as the optimal SNEDDS formulation. The optimized SNEDDS formulation showed excellent dissolution profiles for all the drugs released at 10 min of dissolution due to the increased surface area with a small particle size of approximately 16 nm. Additionally, it was confirmed to be stable without significant differences in physical and chemical properties for 6 months under accelerated conditions (40 ± 2 °C, 75 ± 5% RH) and stressed conditions (60 ± 2 °C). Associated with the high dissolutions of ENZ, pharmacokinetic parameters were also greatly improved. Specifically, the AUC was 1.9 times higher and the Cmax was 1.8 times higher than those of commercial products (Xtandi® soft capsule), resulting in improved oral absorption. Taken together with the results mentioned above, the SNEDDS could be an effective tool as a formulation for ENZ and other similar drugs.

Risk factors associated with the survival of endodontically treated teeth: A retrospective chart review.

BACKGROUND: Studies on risk factors affecting tooth retention after endodontic treatment in dental school settings are limited. Understanding these factors is crucial for preserving teeth. The aim of this retrospective study was to evaluate patient- and tooth-level risk factors associated with the survival of endodontically treated teeth. METHODS: Electronic health records of patients who underwent endodontic treatment at the School of Dental Medicine at the University of Pennsylvania from 2017 through 2020 were analyzed. Patient-level factors included age, sex, American Society of Anesthesiologists Physical Status Classification, smoking history, diabetes status, and amoxicillin allergy. Tooth-level factors included position, presence of restorations, and periodontal conditions with preprosthetic treatments. RESULTS: The results of this study indicate that the patient-level factors significantly associated with tooth retention included age, sex, American Society of Anesthesiologists Physical Classification Status, and amoxicillin allergy. Tooth-level factors such as core buildup, full-coverage crown, healthy periodontium, and scaling and root planing were also associated with higher survival rates. Mandibular premolars had higher survival rates than mandibular molars. CONCLUSIONS: This investigation revealed that the tooth retention rate of endodontically treated teeth was 96.2% after initial root canal treatment, 92.4% for nonsurgical re-treatment, and 97.8% for surgical re-treatment. PRACTICAL IMPLICATIONS: The tooth retention of the endodontic treatment was associated with healthy periodontium, tooth structure, tooth position, tooth restoration, and the patient's overall health.

Increased Purinergic Signaling in Human Dental Pulps With Inflammatory Pain is Sex-Dependent.

An enhanced understanding of neurotransmitter systems contributing to pain transmission aids in drug development, while the identification of biological variables like age and sex helps in the development of personalized pain management and effective clinical trial design. This study identified enhanced expression of purinergic signaling components specifically in painful inflammation, with levels increased more in women as compared to men. Inflammatory dental pain is common and potentially debilitating; as inflammation of the dental pulp can occur with or without pain, it provides a powerful model to examine distinct pain pathways in humans. In control tissues, P2X3 and P2X2 receptors colocalized with PGP9.5-positive nerves. Expression of the ecto-nucleotidase NTPDase1 (CD39) increased with exposure to extracellular adenosine triphosphate (ATP), implying CD39 acted as a marker for sustained elevation of extracellular ATP. Both immunohistochemistry and immunoblots showed P2X2, P2X3, and CD39 increased in symptomatic pulpitis, suggesting receptors and the ATP agonist were elevated in patients with increased pain. The increased expression of P2X3 and CD39 was more frequently observed in women than men. In summary, this study identifies CD39 as a marker for chronic elevation of extracellular ATP in fixed human tissue. It supports a role for increased purinergic signaling in humans with inflammatory dental pain and suggests the contribution of purines shows sexual dimorphism. This highlights the potential for P2X antagonists to treat pain in humans and stresses the need to consider sex in clinical trials that target pain and purinergic pathways. PERSPECTIVE: This article demonstrates an elevation of ATP-marker CD39 and of ATP receptors P2X2 and P2X3 with inflammatory pain and suggests the rise is greater in women. This highlights the potential for P2X antagonists to treat pain and stresses the consideration of sexual dimorphism in studies of purines and pain.

High-Performance Indoor Perovskite Solar Cells by Self-Suppression of Intrinsic Defects via a Facile Solvent-Engineering Strategy.

Lead halide perovskite solar cells have been emerging as very promising candidates for applications in indoor photovoltaics. To maximize their indoor performance, it is of critical importance to suppress intrinsic defects of the perovskite active layer. Herein, a facile solvent-engineering strategy is developed for effective suppression of both surface and bulk defects in lead halide perovskite indoor solar cells, leading to a high efficiency of 35.99% under the indoor illumination of 1000 lux Cool-white light-emitting diodes. Replacing dimethylformamide (DMF) with N-methyl-2-pyrrolidone (NMP) in the perovskite precursor solvent significantly passivates the intrinsic defects within the thus-prepared perovskite films, prolongs the charge carrier lifetimes and reduces non-radiative charge recombination of the devices. Compared to the DMF, the much higher interaction energy between NMP and formamidinium iodide/lead halide contributes to the markedly improved quality of the perovskite thin films with reduced interfacial halide deficiency and non-radiative charge recombination, which in turn enhances the device performance. This work paves the way for developing efficient indoor perovskite solar cells for the increasing demand for power supplies of Internet-of-Things devices.

Factors associated with the response to postnatal dexamethasone use in very low birthweight infants: a nationwide cohort study.

BACKGROUND: Dexamethasone is widely used as a systemic corticosteroid to treat and prevent bronchopulmonary dysplasia (BPD) in preterm infants. We evaluated the current epidemiology of dexamethasone use to prevent BPD and analyse the factors associated with the response to dexamethasone in very low birthweight infants using a nationwide database. METHODS: We included very low birthweight infants born between January 2013 and December 2020 with a gestational age of 23-31 weeks using data from the Korean Neonatal Network registry. Patients were grouped based on their dexamethasone use into 'Dex' or 'No Dex' groups. Clinical variables and data were collected, and the annual trends of dexamethasone use and the proportion of patients who received dexamethasone according to gestational age were analysed. Respiratory outcomes were compared between the groups. Univariate and multivariate analyses were performed to analyse factors associated with the response to dexamethasone in BPD. RESULTS: Of 11 261 eligible infants, 2313 (20.5%) received dexamethasone, and 1714 (74.1%) of them were diagnosed with moderate-to-severe BPD. The 8-year annual prevalence of dexamethasone use was 17.7-22.3%. The 'Dex' group had more moderate-to-severe BPD, more frequent invasive ventilation use at a postmenstrual age of 36 weeks and longer ventilator duration. Birth weight, 5-minute APGAR score, pulmonary hypertension within the first 28 days, surgical treatment of patent ductus arteriosus, medical treatment of patent ductus arteriosus, pathological chorioamnionitis, hydrocortisone or budesonide use, surgical management of necrotising enterocolitis and fungal sepsis were associated with BPD after dexamethasone use. CONCLUSIONS: Approximately 20.5% of preterm infants received dexamethasone, and the frequency increased as gestational age decreased. Poor response to dexamethasone was associated with antenatal and postnatal inflammation, low birth weight and early pulmonary hypertension.

Anti-inflammatory effects of yeast-derived vacuoles on LPS-induced murine macrophage activation.

Saccharomyces cerevisiae is a single-celled fungal microorganism. S. cerevisiae-derived vacuoles are closely related to mammalian lysosomes, which play a role in the degradation of macromolecules by various hydrolytic enzymes. This study evaluated the anti-inflammatory efficacy of S. cerevisiae-vacuoles by inhibiting inflammatory mediators induced by lipopolysaccharide (LPS). The results showed that treatment with 5, 10, and 20 µg/mL of S. cerevisiae-derived vacuoles almost completely inhibited the LPS-induced expression of iNOS protein and mRNA. Moreover, vacuoles significantly reduced the mRNA expression of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6) in LPS-stimulated macrophages compared to the control cells. The immunofluorescence analysis confirmed that S. cerevisiae-derived vacuoles inhibited the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in LPS-stimulated cells. Taken together, the treatment with S. cerevisiae-derived vacuoles alone activated macrophages, but LPS-activated macrophages modulated pro-inflammatory mediators by downregulating the NF-κB pathway. These results suggest that S. cerevisiae-derived vacuoles may have therapeutic potential in the treatment of inflammatory diseases. In conclusion, our study provides new insights into the immunomodulatory effects of S. cerevisiae-derived vacuoles and their potential as a novel anti-inflammatory agent. IMPORTANCE This study investigates the potential of using vacuoles derived from the yeast Saccharomyces cerevisiae as a new anti-inflammatory therapy. Inflammation is a natural response of the immune system to invading pathogens, but when it is dysregulated, it can lead to chronic diseases. The researchers found that treating macrophages with vacuoles significantly reduced the production of pro-inflammatory cytokines and iNOS, markers of inflammation when they were stimulated with lipopolysaccharide. The study also showed that vacuoles inhibited the NF-κB signaling pathway, which is involved in the induction of pro-inflammatory cytokines in macrophages. These findings suggest that S. cerevisiae-derived vacuoles may have potential as a new therapeutic agent for regulating the inflammatory response in various diseases. Further studies are needed to evaluate the efficacy and safety of vacuoles in vivo and to elucidate the underlying mechanisms of their anti-inflammatory effects.

Periapical healing following endodontic microsurgery with collagen-based bone-filling material: A randomized controlled clinical trial.

AIM: To evaluate two- and three-dimensionally the effect of resorbable collagen-based bone-filling material on periapical healing of endodontic lesions with four-wall defects following endodontic microsurgery (EMS). METHODOLOGY: This parallel, randomized controlled superiority clinical trial involved 86 lesions with the strictly endodontic origin and four-wall defect morphology. EMS procedures were performed by calibrated postgraduate residents. Before flap closure, osteotomies were randomized to the control or treatment group. In the control group, the flap was repositioned with no material added. In the treatment group, a collagen-based bone-filling augmentation material was placed into the osteotomy. Clinical and radiographic examinations were completed after 12 months. Periapical healing was evaluated by blinded evaluators using periapical (PA) radiographs according to Molven's criteria and cone beam computed tomography (CBCT) scans according to PENN's 3D criteria. Cortical plate healing was scored according to the RAC/B index. The data were analysed using Fisher's exact test, Logistic regression models and Chi-squared test. The significance level was predetermined at p < .05. RESULTS: Sixty-six cases were evaluated at the 12-month follow-up, with 30 and 36 cases in the control and treatment groups, respectively. Only the asymptomatic cases (control = 26, treatment = 32) were included in the radiographic evaluation. Twenty-three cases (88.5%) in the control and 28 (87.5%) cases in the treatment group demonstrated complete healing on PA radiographs (p = 1.000). On CBCT, 10 (38.4%) and 21 (65.6%) cases had completely healed in the control and treatment groups, respectively (p = .095). The re-establishment of the buccal cortical plate was detected in 12 (46.2%) and 22 (68.8%) cases in the control and treatment groups, respectively (p = .243). CONCLUSION: Within the limitations of the present study, the use of collagen-based bone-filling material had no statistically significant effect on the periapical healing of endodontic lesions with four-wall defect following EMS at the 12-month follow-up when evaluated by PA radiographs or CBCT scans. However, the observed higher percentage of a re-established cortical plate in the treatment group could suggest a clinical benefit that is of interest after surgical endodontic treatment.

Inhibition of tau phosphorylation and Aß accumulation by S. cerevisiae-derived vacuoles in LPS-induced SH-SY5Y cells.

Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by the accumulation of intracellular tau and amyloid beta (Aß) proteins, which lead to neuroinflammation and neuronal apoptosis. In this study, we investigated the potential of a bioengineered vacuoles derived from Saccharomyces cerevisiae-derived vacuoles to treat neuroinflammation and protein accumulation in AD. The yeast-derived vacuole is a small organelle that achieves efficient degradation by utilizing a diverse array of hydrolytic enzymes. These hydrolytic enzymes break down and process proteins into smaller fragments. We found that vacuoles treatment significantly reduced LPS-primed cell apoptosis and diminished Aß42 secretion in vitro, potentially through the inhibition of the NF-kB p65 signaling pathway. Additionally, vacuole pre-treatment down-regulated NF-κB translocation and reduced phosphorylated tau levels in LPS-induced SH-SY5Y cells. Our results suggest that the vacuoles have potential as a therapeutic agent for neurodegenerative diseases. The vacuole's small size and diverse hydrolytic enzymes make it a promising drug delivery system for targeting intracellular proteins. Future studies may explore the use of vacuoles in animal models of AD to determine their therapeutic potential.

Endodontic treatments on permanent teeth in pediatric patients aged 6-12 years old.

Backgroud/purpose: The prevalence of carious lesions and traumatic injury in individuals between ages 6 and 12 is high. This study aimed to characterize pediatric patients aged 6-12 treated in the endodontic clinic and investigate the prevalence and patterns of their provided endodontic treatments. Materials and methods: Clinical and radiographic records of patients (ages 6-12) referred to the postgraduate Endodontics clinic from June 2017 to June 2020 were reviewed. Demographics, pre-and post-operative conditions, type of endodontic treatment, and behavioral management were collected. Results: A total of 6350 teeth from 6089 patients were treated in this period, and 425 teeth (6.7%) from 405 patients were included. Ages 9-11 were the most commonly treated age group. Significantly more lower molars (41.9%) and upper anterior teeth (36.7%) were treated (P < 0.05). The majority of teeth were diagnosed with pulp necrosis (39.5%), and the most common periapical diagnosis was normal apical tissues (39.8%), then symptomatic apical periodontitis (38.8%). The most common etiological factor was caries (63.5%). Two hundred six teeth (48.5%) were treated with root canal therapy, 161 teeth (37.9%) with vital pulp therapy, 46 teeth (10.8%) with apexification or regenerative endodontic procedure, 12 teeth (2.8%) with non-surgical retreatment. A statistically high number of patients (87.8%) tolerated the endodontic procedures without any sedation (P < 0.0001). Conclusion: Pediatric patients aged 6-12 compose around 7% of the population treated at the postgraduate Endodontics clinic, reflecting the high demand for endodontic treatment in a pediatric mixed dentition population.

Harnessing the power of collective intelligence in dentistry: a pilot study in Victoria, Australia.

BACKGROUND: In many dental settings, diagnosis and treatment planning is the responsibility of a single clinician, and this process is inevitably influenced by the clinician's own heuristics and biases. Our aim was to test whether collective intelligence increases the accuracy of individual diagnoses and treatment plans, and whether such systems have potential to improve patient outcomes in a dental setting. METHODS: This pilot project was carried out to assess the feasibility of the protocol and appropriateness of the study design. We used a questionnaire survey and pre-post study design in which dental practitioners were involved in the diagnosis and treatment planning of two simulated cases. Participants were provided the opportunity to amend their original diagnosis/treatment decisions after viewing a consensus report made to simulate a collaborative setting. RESULTS: Around half (55%, n = 17) of the respondents worked in group private practices, however most practitioners (74%, n = 23) did not collaborate when planning treatment. Overall, the average practitioners' self-confidence score in managing different dental disciplines was 7.22 (s.d. 2.20) on a 1-10 scale. Practitioners tended to change their mind after viewing the consensus response, particularly for the complex case compared to the simple case (61.5% vs 38.5%, respectively). Practitioners' confidence ratings were also significantly higher (p < 0.05) after viewing the consensus for complex case. CONCLUSION: Our pilot study shows that collective intelligence in the form of peers' opinion can lead to modifications in diagnosis and treatment planning by dentists. Our results lay the foundations for larger scale investigations on whether peer collaboration can improve diagnostic accuracy, treatment planning and, ultimately, oral health outcomes.

High-Resolution Tactile-Sensation Diagnostic Imaging System for Thyroid Cancer.

In this study, we propose the direct diagnosis of thyroid cancer using a small probe. The probe can easily check the abnormalities of existing thyroid tissue without relying on experts, which reduces the cost of examining thyroid tissue and enables the initial self-examination of thyroid cancer with high accuracy. A multi-layer silicon-structured probe module is used to photograph light scattered by elastic changes in thyroid tissue under pressure to obtain a tactile image of the thyroid gland. In the thyroid tissue under pressure, light scatters to the outside depending on the presence of malignant and positive properties. A simple and easy-to-use tactile-sensation imaging system is developed by documenting the characteristics of the organization of tissues by using non-invasive technology for analyzing tactile images and judging the properties of abnormal tissues.

Role of Hounsfield Unit in Predicting Outcomes of Shock Wave Lithotripsy for Renal Calculi: Outcomes of a Systematic Review.

PURPOSE OF REVIEW: Extracorporeal shock wave lithotripsy success rates depend on several stone and patient-related factors, one of which is stone density which is calculated on computed tomography scan in Hounsfield Units. Studies have shown inverse correlation between SWL success and HU; however, there remains considerable variation between studies. We performed a systematic review regarding the use of HU in SWL for renal calculi to consolidate the current evidence and address current knowledge gaps. RECENT FINDINGS: Database including MEDLINE, EMBASE, and Scopus were searched from inception through August 2022. Studies in English language analysing stone density/attenuation in adult patients undergoing SWL for renal calculi were included for assessment of Shockwave lithotripsy outcomes, use of stone attenuation to predict success, use of mean and peak stone density and Hounsfield unit density, determination of optimum cut-off values, nomograms/scoring systems, and assessment of stone heterogeneity. 28 studies with a total of 4,206 patients were included in this systematic review with sample size ranging from 30 to 385 patients. Male to female ratio was 1.8, with an average age of 46.3 years. Mean overall ESWL success was 66.5%. Stone size ranged from 4 to 30 mm in diameter. Mean stone density was used by two-third of the studies to predict the appropriate cut-off for SWL success, ranging from 750 to 1000 HU. Additional factors such as peak HU and stone heterogeneity index were also evaluated with variable results. Stone heterogeneity index was considered a better indicator for success in larger stones (cut-off value of 213) and predicting SWL stone clearance in one session. Prediction scores had been attempted, with researchers looking into combining stone density with other factors such as skin to stone distance, stone volume, and differing heterogeneity indices with variable results. Numerous studies demonstrate a link between shockwave lithotripsy outcomes and stone density. Hounsfield unit < 750 has been found to be associated with shockwave lithotripsy success, with likelihood of failure strongly associated with values over 1000. Prospective standardisation of Hounsfield unit measurement and predictive algorithm for shockwave lithotripsy outcome should be considered to strengthen future evidence and help clinicians in the decision making. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) database: CRD42020224647.

Identification of TLR2/4-mediated phagocytosis and immune response activation pathways by vacuoles isolated from Saccharomyces cerevisiae.

The vacuoles of the yeast Saccharomyces cerevisiae are closely related to mammalian lysosomes and play a role in macromolecular degradation due to the hydrolytic enzymes present inside. The vacuoles also regulate osmotic pressure and control cellular homeostasis. In previous results, vacuoles were shown to activate the immune response of macrophages by promoting the production of immune-mediated transporters nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory cytokines. In this study, the effects of vacuoles on the phagocytosis activity of RAW264.7 cells and their potential as immune enhancers were evaluated, and receptors capable of recognizing vacuoles were examined. An investigation using the phagocytes assay showed that phagocytosis activity increased by the vacuole. Besides, after treatment with TLR2/4 inhibitor, the expression of pro-inflammatory cytokines by vacuoles was significantly reduced and the inducible nitric oxide synthase (iNOS) protein was also significantly reduced. However, treatment with a TLR2 inhibitor did not reduce the production of interleukin-6 (IL)-6, a pro-inflammatory cytokine. As a result of confirming the activation of TLR2/4 using Western blot and immunofluorescence (IF), the TLR2/4 protein expression and fluorescence intensity increased depending on the concentration of vacuoles. Yeast vacuoles significantly upregulate protein expression of p-p65/p-p38 MAPKs. In summary, the vacuoles isolated from S. cerevisiae in macrophages have increased phagocytic ability at a concentration of 20 (µg/ml) and can function as immune-enhancing agent suggesting that TLR2/4 mediated the p38 MAPK/nuclear factor kappa B signaling pathway.