Dose-related shifts in proteome and function of extracellular vesicles secreted by fetal neural stem cells following chronic alcohol exposure.

Accumulating evidence indicates that extracellular vesicles (EVs) mediate endocrine functions and also pathogenic effects of neurodevelopmental perturbagens like ethanol. We performed mass-spectrometry on EVs secreted by fetal murine cerebral cortical neural stem cells (NSCs), cultured ex-vivo as sex-specific neurosphere cultures, to identify overrepresented proteins and signaling pathways in EVs relative to parental NSCs in controls, and following exposure of parental NSCs to a dose range of ethanol. EV proteomes differ substantially from parental NSCs, and though EVs sequester proteins across sub-cellular compartments, they are enriched for distinct morphogenetic signals including the planar cell polarity pathway. Ethanol exposure favored selective protein sequestration in EVs and depletion in parental NSCs, and also resulted in dose-independent overrepresentation of cell-cycle and DNA replication pathways in EVs as well as dose-dependent overrepresentation of rRNA processing and mTor stress pathways. Transfer of untreated EVs to naïve cells resulted in decreased oxidative metabolism and S-phase, while EVs derived from ethanol-treated NSCs exhibited diminished effect. Collectively, these data show that NSCs secrete EVs with a distinct proteome that may have a general growth-inhibitory effect on recipient cells. Moreover, while ethanol results in selective transfer of proteins from NSCs to EVs, the efficacy of these exposure-derived EVs is diminished.

Healing of Periapical Lesions after Endodontic Treatment with the GentleWave Procedure: A Prospective Multicenter Clinical Study.

INTRODUCTION: This report includes outcomes for a group of patients with significant periapical lesions who were treated and evaluated in two single-arm, multicenter, prospective, nonsignificant risk clinical studies. METHODS: Forty-five teeth were from 45 patients who met the inclusion criteria and consented for the clinical studies and were diagnosed with periapical lesions with periapical index score ≥3. Patients were treated with a standardized treatment protocol including instrumentation to an apical diameter of #20 without orifice enlargement, the GentleWave Procedure, and warm vertical obturation. Clinical signs and radiographic assessments were evaluated at 12 months to assess healing. Success was classified as healing or healed and accounted for the cumulative success rate of healing. Statistical analyses were performed by using Fisher exact test, Pearson correlation, and multivariate logistic regression analyses. RESULTS: At 12 months, 44 of 45 teeth (97.8%) were evaluated. The cumulative success rate for the GentleWave Procedure was 97.7%. Forty-three of 44 teeth were completely functional; all teeth had complete resolution for measured indices of mobility, soft tissue lesions, sinus tract, and furcation involvement. No patients experienced moderate or severe pain at 2, 7, and 14 days after procedure. Although only 1 patient was unsuccessful and the presence of clinical symptoms and type of periradicular diagnosis at 12 months were correlated with an unsuccessful outcome, the analyses were limited by the sample size. CONCLUSIONS: In this case series analysis, treatment of sizable periapical lesions with the GentleWave Procedure resulted in a success rate of 97.7% at 12-month re-evaluation.

Maxillary molar healing after treatment of an uninstrumented canal with a novel root canal procedure: a case report.

A major cause for endodontic failure is the inability to treat all anatomy. Studies report endodontic retreatments contain 42% missed canals. This case illustrates dentin preservation of a molar with an uninstrumented mesiobuccal-3 canal revealed post-GentleWave Procedure. Efficient cleaning and disinfection with maintained healing to 18 months is demonstrated.

Six-month healing success rates after endodontic treatment using the novel GentleWave™ System: The pure prospective multi-center clinical study.

BACKGROUND: This prospective multi-center (PURE) clinical study evaluated healing rates for molars after root canal treatment employing the GentleWave® System (Sonendo, Inc., Laguna Hills, CA). MATERIAL AND METHODS: Eighty-nine patients met the inclusion criteria and consented for this clinical study after referral for a root canal treatment. All enrolled patients were treated with the GentleWave System. Five endodontists performed the clinical procedures and follow-up evaluations. Pre-operative, intra-operative, and post-operative data were collected from the consented patients. Each patient was evaluated for clinical signs and symptoms. Two trained, blinded, and independent evaluators scored the subject tooth radiographs for apical periodontitis using the periapical index (PAI). The teeth classified as healing or healed were considered as a success and composed of a cumulative success rate of healing. Statistical analysis was performed by using the Fisher's exact test, Pearson correlation, and multivariate logistic regression analyses of the pre-operative prognostic factors at 0.05 significance level. RESULTS: Seventy-seven patients were evaluated at six months with a follow-up rate of 86.5%. The cumulative success rate of healing was 97.4%. Eleven prognostic factors were identified using bivariate analyses. Using logistic analyses, the two prognostic significant variables that were directly correlated to healing were the pre-operative presence of periapical index (p value=0.016), and single treatment visits (p value=0.024). CONCLUSIONS: In this six-month PURE clinical study, the cumulative success rate of healing was 97.4% when patients were treated with the GentleWave® System. KEY WORDS: Healing rate, root canal treatment, molar, GentleWave™, Sonendo®, Multisonic Ultracleaning™ .

12-month Healing Rates after Endodontic Therapy Using the Novel GentleWave System: A Prospective Multicenter Clinical Study.

INTRODUCTION: This multicenter, prospective, nonsignificant risk clinical study evaluated healing rates for molars 12 months after endodontic therapy using the GentleWave System (Sonendo, Inc, Laguna Hills, CA). METHODS: Eighty-nine patients needing endodontic therapy who met the inclusion criteria consented for this clinical study. All enrolled patients were treated with a standardized protocol consisting of conservative access, shaping of canals to #20/.07, GentleWave treatment, and warm vertical obturation. Six endodontists performed the clinical procedures and follow-up evaluations. Preoperative, intraoperative, and postoperative data were collected from the consented patients. Each patient was evaluated for clinical signs and symptoms. Two trained, blinded, and independent evaluators scored the subject's radiographs for signs of apical periodontitis using a periapical index. The teeth classified as healing or healed were considered as a success and accounted for the cumulative success rate of healing. Statistical analysis was performed by using the Fisher exact test, Pearson correlation, and multivariate logistic regression analyses of the preoperative prognostic factors at P = .05. RESULTS: Seventy-five teeth in 75 patients were evaluated at 12 months with a follow-up rate of 84.3%. The cumulative success of endodontic therapy was 97.3%. The success rates of necrotic and irreversible pulpitis were 92.9% and 98.4%, respectively; 3.8% of the patients experienced moderate postoperative pain within 2 days and no incidence of pain at 14 days, 6 months, and 12 months of initial therapy. Ten prognostic factors were identified using bivariate analyses. Using logistic analyses, the prognostic significant variable that was directly correlated to healing was the preoperative presence of lesions (P = .026). CONCLUSIONS: In this 12-month prospective multicenter clinical study, the GentleWave System showed a high level of success after a 12-month follow-up.