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The present study referred to the technology-based learning model to conduct a systematic review of the dimensions of nursing activities, research samples, research methods, roles of artificial intelligence, applied artificial intelligence algorithms, evaluation measure of algorithms, and research foci. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses procedure, this study obtained and analyzed a total of 102 high-quality artificial intelligence-associated nursing activities studies published from 2001 to 2020 in the Web of Science database. The results showed: (1) In terms of nursing activities, nursing management was explored the most, followed by nursing assessment; (2) quantitative methods were most frequently adopted in artificial intelligence-associated nursing activities studies to investigate issues related to patients, followed by nursing staff; (3) the most adopted roles of artificial intelligence in artificial intelligence-associated nursing activities studies were profiling and prediction, followed by assessment and evaluation; (4) artificial intelligence-associated nursing activities studies frequently mixed applied artificial intelligence algorithms and evaluation measure of algorithms; (5) in the dimension of research foci, most studies mainly paid attention to the design or evaluation of the artificial intelligence systems/instruments, followed by investigating the correlation and affect issues. Based on the findings, several recommendations are raised as a reference for future researchers, educators, and policy makers.

BACKGROUND: Contemporary clinical trials of HER2-targeted therapies have shown benefits regarding recurrence and survival in patients (pts) with HER2+ early stage breast cancer. The outcomes of pts treated in community practice settings who had a pathologic complete response (pCR) to neoadjuvant therapy or who had residual disease at definitive surgery (non-pCR) have not been well characterized. This preliminary study aimed to describe the patient characteristics, disease-free survival (DFS) and overall survival (OS) in patients with and without pCR following neaoadjuvant HER2-targeted therapy in The US Oncology Network. METHODS: This retrospective cohort study identified pts diagnosed with stage I-III HER2+ breast cancer who initiated neoadjuvant HER2-targeted therapy in the community setting between April 1, 2014 - March 31, 2019. Pts were followed through the date of last visit, death, or study end (March 31, 2021), whichever occurred first. Data were collected from the US Oncology Network’s electronic medical record database, iKnowMed. Natural language processing/artificial intelligence was used to identify pts with pCR status and pts with disease recurrence during the study period. Patient profiles, risk of recurrence (RR), and time to recurrence (TTR) were assessed descriptively. Kaplan-Meier methods were used to evaluate DFS and OS from the start of neoadjuvant therapy. Results were stratified by pCR status. RESULTS: The study included 641 pts (median age, 55 years), 71% had non-pCR and 29% had pCR. The majority of pts were Caucasian (79%) or black (8%). At diagnosis, 78% of pts had stage I/II disease, and 21% stage III. Nearly 74% were HR+. With a median follow-up of 33 months, pts who had non-pCR had a higher risk of disease recurrence (10.3% vs 8.1%) and a shorter median TTR (18.6 vs 21.1 months) compared to pts with pCR. Three-year DFS (87.5% vs 92.2%) and OS (96.0% vs 98.8%) were lower in pts with non-pCR than with pCR. CONCLUSIONS:Findings from this real-world study of HER2+ early stage breast cancer pts who received neoadjuvant HER2-targeted therapy in the community setting suggested that pts with non-pCR had shorter DFS and OS outcomes than pts with pCR. Pts with non-pCR had a risk of recurrence of nearly 10% over approximately a 3-year time period . This residual risk of recurrence among non-pCR pts suggested a potential opportunity to improve long-term outcomes in this group. Future analyses, including HR subgroups, are planned as data mature and longer follow-up time is available. Results on additional pts with known pCR/non-pCR data, with longer follow-up, and outcomes by HR+ vs HR- status will be presented. Disclosure DeclarationThis study was funded by Puma Biotechnology, Inc. Outcomes of pts with pCR or non-pCR following neoadjuvant HER2-targeted therapyNon-pCRpCROverall CohortN=429N=185N=641Follow-up time, months, median (range)30.8 (0.0,81.6)38.4 (2.8,83.3)33.0 (0.0,83.3)Patients with recurrence, n (%)44 (10.3%)15 (8.1%)59 (9.6%)Time to recurrence, median (range)18.6 (0.0,42.4)21.1 (0.0,60.3)18.8 (0.0,60.3)Disease-free survival at 36 months87.5% (83.4,90.7)%92.2% (86.8,95.4)%89.0% (85.9,91.5)%Overall survival at 36 months96.0% (92.8,97.8)%98.8% (95.2,99.7)%97.0% (94.9,98.3)% Citation Format: Joyce O'Shaughnessy, Nina Oestreicher, Nicole Fulcher, Wan-Yu Tseng, April Beeks, Julia Moore, Deepa Lalla. Outcomes of patients with pathologic complete response following neoadjuvant HER2-targeted therapy in patients with HER2+ early stage breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-20.

Introduction While guidelines recommend testing for actionable biomarkers for patients with advanced or metastatic NSCLC, testing rates have varied. This study aimed to assess molecular testing patterns in a large network of US community-based oncology practices. Methods This retrospective observational study examined adult patients with newly diagnosed stage IV NSCLC with ≥2 visits in The US Oncology Network from 01 July 2016 – 30 September 2019. Testing patterns were examined using electronic health record structured fields and chart review. Structured data were analyzed for the overall study population (Cohort A), and structured and unstructured data were analyzed for a select cohort of 300 patients (Cohort B). Results In Cohort A (n=3,337), PD-L1 (37%) was the most frequently tested biomarker documented in structured data, followed by EGFR (36%), ALK (35%), ROS1 (20%), and BRAF (16%). According to unstructured data in Cohort B (n=300). EGFR (80%) was the most frequently tested biomarker, followed by ALK (79%), PD-L1 (72%), ROS1 (71%), and BRAF (56%). The proportion of tests ordered prior to 1L treatment increased from 2016-2018 for all biomarkers, as did the proportion of test results available prior to 1L treatment. However, some of the test results became available after 1L or later lines of treatment were in progress. Conclusion Our study found increased testing rates over time and decreases in testing turnaround times. However, rates of testing for all biomarkers still need to improve, as does completion of testing prior to initiation of therapy. Microabstract Timely testing for actionable biomarkers for patients with advanced or metastatic NSCLC can ensure that they receive the appropriate treatment at the right time, but the real-world rate of testing has varied. This study assessed molecular testing patterns in a large network of US community-based oncology practices. While testing rates increased over time and testing turnaround times decreased, results of testing were not available for a considerable of patients before initiation of first-line treatment.

BACKGROUND/PURPOSE: The objective structured clinical examination (OSCE) is a test designed to test technical, clinical, and practical competency in medicine teaching. This study tried to evaluate the influencing factors of the computer-based tests (CBT) results for dental students. MATERIALS AND METHODS: The 32 5th-year dental students of the dental school of National Taiwan University (NTU) joined preclinical CBT. The contents of CBT included clinical knowledge and practical skills of nine dental specialties. Twenty single-choice questions were played with the PowerPoint 2016 on a desktop, and the playing time for each question was 30 s. Several factors including the gender, age, and dental student admission ways (with or without the skill tests) were evaluated. Also, the comparison between the clerk's grade and CBT scores of nine dental specialties was performed. The students also filled the feedback questionnaire about the examination questions and suggestions for the CBT. RESULTS: There were no significant differences in the mean CBT scores between male and female dental students, between two groups of dental students with or without the skill tests in the admission process, and among three different age groups of dental students. The clerk's scores were not directly related to the CBT scores. CONCLUSION: The CBT has been well-intentioned in dental education since 2022 in Taiwan. The CBT results revealed that the conjunction of knowledge from the textbook and clinical observation should be enhanced. The guideline should be established to integrate CBT into preclinical education and promote the performance of clinical work of dental students.

Synovial sarcoma (shortened to SS) is a rare and aggressive type of soft tissue sarcoma (STS), a group of rare cancers that start in the soft tissues, such as muscle, tendons, fat, lymph and blood vessels and nerves. Usually STS presents in one location, and frequently spreads to other locations, referred to as metastatic SS (mSS). Many studies have explored the characteristics, treatments and outcomes of people with STS. Yet, a limited number of studies have been performed specifically for people with mSS. This study aims to describe characteristics, treatment patterns and clinical outcomes of people with mSS treated in a US community setting. The study showed that more than a third of people diagnosed with SS had disease that spread, mostly to the lung. Of the 71 people with mSS included in the analysis, 39 people received chemotherapy. Of these, 25 people with mSS needed second-line chemotherapy and a further 16 people with mSS required third-line treatment. People with mSS who did not respond well to chemotherapy received a variability of treatments in the US community setting. More lines of treatment were associated with shorter time to next treatment and reduced survival time. Together, these findings highlight the burden of illness and the need for more effective treatments for people with this rare disease. Investigating the characteristics, treatment patterns and clinical outcomes of people with mSS can help to understand the unmet need in this population and pave the way to improving future treatment approaches.

To investigate the surface characteristics of titanium (Ti) implant materials, which were coated with different thicknesses of nanoscale tin oxide (SnOThe thickness of the coating layer on Ti was 0 (Ti0), 20 nm (Ti20), 50 nm (Ti50), and 100 nm (Ti100), respectively. The surface morphology was observed with an SEM and AFM. The root mean square roughness of micron-scale (mRq) and nanoroughness (nRq) of Ti discs' surface were measured. The Alamar blue (AB) assay and F-actin fluorescence staining were used to evaluate the biocompatibility, and the osteocalcin (OCN) was measured to clarify the differentiation of HEPM cells on materials.In the coating groups, the mRq was decreased, but the nRq was increased. The spreading and polygonal morphology of HEPMs was apparent in coating groups. On Day 4, the survival rate of HEPM cells on Ti0 was higher than on Ti20 and Ti50. There was no significant difference on Day 7, Day 10, and Day 14. The OCN was significantly higher on Day 14 in all the coating groups than Ti0.The results showed that the cell growth was intensified with rough surfaces. However, the OCN and morphology change was prominent when the nanoroughness was increased, which meant the increased nanoroughness might enhance OCN production and improve the tendency of osseointegration. The nanoscale SnO

Objective: Synovial sarcoma (SS) is a rare sub-type of soft tissue sarcoma with limited natural history documented. The study objective was to describe characteristics and treatment patterns of metastatic SS (mSS) patients receiving systemic treatments. Methods: This was a retrospective observational cohort study in mSS patients treated in The US Oncology Network practices. Both EHR and chart review data from 2012-2019 were used. All mSS adult patients initiating systemic treatment as first-line (1L) therapy, with >2 visits were included. Patients diagnosed with or treated for other primary tumors were excluded. Demographic and clinical characteristics were reported based on index date (date of first systemic treatment initiation in the metastatic setting). Time to treatment discontinuation (TTD) and time to next treatment (TTNT) were assessed using the Kaplan-Meier method. Results: 39 adult mSS patients were identified receiving 1L systemic treatment. Of these, 25 went on to receive a 2L treatment (64%), and 16 went on to receive 3L+ treatment (41%) during the study observation period. Median age was 41.0 years, 74% male, 70% Caucasian. 25% had metastatic disease at original diagnosis of SS (vs. localized disease). 87% had metastases to lung, 25% had >1 site of metastasis. See Table 1 for treatment distributions by line and for TTD and TTNT. Conclusions: This study provides information on treatment patterns for mSS patients treated across multiple institutions within a US community oncology setting. About 2/3 of mSS patients received 2L systemic treatments. While doxorubicin and ifosfamide regimens were most common in 1L, variability exists in the 2L and onward settings, with ifosfamide and pazopanib being more frequently used than in earlier lines. Additionally, shorter TTD and TTNT with each subsequent line of therapy documents the need for effective treatment options in the 2L+ setting that can further delay progression. Funding: GSK [208280] Distribution of treatments by line Median time to discontinuation in months(95% CI) Median time to next treatment in months(95% CI) 1L systemic treatment (n=39) Doxorubicin + Ifosfamide containing regimen 14 (35.90%) 3.9 (2.2, 5.1) 9.3 (6.2, 11.1) Pazopanib alone or in combination 7 (17.95%) Docetaxel + gemcitabine 6 (15.38%) Ifosfamide monotherapy 6 (15.38%) Doxorubicin + olaratumab combination Citation Format: Shibani Pokras, Wan-Yu Tseng, Janet Espirito, April Beeks, Charlotte Carroll, Ken Culver, Eric Nadler. Treatment patterns among metastatic SS patients in The US Oncology Network [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5876.

// Mei-Chi Chang 1,2 , Yi-Jane Chen 3,* , Eric Jein-Wein Liou 2 , Wan-Yu Tseng 3 , Chiu-Po Chan 2 , Hseuh-Jen Lin 4 , Wan-Chuen Liao 3 , Ya-Ching Chang 5 , Po-Yuan Jeng 3 and Jiiang-Huei Jeng 3 1 Biomedical Science Team, Chang Gung University of Science and Technology, Kwei-Shan, Taoyuan, Taiwan 2 Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan 3 School of Dentistry and Department of Dentistry, National Taiwan University Medical College and National Taiwan University Hospital 4 Department of Dentistry, Show Chwan Memorial Hospital, Changhua, Taiwan 5 Department of Dentistry, Mackey Memorial Hospital, Taipei, Taiwan * This author have contributes equally to the first author Correspondence to: Jiiang-Huei Jeng, email: // Chiu-Po Chan, email: // Keywords : apoptosis, atherosclerosis, cytotoxicity, endothelial cells, inflammation,Gerotarget Received : September 13, 2016 Accepted : October 06, 2016 Published : October 11, 2016 Abstract Cardiovascular diseases (atherosclerosis, stroke, myocardiac infarction etc.) are the major systemic diseases of elder peoples in the world. This is possibly due to increased levels of oxidized low-density lipoproteins (oxLDLs) such as 7-ketocholesterol (7-KC) and lysophosphatidylcholine (LPC) that damage vascular endothelial cells, induce inflammatory responses, to elevate the risk of cardiovascular diseases, Alzheimer’s disease, and age-related macular degeneration. However the toxic effects of 7-KC on endothelial cells are not known. In this study, 7-KC showed cytotoxicity to endothelial cells at concentrations higher than 10 µg/ml. 7-KC stimulated ATM/Chk2, ATR-Chk1 and p53 signaling pathways in endothelial cells. 7-KC also induced G0/G1 cell cycle arrest and apoptosis with an inhibition of Cyclin dependent kinase 1 (Cdk1) and cyclin B1 expression. Secretion and expression of IL-8 in endothelial cells were stimulated by 7-KC. 7-KC further induced intracellular ROS production as shown by increase in DCF fluorescence and Akt phosphorylation. LY294002 attenuated the 7-KC-induced apoptosis and IL-8 mRNA expression of endothelial cells. These results indicate that oxLDLs such as 7-KC may contribute to the pathogenesis of atherosclerosis, thrombosis and cardiovascular diseases by induction of endothelial damage, apoptosis and inflammatory responses. These events are associated with ROS production, activation of ATM/Chk2, ATR/Chk1, p53 and PI3K/Akt signaling pathways.

The current study aimed to assess the economic burden of progressive disease among patients with Hodgkin lymphoma (HL) receiving second- or third-line therapy in a large US network of community-based practices. This retrospective, observational cohort analysis used electronic health records to examine adult patients with classical HL who received chemotherapy between 2007 and 2011. Of 291 observations, 112 had non-progressive disease (received only one line of therapy; LOT1), 114 received second-line therapy (LOT2), and 65 received third-line therapy (LOT3). In LOT2, 49 patients (43%) underwent transplant. In LOT3, 13 patients (20%) underwent transplant. The mean total cost per line of therapy was $21 956 in LOT1, $77 219 in LOT2, and $59 442 in LOT3. When transplant was required, the mean total cost per line of therapy increased 7- to 8-fold when compared with the cost of LOT1 (approximately $154 000 for LOT2 and $193 000 for LOT3). Future therapies that intervene as early as possible in the treatment algorithm to prevent or significantly delay relapse will likely result in significant cost savings.

Background/Purpose Dentin bonding agents (DBAs) are cytotoxic to dental pulp cells. This study aimed to evaluate the effects of three DBAs (Optibond Solo Plus, Op; Clearfil SE Bond, SE; and Xeno III, Xe) after diffusion through 0.2-mm or 0.5-mm dentin slices on reactive oxygen species (ROS) production and apoptosis in dental pulp cells. Methods The amounts of DBAs diffusing through 0.2-mm or 0.5-mm dentin slices were quantified using a UV-Vis spectrophotometer. The effects of diffused DBAs on ROS production and viability of dental pulp cells were investigated using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay on Days 1 and 2. Flow cytometric analysis and double staining of treated dental pulp cells with Annexin V-fluorescein isothiocyanate (V-FITC) and propidium iodide (PI) were performed on Day 2. Results Xe showed greatest diffusion through dentin slices after 8-hour period, followed by SE and Op. Dental pulp cells produced a lesser amount of ROS, when treated with DBAs diffusing through a 0.5-mm dentin slice than through a 0.2-mm dentin slice for the same period of time. A small proportion of cells were TUNEL-positive after treatment with any of the three diffused DBAs. Annexin V-FITC/PI staining identified apoptotic cells; cell survival was higher in those cells treated with DBAs diffusing through a 0.5-mm dentin slice than through a 0.2-mm dentin slice. Conclusion The three DBAs after diffusion through 0.2- or 0.5-mm dentin slice still exhibit cytotoxicity to dental pulp cells. However, the 0.5-mm dentin slice is found to be a better barrier than the 0.2-mm dentin slice to protect dental pulp cells from DBA-induced cytotoxicity.

Background/Purpose To reduce the polymerization shrinkage of dental composite resin, we used two different ratios of toluene 2,4-diisocyanate (TDI) or 1,6-hexamethylene diisocyanate (HDI) as functional side chains of bisphenol A-glycidyl methacrylate (bis-GMA) to synthesize two series of new dental resin matrices. This study evaluated the biocompatibility and cytotoxicity of these two series of new resin matrices. Methods Two series of new dental resin matrices with the ratios of TDI or HDI functional side chain to bis-GMA (defined as B group) being 1:4, 1:2, 1:1 and 3:2 (defined as T1/4, T1/2, T1, T3/2, and H1/4, H1/2, H1, H3/2 groups, respectively) were synthesized. Each resin sample was light cured and immersed in the culture medium for 24 hours to make the extract solution. Then, human gingival fibroblasts were cultured in different extract solutions for 72 hours. The cytotoxicities of different resins were evaluated by microtitertetrazolium (MTT) assay, the levels of cell-produced reactive oxygen species (ROS) induced by different extract solutions was measured. Results Resins of the T1/4 and B groups revealed significantly higher cytotoxicity than resins of other groups. However, resins of the T1 and T3/2 groups exhibited less cytotoxicity. In general, resins of the TDI-modified groups showed equal or less cytotoxicity and induced equal or lower levels of ROS than the corresponding resins of the HDI-modified and B groups. Conclusion Our results showed that the TDI-modified resin matrices containing more functional side chains were less cytotoxic than the corresponding HDI-modified resin matrices. When the ratio of functional side chain to bis-GMA is increased, the stereo hindrance of resin structure is increased, more toxic resin monomers are trapped in the complicated resin structure, and thus the resin matrix reveals less cytotoxicity. The TDI-modified resin matrices exhibit higher stereo hindrance of resin structure and thus show less cytotoxicity than the corresponding HDI-modified resin matrices.

Purpose. To assess epidemiology, treatment patterns, and outcomes of metastatic soft tissue sarcoma (mSTS) patients in USA community oncology practices.Methods. This retrospective, descriptive study used US Oncology’s iKnowMed electronic health records database. Adults (≥18 years) with mSTS and at least two visits between July 2007 and June 2010 were included. Key outcomes were practice patterns, overall survival (OS), and progression-free survival (PFS).Results. 363 mSTS patients (174 treated and 189 untreated) met the prespecified exclusion/inclusion criteria. The most common subtypes were leiomyosarcoma (n=104; 29%), liposarcoma (n=40; 11%), and synovial sarcoma (n=12; 3%); the remainder (n=207; 57%) comprised 27 histologic subtypes. Treated patients were younger and had lower ECOG scores; 75% and 25% received first-line combination or monotherapy, respectively. Median OS of treated and untreated patients was 22 and 17 months, respectively, and 29 months in patients with the three most common subtypes. Before controlling for effects of covariates, younger age and lower ECOG scores were associated with better OS and PFS.Conclusion. This study provides insights into mSTS epidemiology, treatment patterns, and outcomes in a large community-based oncology network. These results warrant further studies with larger cohorts.

Purpose: Oncotype Dx 21-gene assay recurrence score (RS) predicts recurrence of early-stage breast cancer (ESBC). We investigated whether patient, tumor, or practice characteristics drive its use and explored Oncotype DX RS and chemotherapy use in subgroups. Methods: Patients with ESBC with documented estrogen receptor–positive, lymph node–negative, human epidermal growth factor receptor 2–negative tumors registered within McKesson Specialty Health’s iKnowMed electronic health record were included. Patient and practice characteristics by region and size were analyzed. The association between Oncotype DX RS value and use of chemotherapy were assessed. Results: The study included 6,229 patients. Of these, 1,822 (29%) had an Oncotype DX RS result. Test use was 36%, 38%, 34%, 25%, and 6%, respectively, in patients age 45, 46-55, 56-65, 66-75, and 76 years; 33%, 25%, and 9% in patients with Eastern Cooperative Oncology Group performance status of 0, 1, and 2; 7%, 9%, 25%, 38%, 27%, and 10% in T1mic, T1a, T1b, T1c, T2, and T3 tumors; and 26%, 32%, and 33% for grades 1, 2 ,and 3 tumors. Of the 1,822 patients with available Oncotype DX RS, adjuvant chemotherapy use was 6%, 42%, and 84% in the low-, intermediate-, and high-risk groups. Conclusion: Patients who were younger, had better ECOG performance status, or had higher grade tumors were more likely to undergo RS testing. It appears that the RS test may have influenced the decision about whether to administer adjuvant chemotherapy: a low RS score was associated with lower chemotherapy use and a high RS score was associated with higher chemotherapy use.

Pulse-modulated direct-current methane plasmas are used to deposit amorphous diamond-like carbon films on Si and dentistry-use polymethyl methacrylate (PMMA) substrates as a function of the negative pulse voltage applied to the substrate (Vmax). The films on PMMA show a transition from diamond-like to more graphitic carbon in the Raman spectra with increasing Vmax, dissimilar to those on Si. This is attributed to easy deformation of PMMA, leading to the low compressive stress of the films (1 to 2 GPa). The contact angle of water for the films on both Si and PMMA is large, ranging from 79° to 94° almost independent of Vmax, confirming that the films are hydrophobic despite the difference in carbon bonding state. The large dispersion component (41-43 mJ/m2) of the surface free energy of the films measured from the contact angle of water and 1-bromonaphthalene indicates the high mass density of the films. The small polar component (0.2-3.5 mJ/m2) is attributed to hydrogen saturation of the surface sites forming nonpolar C-H bonds and, thus, responsible for the hydrophobic behavior.

Biocompatibility of dentin bonding agents (DBA) and composite resin may affect the treatment outcome (e.g., healthy pulp, pulpal inflammation, pulp necrosis) after operative restoration. Bisphenol-glycidyl methacrylate (BisGMA) is one of the major monomers present in DBA and resin. Prior studies focused on salivary esterase for metabolism and degradation of resin monomers clinically. This study found that human dental pulp cells expressed mainly carboxylesterase-2 (CES2) and smaller amounts of CES1A1 and CES3 isoforms. Exposure to BisGMA stimulated CES isoforms expression of pulp cells, and this event was inhibited by catalase. Exogenous addition of porcine esterase prevented BisGMA- and DBA-induced cytotoxicity. Interestingly, inhibition of CES by bis(p-nitrophenyl) phosphate (BNPP) and CES2 by loperamide enhanced the cytotoxicity of BisGMA and DBA. Addition of porcine esterase or N-acetyl-l-cysteine prevented BisGMA-induced prostaglandin E(2) (PGE(2)) and PGF(2α) production. In contrast, addition of BNPP and loperamide, but not mevastatin, enhanced BisGMA-induced PGE(2) and PGF(2α) production in dental pulp cells. These results suggest that BisGMA may induce the cytotoxicity and prostanoid production of pulp cells, leading to pulpal inflammation or necrosis via reactive oxygen species production. Expression of CES, especially CES2, in dental pulp cells can be an adaptive response to protect dental pulp against BisGMA-induced cytotoxicity and prostanoid release. Resin monomers are the main toxic components in DBA, and the ester group is crucial for monomer toxicity.

Betel quid (BQ) chewing is a common oral habit in South Asia and Taiwan. BQ consumption may increase the risk of oral squamous cell carcinoma (OSCC), oral submucous fibrosis (OSF), and periodontitis as well as systemic diseases (atherosclerosis, hypertension, etc.). However, little is known about the toxic effect of BQ components on endothelial cells that play important roles for angiogenesis, carcinogenesis, tissue fibrosis, and cardiovascular diseases. EAhy 926 (EAHY) endothelial cells were exposed to arecoline, a major BQ alkaloid, for various time periods. Cytotoxicity was estimated by 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. The cell cycle distribution of EAHY cells residing in sub-G0/G1, G0/G1, S-, and G2/M phases was analyzed by propidium iodide staining of cellular DNA content and flow cytometry. Some EAHY cells retracted, became round-shaped in appearance, and even detached from the culture plate after exposure to higher concentrations of arecoline (> 0.4 mM). At concentrations of 0.4 and 0.8 mM, arecoline induced significant cytotoxicity to EAHY cells. At similar concentrations, arecoline induced G2/M cell cycle arrest and increased sub-G0/G1 population, a hallmark of apoptosis. Interestingly, prolonged exposure to arecoline (0.1 mM) for 12 and 21 days significantly suppressed the proliferation of EAHY cells, whereas EAHY cells showed adaptation and survived when exposed to 0.05 mM arecoline. These results suggest that BQ components may contribute to the pathogenesis of OSF and BQ chewing-related cardiovascular diseases via toxicity to oral or systemic endothelial cells, leading to impairment of vascular function. During BQ chewing, endothelial damage may be induced by areca nut components and associate with the pathogenesis of OSF, periodontitis, and cardiovascular diseases.

Dental pulp stem cells (DPSCs) are clonogenic, self-renewing, and multi-potential DPSCs capable of differentiating into osteoblasts. In this study, primary cell cultures were obtained from human dental pulp tissue of developing third molars, and flow cytometry was used to sort the subpopulation of DPSCs with STRO-1 and CD146 double-positive expression (denoted “DPSCs”). It was noted that DPSCs exhibited superior clonogenic potential and osteogenic differentiation capability than the dental pulp cell subpopulation with STRO-1 and CD146 double-negative expression (denoted DPCs). Furthermore, a low concentration (0.005 mg/ml) of exogenous glucosamine (GlcN) was effective in promoting the early osteogenic differentiation of DPSCs through the transforming growth factor-β receptor (TGF-βr) type I and Smads signal pathways, which upregulated the Runt-related transcription factor 2/core-binding factor alpha1 (Runx2/Cbfa1) and alkaline phosphatase at both the mRNA and protein levels. In the presence of osteogenic supplements, GlcN-treated DPSCs produced more mineralized-matrix deposition than did the untreated groups. Taken together, this study demonstrates the capacity of GlcN to promote the osteogenic differentiation of human DPSCs, and the underlying mechanism involves a TGF-βr-dependent Smad signal pathway. J. Cell. Physiol. 225: 140–151, 2010. © 2010 Wiley-Liss, Inc.

To compare the cytotoxicity of three nano-dentin bonding agents (nano-DBAs) and two non-nano-DBAs using Chinese hamster ovary (CHO-K1) cells. We found that nano fillers were not the major contributing factor in DBA cytotoxicity, as analyzed by colony forming assay and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Exposure of CHO-K1 cells to all three tested total-etching DBAs led to G(0)/G(1) cell cycle arrest, whereas exposure to higher concentrations of two tested nano-DBAs induced G(2)/M arrest. All five DBAs further induced apoptosis at the highest concentration, as analyzed by propidium iodide staining flow cytometry. The toxicity of all DBAs (1:4000v/v or higher) is related to increased reactive oxygen species (ROS) production, as analyzed by single cell DCF fluorescence flow cytometry. These results indicate that clinical application of DBAs may be potentially toxic to dental pulp tissues. Cytotoxicity of DBAs is associated with ROS production, cell cycle deregulation and apoptosis. Presence of methacrylate monomers such as PENTA and UDMA is possibly the major cytotoxic factor for DBAs. Further studies on other toxicological endpoints of nano-DBAs are necessary to highlight their safe use.

After operative restoration, some monomers released from dentin bonding agents or composite resin may induce tissue inflammation and affect the vitality of dental pulp. Whether BisGMA, a major monomer of composite resin, may induce prostaglandin release and cytotoxicity to pulp cells and their mechanisms awaits investigation. We found that BisGMA induced cytotoxicity to human dental pulp cells at concentrations higher than 0.075 mm as analyzed by 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. BisGMA (0.1 mm) also stimulated ERK phosphorylation, PGE(2) production, COX-2 mRNA and protein expression as well as ROS production (as indicated by an increase in cellular DCF fluorescence) in dental pulp cells. Catalase (500 and 1000 U/ml) and U0126 (10 and 20 microm, a MEK inhibitor) effectively prevented the BisGMA-induced ERK activation, PGE(2) production and COX-2 expression. Moreover, catalase can protect the pulp cells from BisGMA cytotoxicity, whereas aspirin and U0126 lacked of this protective activity. These results suggest that BisGMA released from composite resin may potentially affect the vitality of dental pulp and induce pulpal inflammation via stimulation of ROS production, MEK/ERK1/2 activation and subsequent COX-2 gene expression and PGE(2) production. Cytotoxicity of BisGMA to dental pulp cells is related to ROS production, but not directly mediated by MEK activation and PGE(2) production.

Epidemiological studies have shown a strong association between environmental exposure to betel quid (BQ) and oral cancer. Areca nut (AN), an ingredient of BQ, contains genotoxic and mutagenic compounds. In this study, we found that AN extract (ANE) inhibited the growth of Chinese hamster ovary cells (CHO-K1) in a dose- and time-dependent manner. Intracellular reactive oxygen species (ROS) levels and micronuclei (MN) frequency were significantly increased following ANE treatment in CHO-K1 cells. Addition of catalase markedly inhibited ANE-induced MN formation, indicating that ANE-induced genotoxicity was correlated with intracellular H(2)O(2). Incubation of CHO-K1 cells with ANE (400-800 microg/ml) for 24 hr caused G2/M arrest, and prolonged exposure to ANE (800 microg/ml) significantly induced cell death. Surprisingly, ANE itself caused cytokinesis failure and subsequent increase in binucleated cell formation. Coexposure to catalase (2,000 U/ml) and ANE (800 microg/ml) reduced the generation of binucleated cells, indicating that ANE-induced cytokinesis failure was associated with oxidative stress. Following prolonged exposure to ANE, an accumulation of hyperploid/aneuploid cells concomitant with bi-, micro- or multinucleated cells was found. In summary, our results demonstrate that ANE exposure to CHO-K1 cells caused increased MN frequency, G2/M arrest, cytokinesis failure, and an accumulation of hyperploid/aneuploid cells. These events are associated with an increase in intracellular H(2)O(2) level and actin filament disorganization.

Prostaglandin F(2alpha) (PGF(2alpha)) and interleukin-1beta (IL-1beta) levels are elevated in inflamed dental pulp. The roles of IL-1beta and PGF(2alpha) in the pathogenesis of pulpal inflammation await investigation. We found that IL-1beta stimulated PGF(2alpha) production of human dental pulp cells. IL-1beta and PGF(2alpha) (0.5-10 mumol/L) also induced IL-8 production and mRNA expression in pulp cells. Aspirin inhibited IL-1beta-induced PGF(2alpha), but not IL-8 production. PGF(2alpha)-induced IL-8 production and mRNA expression were inhibited by U0126 (an inhibitor of mitogen-activated protein kinase kinase [MEK1/2]) inhibitor), whereas SQ22536 (an adenylate cyclase inhibitor) enhanced this event. These results indicate that IL-1beta-induced IL-8 production in pulp cells is not mainly via direct activation of cyclooxygenase and PGF(2alpha) generation. PGF(2alpha)-induced IL-8 production is possibly via activation of MEK/extracellular signal-regulated kinase signaling, but not by activation of adenylate cyclase. IL-1beta and PGF(2alpha) might involve the pathogenesis of pulpal inflammation via induction of IL-8 production.

The flowable resin composite, Tetric Flow, was used to measure microstrain and degree of conversion after hardening with each of three curing machines: XL3000(XL) for 10, 20, 30, and 40 s; Optilux 501 using conventional mode (OC) for 10, 20, 30, and 40 s, as well as Optilux boost (OB, 10 s) and ramp modes (OR, 20 s); and LEDemetron (LEDe) for 10, 20, 30, and 40 s. The emitted power density and spectral distribution of the three light curing units were also measured. The LEDe output energy spectrum was centralized between 425 and 490 nm, which encompasses the excited wavelength of camphorquinone. The microstrain produced by the curing process is as a second-degree polynomial for each light source. The OB microstrain was highest, while the OR microstrain was lower. The ranking in order of degree of monomer conversion was as follows: XL10

Objectives . Dentin bonding agents (DBA) have been widely used in operative restoration to prevent leakage and promote bonding strength in the resin–dentin interface. However, DBA may exert potentially harmful effects to the dental pulp. In the present study, differential cytotoxicity of three DBA (Syntac Sprint, SP; Prime and Bond 2.1, PB; and Single Bond, SB) on the pulp cells was tested. Methods . Three DBA were diluted with the culture medium by a ratio of 1:1000, 1:2000 and 1:4000 (v/v). Pulp cells (5×10 4 cells/well) were then exposed to culture medium containing different diluents of three DBA for 12, 24 h and 3 days. Cytotoxicity was measured with a modified 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Results . A 12 h experiment revealed that SP was the strongest cytotoxic agent, followed sequentially by SB and PB. Exposure of pulp cells to 1:4000 (v/v) dilution of SP, PB and SB for 24 h reduced the cell number by 23, 6 and 45%, respectively. A 1:2000 (v/v) of DBA diluents reduced the cell number for 32, 13 and 65%, respectively, by SP, PB and SB. Dilution of DBA by 1000-fold of culture medium further enhanced the cytotoxic response. Cell number decreased by 89, 65 and 72%, respectively, by SP, PB and SB. Similar to the 12 h-cytotoxicity data, SB is more toxic at high dilution condition, whereas, at low dilution condition, SP is the most toxic agent to pulp cells. Similar cytotoxicity was noted when pulp cells were exposed to DBA for 3 days. Toxicity of DBA was concomitant with marked retraction and rounding of dental pulp cells. Significance . These results indicate that DBA exerts potential harmful effects to the pulp. Differential toxic effects of DBA on the pulp cells should be considered during selection of a suitable DBA for operative restoration.

The aim of the study was to compare the monomer conversion and cytotoxicity of two resin composites, Tetric Ceram (TC) and Heliomolar (HM), irradiated with a halogen light-curing unit (Optilux 501) using a number of curing modes, boost (OB), ramp (OR), and conventional (OC), as well as a light-emitting diode (LED) curing unit (LEDemetron; LEDe). The effects of irradiation times (10, 20, 30, and 40 s) were also investigated. The monomer conversion of resin composites was measured using Fourier transform infrared (FTIR) analysis. Resin samples were preimmersed in Dulbeco's modified engles medium (DMEM) for 24 h, and the periodontal ligament cells (PDL) were cultured with aged medium for 72 h to evaluate the cytotoxic effects of resin samples using the microtiter-tetrazolium (MTT) method. The spectral outputs of the curing units were also compared. After irradiation using the same curing mode, the TC monomer conversion was higher than the HM analog. The TC conversion value was lower after OC and LEDemetron irradiation for 10 s compared to exposures of 30 and 40 s. The HM conversion value was lowest for the 10-s OC irradiation, and highest for the 40-s OC exposure. In cytotoxicity tests, the negative control group was without irradiation. The succinate dehydrogenase (SDH) activities of the OB and OR-irradiated TC samples were significantly lower than analogs irradiated with LEDemetron for 40 s; however, no significant differences were demonstrated between OB, OR, and control groups. Further, no significant differences in SDH activity were demonstrated for OB, OR, and control groups of the HM.

e19538 Background: Most patients (pts) with HL are cured with conventional chemotherapy (CT) +/-radiotherapy. For pts with PD, treatment options include conventional CT, autologous transplant, and allogeneic transplant. Few studies have defined the cost of therapy for PD. This study aimed to assess the economic burden of PD among pts with HL receiving 2nd and 3rd line therapy in a large network of community-based practices in the U.S.A. Methods: This retrospective, observational cohort analysis used the electronic health record (EHR) database maintained by McKesson Specialty Health/US Oncology Network to examine adult pts with classical HL who received CT (1st, 2nd, or 3rd line) between 1 Jan 2007 and 31 Dec 2011 and met all eligibility criteria. EHRs were supplemented with chart review and with data from the Claims Data Warehouse. Costs were derived from 2007 Medicare reimbursement rates and presented descriptively. Follow up time was censored at the last entry for disease status or 8 months after the da...