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Objective: Dentin hypersensitivity (DH) is characterized by a short, sharp pain in response to a thermal or tactile stimulus. The application of desensitizing agents such as GLUMA and laser is a non-invasive and safe approach to decrease sensitivity. The evidence for the efficacy of GLUMA desensitizer compared to laser desensitization in patients with DH was evaluated for 6 months., Design: In March 2022, an electronic search of PubMed, Scopus, and Web of Science databases was conducted. Articles published in English that compared GLUMA and laser in the treatment of DH with a follow-up of 6 months or more were included. Randomized, non-randomized controlled trials, and clinical trials were included. Risk of bias assessment tools developed by the Cochrane collaboration ROB 2 and ROBINS-I were used to assess the quality of studies. The GRADE assessment method was used to assess the certainty of evidence., Results: About 36 studies were identified in the search results. After applying the predefined eligibility criteria, eight studies with 205 participants and 894 sites were included in this review. Of the eight studies, four were judged to be at high risk of bias, three had some concerns, and one had a serious risk of bias. The certainty of the evidence was graded as low., Conclusion: Based on limited evidence, GLUMA and laser appear to be equally effective in providing relief from DH. GLUMA showed an immediate effect and provided pain relief. Over the course of a week, laser showed long-term stable results. GLUMA is effective in providing immediate relief.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in rapid T lymphocytopenia and functional impairment of T cells. The underlying mechanism, however, remains incompletely understood. In this study, we focused on characterizing the phenotype and kinetics of T-cell subsets with mitochondrial dysfunction (MD) by multicolor flow cytometry and investigating the association between MD and T-cell functionality. While 73.9% of study subjects displayed clinical lymphocytopenia upon hospital admission, a significant reduction of CD4 or CD8 T-cell frequency was found in all asymptomatic, symptomatic, and convalescent cases. CD4 and CD8 T cells with increased MD were found in both asymptomatic and symptomatic patients within the first week of symptom onset. Lower proportion of memory CD8 T cell with MD was found in severe patients than in mild ones at the stage of disease progression. Critically, the frequency of T cells with MD in symptomatic patients was preferentially associated with CD4 T-cell loss and CD8 T-cell hyperactivation, respectively. Patients bearing effector memory CD4 and CD8 T cells with the phenotype of high MD exhibited poorer T-cell responses upon either phorbol 12-myristate-13-acetate (PMA)/ionomycin or SARS-CoV-2 peptide stimulation than those with low MD. Our findings demonstrated an MD-associated mechanism underlying SARS-CoV-2-induced T lymphocytopenia and functional impairment during the acute phase of infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mo, To, Zhou, Liu, Cao, Huang, Du, Lim, Yim, Luk, Chan, Chik, Lau, Tsang, Tam, Hung, Yuen and Chen.)

Dentinal hypersensitivity (DH) is a condition that causes patient discomfort. To evaluate the clinical efficacy of Gluma, fluoride varnish and Tetric N-Bond self-etch system in relieving DH immediately and over 30 days following a single topical application. The present randomized clinical trial was conducted on 55 patients with an age range 20-49 years. 70 teeth in total were incorporated and randomly assigned to the three groups. Parameters examined were: Tactile, air blast, and cold stimuli. VAS was used to assess tactile stimulus whereas the Schiff Cold Scale for air blast and cold stimuli. DH was evaluated immediately, at two weeks and 1 month follow up. Gluma showed a statistically significant reduction in DH scores over other materials. It was concluded that Gluma have statistically significant results over other materials in relieving DH immediately and over 30 days following a single topical application.Trial Registration: Clinical Trials.gov Identifier: NCT04351412, King Abdulaziz University Protocol Record 129-09-19. Registered 17 April 2020 - Retrospectively registered. http://ClinicalTrials.gov/NCT04351412 .

There are many proteins and enzymes in the human body, and their dysfunction can lead to the emergence of a disease. The use of proteins as a drug is common in various diseases such as diabetes. Proteins are hydrophilic molecules whose spatial structure is critical to their correct function. There are different ways for the administration of proteins. Protein structures are degraded by gastric acid and enzymes in the gastrointestinal tract and have a slight ability to permeate from the gastrointestinal epithelium due to their large hydrophilic nature. Therefore, their oral use has limitations. Since the oral route for the administration of drugs is one of the best and easiest routes for patients, many studies have been done to increase the stability, penetration, and ultimately, the bioavailability of proteins through oral administration. One of the studied strategies for oral delivery of protein is the use of pH-sensitive polymer-based carriers. These carriers use different pH-sensitive polymers, such as eudragit®, chitosan, dextran, and alginate. The use of pH-sensitive polymer- based carriers by protecting the protein from stomach acid (low pH) and degrading enzymes, increasing permeability and maintaining the spatial structure of the protein, leads to increased bioavailability. In this review, we focus on the various polymers used to prepare pH-sensitive polymer- based carriers for the oral delivery of proteins., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Water-soluble polymer-drug conjugates were obtained and analyzed towards their potential use as prodrugs for two hydrophobic antipsoriatic agents, including methotrexate (MTX) and acitretin (AC). The conjugation efficacy of MTX decreased with a decreasing molar ratio of N,N-dimethylaminoethyl methacrylate (DMAEMA) repeating units in the polymethacrylic chains. Cytotoxicity of positively charged (from +5 to +10 mV) nano- and microparticles (3-1500 nm in DMEM at 37 °C) were estimated by in vitro MTT and Annexin-V apoptosis assays on Me45, NHDF, HaCaT and BEAS-2B cell lines. Further, cell cycle analysis revealed arrest in G0/G1 phase in melanoma cells, while neither apoptosis induction nor cell cycle arrest occurred in normal epidermal and epithelial cells. Tested conjugates displayed a novel cytostatic effect in Me45 cells and a pro-apoptotic effect in HaCaT cells. Epithelial BEAS-2B cells were the most sensitive to the tested conjugates and responded via induction of necrosis. Cell line models allowed for characterization of the biologically relevant potential action of pro-drugs. Additionally, a skin in vitro evaluation assay provided the first known evidence of side-effect reduction with pro-drug use. Histological examinations confirmed the lack of negative effects of conjugates on the skin and showed no irritating properties., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background/aims: Inflammatory bowel disease is a chronic or remitting/relapsing intestinal inflammation, which comprises Crohn's disease and ulcerative colitis (UC). Severe UC is a life-threatening condition that requires corticosteroids (CS) as a first-line rescue therapy. Some patients are refractory to CS and may require alternative immunosuppressive therapy. Oral tacrolimus (FK506), an immunosuppressive agent, has been reported to be effective in the management of severe refractory UC, but it can cause serious adverse effects. This work aims to study the effect of tacrolimus delivered by a colon-targeted delivery system (CTDS) in a dextran sulfate sodium (DSS)-induced animal model of colitis., Materials and Methods: We developed and evaluated an oral CTDS of tacrolimus (FK506) loaded pH-dependent polymeric microspheres, composed of Eudragit® S100 as a pH-sensitive polymer using the oil-in-water emulsion method. The physicochemical properties and drug release profiles of these microparticles in gastrointestinal tract (GIT) conditions were examined. A DSS-induced colitis rat model was used to evaluate the potential remedial and in vivo distribution of microspheres., Results: The pH-microspheres prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. The in vivo distribution study in the rat GIT demonstrated that pH-microspheres were successfully delivered to the inflamed colon. Moreover, it also demonstrated a significant decrease of disease activity and expression of proinflammatory cytokines, such as tumor necrosis factor α, interleukin-1β (IL-1β), and IL-6, and minimized the histological and morphometric changes., Conclusion: The results confirmed the efficacy of tacrolimus (FK506) CTDs in the management of DSS-induced colitis., (© 2020 S. Karger AG, Basel.)

Bacterial infections require special care since the indiscriminate use of antibiotics to treat them has been linked to the emergence of resistant strains. In this sense, phytoterapeutic alternatives such as curcumin and its nanocapsules have emerged as a promising supplement in optimizing availability of bioactives and reducing the development of antimicrobial resistance. Thus, the aim of this study was to verify the effects of pure and nanoencapsulated curcumin in the treatment of experimental listeriosis in gerbils regarding many aspects including antibacterial effect, antioxidant mechanisms involved and the energetic metabolism. Four groups were used containing 6 animals each: T0 (control), T1 (infected), T2 (infected and treated with free curcumin - dose of 30 mg/kg/day) and T3 (infected and treated with nanocapsules containing curcumin - a dose of 3 mg/kg/day). Treated animals received curcumin for 6 consecutive days starting 24 h after Listeria monocytogenes infection. All animals were euthanized on the 12th day after L. monocytogenes infection. Quantitative polymerase chain reaction (qPCR) identified L. monocytogenes DNA in the spleens of all animals of the T1 group, as well as T2 (2 out of 6) and T3 (5 out of 6). The weight of the spleens confirmed the infection, since it was larger in the T1 group, differing statistically from T0, and similarly to T2 and T3. Hepatic histopathological examination showed mild infiltration of neutrophils and macrophages, except for the T3 group (only 1/6). In the liver, the pyruvate kinase activity was higher in T1 and T2 compared to T0 and T3. The adenylate kinase activity did not differ between groups. The Na + /K + ATPase activity was lower in T1 group compared to T0 and T3. Lipoperoxidation was lower in the T3 group compared to groups T0, T1 and T2. The antioxidant capacity against peroxyl radicals was higher in T1, T2 and T3 groups compared to T0. In conclusion, free curcumin showed potent antibacterial effects; however, the nanoencapsulated form was able to minimize the effects caused by L. monocytogenes regarding tissue injury, changes on enzymes of the energetic metabolism, in addition to an antioxidant effect against lipoperoxidation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This in vitro study examined the sealing ability of different desensitizing agents under a chemo-mechanical stress condition. For the study, a total of 144 extracted, caries-free human third molars were used to produce 1 mm-thick dentin discs. The specimens were divided randomly into four groups: Superseal (SS), Gluma (GL), Gluma Self-etch (GS), and Tooth Coat (TC). For each group, the permeability was measured before and after applying the desensitizer, after being exposed to Coca Cola for 5 minutes, and after 3150 strokes of a brushing abrasion. The decrease in permeability after the erosive and abrasive stress was analyzed by ANOVA and Tukey post hoc test. As a result, the dentin permeability decreased significantly for all desensitizers immediately after application (p < 0.05). SS and GS showed a significant difference in permeability reduction observed immediately after application and after acid action with Coca Cola (p < 0.05). After brushing abrasion, the permeability reduction decreased significantly for all desensitizers tested in this study (p < 0.05). TC showed the largest decrease in dentinal permeability compared to that of the other desensitizers and the differences were significant after brushing abrasion (p < 0.05). All tested desensitizers were effective in reducing dentin permeability. The behavioral characteristics under erosive and abrasive stress varied according to the products used. TC exhibited excellent sealing ability among the other desensitizers., Competing Interests: The authors have declared that no competing interests exist.

Background: Many smokers give up smoking on their own, but materials that provide a structured programme for smokers to follow may increase the number who quit successfully., Objectives: The aims of this review were to determine the effectiveness of different forms of print-based self-help materials that provide a structured programme for smokers to follow, compared with no treatment and with other minimal contact strategies, and to determine the comparative effectiveness of different components and characteristics of print-based self-help, such as computer-generated feedback, additional materials, tailoring of materials to individuals, and targeting of materials at specific groups., Search Methods: We searched the Cochrane Tobacco Addiction Group Trials Register, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP). The date of the most recent search was March 2018., Selection Criteria: We included randomised trials of smoking cessation with follow-up of at least six months, where at least one arm tested print-based materials providing self-help compared with minimal print-based self-help (such as a short leaflet) or a lower-intensity control. We defined 'self-help' as structured programming for smokers trying to quit without intensive contact with a therapist., Data Collection and Analysis: We extracted data in accordance with standard methodological procedures set out by Cochrane. The main outcome measure was abstinence from smoking after at least six months' follow-up in people smoking at baseline. We used the most rigorous definition of abstinence in each study and biochemically validated rates when available. Where appropriate, we performed meta-analysis using a random-effects model., Main Results: We identified 75 studies that met our inclusion criteria. Many study reports did not include sufficient detail to allow judgement of risk of bias for some domains. We judged 30 studies (40%) to be at high risk of bias for one or more domains.Thirty-five studies evaluated the effects of standard, non-tailored self-help materials. Eleven studies compared self-help materials alone with no intervention and found a small effect in favour of the intervention (n = 13,241; risk ratio (RR) 1.19, 95% confidence interval (CI) 1.03 to 1.37; I² = 0%). We judged the evidence to be of moderate certainty in accordance with GRADE, downgraded for indirect relevance to populations in low- and middle-income countries because evidence for this comparison came from studies conducted solely in high-income countries and there is reason to believe the intervention might work differently in low- and middle-income countries. This analysis excluded two studies by the same author team with strongly positive outcomes that were clear outliers and introduced significant heterogeneity. Six further studies of structured self-help compared with brief leaflets did not show evidence of an effect of self-help materials on smoking cessation (n = 7023; RR 0.87, 95% CI 0.71 to 1.07; I² = 21%). We found evidence of benefit from standard self-help materials when there was brief contact that did not include smoking cessation advice (4 studies; n = 2822; RR 1.39, 95% CI 1.03 to 1.88; I² = 0%), but not when self-help was provided as an adjunct to face-to-face smoking cessation advice for all participants (11 studies; n = 5365; RR 0.99, 95% CI 0.76 to 1.28; I² = 32%).Thirty-two studies tested materials tailored for the characteristics of individual smokers, with controls receiving no materials, or stage-matched or non-tailored materials. Most of these studies used more than one mailing. Pooling studies that compared tailored self-help with no self-help, either on its own or compared with advice, or as an adjunct to advice, showed a benefit of providing tailored self-help interventions (12 studies; n = 19,190; RR 1.34, 95% CI 1.20 to 1.49; I² = 0%) with little evidence of difference between subgroups (10 studies compared tailored with no materials, n = 14,359; RR 1.34, 95% CI 1.19 to 1.51; I² = 0%; two studies compared tailored materials with brief advice, n = 2992; RR 1.13, 95% CI 0.86 to 1.49; I² = 0%; and two studies evaluated tailored materials as an adjunct to brief advice, n = 1839; RR 1.72, 95% CI 1.17 to 2.53; I² = 10%). When studies compared tailored self-help with non-tailored self-help, results favoured tailored interventions when the tailored interventions involved more mailings than the non-tailored interventions (9 studies; n = 14,166; RR 1.42, 95% CI 1.20 to 1.68; I² = 0%), but not when the two conditions were contact-matched (10 studies; n = 11,024; RR 1.07, 95% CI 0.89 to 1.30; I² = 50%). We judged the evidence to be of moderate certainty in accordance with GRADE, downgraded for risk of bias.Five studies evaluated self-help materials as an adjunct to nicotine replacement therapy; pooling three of these provided no evidence of additional benefit (n = 1769; RR 1.05, 95% CI 0.86 to 1.30; I² = 0%). Four studies evaluating additional written materials favoured the intervention, but the lower confidence interval crossed the line of no effect (RR 1.20, 95% CI 0.91 to 1.58; I² = 73%). A small number of other studies did not detect benefit from using targeted materials, or find differences between different self-help programmes., Authors' Conclusions: Moderate-certainty evidence shows that when no other support is available, written self-help materials help more people to stop smoking than no intervention. When people receive advice from a health professional or are using nicotine replacement therapy, there is no evidence that self-help materials add to their effect. However, small benefits cannot be excluded. Moderate-certainty evidence shows that self-help materials that use data from participants to tailor the nature of the advice or support given are more effective than no intervention. However, when tailored self-help materials, which typically involve repeated assessment and mailing, were compared with untailored materials delivered similarly, there was no evidence of benefit.Available evidence tested self-help interventions in high-income countries, where more intensive support is often available. Further research is needed to investigate effects of these interventions in low- and middle-income countries, where more intensive support may not be available.

Objective: The aim of this randomized, controlled, prospective clinical trial was to evaluate the performances of two different universal adhesives and one etch-rinse adhesive for restoration of non-carious cervical lesions (NCCLs)., Material and Methods: Twenty patients with at least seven NCCLs were enrolled. Lesions were divided into seven groups according to adhesive systems and application modes: GSE: GLUMA Universal-self-etch, GSL: GLUMA Universal-selective etching, GER: GLUMA Universal-etch-and-rinse, ASE: All-Bond Universal-self-etch, ASL: All-Bond Universal-selective etching, AER: All-Bond Universal-etch-and-rinse, SBE (Control): Single Bond2-etch-and-rinse. A total of 155 NCCLs were restored with a nano hybrid composite (Tetric N-Ceram). Restorations were scored with regard to retention, marginal discoloration, marginal adaptation, recurrent caries and post-operative sensitivity using modified United States Public Health Service (USPHS) criteria after one week, 6, 12 and 24 months. Statistical evaluations were performed using Chi-square tests (p=0.05)., Results: The recall rate was 81.9% after the 24-month follow-up. The cumulative retention rates for self-etch groups (GSE: 72.2%, ASE:75%) were significantly lower than other experimental groups (GSL: 93.7%, GER: 100%, ASL: 94.1%, AER: 100%, SBE: 100%) at the 24-month follow-up (p<0.05). Regarding marginal adaptation and marginal discoloration, GSE and ASE groups demonstrated more bravo scores after 6 and 12-month observations but differences were not significant (p>0.05). Only one restoration from ASL group demonstrated post-operative sensitivity at 6 and 12-month observations. No secondary caries was observed on the restorations at any recall. At the end of 24-month observations, no significant differences were detected among groups regarding any of the criteria assessed, except retention., Conclusion: GLUMA Universal and All-Bond Universal showed better results in etch-and-rinse and selective etching mode compared to the self-etch mode regarding retention. Etch-and-rinse and selective etching application modes of the current universal adhesives tended to provide better clinical outcomes considering the criteria evaluated at the end of 24-month evaluation.

The breakdown of the polymeric component of contemporary composite dental restorative materials compromises their longevity, while leachable compounds from these materials have cellular consequences. Thus, a new generation of composite materials needed to be designed to have a longer service life and ensure that any leachable compounds are not harmful to appropriate cell lines. To accomplish this, we have developed concurrent thiol-ene-based polymerization and allyl sulfide-based addition-fragmentation chain transfer chemistries to afford cross-linked polymeric resins that demonstrate low shrinkage and low shrinkage stress. In the past, the filler used in dental composites mainly consisted of glass, which is biologically inert. In several of our prototype composites, we introduced fluorapatite (FA) crystals, which resemble enamel crystals and are bioactive. These novel prototype composites were benchmarked against similarly filled methacrylate-based bisphenol A diglycidyl ether dimethacrylate / triethylene glycol dimethacrylate (bisGMA/TEGDMA) composite for their cytotoxicity, mechanical properties, biofilm formation, and fluoride release. The leachables at pH 7 from all the composites were nontoxic to dental pulp stem cells. There was a trend toward an increase in total toughness of the glass-only-filled prototype composites as compared with the similarly filled bisGMA/TEGDMA composite. Other mechanical properties of the glass-only-filled prototype composites were comparable to the similarly filled bisGMA/TEGDMA composite. Incorporation of the FA reduced the mechanical properties of the prototype and bisGMA/TEGDMA composite. Biofilm mass and colony-forming units per milliliter were reduced on the glass-only-filled prototype composites as compared with the glass-only-filled bisGMA/TEGDMA composite and were significantly reduced by the addition of FA to all composites. Fluoride release at pH 7 was greatest after 24 h for the bisGMA/TEGDMA glass + FA composite as compared with the similarly filled prototypes, but overall the F - release was marginal and not at a concentration to affect bacterial metabolism.

Objective: Reports indicate Gluma and Duraphat are commonly used in-office agents to treat hypersensitive teeth. Considering this, the aim of this paper is to compare Gluma and Duraphat using a randomized controlled trial, meta-analysis collating evidences from previous studies and trial sequential analysis., Materials and Methods: Thirty-eight participants were randomized. Hypersensitivity and visual analog scale (VAS) scores were recorded at baseline, 5 min and 7 days. Oral health-related quality of life (OHIP) questionnaire was administered at baseline and 7 days. Statistical analysis was performed to identify significant differences between the variables. For the meta-analysis, electronic data bases were searched and eligible data was extracted and analysed using RevMan 5.0. Trial sequential analysis was performed using O'Brien-Fleming boundary approach for the primary outcome., Results: Both agents caused significant reduction in hypersensitivity and VAS score at 5 min and 7 days in the randomized trial with no superiority. The quality of life significantly improved in patients treated with both the agents. Four studies including the present trial in meta-analysis and trial sequential analysis indicated that Gluma produced significant reduction in VAS scores at 7 days., Conclusion: Gluma produces significant reduction in hypersensitivity at 7 days post treatment compared with Duraphat. There is definite lack of evidence on the long-term effect of these agents., Clinical Relevance: This paper provides strong evidence on the use of Gluma for hypersensitive teeth. This also is a way forward to future research on long-term effects, adverse effects and cost-effectiveness studies.

Objective: To evaluate the risk and intensity of bleaching-induced tooth sensitivity (TS) after in-office bleaching following topical application of a resin-based glutaraldehyde desensitizer., Methods: Thirty-three patients were randomly assigned to the experimental (Gluma Desensitizer Liquid, Heraeus Kulzer, Hanau, Germany) and placebo groups. The placebo or Gluma Desensitizer Liquid was applied for one minute prior to application of an in-office bleaching gel. Bleaching was performed with 35% hydrogen peroxide gel (three applications × 15 minutes each) over two sessions, one week apart. The color of the anterior teeth was evaluated before and 21 days after treatment using the VITA Classical shade guide, Bleachedguide 3D, and Easyshade spectrophotometer. TS during and after the bleaching was recorded according to the visual analog (VAS) and numerical rating (NRS) scales. All data were submitted to statistical analysis (α=0.05)., Results: There was no significant difference in absolute risk or intensity of TS between the two groups (risk and VAS, p=0.93 and 0.31, respectively; NRS, p≥0.45). At the end of the bleaching protocol, tooth whitening was observed in both groups, as evident from color change in shade guide units (ΔSGU, 4.1-7.1; both guides) and overall color change (ΔE, 7.4-9.3 units); however, there were no significant differences in whitening between the two groups ( p>0.11)., Conclusion: Gluma Desensitizer Liquid was not able to reduce the risk or intensity of TS. Bleaching efficacy was not affected by application of the desensitizer.

This study evaluated the influence of timing after endodontic treatment and type of resin cement used on the bond strength of fiber posts to epoxy resin-obturated canals. A total of 80 bovine incisor roots were divided into four groups (n = 20). Glass fiber posts were cemented at two different times, immediately or 7 days after endodontic treatment, using either a dual-curing resin cement (RelyX ARC, 3M ESPE) or a self-adhesive resin cement (RelyX U200, 3M ESPE). Following post cementation, the samples were cross-sectioned into slices containing root dentin, cement, and fiber post at the cervical, mid, and apical root thirds. The push-out test was performed on a universal testing machine. Three-way analysis of variance for randomized blocks showed no significant effect within the triple interaction (P = .394) or between the double interactions cement-timing (P = .395), cement-root thirds (P = .996), and timing-root thirds (P = .331). The main factor cement revealed a significant effect, showing that regardless of the timing and root third, RelyX ARC provided significantly higher bond strength values than U200. Regardless of root third and timing, the dual-curing resin cement showed higher bond strength to root dentin when the canals were filled with epoxy resin-based cement.

Objective: To evaluate the clinical performance of Scotchbond Universal (3M Oral Care) and Prime & Bond Elect (Dentsply Sirona) in the restoration of noncarious cervical lesions (NCCLs)., Methods and Materials: This was a randomized controlled clinical trial involving 63 subjects. Two hundred and three NCCLs were restored using Scotchbond Universal and Prime & Bond Elect using both an etch-and-rinse and a self-etch technique. Lesions were notch-shaped NCCLs, and the restorations were placed without any mechanical retention. Restorations were finished immediately after placement and scored with regard to retention, marginal discoloration, marginal adaptation, and secondary caries. Similar assessment of the restorations was performed 18 months after placement. Logistic regression was performed for each outcome separately with a compound symmetric variance-covariance structure assumed to consider a correlation of restorations within subjects. All analyses were conducted using SAS version 9.4 (SAS Inc)., Results: One hundred and fifty-eight teeth (77.8% of the restorations placed) in 46 subjects (73% of subjects enrolled) were available for the 18-month follow-up. A statistically significant difference was reached only for the comparison Scotchbond Universal/self-etch (SU&#95;SE) and Prime & Bond Elect/etch-and-rinse (PBE&#95;E&R) groups ( p=0.01), where a restoration with SU&#95;SE was 66% less likely to maintain a score of Alpha for marginal discoloration than a restoration performed with PBE&#95;E&R., Conclusions: Scotchbond Universal and Prime & Bond Elect presented acceptable clinical performance after 18 months of clinical service. However, Scotchbond Universal, when applied with a self-etch approach, did demonstrate a relatively high level of marginal discoloration when compared to the other groups.

Step-growth thiol-Michael photopolymerizable resins, constituting an alternative chemistry to the current methacrylate-based chain-growth polymerizations, were developed and evaluated for use as dental restorative materials. The beneficial features inherent to anion-mediated thiol-Michael polymerizations were explored, such as rapid photocuring, low stress generation, ester content tunability, and improved mechanical performance in a moist environment. An ester-free tetrafunctional thiol and a ultraviolet-sensitive photobase generator were implemented to facilitate thiol-Michael photopolymerization. Thiol-Michael resins of varied ester content were fabricated under suitable light activation. Polymerization kinetics and shrinkage stress were determined with Fourier-transform infrared spectroscopy coupled with tensometery measurements. Thermomechanical properties of new materials were evaluated by dynamic mechanical analysis and in 3-point bending stress-strain experiments. Photopolymerization kinetics, polymerization shrinkage stress, glass transition temperature, flexural modulus, flexural toughness, and water sorption/solubility were compared between different thiol-Michael systems and the BisGMA/TEGDMA control. Furthermore, the mechanical performance of 2 thiol-Michael composites and a control composite were compared before and after extensive conditioning in water. All photobase-catalyzed thiol-Michael polymerization matrices achieved >90% conversion with a dramatic reduction in shrinkage stress as compared with the unfilled dimethacrylate control. One prototype of ester-free thiol-Michael formulations had significantly better water uptake properties than the BisGMA/TEGDMA control system. Although exhibiting relatively lower Young's modulus and glass transition temperatures, highly uniform thiol-Michael materials achieved much higher toughness than the BisGMA/TEGDMA control. Moreover, low-ester thiol-Michael composite systems show stable mechanical performance even after extensive water treatment. Although further resin/curing methodology optimization is required, the photopolymerized thiol-Michael prototype resins can now be recognized as promising candidates for implementation in composite dental restorative materials.

This study evaluated the influence of formulation and thermal treatment on the degree of conversion, fracture toughness, flexural strength, and elastic modulus of experimental composites. Six composites were analyzed at BisGMA : TEGDMA molar ratios of 1 : 1 and 7 : 3 with filler at 30, 50, and 70 wt%. The degree of conversion was analyzed by Fourier transform infrared spectroscopy, fracture toughness was measured using the single-edge notched beam, and flexural strength and elastic modulus were measured with the 3-point bend test. For all tests, one-half of the specimens received thermal treatment at 170°C for 10 min. Data were analyzed by the Kruskal-Wallis or ANOVA/Tukey's test ( α = 5%). The 1 : 1 BisGMA : TEGDMA ratio showed higher properties than the 7 : 3 ratio. Although the material with 70% filler had a conversion lower than the one with 50%, it showed higher mechanical properties. The thermal treatment improved all properties in all materials. Therefore, the use of an equimolar ratio of BisGMA : TEGDMA can be paired with 70 wt% filler to design dental composites that possess increased advantageous physical and chemical properties. Furthermore, the simple and low-cost method of thermal treatment proposed for use in clinical dentistry has been shown to effectively improve the properties of all evaluated materials.

This study aimed to evaluate the effect of various silane-containing solutions on bonding between resin cement and glass ceramic after 24 hours and after six months of water storage. Glass-ceramic plaques (IPS e.max CAD) were sandblasted with aluminum oxide, etched with 10% hydrofluoric acid (HF), and divided into five "silane treatment" groups: RelyX Ceramic Primer (RCP), RelyX Ceramic Primer and Single Bond Plus (RCP+SB), Scotchbond Universal (SBU), Clearfil Ceramic Primer (CP), and no solution (HF-only control). Each group was divided into two "storage time" subgroups: 24 hours or six months in 37°C water. Eighteen resin cement cylinders (RelyX Ultimate) were bonded to each treatment group substrate (n=18) and then subjected to microshear testing. Failure mode was analyzed using scanning electron microscopy. Debond data were analyzed using a two-way analysis of variance and the Tukey post hoc test (α=0.05) as well as Weibull distributions. The factors "silane treatment," "storage time," (p<0.0001), and their interaction were statistically significant (p<0.0010). Group means (MPa±SD), RCP (24 hours: 27.2±3.1; six months: 18.0±4.9), and HF-only control (24 hours: 21.1±3.4; six months: 15.7±5.8) showed a reduced bond strength after six months of water storage, while RCP + SB (24 hours: 23.4±4.4; six months: 22.2±5.4), SBU (24 hours: 18.8±3.0; six months: 17.2±3.6), and CP (24 hours: 21.7±4.3; six months: 17.4±4.8) remained constant. Weibull analysis revealed that more reliable bond strengths were obtained after six months for SBU and RCP + SB. Evaluation by scanning electron microscopy revealed that all groups demonstrated hydrolytic degradation at six months of storage, but RCP + SB and SBU indicated less. Use of a separate application of silane and adhesive system improved short and long-term ceramic/resin cement bond strength.

Resin cements are often used for single crown cementation due to their physical properties. Self-adhesive resin cements gained widespread due to their simplified technique compared to regular resin cement. However, there is lacking clinical evidence about the long-term behavior of this material. The aim of this prospective clinical trial was to assess the survival rates of metal-ceramic crowns cemented with self-adhesive resin cement up to six years. One hundred and twenty-nine subjects received 152 metal-ceramic crowns. The cementation procedures were standardized and performed by previously trained operators. The crowns were assessed as to primary outcome (debonding) and FDI criteria. Statistical analysis was performed using Kaplan-Meier statistics and descriptive analysis. Three failures occurred (debonding), resulting in a 97.6% survival rate. FDI criteria assessment resulted in scores 1 and 2 (acceptable clinical evaluation) for all surviving crowns. The use of self-adhesive resin cement is a feasible alternative for metal-ceramic crowns cementation, achieving high and adequate survival rates.

Novel "zwitterionic" gold nanorods (Au NRs) were constructed through a facile ligand exchange process between cetyltrimethylammonium bromide (CTAB)-Au NRs and the zwitterionic block polymer {poly(2-methacryloyloxyethyl phosohorylcholine)-b-poly(lipoic methacrylate) (pMPC-b-pLA)}. In vitro, they exhibited low dark cytotoxicity and a high therapeutic efficacy to cancer cells. Their blood circulation half-life in vivo (t 1/2 , ∼10 h) was 20-fold longer than that of CTAB-Au NRs (t 1/2 , <30 min). After intravenous administration, they accumulated in tumour sites via an enhanced permeability and retention (EPR) effect and enabled destruction of human xenograft tumours in mice after exposure of the tumour location to NIR laser irradiation at 808 nm. These studies showed that the "zwitterionic" Au NRs had low toxicity and high photothermal efficacy both in vitro and in vivo due to the suprahydrophilic, biocompatible zwitterionic polymer coating layer. They may have the potential to be a promising NIR PTT agent in the biomedical field.

Objective: The regional specific modulation of neuronal activation following drug administration is of interest to determine brain areas involved in the behavioural effects of experimental test compounds. In the current investigation the effects of the L-arginine related NOS inhibitor N ω -l-nitroarginine (L-NA) and the structurally unrelated selective neuronal NOS inhibitor 1-(2-Trifluoro-methyl-phenyl) imidazole (TRIM) were assessed in the rat for changes in regional c-FOS immunoreactivity, a marker of neuronal activation, upon exposure to the forced swimming test (FST). Behaviour and regional FOS and FosB/ΔFosB expression was assessed in naive animals and in animals exposed to stress with central serotonin-depletion which exhibit a stress related phenotype in the FST., Methods: Male Sprague-Dawley rats (n=5- 6 per group) were treated with the irreversible tryptophan hydroxylase inhibitor, DL-4-p-chlorophenylalanine (pCPA, 150mg/kg, i.p.), to achieve central serotonin-depletion followed by repeated exposures to restraint stress and were then subjected to the FST. 24, 5 and 1h prior to the test, animals were treated with either L-NA (10mg/kg, i.p.), TRIM (50mg/kg, i.p.) or saline vehicle (1mg/kg i.p)., Results: pCPA treatment coupled with restraint stress increased immobility in the FST compared to naïve controls. Both NOS inhibitors decreased immobility time in 5-HT depleted and stressed animals only in keeping with their antidepressant-like properties. Brain regions analyzed for c-FOS immunoreactivity included the pre-limbic cortex, lateral septum (LS), nucleus accumbens, paraventricular hypothalamic nucleus (PVN), central amygdala, hippocampus (dorsal dentate gyrus and ventral CA1), and the dorsal raphe nucleus (DRN). Exposure to the FST increased c-FOS immunoreactivity in the LS, PVN, dentate gyrus, vCA1 and the DRN when compared to non-FST exposed controls. FST-induced c-FOS immunoreactivity was further increased in the LS following treatment with L-NA or TRIM when compared to vehicle-treated FST controls. By contrast, FST-induced c-FOS immunoreactivity was reduced in dorsal dentate gyrus, vCA1 and the DRN following treatment with L-NA or TRIM when compared to vehicle-treated FST controls. There was no difference observed in FST-induced expression of c-FOS between naïve animals and animals exposed to pCPA and restraint stress. This combination however provoked an increase in FosB/ΔFosB immunoreactivity in the infra-limbic cortex and nucleus accumbens with a concomitant reduction in the lateral septum, suggesting alterations to long-term, adaptive neuronal activation., Conclusion: This study identified a pattern of enhanced and reduced FST-related c-FOS immunoreactivity indicative of a NO-regulated network where inhibition of NO leads to activation of the septum with concomitant inhibition of the hippocampus, and the DRN. No link between FST-induced regional expression of c-FOS and increased immobility in the FST was observed in animals exposed to pCPA and stress. However, the 5-HT depletion regime combined with restraint stress provoked regional changes in the expression of ΔFosB which may relate to increased immobility in the FST., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Hydrogels have been widely explored for biomedical applications, with injectable hydrogels being of particular interest for their ability to precisely deliver drugs and cells to targets. Although these hydrogels have demonstrated satisfactory properties in many cases, challenges still remain for commercialization. In this paper, we describe a simple injectable hydrogel based on poly(ethylene glycol) (PEG) and a vitamin E (Ve) methacrylate copolymer prepared via simple free radical polymerization and delivered in a solution of low molecular weight PEG and Ve as the solvent instead of water. The hydrogel formed immediately in an aqueous environment with a controllable gelation time. The driving force for gelation is attributed to the self-assembly of hydrophobic Ve residues upon exposure to water to form a physically cross-linked polymer network via polymer chain rearrangement and subsequent phase separation, a spontaneous process with water uptake. The hydrogels can be customized to give the desired water content, mechanical strength, and drug release kinetics simply by formulating the PEGMA-co-Ve polymer with an appropriate solvent mixture or by varying the molecular weight of the polymer. The hydrogels exhibited no significant cytotoxicity in vitro using fibroblasts and good tissue compatibility in the eye and when injected subcutaneously. These polymers thus have the potential to be used in a variety of applications where injection of a drug or cell containing depot would be desirable.

Objective: This study aimed to compare the efficacy of a 940-nm diode laser and Gluma desensitizer on post-preparation sensitivity of prepared teeth., Materials and Methods: Twenty patients with 76 teeth participated in the study. For each patient, prepared molar or premolar in one quadrant were individually irradiated by laser. In the symmetrical quadrant, Gluma was applied onto the prepared teeth. No treatment was performed in the control group. Temporary crowns were placed after preparation. Pain response to tactile stimulus was assessed at one day, one week, and two weeks using visual analog scale (VAS). Intergroup comparisons were made with Kruskal Wallis test (p < 0.05)., Results: Mean VAS scores of the control group were statistically higher than laser and Gluma groups (p < 0.017). The difference between VAS scores of the laser and Gluma groups was statistically insignificant (p > 0.05)., Conclusions: A significant reduction in level of sensitivity after both treatments was observed. The reduction of sensitivity with Gluma was not significantly superior to laser. No significant additional reduction occurred in level of sensitivity from the first day to the second week after both treatments., Clinical Significance: The application of Gluma or a 940-nm diode laser may be considered as effective in reducing sensitivity after tooth preparation without superiority of either method. (J Esthet Restor Dent 28:405-411, 2016)., (© 2016 Wiley Periodicals, Inc.)

Conjugating therapeutic proteins and peptides to poly(ethylene glycol) (PEG) can improve their pharmacokinetics and therapeutic potential. However, PEGylation suffers from non-specific conjugation, low yield and immunogenicity. Herein we report a new and general methodology to synthesize a protein-polymer conjugate with site-specificity, high yield and activity, long circulation half-life and excellent therapeutic efficacy. A phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), was grown solely from the C-terminus of interferon-alpha to form a site-specific (C-terminal) and stoichiometric (1:1) PMPC conjugate of interferon-alpha in high yield. Notably, the PMPC conjugate showed 194- and 158-fold increases in systemic exposure and tumor uptake as compared with interferon-alpha, respectively. The in vitro antiproliferative bioactivity of the PMPC conjugate was 8.7-fold higher than that of PEGylated interferon-alpha (PEGASYS). In a murine cancer model, the PMPC conjugate completely inhibited tumor growth and cured 75% mice, whereas at the same dose, no mice treated with interferon-alpha or PEGASYS survived. We believe that this new approach to synthesize C-terminal protein conjugates of PMPC may be applicable to a large subset of protein and peptide drugs, thereby providing a general platform for the development of next-generation protein therapeutics., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Previously, poly(methacrylic acid-co-methyl methacrylate) (MAA) beads were shown to improve vessel formation with a concomitant increase in the expression of the sonic hedgehog (Shh) gene, a pleiotropic factor implicated in vascularization. The aim of this study was to follow up on this observation in the absence of the confounding factors of diabetes in non-diabetic Shh-Cre-eGFP/Ptch1-LacZ mice; in this mouse, expression of GFP and β-Gal is consistent with the transcription patterns of Shh and its receptor patched 1 (Ptch1), respectively. In agreement with studies in diabetic males, MAA beads improved vascularization in large (15 mm × 15 mm) wounds in non-diabetic males at day 7. Shh pathway activation was suggested, as the numbers of GFP+ (Shh) and β-Gal+ (Ptch1, a target of the pathway) cells increased in the granulation tissue. Shh signaling pathway modulation was also suggested in the healthy skin surrounding the wound bed, as evidenced by an increase in the number of GFP+ and β-Gal+ cells in males at day 4. Gene expression analysis of the wounds confirmed increase in Ptch1 and showed the upregulation of a downstream transcription factor Gli3, involved in the vascular effect of the Shh pathway, implicating the pathway in the effect of MAA beads. The efficacy of MAA beads was also investigated in females; MAA beads modulated the Shh pathway within granulation tissue similarly as in males, but had no enhancement effect on the healthy skin and on vascularization. We believe that understanding the molecular and cellular mechanisms of MAA-based biomaterials and testing the efficacy of therapeutics in both sexes will inform the development of novel therapeutic biomaterials., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Biodegradable materials used for drug delivery are of great demand due to their ability to degrade into low molecular weight species and further excrete from the body by metabolism. Herein, we report a new kind of zinc(II) crosslinked poly(methacrylic acid) nanohydrogels (ZCLNs) inspired by zinc finger proteins with dual stimuli-triggered degradation (glutathione and pH) for the first time. Compared with the disulfide bond crosslinked nanohydrogels, this new kind of ZCLNs is beneficial to the degradation of a wide range of cells, including normal cells. Ex vivo fluorescence images showed that the DOX-loaded folate-PEG conjugated zinc(II)-crosslinked polymeric nanohydrogels (FPZCLNs-15) preferentially accumulated in tumor tissue and the accumulation in normal tissues was much less compared with DOX-loaded PZCLNs-15 (non-targeted nanohydrogels) and free DOX, the FPZCLNs-15 (targeting system) delivered DOX to the tumor site with approximately 3.6- and 1.6-fold higher than free DOX and PZCLNs-15, respectively. Meanwhile, the PZCLNs-15 and FPZCLNs-15 reduced the concentration of DOX in the heart by 3.2- and 5.0-fold respectively, as compared to the free DOX. Moreover, a superior tumor growth inhibition and negligible damage to normal organs like the heart and kidney, which is reported to be vulnerable to DOX-associated side effects, are further demonstrated., (Copyright © 2016 Elsevier B.V. All rights reserved.)

This in vitro study evaluated the effect of air-drying time on degree of solvent evaporation (DE), dentin microtensile bond strength (µTBS), and degree of conversion (DC) of 5 adhesive systems: Adper Single Bond 2, XP Bond, Prime & Bond 2.1, OptiBond Solo, and Adper Easy One. For DE testing, 20 µL of each material was submitted to measurements in a digital balance after an air stream of 3, 5, 10, 20, 30, or 60 seconds; the weight loss was computed and converted to a percentage (DE). For µTBS testing, 50 sound human molars were divided into groups (n = 5). The 5 adhesive systems were applied either in accordance with manufacturers' instructions for solvent drying time (control) or with a prolonged drying time (20-30 seconds). After composite resin was built up on the hybridized surfaces, the teeth were stored for 24 hours and then sectioned to obtain beams that were loaded until fracture. For DC testing, specimens of each adhesive and air-drying condition (n = 3) were evaluated by means of attenuated total reflectance Fourier transform infrared spectroscopy. Data were submitted to 2-way analysis of variance, t test, and Spearman test for correlation analysis. Prolonged air drying resulted in significantly greater DE than did the time suggested by the manufacturers. The adhesives XP Bond and Adper Easy One showed significantly greater µTBS with prolonged air drying. The DC was not affected by air-drying time. No statistically significant correlation was found between DC and µTBS values. Depending on the material, bond strength can be improved by prolonged air-drying times.

To integrate biological imaging and multimodal therapies into one platform for enhanced anti-cancer efficacy, we have designed a novel core/shell structured nano-theranostic by conjugating photosensitive Au25(SR)18 - (SR refers to thiolate) clusters, pH/temperature-responsive polymer P(NIPAm-MAA), and anti-cancer drug (doxorubicin, DOX) onto the surface of mesoporous silica coated core-shell up-conversion nanoparticles (UCNPs). It is found that the photodynamic therapy (PDT) derived from the generated reactive oxygen species and the photothermal therapy (PTT) arising from the photothermal effect can be simultaneously triggered by a single 980 nm near infrared (NIR) light. Furthermore, the thermal effect can also stimulate the pH/temperature sensitive polymer in the cancer sites, thus realizing the targeted and controllable DOX release. The combined PDT, PTT and pH/temperature responsive chemo-therapy can markedly improve the therapeutic efficacy, which has been confirmed by both in intro and in vivo assays. Moreover, the doped rare earths endow the platform with dual-modal up-conversion luminescent (UCL) and computer tomography (CT) imaging properties, thus achieving the target of imaging-guided synergistic therapy under by a single NIR light., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Unlabelled: Bioresorbable devices are commonly used in traumatology. The biomechanical stability of these materials has improved in the past decade, and they have proven to be biologically non-hazardous, while their main advantage is that their use avoids reintervention for removal of the device. A prospective monocentric study was conducted: 24 patients presenting with a fracture that was amenable to osteosynthesis by small-diameter screws were included. These comprised ten tibial spine fractures, four osteochondritis dissecans of the distal femur, eight fractures of the medial epicondyle of the distal humerus, and two distal tibial apophyseal fractures. One or more screws were used that were made of a copolymer of poly-L-lactide-poly-D-lactide acid and trimethylene carbonate with a diameter of 2.8 mm. All patients were immobilized with a cast. Clinical and radiographic monitoring was conducted every month. The entire follow-up protocol had a duration of 24 months. One patient with osteochondritis dissecans presented with joint effusion. Joint stiffness at the time of cast removal resolved completely after 4 months, except for with three children (one epicondyle fracture, two tibial spine fractures). No subjective or objective instability could be detected by clinical examination. Radiographic follow-up revealed no secondary displacement, and all of the fractures had healed. No osteolysis was seen around the screws. No growth disturbances were noticed. Bioresorbable materials thus appear to be a suitable alternative approach for certain pediatric fractures. Their use resulted in outcomes similar to traditional techniques in terms of functional properties and bone healing. Although initial costs are presumably slightly higher, by avoiding a removal operation the total financial burden is most likely reduced., Level of Evidence: III.

It was recently reported that ethanolamine-functionalized poly(glycidyl methacrylate) (PGEA) possesses great potential applications in gene therapy due to its good biocompatibility and high transfection efficiency. Importing responsivity into PGEA vectors would further improve their performances. Herein, a series of responsive star-shaped vectors, acetaled β-cyclodextrin-PGEAs (A-CD-PGEAs) consisting of a β-CD core and five PGEA arms linked by acid-labile acetal groups, were proposed and characterized as therapeutic pDNA vectors. The A-CD-PGEAs owned abundant hydroxyl groups to shield extra positive charges of A-CD-PGEAs/pDNA complexes, and the star structure could decrease charge density. The incorporation of acetal linkers endowed A-CD-PGEAs with pH responsivity and degradation. In weakly acidic endosome, the broken acetal linkers resulted in decomposition of A-CD-PGEAs and morphological transformation of A-CD-PGEAs/pDNA complexes, lowering cytotoxicity and accelerating release of pDNA. In comparison with control CD-PGEAs without acetal linkers, A-CD-PGEAs exhibited significantly better transfection performances.

The aim of this in vitro study was to evaluate the nanoleakage of fiber posts luted using different adhesive strategies and to investigate the effect of 2% chlorhexidine (CHX) on nanoleakage at the resin-dentin interfaces of self-adhesive cements. The self-adhesive and etch-and-rinse adhesive groups tested demonstrated similar results with regard to nanoleakage. Pretreatment with CHX promoted an adequate seal at the resin-dentin interface for self-adhesive cements.

The purpose of this in vitro study was to evaluate the effect of air-abrasion/zirconia sintering order on the yttria partially stabilized tetragonal zirconia polycrystal (Y-TZP) surface characterization (roughness, morphology, and phase transformation), flexural strength (FS), and shear bond strength (SBS) to a resin cement. Y-TZP specimens were air abraded with 50-μm Al2O3 particles after (AS), before (BS), or before and after zirconia sintering (BAS). For roughness (Ra), 30 block specimens (12×12×3.0 mm; n=10) had their surfaces analyzed by a profilometer. Next, on the air-abraded surfaces of these specimens, composite resin discs (n=30) were bonded with RelyX ARC. The bonded specimens were stored for 24 hours in distilled water at 37°C before shear testing. Failure mode was determined with a stereomicroscope (20×). The surface morphology (n=2) was evaluated by SEM (500×). For the four-point flexural strength test (EMIC DL2000), 39 bar-shaped specimens (20×4.0×1.2 mm; n=13) were air abraded according to the three conditions proposed, and an additional group (nonabraded) was evaluated (n=13). The quantitative analysis of phase transformation (n=1) was completed with Rietveld refinement with X-ray diffraction data. Ra (μm) and SBS (MPa) data were analyzed by one-way analysis of variance (ANOVA) and the Tukey test (α=0.05). Pearson correlation analysis was used to determine if there was a correlation between roughness and SBS. For FS (MPa) data, one-way ANOVA and the Dunnett C-test (α=0.05) were used. The air-abrasion/zirconia sintering order influenced significantly (p<0.001) Ra, SBS, and FS. The BS and AS groups presented the highest (1.3 μm) and the lowest (0.7 μm) Ra. The highest SBS (7.0 MPa) was exhibited by the BAS group, followed by the AS group (5.4 MPa) and finally by the BS group (2.6 MPa). All groups presented 100% adhesive failure. A weak correlation (r=-0.45, p<0.05) was found between roughness and SBS. The air-abrasion/zirconia sintering order provided differences in the surface morphology. The nonabraded (926.8 MPa) and BS (816.3 MPa) groups exhibited statistically similar FS values but lower values than the AS (1249.1 MPa) and BAS (1181.4 MPa) groups, with no significant difference between them. The nonabraded, AS, BS, and BAS groups exhibited, respectively, percentages of monoclinic phase of 0.0 wt%, 12.2 wt%, 0.0 wt%, and 8.6 wt%. The rougher surface provided by the air-abrasion before zirconia sintering may have impaired the bonding with the resin cement. The morphological patterns were consistent with the surface roughness. Considering the short-term SBS and FS, the BAS group exhibited the best performance. Air abrasion, regardless of its performance order, provides tetragonal to monoclinic transformation, while sintering tends to zero the monoclinic phase content.

The wear and creep deformation resistances of polymeric orthopedic bearing materials are both important for extending their longevity. In this study, we evaluated the wear and creep deformation resistances, including backside damage, of different polyethylene (PE) materials, namely, conventional PE, cross-linked PE (CLPE), and poly(2-methacryloyloxyethyl phosphorylcholine)- (PMPC-) grafted CLPE, through wear tests and finite element analysis. The gravimetric and volumetric degrees of wear of disks (3 or 6 mm in thickness) of these materials against a cobalt-chromium-molybdenum alloy pin were examined using a multidirectional pin-on-disk tester. Cross-linking and PMPC grafting decreased the gravimetric wear of the PE disks significantly. The volumetric wear at the bearing surface and the volumetric penetration in the backside of the 3-mm thick PE disk were higher than those of the 6-mm thick PE disk, regardless of the bearing material. The geometrical changes induced in the PE disks consisted of creep, because the calculated internal von Mises stress at the bearing side of all disks and that at the backside of the 3-mm thick disks exceeded their actual yield strengths. A highly hydrated bearing surface layer, formed by PMPC grafting, and a cross-linking-strengthened substrate of adequate thickness are essential for increasing the wear and creep deformation resistances.

This study evaluated the effect of the cement type (adhesive resin, self-adhesive, glass ionomer, and zinc phosphate) on the retention of crowns made of yttria-stabilized polycrystalline tetragonal zirconia (Y-TZP). Therefore, 108 freshly extracted molars were embedded in acrylic resin, perpendicular to their long axis, and prepared for full crowns: the crown preparations were removed and reconstructed using composite resin plus fiber posts with dimensions identical to the prepared dentin. The preparations were impressed using addition silicone, and Y-TZP copings were produced, which presented a special setup for the tensile testing. Cementation was performed with two adhesive resin cements (Multilink Automix, Ivoclar-Vivadent; RelyX ARC, 3M ESPE, St Paul, MN, USA), one self-adhesive resin cement (RelyX U100, 3M ESPE), one glass ionomer based cement (RelyX Luting, 3M ESPE), and one zinc phosphate cement (Cimento de Zinco, SS White, Rio de Janeiro, Brazil). For the resin cement groups, the inner surfaces of the crowns were subjected to three surface treatments: cleaning with isopropyl alcohol, tribochemical silica coating, or application of a thin low-fusing glass porcelain layer plus silanization. After 24 hours, all groups were subjected to thermocycling (6000 cycles) and included in a special device for tensile testing in a universal testing machine to test the retention of the infrastructure. After testing, the failure modes of all samples were analyzed under a stereomicroscope. The Kruskal-Wallis test showed that the surface treatment and cement type (α=0.05) affected the tensile retention results. The Multilink cement presented the highest tensile retention values, but that result was not statistically different from RelyX ARC. The surface treatment was statistically relevant only for the Multilink cement. The cement choice was shown to be more important than the crown surface treatment for cementation of a Y-TZP crown to a composite resin substrate.

Summary Background/objectives: White spot lesions (WSLs) are unwelcome side effects of fixed appliances that compromise the treatment outcome. Recently, infiltration of WSLs has been introduced as a viable treatment alternative. The objective was to evaluate the colour improvement of WSLs and their stability against discolouration following infiltration, fluoride, or micro-abrasion treatments in vitro., Materials/methods: Artificial WSLs were created in bovine enamel (N = 96) using acidic buffer solution (pH 5, 10 days) and were randomly allocated to four groups. Specimens were treated with infiltration (Icon, DMG), fluoride (Elmex Caries Protection, GABA), and micro-abrasion (Opalustre, Ultradent) or remained untreated (control). Groups were discoloured for 24 hours in tea or tea + citric acid. Colour components and visible colour change (L*, a*, b*, ΔE) were measured spectrophotometrically on following time points: baseline, after WSL formation, after treatment, and during discolouration (8, 16, and 24 hours). Data were analysed using Kruskal-Wallis and Mann-Whitney tests., Results: WSL formation increased (L*) in all groups. Only infiltration reduced this effect to baseline. Highest ΔE improvement was obtained by infiltration and micro-abrasion followed by fluoride. This improvement was stable only for infiltration during discolouration. L*, a*, and b* changed significantly during discolouration in all groups except infiltration. Within the same treatment group, discolouration solutions did not differ significantly., Limitations: In vitro testing cannot replicate the actual mode of colour improvement or stability but can be used for ranking materials and techniques., Conclusions/implications: Infiltration and micro-abrasion treatments were capable of diminishing the whitish appearance of WSLs. Only infiltrated WSLs were stable following discolouration challenge., (© The Author 2014. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Many smokers give up smoking on their own, but materials giving advice and information may help them and increase the number who quit successfully., Objectives: The aims of this review were to determine: the effectiveness of different forms of print-based self-help materials, compared with no treatment and with other minimal contact strategies; the effectiveness of adjuncts to print-based self help, such as computer-generated feedback, telephone hotlines and pharmacotherapy; and the effectiveness of approaches tailored to the individual compared with non-tailored materials., Search Methods: We searched the Cochrane Tobacco Addiction Group trials register. Date of the most recent search April 2014., Selection Criteria: We included randomized trials of smoking cessation with follow-up of at least six months, where at least one arm tested a print-based self-help intervention. We defined self help as structured programming for smokers trying to quit without intensive contact with a therapist., Data Collection and Analysis: We extracted data in duplicate on the participants, the nature of the self-help materials, the amount of face-to-face contact given to intervention and to control conditions, outcome measures, method of randomization, and completeness of follow-up.The main outcome measure was abstinence from smoking after at least six months follow-up in people smoking at baseline. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates when available. Where appropriate, we performed meta-analysis using a fixed-effect model., Main Results: We identified 74 trials which met the inclusion criteria. Many study reports did not include sufficient detail to judge risk of bias for some domains. Twenty-eight studies (38%) were judged at high risk of bias for one or more domains but the overall risk of bias across all included studies was judged to be moderate, and unlikely to alter the conclusions.Thirty-four trials evaluated the effect of standard, non-tailored self-help materials. Pooling 11 of these trials in which there was no face-to-face contact and provision of structured self-help materials was compared to no intervention gave an estimate of benefit that just reached statistical significance (n = 13,241, risk ratio [RR] 1.19, 95% confidence interval [CI] 1.04 to 1.37). This analysis excluded two trials with strongly positive outcomes that introduced significant heterogeneity. Six further trials without face-to-face contact in which the control group received alternative written materials did not show evidence for an effect of the smoking self-help materials (n = 7023, RR 0.88, 95% CI 0.74 to 1.04). When these two subgroups were pooled, there was no longer evidence for a benefit of standard structured materials (n = 20,264, RR 1.06, 95% CI 0.95 to 1.18). We failed to find evidence of benefit from providing standard self-help materials when there was brief contact with all participants (5 trials, n = 3866, RR 1.17, 95% CI 0.96 to 1.42), or face-to-face advice for all participants (11 trials, n = 5365, RR 0.97, 95% CI 0.80 to 1.18).Thirty-one trials offered materials tailored for the characteristics of individual smokers, with controls receiving either no materials, or stage matched or non-tailored materials. Most of the trials used more than one mailing. Pooling these showed a benefit of tailored materials (n = 40,890, RR 1.28, 95% CI 1.18 to 1.37) with moderate heterogeneity (I² = 32%). The evidence is strongest for the subgroup of nine trials in which tailored materials were compared to no intervention (n = 13,437, RR 1.35, 95% CI 1.19 to 1.53), but also supports tailored materials as more helpful than standard materials. Part of this effect could be due to the additional contact or assessment required to obtain individual data, since the subgroup of 10 trials where the number of contacts was matched did not detect an effect (n = 11,024, RR 1.06, 95% CI 0.94 to 1.20). In two trials including a direct comparison between tailored materials and brief advice from a health care provider, there was no evidence of a difference, but confidence intervals were wide (n = 2992, RR 1.13, 95% CI 0.86 to 1.49).Only four studies evaluated self-help materials as an adjunct to nicotine replacement therapy, with no evidence of additional benefit (n = 2291, RR 1.05, 95% CI 0.88 to 1.25). A small number of other trials failed to detect benefits from using additional materials or targeted materials, or to find differences between different self-help programmes., Authors' Conclusions: Standard, print-based self-help materials increase quit rates compared to no intervention, but the effect is likely to be small. We did not find evidence that they have an additional benefit when used alongside other interventions such as advice from a healthcare professional, or nicotine replacement therapy. There is evidence that materials that are tailored for individual smokers are more effective than non-tailored materials, although the absolute size of effect is still small. Available evidence tested self-help interventions in high income countries; further research is needed to investigate their effect in contexts where more intensive support is not available.

Objectives: To evaluate the influence of operator experience (dentist vs student) and cementation system (Adper Scotchbond Multi-Purpose [SBMP] + RelyX ARC [1]; Adper Single Bond 2 [SB] + RelyX ARC [2] and RelyX U100 [3]) on the push-out bond strength (BS) of fiber post to radicular dentin., Materials and Methods: The roots of 48 extracted human maxillary central incisors were prepared and divided into six groups (n=8), according to combination of the above factors. Glass fiber posts were cemented in accordance with the instructions of the manufacturer of each cementation system. After water storage at 37°C for one week, the roots were cross-sectioned into six 1-mm thick slices and the push-out test was performed (0.5 mm/min). Data were statistically analyzed by two-way analysis of variance and Tukey tests (α=0.05). The BS results obtained by dentist and student for each cementation system were compared using the Student t-test (α=0.05)., Results: Higher BS means were observed for the expert operators, irrespective of the cementation system used (p=0.006). RelyX U100 showed the highest bond strength, but it did not differ from SBMP + RelyX ARC. The Student t-test revealed that only RelyX U100 was not affected by the operator's experience., Conclusion: Within the limitations of this in vitro study, it can be concluded that the self-adhesive cement RelyX U100 showed the highest bond strength to the root canal in the student's group, and its performance was not affected by the operator's experience.

This study aimed to evaluate the bond durability of dentin restorations bonded with light- or dual-cured etch-and-rinse adhesive systems. A three-step adhesive system (Scotchbond Multipurpose Plus), an acetone-based two-step adhesive system (Prime & Bond 2.1), and an ethanol-based two-step adhesive system (Excite) were tested. Both the light- and the dual-cured versions were evaluated. High C-factor dentin cavities were prepared on 120 bovine incisors, which were then restored with resin composite (n=10). The samples were stored in water for 24 hours, and half of them were subjected to additional degradation with 10% NaOCl for five hours. The push-out bond strength test was performed in a universal testing machine until failure. Failure modes were evaluated by scanning electron microscopy. Data were analyzed by three-way analysis of variance and Tukey tests (p<0.05). The dual-cured adhesive system presented a higher immediate bond strength and durability than those that were light cured. The three-step adhesive system produced the highest values, whereas the acetone-based adhesive system produced the lowest result. Therefore, the use of dual-cured etch-and-rinse adhesive systems can induce increased bond durability to direct coronal dentin restorations.

Glutaraldehyde/2-Hydroxyethylmethacrylate (GLUMA) is a chemical frequenty used for desensitization of teeth and has other uses as suggested in the literature. Some newer recommendations have been made relative to its use during tooth preparation, as a disinfectant, rewetting during bonding, prior to cementation of crowns and bridges, and in dealing with pulpal exposures. This article will explore the science behind these and other applications for this chemical and its effect on the tooth structure and its local environment.

Background and Purpose: We have developed a new thermosensitive liquid embolic agent, PIB nanogel, that can be solidified at body temperature. We thus further investigated the distribution, durability of vascular occlusion, and inflammatory reactions of PIB in embolization of the renal artery of rabbits., Materials and Methods: The bilateral renal arteries of 9 rabbits were first embolized with PIB at different injection rates. The distribution pattern of PIB was investigated by contact radiography and histology 1 hour after embolization. The right renal arteries of 20 rabbits were then embolized with PIB at the proper injection rate. Angiography and pathologic examination of the kidneys were performed at 1 week and 1, 2, and 3 months after embolization to evaluate the long-term outcomes., Results: With the injection rate increasing, PIB could reach the more distal branch of the renal artery. The proper injection rate was chosen as 0.10 mL/s due to the homogeneous distribution of PIB from the main renal artery to the precapillary level at this rate. During a 3-month follow-up observation period, no angiographic recanalization was observed. Histologically, we found no disruption of the vessel wall or subintimal bleeding, no extravasation of PIB, and no evidence of neovascularization. Moreover, there was only a mild inflammatory response, manifested by few lymphocytic and monocellular infiltration, without foreign body granuloma formation., Conclusions: Embolization of the renal artery with PIB was easy and controllable, which could lead to a homogeneous and persistent occlusion without severe inflammatory changes. PIB might be a suitable material for intravascular embolization.

A novel actively targeted polymer carrier for anticancer drugs based on an N-(2-hydroxypropyl)methacrylamide copolymer (PHPMA) is proposed. An oligopeptide sequence GE7, attached to the polymer, is a specific ligand for the EGF receptor overexpressed on most tumor cells. Co-attachment of selected chemotherapeutics will therefore lead to formation of tumor-specific polymer therapeutics, further enhanced by the EPR effect. FACS measurements prove elevated binding activity of the fluorescently labeled PHPMA/GE7 conjugate in EGFR-rich cells (FaDu, MCF-7), compared to conjugates of scrambled peptides. Cell lines with low EGFR level (SW620, B16F10) bind the GE7 conjugate significantly less., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

When the intervertebral disc is removed to relieve chronic pain, subsequent segment stabilization should restore the functional mechanics of the native disc. Because of partially constrained motions and the lack of intrinsic rotational stiffness ball-on-socket implants present many disadvantages. Composite disc substitutes mimicking healthy disc structures should be able to assume the role expected for a disc substitute with fewer restrictions than ball-on-socket implants. A biomimetic composite disc prototype including artificial nucleus fibre-reinforced annulus and endplates was modelled as an L4-L5 disc substitute within a L3-L5 lumbar spine finite element model. Different device updates, i.e. changes of material properties fibre distributions and volume fractions and nucleus placements were proposed. Load- and displacement-controlled rotations were simulated with and without body weight applied. The original prototype reduced greatly the flexibility of the treated segment with significant adjacent level effects under displacement-controlled or hybrid rotations. Device updates allowed restoring large part of the global axial and sagittal rotational flexibility predicted with the intact model. Material properties played a major role, but some other updates were identified to potentially tune the device behaviour against specific motions. All device versions altered the coupled intersegmental shear deformations affecting facet joint contact through contact area displacements. Loads in the bony endplates adjacent to the implants increased as the implant stiffness decreased but did not appear to be a strong limitation for the implant biomechanical and mechanobiological functionality. In conclusion, numerical results given by biomimetic composite disc substitutes were encouraging with greater potential than that offered by ball-on-socket implants.

Purpose: To compare the desensitizing effects of a glutaraldehyde-based desensitizing system (Gluma) and an Er:YAG laser treatment on cervically exposed hypersensitive dentin., Methods: A total of 22 subjects (mean age: 39 +/- 13.7 years; 15 females, 7 males) suffering from cervical dentin hypersensitivity was included in a prospective, split-mouth clinical study. The teeth were treated on one side of the mouth with the glutaraldehyde-based desensitizing system and on the other side with the Er:YAG laser. Sensitivity perception was recorded before treatment (baseline), during and immediately after treatment, after 1 week, 1 month, 3 months and 6 months. The subjects were asked to rate the sensitivity experienced during air stimulation by placing a mark on a visual analogue scale (VAS)., Results: Both techniques showed an effective reduction of cervical dentin hypersensitivity. The subjects experienced equal improvements compared to their status before and 6 months after treatment with both methods (P<0.001).

Objective: Cervical tooth erosion is increasingly observed among adults and frequently associated with dentin sensitivity (DS). This study evaluated the effectiveness on DS of a biomimetic mineralization system (BIMIN) in comparison to the current standard treatment (Gluma(®) Desensitizer, Gluma)., Methods: In this single-blind, 2-arm study, 40 patients with confirmed cervical DS were randomized to either the test group or the positive control group. A Visual-Analog-Scale (VAS) was used to assess DS following stimulation of the exposed dentin with a 2-s air blast. Assessments were made at baseline (pre-treatment), 2 days, 4, 8 and 12 weeks, and 12 months after treatment. Two-stage replicas were obtained from the treated teeth and gold sputtered at baseline, and 2 days, 3 and 12 months after treatment. Surface topography of the treated cervical lesions and occlusion of dentinal tubules were investigated using scanning electron microscopy (SEM)., Results: Both treatments led to a statistically significant reduction (P<0.0001) in DS that persisted over the entire 12-month observation period. Differences in DS between the treatments were not statistically significant. SEM photomicrographs demonstrated that a mineral layer concealed the dentinal tubules in the test group. In contrast, numerous dentinal tubules remained visible in cervical defects that were treated with Gluma., Significance: A biomimetic mineralization kit was successfully used to treat patients exhibiting DS. The effect was similar to using Gluma, and was likely the result of the deposition of an enamel-like layer on the exposed cervical dentin., (Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

The authors report their experience with the application of the local antiseptic preparation Ambipor for the treatment of operative wound infection in the patients presenting with malignant neoplasms. Ambipor was used in 23 patients receiving surgical treatment of locally advanced intranasal and paranasal tumours. It was shown that the application of ambipor allows decreasing the risk of development of wound infection in the postoperative period.

Background: Different oral formulations of 'mesalazine (mesalamine)' may have different efficacy in distal ulcerative colitis., Aim: To evaluate the efficacy of mesalazine granules (Salofalk granules) vs. mesalazine tablets (Salofalk tablets) as induction therapy in patients with distinct extensions of ulcerative colitis., Methods: A pooled analysis of 705 patients from four prospective, randomised, double-blind phase III trials was performed. The efficacy of 8 weeks' induction with 3 g/day mesalazine granules [3 g once daily (o.d.) or 1 g three times daily (t.d.s)] vs. 3 g/day mesalazine tablets (1 g t.d.s.) was compared in terms of clinical remission (CR: CAI ≤ 4) and endoscopic remission (ER: EI ≤ 3) (both according to Rachmilewitz) in subgroups with pancolitis, left-sided colitis, or proctosigmoiditis., Results: Mesalazine granules were equipotent to mesalazine tablets in pancolitis regarding CR (72% vs. 71%, P = 0.909) and ER (58% vs. 49%, P = 0.338). In left-sided colitis, both mesalazine formulations were equipotent regarding CR (66% vs. 67%; P = 0.843) but mesalazine granules were superior regarding ER (56% vs. 37%; P = 0.025). In proctosigmoiditis, mesalazine granules were significantly more effective than mesalazine tablets regarding CR (78% vs. 55% P < 0.001) and ER (67% vs. 43% P < 0.001). Furthermore, o.d. application of mesalazine granules was more effective than t.d.s. dosing in left-sided colitis (CR 73% vs. 62%, P = 0.181; ER 71% vs. 48% P = 0.005) and proctosigmoiditis (CR 86% vs. 73%, P = 0.020; ER 75% vs. 61%, P = 0.021), but not in pancolitis., Conclusion: This pooled analysis supports the hypothesis that mesalazine granules are superior to mesalazine tablets in induction of remission in distal colitis and should be taken once daily., (© 2011 Blackwell Publishing Ltd.)

Cutaneous leishmaniasis (CL) is a neglected tropical disease that causes prominent skin scaring. No water soluble, non-toxic, short course and low cost treatment exists. We developed a new water soluble amphotericin B-polymethacrylic acid (AmB-PMA) using established and scalable chemistries. AmB-PMA was stable for 9 months during storage. In vitro, it was effective against Leishmania spp. promastigotes and amastigote infected macrophages. It was also less toxic and more effective than deoxycholate-AmB, and similar to liposomal AmB. Its in vivo activity was determined in both early and established CL lesion models of Leishmania major infection in genetically susceptible non-healing BALB/c mice. Intradermal AmB-PMA at a total dose of 18 mg of AmB/kg body weight led to rapid parasite killing and lesion healing. No toxicity was seen. No parasite relapse occurred after 80 days follow-up. Histological studies confirmed rapid parasite clearance from macrophages followed by accelerated fibroblast mediated tissue repair, regeneration and cure of the infection. Quantitative mRNA studies of the CL lesions showed that accelerated healing was associated with increased Tumour Necrosis Factor-α and Interferon-γ, and reduced Interleukin-10. These results suggest that a cost-effective AmB-PMA could be used to pharmacologically treat and immuno-therapeutically accelerate the healing of CL lesions., (Copyright © 2011 Elsevier Ltd. All rights reserved.)