IL-1ß-MyD88-mTOR Axis Promotes Immune-Protective IL-17A+Foxp3+ Cells During Mucosal Infection and Is Dysregulated With Aging.

CD4+Foxp3+Tregs maintain immune homeostasis, but distinct mechanisms underlying their functional heterogeneity during infections are driven by specific cytokine milieu. Here we show that MyD88 deletion in Foxp3+ cells altered their function and resulted in increased fungal burden and immunopathology during oral Candida albicans (CA) challenge. Excessive inflammation due to the absence of MyD88 in Tregs coincided with a reduction of the unique population of IL-17A expressing Foxp3+ cells (Treg17) and an increase in dysfunctional IFN-γ+/Foxp3+ cells (TregIFN-γ) in infected mice. Failure of MyD88-/- Tregs to regulate effector CD4+ T cell functions correlated with heightened levels of IFN-γ in CD4+ T cells, as well as increased infiltration of inflammatory monocytes and neutrophils in oral mucosa in vivo. Mechanistically, IL-1ß/MyD88 signaling was required for the activation of IRAK-4, Akt, and mTOR, which led to the induction and proliferation of Treg17 cells. In the absence of IL-1 receptor signaling, Treg17 cells were reduced, but IL-6-driven expansion of TregIFN-γ cells was increased. This mechanism was physiologically relevant during Candida infection in aged mice, as they exhibited IL-1 receptor/MyD88 defect in Foxp3+ cells, loss of p-mTORhighTreg17 cells and reduced levels of IL-1ß in oral mucosa, which coincided with persistent tongue inflammation. Concurrent with Treg dysfunction, aging was associated with increased CD4+ T cell hyperactivation and heightened levels of IL-6 in mice and humans in oral mucosa in vivo. Taken together, our data identify IL-1ß/MyD88/Treg axis as a new component that modulates inflammatory responses in oral mucosa. Also, dysregulation of this axis in an aging immune system may skew host defense towards an immunopathological response in mucosal compartments.

Evaluation of the Surface Roughness and Accelerated Aging of CAD/CAM Materials.

PURPOSE: To compare the influence of surface roughness and accelerated aging on the mechanical properties of polymer-based and ceramic CAD/CAM materials. MATERIALS AND METHODS: Three polymers (Lava Ultimate [LVU], VITA ENAMIC [ENA], and Shofu Block HC [SFB]) and one ceramic (IPS Empress CAD [EMP]) were selected for this study. The specimens were treated with the aim of measuring surface roughness (Ra [mm]) and its influence on the mechanical properties. The treatments were: polishing (POL); etching with 9.6% hydrofluoric acid for 90 seconds (ETC); airborne-particle abrasion with 50-µm aluminum oxide at 2-bar pressure (SBT); and airborne-particle abrasion with 50-µm aluminum oxide at 2-bar pressure plus etching with 9.6% hydrofluoric acid (SAC) for 90 seconds. Before and after the accelerated aging (AA) protocol (30,000 cycles, 5°C and 55°C), the specimens were subjected to the 3-point bending test. The data were analyzed with two-way and three-way ANOVA and post hoc Tukey test (P < .05). RESULTS: The surface roughness ranged from 0.24 µm to 1.96 µm, with statistically significant differences (P < .05). The highest surface roughness, in descending order, was exhibited by: LVU > SFB > EMP > ENA. The AA demonstrated an influence on the flexural strength of LVU, ENA, and SFB. The surface treatment did not affect the flexural moduli of the materials tested. The LVU and SFB showed decreased moduli of resilience after the AA; however, modulus of resilience was not influenced by surface treatment. CONCLUSION: The polymer-based materials were affected by AA. In addition, surface treatment could jeopardize their mechanical properties in certain conditions.

Brittleness index and its relationship with materials mechanical properties: Influence on the machinability of CAD/CAM materials.

The aim of this study is to evaluate the machinability of four CAD/CAM materials (n = 13) assessed by brittleness index, Vickers hardness, and fracture toughness and interaction among such mechanical properties. The materials selected in this in vitro study are Feldspathic ceramic [FC], Lithium-disilicate glass ceramic [LD], leucite-reinforced glass ceramic [LR], and nanofilled resin material [RN]. Slices were made from the blocks following original dimensions 14 × 12 × 3 mm (L × W × H), using a precision slow-speed saw device and then surfaces were regularized through a polishing device. Brittleness index and fracture toughness were calculated by the use of specific equations for each one of the properties. The Vickers hardness was calculated automated software in the microhardness device. One-way Anova and Pearson's correlation were applied to data evaluation. LD obtained the highest values for brittleness index and was not significantly different from FC. LR presented statistically significant difference compared with RN, which had the lowest mean. Vickers hardness showed LD with the highest average, and no statistical difference was found between FC and LR. RN presented the lowest average. Fracture toughness showed FC and LR not statistically different from each other, likewise LD and RN. The brittleness index, considered also as the machinability of a material, showed within this study as positively dependent on Vickers hardness, which leads to conclusion that hardness of ceramics is related to its milling capacity. In addition, fracture toughness of pre-sintered ceramics is compared to polymer-based materials.

Effect of storage and aging conditions on the flexural strength and flexural modulus of CAD/CAM materials.

Computer-aided design/computer-aided manufacturing (CAD/CAM) materials were submitted to thermocycling, to identify changes in mechanical behavior. Four CAD/CAM materials were divided in four subordinate groups (n=9): (1) dry out for 7 days, (2) distilled water at 37oC for 7 days, (3) 60,000 thermocycles, and (4) 120,000 thermocycles. Following thermocycling, samples were submitted to three-point bending test. Two-way ANOVA and post-hoc Tukey's test were performed (α=0.05). The IPS e.max CAD had a flexural strength of 396±75 MPa and flexural modulus of 84±11 GPa, followed by Vita Enamic with values of 153±17 MPa and 28±5 GPa respectively. The flexural strength recorded for Lava Ultimate was 149±28 MPa and the flexural modulus was 12±3 GPa. Vitablocs Mark II had the lowest flexural strength values (125±10 MPa) and a flexural modulus of 49±15 GPa. Although polymer-based materials have similar mechanical properties compared to ceramics, they are affected by thermo cycling conditions.

Brittleness index and its relationship with materials mechanical properties: Influence on the machinability of CAD/CAM materials

Abstract: The aim of this study is to evaluate the machinability of four CAD/CAM materials (n = 13) assessed by brittleness index, Vickers hardness, and fracture toughness and interaction among such mechanical properties. The materials selected in this in vitro study are Feldspathic ceramic [FC], Lithium-disilicate glass ceramic [LD], leucite-reinforced glass ceramic [LR], and nanofilled resin material [RN]. Slices were made from the blocks following original dimensions 14 × 12 × 3 mm (L × W × H), using a precision slow-speed saw device and then surfaces were regularized through a polishing device. Brittleness index and fracture toughness were calculated by the use of specific equations for each one of the properties. The Vickers hardness was calculated automated software in the microhardness device. One-way Anova and Pearson's correlation were applied to data evaluation. LD obtained the highest values for brittleness index and was not significantly different from FC. LR presented statistically significant difference compared with RN, which had the lowest mean. Vickers hardness showed LD with the highest average, and no statistical difference was found between FC and LR. RN presented the lowest average. Fracture toughness showed FC and LR not statistically different from each other, likewise LD and RN. The brittleness index, considered also as the machinability of a material, showed within this study as positively dependent on Vickers hardness, which leads to conclusion that hardness of ceramics is related to its milling capacity. In addition, fracture toughness of pre-sintered ceramics is compared to polymer-based materials.

Effect of thermal cycling on fracture toughness of CAD/CAM materials.

PURPOSE: To compare the fracture toughness of four different CAD/CAM materials, (VM) Vitablocs Mark II, (IP) IPS e.max CAD, (LU) LAVA Ultimate, and (VE) Vita Enamic under long thermocycling conditions. METHODS: Each type of ceramic block was sectioned into beams (n=9) with dimensions of 14×3×2.5 mm (L × W × H). All four ceramics were submitted to different conditions: the desiccator or distilled water, each for 7 days. The third and fourth conditions involved the specimens being submitted to 60,000 and 120,000 thermocycles in water respectively. The dwelling time was 52 seconds at 5° and 55°C. A three-point bend test with a universal loading machine on notched samples was per-formed. Furthermore, a fractographic analyses was made by scanning electron microscopy (SEM) to determine if any of these conditions influenced the type of fracture. Data were analyzed by two-way ANOVA (α= 0.05). RESULTS: A significant difference in fracture toughness (P< 0.05) was found among the groups; IP (4.20±1.23) had the highest value followed by VE (2.02±0.39), which did not have a statistically significant difference from LU (1.96±0.42). The lower value and statistical difference for VM was 1.52±0.35. The ceramics performed better after they were hydrated, while the polymer-based materials had the fracture toughness means decreased after the thermocycles. CLINICAL SIGNIFICANCE: A significant difference in fracture toughness (P<0.05) was found among the groups; IP had the highest value followed by VE, which was not statistically significantly different from LU. The ceramics performed better after they were hydrated, while the polymer-based materials had fracture toughness means decreased after thermocycling.

Effect of polyethelene oxide on the thermal degradation of cellulose biofilm - Low cost material for soft tissue repair in dentistry.

BACKGROUND: Bio cellulose is a byproduct of sweet tea fermentation known as kombusha. During the biosynthesis by bacteria cellulose chains are polymerized by enzyme from activated glucose. The single chains are then extruded through the bacterial cell wall. Interestingly, a potential of the Kombucha's byproduct bio cellulose (BC) as biomaterial had come into focus only in the past few decades. The unique physical and mechanical properties such as high purity, an ultrafine and highly crystalline network structure, a superior mechanical strength, flexibility, pronounced permeability to gases and liquids, and an excellent compatibility with living tissue that reinforced by biodegradability, biocompatibility, large swelling ratios. MATERIAL AND METHODS: The bio-cellulose film specimens were provided by the R.P Dressel dental materials laboratory, Department of Comprehensive Care, School of Dental Medicine, Case Western Reserve University, Cleveland, US. The films were harvested, washed with water and dried at room temperature overnight. 1wt% of PEG-2000 and 10wt% of NaOH were added into ultrapure water to prepare PEG/NaOH solution. Then bio-cellulose film was added to the mixture and swell for 3 h at room temperature. All bio-cellulose film specimens were all used in the TA Instruments Q500 Thermogravmetric Analyzer to investigate weight percent lost and degradation. The TGA was under ambient air conditions at a heating rate of 10ºC/min. RESULTS AND CONCLUSIONS: PEG control exhibited one transition with the peak at 380ºC. Cellulose and cellulose/ PEG films showed 3 major transitions. Interestingly, the cellulose/PEG film showed slightly elevated temperatures when compared to the corresponding transitions for cellulose control. The thermal gravimetric analysis (TGA) degradation curves were analyzed. Cellulose control film exhibited two zero order transitions, that indicate the independence of the rate of degradation from the amount on the initial substance. The activation energies for three transitions for cellulose and cellulose/PEG showed increasingly higher values for the transitions at higher temperatures. Key words:TGA, Bio-cellulose, PEG.

Image quality evaluation of eight complementary metal-oxide semiconductor intraoral digital X-ray sensors.

PURPOSE: To evaluate the image quality generated by eight commercially available intraoral sensors. METHODS: Eighteen clinicians ranked the quality of a bitewing acquired from one subject using eight different intraoral sensors. Analytical methods used to evaluate clinical image quality included the Visual Grading Characteristics method, which helps to quantify subjective opinions to make them suitable for analysis. RESULTS: The Dexis sensor was ranked significantly better than Sirona and Carestream-Kodak sensors; and the image captured using the Carestream-Kodak sensor was ranked significantly worse than those captured using Dexis, Schick and Cyber Medical Imaging sensors. The Image Works sensor image was rated the lowest by all clinicians. Other comparisons resulted in non-significant results. CONCLUSIONS: None of the sensors was considered to generate images of significantly better quality than the other sensors tested. Further research should be directed towards determining the clinical significance of the differences in image quality reported in this study.

In vitro effect of over-the-counter probiotics on the ability of Candida albicans to form biofilm on denture strips.

PURPOSE: There is a burgeoning recognition and interest in the potential of probiotics in the treatment and prevention of oral candidiasis associated with the use of dentures. Our aim was to investigate if commercially available over-the-counter probiotics can influence the ability of Candida albicans to form biofilms, which is considered a hallmark of the initiation and progression of oral candidiasis. METHODS: We conducted a 2×5 factorial in vitro study to culture C. albicans on denture strips and challenge with one of the following four commercially available probiotics in bacterial or cell-free supernatant form: Accuflora®, Align®, Culturelle® and Sustenex®. C. albicans biofilm formation was studied in triplicates in all factorial combinations of the study and assessed qualitatively with fluorescence microscopy and quantitatively with tetrazolium salt (XTT) reduction assay. Quality control measures included determination of coefficient of variation, Bland Altman plots and Pittman's test. Results were analyzed using two-way analysis of variance (ANOVA) with pairwise post-hoc Scheffe's tests. RESULTS: Our experimental conditions passed the quality control checks. Two-way ANOVA results indicated that cell-free supernatants provided a stronger and significant inhibitory effect on biofilm formation than their bacterial counterparts (2-way ANOVA p=3.8×10(-6)). Further, Lactobacillus-containing probiotic formulations (Accuflora® and Culturelle®) significantly reduced biofilm formation especially in supernatant form. CONCLUSION: Commercially available probiotics that contain Lactobacilli species interfere with the in vitro ability of C. albicans to form biofilms on dentures. The mechanistic and clinical implications of our results need to be addressed by larger in vivo studies.

Lean management-the journey from toyota to healthcare.

The evolution of production systems is tightly linked to the story of Toyota Motor Company (TMC) that has its roots around 1918. The term "lean" was coined in 1990 following the exploration of the Toyota model that led to the "transference" thesis sustaining the concept that manufacturing problems and technologies are universal problems faced by management and that these concepts can be emulated in non-Japanese enterprises. Lean is a multi-faceted concept and requires organizations to exert effort along several dimensions simultaneously; some consider a successful implementation either achieving major strategic components of lean, implementing practices to support operational aspects, or providing evidence that the improvements are sustainable in the long term. The article explores challenges and opportunities faced by organizations that intend incorporating lean management principles and presents the specific context of the healthcare industry. Finally, the concepts of "essential few" and customer value are illustrated through a simple example of process change following lean principles, which was implemented in a dental school in the United States.

Relationship between broken appointments and dental students' clinical experience level.

As more dental schools adopt a comprehensive care model focused on patients' needs rather than a certain number of required procedures, clinic time utilization by students is coming under increasingly close scrutiny. This article presents an analysis of the influence of broken appointment rates on dental students' clinical experience levels. The total percentage of broken appointments experienced by each student from the classes of 2010 and 2011 at Case Western Reserve University School of Dental Medicine during his or her clinical education in the junior and senior years was determined, and the impact of the broken appointment rate on students' clinical experience levels was analyzed. The results show a statistically significant difference regarding the percentage of broken appointments between the classes of 2010 and 2011: 18.64 percent and 14.44 percent, respectively. When the rate of no-shows was compared to the students' clinical experience level, a weak but significant negative correlation was determined for the class of 2010 but not for the class of 2011. It is concluded that the rate of broken appointments accounts for a small part of the variability observed in the number of clinical procedures performed in the predoctoral clinic. When this rate is lowered below a threshold of 14.5 percent, broken appointments seem to have no influence on students' clinical experience level.

Clinical assessment of peri-implant tissues in patients with varying severity of chronic periodontitis.

PURPOSE: This retrospective study assessed the health of peri-implant tissues in patients with varying severity of chronic periodontitis. MATERIALS AND METHODS: Sixty-one subjects aged 44 to 70 years (median age 58 years) were recruited. Based on severity of periodontitis, 31 subjects were classified as having severe generalized chronic periodontitis, and the remaining 30 subjects had mild or no periodontitis. Social and medical histories were obtained from each patient. A comprehensive periodontal examination included: plaque index, gingival index, bleeding index, probing depth, clinical attachment level, and radiographic bone loss. Data were analyzed using Fisher's exact and chi-square tests for categorical variables, and t-test for continuous variables. RESULTS: There was a statistically significant greater loss of attachment (p < .05) around implants in the group with severe periodontitis compared to the no/mild periodontitis group. CONCLUSION: Because of the greater loss of clinical attachment around implants placed in patients with generalized severe chronic periodontitis, close monitoring of these patients is suggested to prevent both development of peri-implantitis and recurrence of periodontal infection.

Width of keratinized gingiva and the health status of the supporting tissues around dental implants.

PURPOSE: This cross-sectional study was performed to determine whether an association exists between the width of keratinized mucosa and the health of implant-supporting tissues. MATERIALS AND METHODS: Data on 200 dental implants were collected. Periodontal parameters measured included Plaque Index, Gingival Index, width of keratinized mucosa, thickness of keratinized mucosa, radiographic bone level, and bleeding on probing. Statistical analysis was accomplished with the t test, Wilcoxon rank sum test, and logistic and linear regression models. Significance was established when P was less than .05. RESULTS: The mean Gingival Index score, Plaque Index score, and radiographic bone loss were significantly higher for those implants with a narrow zone (< 2 mm) of keratinized mucosa. Implants with a narrow zone of keratinized mucosa also were more likely to bleed upon probing, even after adjusting for Plaque Index, smoking, thickness of the gingiva, and time since implant placement (adjusted odds ratio, 2.37; 95% confidence interval, 1.04 to 5.83). Significant independent association also was found between the width of keratinized mucosa and radiographic bone loss in favor of wider zone of keratinized mucosa. CONCLUSION: Increased width of keratinized mucosa around implants is associated with lower mean alveolar bone loss and improved indices of soft tissue health.

RT-PCR analysis of Candida albicans ALS gene expression in a hyposalivatory rat model of oral candidiasis and in HIV-positive human patients.

ALS gene expression was studied in the hyposalivatory rat model of oral candidiasis and in clinical specimens collected from HIV-positive patients to assess similarities in expression patterns between the model system and clinical isolates. Two Candida albicans strains, SC5314 and OY-2-76, were used in the rat model system and infection progressed for 3 or 5 days. The strains produced similar oral lesions at 3 days. At 5 days, strain OY-2-76 produced more superficial lesions containing relatively more yeast forms compared to invasive hyphal forms observed for strain SC5314. For all infections, the most severe lesions were observed on the tongue and gingiva overlying the mandible. ALS transcripts were easier to detect by RT-PCR later in infection and under other conditions where more fungal cells were present. Expression of ALS1, ALS2, ALS3 and ALS4 was observed in rats infected for 3 days with ALS5 and ALS9 transcripts detected after 5 days of infection. Expression of ALS6 was observed in a single specimen from a 5-day infection while ALS7 transcript was never found. Expression of all ALS genes was observed in oral clinical material collected from HIV-positive patients although ALS6 and ALS7 transcripts required an extra PCR amplification step to be detected. Overall, the patterns of ALS gene expression were similar between the rat model and human clinical specimens, suggesting that the model would be useful for studying the phenotype of al delta/al delta mutant strains.