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Purpose: The Area Deprivation Index (ADI) is a validated quantifiable measure of neighborhood disadvantage and social determinants of health (SDoH). Higher percentiles in ADI correlate with the most disadvantaged neighborhoods: lower income, lower education, and less access to transportation. Using ADI, we aimed to investigate the impact of SDoH on bilateral breast reduction (BBR) complication rates., Methods: A retrospective study of BBR patients from 2015 to 2021 was conducted. Patient addresses were matched to ADI percentiles and grouped into most (top 80% ADI) and least disadvantaged. Multivariable regressions were used to compare postoperative treatment between groups and adjust for confounders., Results: In total, 568 patients were analyzed and 47% were high ADI. Time-to-event analysis revealed a 155% (β = 2.55; CI, 1.87-3.48; P < 0.001) increase in time to presentation for treatment of wound-related complications among higher-deprivation patients compared to their lower-deprivation counterparts. This difference in time to presentation equated to approximately 3 days overall when comparing higher to lower deprivation patients; however, this difference between the groups increased to 12 days when comparing those who experienced wound-related complications beyond day 30., Conclusions: High deprivation was associated with increased delays to treatment after complications. More research is needed to determine the factors that impact postoperative courses among high ADI patients., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Gender-affirming mastectomy is a common surgery for the treatment of gender incongruence and gender dysphoria and improves quality of life. Hematoma rates for gender-affirming double incision mastectomies are between 2.8% and 8.1%. This study aims to investigate the utility of a blood pressure challenge, whereby the patient's blood pressure is medically increased intraoperatively to reveal bleeding vessels that can be addressed with additional hemostasis before skin closure, to reduce postoperative hematoma., Methods: A retrospective chart review of patients who underwent gender-affirming double incision mastectomies over a 6-year period by a single surgeon was conducted. Surgeries were separated into a blood pressure challenge experimental group and a non-blood pressure challenge control group. Demographics, surgical characteristics, and postoperative complications were compared between the 2 cohorts using Pearson χ2, Fisher exact, t tests, univariate logistic regression, and multivariable logistical regression. Significance was established at P < 0.05., Results: A total of 92 patients (184 breasts) were included with 32 patients (64 breasts) in the control group and 60 (120 breasts) in the blood pressure challenge group. In the control group, there were 5 hematomas (7.81%) compared with 1 (0.83%) in the blood pressure challenge group (P = 0.02). On univariate logistical regression analysis, blood pressure challenge was the only variable significantly associated with hematoma (odds ratio, 0.1; 95% confidence interval, 0.01-0.63; P = 0.04). On multivariable logistical regression, after controlling for age, body mass index, smoking status, and mass of excised breast tissue, patients who underwent blood pressure challenge demonstrated lower hematoma rates (odds ratio, 0.08; 95% CI, 0.004-0.59; P = 0.04)., Conclusions: Using an intraoperative blood pressure challenge was associated with reduced hematoma rates. Guidelines for blood pressure challenge goals should be established to standardize care and reduce complications in gender-affirming mastectomies., Competing Interests: Conflicts of interest and sources of funding: None declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Irisin is an exercise induced myokine first shown to induce the browning of white adipose tissue (WAT) which increases energy expenditure, improves glucose tolerance, and reduces insulin resistance. Among irisin's involvement in lipid homeostasis, osteoblast proliferation, and muscle growth, it also acts as a mediator of many inflammatory pathways throughout the body. This review aims to describe the role of irisin in inflammatory processes and understand how targeting irisin can alter the inflammatory response in metabolic syndrome (MetS). The mechanisms involved in irisin's anti-inflammatory functions include reducing production of pro-inflammatory cytokines while increasing production of anti-inflammatory cytokines, reducing macrophage proliferation, inducing alternatively activated (M2-type) macrophage polarization, inhibiting pathways of increased vascular permeability, and preventing the formation of inflammasomes. While there are some contradictory results, most studies found reduced levels of irisin in MetS and type II diabetes mellitus (T2DM). Irisin treatment of cells exposed to inflammatory stimuli ameliorates the inflammatory response and promotes cellular viability. Numerous methods have been studied to increase plasma irisin levels including dietary, behavioral, and pharmaceutical. Further investigation is necessary to understand how irisin can be targeted for disease modification., (Copyright © 2022 Elsevier B.V. All rights reserved.)

RIP2 kinase has been identified as a key signal transduction partner in the NOD2 pathway contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP2 kinase or its signaling partners on the NOD2 pathway that are suitable for advancement into the clinic have yet to be described. Herein, we report our discovery and profile of the prodrug clinical compound, inhibitor 3 , currently in phase 1 clinical studies. Compound 3 potently binds to RIP2 kinase with good kinase specificity and has excellent activity in blocking many proinflammatory cytokine responses in vivo and in human IBD explant samples. The highly favorable physicochemical and ADMET properties of 3 combined with high potency led to a predicted low oral dose in humans.

RIP2 kinase was recently identified as a therapeutic target for a variety of autoimmune diseases. We have reported previously a selective 4-aminoquinoline-based RIP2 inhibitor GSK583 and demonstrated its effectiveness in blocking downstream NOD2 signaling in cellular models, rodent in vivo models, and human ex vivo disease models. While this tool compound was valuable in validating the biological pathway, it suffered from activity at the hERG ion channel and a poor PK/PD profile thereby limiting progression of this analog. Herein, we detail our efforts to improve both this off-target liability as well as the PK/PD profile of this series of inhibitors through modulation of lipophilicity and strengthening hinge binding ability. These efforts have led to inhibitor 7 , which possesses high binding affinity for the ATP pocket of RIP2 (IC 50 = 1 nM) and inhibition of downstream cytokine production in human whole blood (IC 50 = 10 nM) with reduced hERG activity (14 μM)., Competing Interests: The authors declare the following competing financial interest(s): All GSK authors are/were employees and stockholders of GlaxoSmithKline when this work was completed.

Objectives: To evaluate the enamel resistance and permeability of rat teeth to acid challenges after systemic use of sodium alendronate., Materials and Methods: Eighteen Wistar rats (36 teeth), aged 36-42 days (200-230 g), were assigned into two groups: alendronate group (n = 20 teeth), which received two weekly doses of 1 mg/kg of alendronate, via gavage; and a non-alendronate group (n = 16 teeth), which received only distilled water. After 60 days, the animals were killed, the maxillary incisors were extracted and used for the artificial induction of the caries lesion (pH cycling regimen) and erosion area (immersion cycles in cola-type soft drink) and for the enamel permeability test (dye penetration). The teeth were divided into alendronate group (n = 10) or non-alendronate group (n = 8) for each test. The quantitative response variables were the percent longitudinal change in Knoop microhardness (%LMC), the enamel carious/erosion lesion area (CELA) and enamel permeability., Results: Groups were not significantly different (p > 0.05) with regard to the %LMC and enamel permeability (25.58 μm ± 12.73 and 25.40 μm ± 4.6 for the experimental and control groups, respectively). For CELA, it was not observed significant difference (p > 0.05) between the non-alendronate group (24.08 ± 1.36 and 25.22 ± 1.60, for caries and erosion, respectively) and the alendronate group (25.46 ± 1.60 and 25.0 ± 1.26) for caries and erosion, respectively)., Conclusions: Based on the methodological conditions and the presented results of this study, sodium alendronate did not affect the longitudinal microhardness, demineralisation lesion area or permeability of the enamel after acid challenge; therefore, alendronate did not become the enamel of rats more resistant., Clinical Relevance: The systemic alendronate treatment for 60 days did not change the enamel of rats regarding the susceptibility to acids.

The present investigation tested the hypotheses that systolic arterial pressure (SAP) responses to voluntary apnea (a) serve as a surrogate of sympathetic nerve activity (SNA), (b) can distinguish Obstructive Sleep Apnea (OSA) patients from control subjects and (c) can document autonomic effects of treatment. 9 OSA and 10 control subjects were recruited in a laboratory study; 44 OSA subjects and 78 control subjects were recruited in a clinical study; and 21 untreated OSA subjects and 14 well-treated OSA subjects were recruited into a treatment study. Each subject performed hypoxic and room air voluntary apneas in triplicate. Muscle SNA (MSNA) and continuous AP were measured during each apnea in the laboratory study, while systolic arterial pressure (SAP) responses were measured continuously and by standard auscultation in the clinical and treatment studies. OSA subjects exhibited increased mean arterial pressure (MAP), SAP and MSNA responses to hypoxic apnea (all P<0.01) and the SAP response highly correlated with the MSNA response (R(2)=0.72, P<0.001). Clinical assessment confirmed that OSA subjects exhibited markedly elevated SAP responses (P<0.01), while treated OSA subjects had a decreased SAP response to apnea (P<0.04) compared to poorly treated subjects. These data indicate that (a) OSA subjects exhibit increased pressor and MSNA responses to apnea, and that (b) voluntary apnea may be a clinically useful assessment tool of autonomic dysregulation and treatment efficacy in OSA., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to assess any long-term chemical and morphological Nd:YAG laser modifications on irradiated primary enamel., Background Data: Previous studies on irradiated primary human enamel employed methodologies that evaluated the short-term effects only., Methods: One hundred and eighty-six irradiated (with and/or without fluoride) primary enamel teeth from high-caries-risk children, which were exfoliated over a 1-year period, were collected, and the sample surface area was submitted for scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and X-ray energy-dispersive spectrometry (EDS). The subsurface was analyzed by Knoop microhardness and light microscopy (LM). Data were analyzed by one way ANOVA and Tukey tests (α=0.05) and Kruskall-Wallis and Tukey tests (α=0.05)., Results: FTIR analysis revealed a higher concentration of phosphate and carbonate in the irradiated (0.987±0.064) and lower concentration in the control groups (1.477±0.310). SEM analysis showed that the control samples exhibited a slightly smoother surface than the irradiated groups. The EDS analysis did not show any differences in the amount of calcium, phosphorus, or fluoride among the groups. The microhardness analysis revealed that sealant (249.86±7.15) and laser irradiation (262.44±22.69) led to higher hardness values than the negative control group (128.35±25.19). LM indicated significantly reduced caries formation in the laser (5.35±5.38%) and the laser plus acidulated phosphate fluoride (APF) groups (10.35±0.88%) compared with the negative control group (72.56±12.86%)., Conclusions: Even with the limitations of the present study, these results suggest that Nd:YAG irradiation clinically modified the chemical composition of the enamel surface regardless of fluoride concentration, which successfully inhibited demineralization of primary tooth enamel over a 1-year period without significant morphological changes.

Dental caries is still the most prevalent chronic disease affecting human populations. Among the preventive treatments performed, it has been reported that laser irradiation combined with topical fluoride can induce an even greater increase in enamel caries resistance. The aim of this study was to evaluate the Nd:YAG laser, with or without fluoride, in occlusal caries prevention of the primary dentition. A double-blind split-mouth study design was used. Fifty-two children with high caries risk (7.6 ± 1.4 years) were selected and received the following: G1--the first molar was a negative control, and the second received a resin sealant; G2--the first molar was a negative control, and the second received laser irradiation (50 mJ, 10 Hz, 0.5 W); G3--the first molar received only acidulate phosphate fluoride (APF), and the second received APF + laser; G4--fisrt molar received only fluoride varnish, and the second received fluoride varnish + laser. Patients were followed up to 12 months to evaluate the presence of white-spot lesions and/or caries cavities by three calibrated observers. Thirty-five patients completed the study. Significant differences were found between the treatment and control groups (p < 0.05). The laser-alone and resin sealant resulted in statistically lower caries formation than the negative control group (p < 0.05). Nd:YAG laser irradiation in primary teeth effectively prevented occlusal caries in pits and fissures when used alone with lower energy over a 1-year period.

The aim of this study was to evaluate the effect of the Er:YAG laser and its association with fluoride (1.23% acidulate phosphate fluoride gel) on the prevention of enamel erosion. Sixty specimens were obtained from bovine enamel (4 × 4 mm), which were ground flat, polished, and randomly divided into five groups according to the preventive treatments: control-fluoride application; L--Er:YAG laser; L+F--laser + fluoride; F+L--fluoride + laser; L/F--laser/fluoride simultaneously. Half of the enamel surface was covered with nail varnish (control area), and the other half was pretreated with one of the preventive strategies to subsequently be submitted to erosive challenge. When the laser was applied, it was irradiated for 10 s with a focal length of 4 mm and 60 mJ/2 Hz. Fluoride gel was applied for 4 min. Each specimen was individually exposed to regular Coca-Cola® for 1 min, four times/day, for 5 days. Wear analysis was performed with a profilometer, and demineralization was assessed with an optical microscope. Data were analyzed using the Kruskal-Wallis test (wear)/Dunn test and ANOVA/Fisher's exact tests. The group L/F was similar to control group. The other groups showed higher wear, which did not present differences among them. In the demineralization assessment, the groups F+L and L/F showed lower demineralization in relation to the other groups. It can be concluded that none preventive method was able to inhibit dental wear. The treatments L/F and F+L showed lower enamel demineralization.

Unlabelled: The use of erbium lasers to prevent caries in enamel has shown positive results. However, it is not known if Er,Cr:YSGG laser can also be used to increase acid resistance of root dentine, which is another dental tissue susceptible to the action of cariogenic bacteria., Objective: To analyze the effects of the Er,Cr:YSGG laser (λ=2.78 μm, 20 Hz) irradiation associated with 2% neutral sodium fluoride (NaF) to prevent root dentin demineralization., Material and Methods: One hundred human root dentin samples were divided into 10 groups (G) and treated as follows: G1: no treatment; G2: NaF; G3: laser (4.64 J/cm2) with water cooling (WC=5.4 mL/min); G4: laser (4.64 J/cm2) without WC; G5: laser (8.92 J/cm2) with WC; G6: laser (8.92 J/cm2) without WC; G7: laser (4.64 J/cm2) with WC and NaF; G8: laser (4.64 J/cm2) without WC and NaF; G9: laser (8.92 J/cm2) with WC and NaF; G10: laser (8.92 J/cm2) without WC and NaF. The NaF gel was applied alone or after 4 min of irradiation. After 14 days of acid challenge, the samples were sectioned and the Knoop microhardness (KHN) test was done at different depths (30, 60, 90 and 120 μm) from the outer dentin surface. Data were analyzed by one-way ANOVA and Fisher's test (α=5%)., Results: The results showed that G8 and G10 presented higher KHN than the G1 for the depths of 30 and 60 μm, indicating an increase of the acid resistance of the dentin in up to 35% (p<0.05)., Conclusions: The use of Er,Cr:YSGG laser irradiation at 4.64 J/ cm2 and 8.92 J/cm2 without water cooling and associated with 2% NaF can increase the acid resistance of human root dentin.

The purpose of this study was to analyze, correlate, and compare the demineralization and permeability of dentin remaining after caries removal with either an Er:YAG laser, a bur, or a curette. Thirty human dentin fragments were immersed in a demineralizing solution for 20 days and were randomly divided into three groups (n = 10) for the removal of the demineralized lesion. The groups were G1-Er:YAG laser (200 mJ/6 Hz; noncontact at 12 mm; spot: 0.63 mm), G2-Bur, and G3-Curette. The specimens were then immersed in a 10% copper sulfate solution, then in a 1% dithiooxamide alcoholic solution for 30 min and kept in ammonia vapor for 7 days. Next, the specimens were examined with optical microscopy. The amount of demineralized dentin and the level of copper ion infiltration in the dentin were quantified in μm using Axion Vision software. Data were analyzed with the Kruskal-Wallis test (p < 0.05) and Pearson's Correlation test. The analysis revealed no significant differences between the three caries removal methods in terms of their capacity to remove demineralized tissue (G1: 10.6 μm; G2: 8.4 μm; G3: 11 μm), although the laser removal generated more tissue permeability than the others methods (G1: 17.6 μm; G2: 6.6 μm; G3: 5.5 μm). The correlation between the remaining demineralized dentin and the dentin permeability was moderate for the conventional methods and higher for the Er:YAG laser. It can therefore be concluded that the laser produced an increase in permeability that was directly proportional to the amount of demineralized tissue removal., (Copyright © 2012 Wiley Periodicals, Inc.)

A series of macrocyclic compounds containing a cyclic constraint in the P2-P4 linker region have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155K, A156T, A156V, and D168V mutant activity while maintaining high rat liver exposure. The effect of the constraint is most dramatic against gt 1b A156 mutants where ~20-fold improvements in potency are achieved by introduction of a variety of ring systems into the P2-P4 linker., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A series of macrocyclic compounds containing 2-substituted-quinoline moieties have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155K mutant activity while maintaining the high rat liver exposure. Cyclization of the 2-substituted quinoline substituent led to a series of tricyclic P2 compounds which also display superb gt3a potency., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A new class of HCV NS3/4a protease inhibitors containing a P2 to P4 macrocyclic constraint was designed using a molecular modeling-derived strategy. Building on the profile of previous clinical compounds and exploring the P2 and linker regions of the series allowed for optimization of broad genotype and mutant enzyme potency, cellular activity, and rat liver exposure following oral dosing. These studies led to the identification of clinical candidate 15 (MK-5172), which is active against genotype 1-3 NS3/4a and clinically relevant mutant enzymes and has good plasma exposure and excellent liver exposure in multiple species.

Most studies dealing with the caries preventive action of Nd:YAG laser have been done in permanent teeth and studies on primary teeth are still lacking. The aim of this study was to evaluate in vitro the effect of Nd:YAG laser combined or not with fluoride sources on the acid resistance of primary tooth enamel after artificial caries induction by assessing longitudinal microhardness and demineralization depth. Sixty enamel blocks obtained from the buccal/lingual surface of exfoliated human primary molars were coated with nail polish/wax, leaving only a 9 mm² area exposed on the outer enamel surface, and randomly assigned to 6 groups (n=10) according to the type of treatment: C-control (no treatment); APF: 1.23% acidulated phosphate fluoride gel; FV: 5% fluoride varnish; L: Nd:YAG laser 0.5 W/10 Hz in contact mode; APFL: fluoride gel + laser; FVL: fluoride varnish + laser. After treatment, the specimens were subjected to a des-remineralization cycle for induction of artificial caries lesions. Longitudinal microhardness data (%LMC) were analyzed by the Kruskal-Wallis test and demineralization depth data were analyzed by oneway ANOVA and Fisher's LSD test (á=0.05). APFL and APF groups presented the lowest percentage of microhardness change (p<0.05). Demineralization depth was smaller in all treated groups compared with the untreated control. In conclusion, Nd:YAG laser combined or not with fluoride gel/varnish was not more effective than fluoride alone to prevent enamel demineralization within the experimental period.

The discovery of MK-1220 is reported along with the development of a series of HCV NS3/4A protease inhibitors containing a P2 to P4 macrocyclic constraint with improved preclinical pharmacokinetics. Optimization of the P2 heterocycle substitution pattern as well as the P3 amino acid led to compounds with greatly improved plasma exposure following oral dosing in both rats and dogs while maintaining excellent enzyme potency and cellular activity. These studies led to the identification of MK-1220.

A new class of HCV NS3/4a protease inhibitors which contain a P2 to P4 macrocyclic constraint was designed using a molecular-modeling derived strategy. Exploration of the P2 heterocyclic region, the P2 to P4 linker, and the P1 side chain of this class of compounds via a modular synthetic strategy allowed for the optimization of enzyme potency, cellular activity, and rat liver exposure following oral dosing. These studies led to the identification of clinical candidate 35b (vaniprevir, MK-7009), which is active against both the genotype 1 and genotype 2 NS3/4a protease enzymes and has good plasma exposure and excellent liver exposure in multiple species.

A novel series of annulated tricyclic compounds was synthesized and evaluated as NMDA/NR2B antagonists. Structure-activity development was directed towards in vitro optimization of NR2B activity and selectivity over the hERG K(+) channel. Preferred compounds were subsequently evaluated for selectivity in an alpha(1)-adrenergic receptor binding counter-screen and a cell-based assay of NR2B activity.

Purpose: To evaluate the effect of a 10% carbamide peroxide-containing bleaching agent on brushing abrasion of esthetic restorative materials., Methods: Using a randomized complete block design, 150 specimens (n = 15) measuring 3 x 3 x 2 mm were fabricated into acrylic resin cylinders, using one of the restorative materials: a microfilled resin composite (Al), a hybrid resin composite (Ch), a flowable resin composite (Wa), a resin-modified glass-ionomer cement (Fj) and a polyacid-modified resin composite (Dy). The bleaching agent or artificial saliva (control) was applied for 2 hours/day. After that, 120 brushing strokes were simulated automatically and the samples were kept in artificial saliva. Such bleaching/brushing cycle was performed daily for 21 days. Wear depth was assessed using profilometry., Results: Bleaching did not show significant effect on wear depth. There was a significant difference among the restorative materials. Tukey's test showed that (Al = Ch) < (Wa) < (Fj) and that Dy was only different from Fj.

Objectives: This triple-blind, 2x2 crossover in situ study, was undertaken to verify whether the wear resistance of enamel and root dentine would be affected by bleaching with a 10% carbamide peroxide agent and a placebo agent., Methods: Thirty slabs of each substrate (2mm x 3mm x 2mm) were selected for each phase, after flattening and polishing procedures and microhardness test. After a 7-day lead-in period, one specimen of each substrate was randomly bonded on the facial surface of each one of 30 subject's upper second premolars. The volunteers received instructions on how to perform toothbrushing and application of gel in the tray. Fifteen volunteers bleached their maxillary arch with a 10% carbamide peroxide bleaching agent for a 2-week period, while the remainders used a placebo agent. After a 1-week washout period, a new set of enamel and root dentine slabs were bonded to the premolars and volunteers were crossed over to the alternate agent for 14 days. The resistance of enamel and root dentine to wear following bleaching, toothbrushing and intraoral exposure was measured with a profilometer, using reference areas., Results: For enamel, ANOVA did not demonstrate significant difference between wear provided by placebo and bleaching agent (p=0.3713), but higher wear depth was observed for bleached root dentine (p=0.0346)., Conclusions: While overnight bleaching caused no alteration in wear resistance of enamel, root dentine showed increased tissue loss.

Molecular modeling of inhibitor bound full length HCV NS3/4A protease structures proved to be a valuable tool in the design of a new series of potent NS3 protease inhibitors. Optimization of initial compounds provided 25a. The in vitro activity and selectivity as well as the rat pharmacokinetic profile of 25a compare favorably with the data for other NS3/4A protease inhibitors currently in clinical development for the treatment of HCV.

Purpose: To evaluate the effect of low and highly concentrated bleaching agents on microhardness and surface roughness of bovine enamel and root dentin., Methods: According to a randomized complete block design, 100 specimens of each substrate were assigned into five groups to be treated with bleaching agents containing carbamide peroxide (CP) at 10% (CP10); hydrogen peroxide (HP) at 7.5% (HP7.5) or 38% (HP38), or the combination of 18% of HP and 22% of CP (HP18/CP22), for 3 weeks. The control group was left untreated. Specimens were immersed in artificial saliva between bleaching treatments. Knoop surface microhardness (SMH) and average surface roughness (Ra) were measured at baseline and post-bleaching conditions., Results: For enamel, there were differences between bleaching treatments for both SMH and Ra measurements (p = 0.4009 and p = 0.7650, respectively). SMH significantly increased (p < 0.0001), whereas Ra decreased (p = 0.0207) from baseline to post-bleaching condition. For root dentin, the group treated with CP10 exhibited the significantly highest SMH value differing from those groups bleached with HP18/CP22, HP7.5, which did not differ from each other. Application of HP38 resulted in intermediate SMH values. No significant differences were found for Ra (p = 0.5975). Comparing the baseline and post-bleaching conditions, a decrease was observed in SMH (p < 0.0001) and an increase in Ra (p = 0.0063)., Conclusion: Bleaching agents with varying concentrations of CP and/or HP are capable of causing mineral loss in root dentin. Enamel does not perform in such bleaching agent-dependent fashion when one considers either hardness or surface roughness evaluations. CLINICAL SIGNIFICANCE Bleaching did not alter the enamel microhardness and surface roughness, but in root dentin, microhardness seems to be dependent on the bleaching agent used.

Background: A novel soft tissue filler composed of polymethylmethacrylate (PMMA) microspheres suspended in a collagen gel matrix containing 0.3% lidocaine (ArteFill, Artes Medical, Inc.) was recently approved by the Food and Drug Administration for the correction of nasolabial folds. A randomized, multicenter, controlled pivotal trial performed in the United States established the safety and efficacy of this medical device throughout a 12-month study period., Objective: The objective was to substantiate the long-term 5-year safety and efficacy of this novel soft tissue PMMA filler., Methods and Materials: Attempts were made to contact all subjects treated with the PMMA filler that were enrolled in the original pivotal study. Safety was assessed by standard adverse event reporting methods. Efficacy was determined using a validated six-point facial fold assessment photometric grading scale using blinded observers' assessment of standardized photographs., Results: Subjects (n=119) demonstrated significant improvement in nasolabial folds comparing baseline (before any treatment) to 5 years after their last treatment (p<.001). Notably, subjects also demonstrated continued improvement between 6 months after their last treatment and Year 5 (p=.002). No serious unanticipated device-related adverse events were reported., Conclusion: This PMMA filler is the first soft tissue filler to demonstrate continued improvement and persistence of correction over a 5-year period posttreatment.

Purpose: To evaluate in vitro the susceptibility of caries-like lesion formation on enamel and root dentin that had been bleached with carbamide peroxide agents., Methods: 150 slabs of bovine enamel and root dentin were ground flat and polished. According to a randomized complete block design, the specimens were then allocated to be bleached with agents (Rembrandt) containing 12% [CP12], 16% [CP16], 22% [CP22] or 30% [CP30] of carbamide peroxide over 21 days. The control group remained unbleached. Afterwards, all specimens were randomly distributed between two subgroups (n= 15): one was subjected to alternating demineralizing and remineralizing solutions to induce caries-like lesions and the other was not. Enamel specimens were cycled four times in demineralizing (pH 5.0) and remineralizing solutions (pH 7.0), while root dentin specimens were cycled twice. Microhardness measurements were carried out at the post-bleaching and at the post-caries lesion formation phases., Results: In the post-bleaching condition, microhardness values for both enamel and root dentin were dependent on the bleaching agent used. At the post-caries formation stage, there was a significant interaction between the bleaching treatment and substrate condition (carious or noncarious) for enamel and root dentin. Regardless of the bleaching agent, carious enamel and root dentin presented significantly lower microhardness values as compared to the noncarious counterparts. For carious enamel, those specimens exposed to CP16 exhibited higher microhardness values than the subset group formed by CP22, CP30 and unbleached samples. Both subsets did not differ from CP12. For carious root dentin, no difference was observed among the microhardness values attained as a result of the different bleaching treatments.

Purpose: To evaluate the microhardness and surface roughness of enamel and root dentin bleached with 10%, 15% and 22% carbamide peroxide agents., Methods: 52 slabs of enamel and root dentin (6 x 3 x 2 mm) were cut from bovine incisors, ground flat and polished. According to a randomized complete block design, enamel and root dentin slabs (n = 13) were independently allocated to be bleached with one of the following carbamide peroxide-containing agents (CP): 10% (Rembrandt Bleaching Gel Plus), 15% (Rembrandt Xtra Comfort), or 22% (Rembrandt Xtra Comfort Ultra Strength). The control groups were mock-treated with artificial saliva. The bleaching procedures consisted of daily application of the agents on dental substrate surfaces for 2 hours, followed by immersion in artificial saliva for 22 hours over 21 days. Knoop microhardness and surface roughness were measured initially, on sound dental tissues, and at the postbleaching phase., Results: In enamel, microhardness attained after bleaching with 10% CP and 15% CP were similar and significantly lower than that observed for the control group. Specimens bleached with CP 22% did not differ from any of the other groups tested. In root dentin, microhardness changes were indistinguishable. ANOVA showed no significant difference among treatments with respect to surface roughness.

This investigation sought to compare the abrasive wear rates of resin composites designed for posterior applications. Seventy-five specimens were fabricated with conventional hybrid (Charisma and Filtek Z250) or packable composites (Filtek P60, Solitaire II and Tetric Ceram HB), according to a randomized complete block design (n = 15). Specimens were finished and polished metallographically and subjected to abrasive wear which was performed under a normal load of 13N at a frequency of 2 Hz using a pneumatic device (MSM/Elquip) in the presence of a mucin-containing artificial saliva. Wear was quantified profilometrically in five different locations of each specimen after 1,000, 5,000, 10,000, 50,000 and after every each 50,000 through 250,000 cycles. A split-plot ANOVA showed a significant difference between the wear resistance of composites (alpha = 0.05). Tukey's test ascertained that while the composites Filtek Z250 and Charisma wore significantly less than any other of the materials tested, Tetric Ceram HB experienced the greatest wear rates. Filtek P60 and Solitaire II showed intermediate rates of material removal. The wear pattern of composites proved to be biphasic with the primary phase having the faster wear rate. In conclusion, packable resin composites may not have superior wear compared to conventional hybrid composites.

Objective: This study sought to evaluate whether root dentine caries-like lesions could be remineralised by saliva substitutes., Methods: Root dentine slabs (3 x 3 x 2 mm) were cut from bovine incisors, ground flat, polished and pre-tested for Knoop microhardness (KHN) at five locations spaced 500 microm apart and 500 microm from the left edge of each sectioned piece. After 60 out of the 100 slabs had been selected based upon their KHN values, specimens were coated with wax except for their outer surface. Specimens were then cycled through a highly cariogenic challenge model to induce caries-like lesions, whose formation was confirmed by KHN measurements located 500 microm from the right edge of the specimen. According to a randomised complete block design, the experimental units (n = 15) were exposed to 1.5 ml of saliva substitutes, based on either mucin (MC) or carboxymethylcellulose (CM), to natural human saliva (HS) or to 100% relative humidity (RH) over 20 days. Remineralisation was verified by KHN measurements located 1000 microm apart from the right edge of the specimen., Results: Analysis of variance indicated a significant (p < 0.0001) difference among the KHN values attained by the carious root dentine after exposure to the remineralising agents. Tukey's test ascertained that remineralisation was greatest with MC, intermediate with CM and least with HS, but rehardening did not reach the pre-caries lesion formation values., Conclusion: Saliva substitutes may provide partial remineralisation to preformed caries-like lesions in root dentine.

ArteFill, the successor product to Artecoll, is an injectable wrinkle filler composed of polymethylmethacrylate microspheres and bovine collagen, which offers long-lasting and probably permanent augmentation of wrinkles and skin contour deformities. The pivotal U.S. Food and Drug Administration study consisted of 251 subjects at eight centers in the United States who received injections of ArteFill or bovine collagen dermal filler (control) in 1334 wrinkles of the glabella, nasolabial folds, radial upper lip lines, and corners of the mouth. The efficacy data generated by masked observers using a photographic Facial Fold Assessment Scale demonstrated a significant improvement with ArteFill compared with collagen at 6 months (p < 0.001) in the nasolabial folds. In the ArteFill group, 12-month follow-up was obtained for 111 subjects (86.7 percent) and showed persistence of significant wrinkle correction. A subgroup of 69 patients who received ArteFill were recalled 4 to 5 years later. Five patients reported six late adverse events that occurred from 2 to 5 years after the initial injection; four of the adverse events were mild cases of lumpiness and two were severe. The total number of late adverse events was six of 272 (2.2 percent) wrinkles injected. Among the 272 wrinkles evaluated at 5 years, two events (0.7 percent) in one patient were rated as severe (a nodular, minimally inflammatory to noninflammatory reaction in both nasolabial folds). Investigator Facial Fold Assessment ratings at 4 to 5 years were improved from baseline by 1.67 points (p < 0.001).

Two classes of 5-substituted benzimidazoles were identified as potent antagonists of the NR2B subtype of the N-methyl-d-aspartate (NMDA) receptor. Selected compounds show very good selectivity versus the NR2A, NR2C, and NR2D subtypes of the NMDA receptor as well as versus hERG-channel activity and alpha(1)-adrenergic binding. Benzimidazole 37a shows excellent activity in the carrageenan-induced mechanical hyperalgesia assay in rats as well as good pharmacokinetic behavior in dogs.

Most of the biologic filler materials that increase the thickness of the corium in a wrinkle line are phagocytosed within a certain time. Therefore, a lasting effect can only be achieved with nonresorbable synthetic substances. Artefill consists of 20 volume percent microspheres of polymethyl-methacrylate and 80 volume percent of bovine collagen. Beneath the crease, the microspheres with their exceptional surface smoothness stimulate fibroblasts to encapsulate each individual one of the 6-million microspheres contained in 1 mL of Artefill. Collagen is merely a carrier substance that prevents the microspheres from agglomerating during tissue ingrowth. The 20 volume percent of microspheres in Artefill provides the scaffold for the 80% volume of connective tissue deposition, a complete replacement of the injected collagen. The filler material beneath a crease acts like a splint and prevents the possibility of its further folding, thereby allowing the diminished thickness of the corium in a crease to recover. This recovery process is well known even in older patients with facial paralysis or after a stroke, whose facial wrinkles and furrows on the paralyzed side disappear over time.

Use of alloplastic materials in facial bone reconstruction is still controversial. Medpor porous polyethylene is a relatively new implant material that is well suited for this purpose and has a number of advantages over other alloplasts. It is a pure polyethylene with a unique manufacturing process and pore size. Technically, it is easy to work with; it can be carved, contoured, adapted, and fixated to obtain a precise three-dimensional construct. Physically, it is a pure, biocompatible, strong substance that does not resorb or degenerate. It demonstrates long-term stability, high tensile strength, resistance to stress and fatigue, and a virtual lack of surrounding soft-tissue reaction. Rapid tissue ingrowth occurs into the pores. Extensive vascular ingrowth creates the potential to transport cellular products that fight infection deep into the implant. The implant was used in 140 patients from June 1988 to August 1991 to treat acute orbitozygomatic injuries (71), acute Le Fort injuries (24), delayed orbitozygomatic injuries (33), and delayed onlay augmentation (12). In this series, there was 1 instance of implant infection requiring removal, and no implant migration, or exposure.

Large soft-tissue defects of the lower extremity can present a challenging reconstructive problem. The extended deep inferior epigastric pedicle flap is a versatile and reliable flap that can be used for the coverage of complex lower extremity soft-tissue defects as far distal as the knee. We reviewed our 5-year experience with 20 consecutive extended deep inferior epigastric pedicle flaps used to cover lower extremity defects. All wounds, including 4 soft-tissue defects of the knee, were successfully covered. Two minor complications occurred. Flap anatomy, surgical approach, and new refinements in flap design are presented. The indications for the flap and its role in ablative tumor surgery are discussed. This flap has proved to be versatile, easy to raise, and extremely hardy. The ample skin island with its large arc of rotation is well vascularized, healing well even in irradiated wounds, and the flap tolerates both postoperative pressure and radiation.

Eight patients with large panniculi are described where severe problems with hygiene, immobility, and chronic infection were caused by the lymphedematous, chronically infected pannus. Protracted nonsurgical management of the infected panniculus had failed in all 8 patients. Wedge resection without fat undermining removed diseased tissue. Infection and sepsis were eliminated and ambulation was restored in all patients. Formerly immobile patients were returned to normal activity. Significant self-induced weight loss was not observed in a 2-year follow-up period; weight gain, however, was not experienced. The primary anesthetic method was thoracic epidural reducing the requirements for general endotracheal anesthesia. The chronically infected pannus is a surgical problem deserving earlier recognition and resection.

Free nipple graft reduction mammoplasty is the procedure of choice in patients with massive breast hypertrophy, or those high-risk patients less able to undergo a more extensive procedure. A major criticism of the technique is that it creates a flat, boxy breast that lacks projection. A technical modification of free nipple graft reduction mammoplasty is presented. In this modification, a central, bulky, superiorly based dermal-parenchymal flap extending from the "key-hole" site to the superior aspect of the areola is designed. After tailoring, this central flap is folded superiorly and secured beneath the medial and lateral flaps to create the bulk of the breast mound. This central flap can be accurately tailored to achieve the desired breast size and projection. The medial and lateral breast flaps do not create the breast mound, and are only contoured over the top of this central flap to complement the final breast form.

The Le Fort fracture without maxillary mobility constitutes 9 percent of maxillary fractures observed over a 3-year period. A high Le Fort (level II or III) injury exists as a one- or two-piece incomplete fracture. The degree of fracture is insufficient to permit mobility of the maxillary alveolus. Frequently, an obvious unilateral zygomatic fracture is present. Physical findings consist of bilateral eyelid ecchymosis and malocclusion. The occlusal disturbance may consist of either crossbite, open bite, maxillary rotation, or lack of proper dental intercuspation. On CT scan, fractures are best demonstrated in the posterior and medial maxillary walls at the Le Fort I level; they are most obvious unilaterally with contralateral fractures that may be subtle. Bilateral maxillary sinus fluid is consistently present on CT. Treatment usually consists of observation and traction elastics but may require mobilization of the fragments followed by open reduction and rigid fixation.

Experiments were conducted on anesthetized rabbits to determine the effect of internal carotid artery injection of various contrast media on permeability changes in the blood-brain barrier. Changes in respiratory pattern, neuromuscular effects, and trypan blue extravasation were recorded after 3-ml injections of ionic and nonionic contrast media. Metrizamide and iothalamate meglumine were compared at iodine doses of 300, 400, and 500 mg I/ml. Metrizoate at 280 and 440 mg I/ml and diatrizoate meglumine at 385 mg I/ml were also included for comparison. The results demonstrated that metrizamide at all three iodine concentrations used caused minimal disruption of the blood-brain barrier, the effect being no greater, statistically, than saline controls. Iothalamate was benign at the lowest iodine concentration, but caused significant barrier breakdown at the two higher concentrations. These results suggest that alterations in blood-brain barrier permeability following angiography are mediated by both hyperosmolality of the contrast medium and the chemotoxicity of the contrast molecule.