There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address the mechanisms of antibacterial activity, we determined MICs and minimum bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity-the sphingoid bases D-sphingosine, phytosphingosine, and dihydrosphingosine and the fatty acids sapienic acid and lauric acid-against four Gram-negative bacteria and seven Gram-positive bacteria. Exact Kruskal-Wallis tests of these values showed differences among lipid treatments (P < 0.0001) for each bacterial species except Serratia marcescens and Pseudomonas aeruginosa. D-Sphingosine (MBC range, 0.3 to 19.6 g/ml), dihydrosphingosine (MBC range, 0.6 to 39.1 g/ml), and phytosphingosine (MBC range, 3.3 to 62.5 g/ml) were active against all bacteria except S. marcescens and P. aeruginosa (MBC > 500 g/ml). Sapienic acid (MBC range, 31.3 to 375.0 g/ml) was active against Streptococcus sanguinis, Streptococcus mitis, and Fusobacterium nucleatum but not active against Escherichia coli, Staphylococcus aureus, S. marcescens, P. aeruginosa, Corynebacterium bovis, Corynebacterium striatum, and Corynebacterium jeikeium (MBC > 500 g/ml). Lauric acid (MBC range, 6.8 to 375.0 g/ml) was active against all bacteria except E. coli, S. marcescens, and P. aeruginosa (MBC > 500 g/ml). Complete killing was achieved as early as 0.5 h for some lipids but took as long as 24 h for others. Hence, sphingoid bases and fatty acids have different antibacterial activities and may have potential for prophylactic or therapeutic intervention in infection.C ommon sphingolipids and fatty acids are involved in the physical barrier, permeability barrier, and immunologic barrier functions of the skin and oral mucosa (8,14). Epithelial layers contain ceramides, free fatty acids, and cholesterol; sebaceous lipids at the skin surface include a complex mixture of triglycerides, fatty acids, wax esters, squalene, cholesterol, and cholesterol esters; and saliva contains the same sebaceous lipids (6,14,19). These sebaceous secretions contribute to (i) the transport of fatsoluble antioxidants to the skin and mucosal surfaces, (ii) the proand anti-inflammatory properties of the skin and mucosal surfaces, and (iii) the innate antimicrobial activity of the skin and mucosal surfaces (20,26,27).Although the composition, biosynthesis, secretion, and function of cutaneous lipids are well characterized from extensive and elegant work done in the 1970s, little is known about their role in controlling microbial infection and colonization. Certain fatty acids and sphingoid bases found at the skin and mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role than previously thought in innate immune defense against epidermal and mucosal bacterial infections (10). They include free sphingosines, dihydrosphingosines, lauric acid, and sapienic aci...

Alveolar ridge preservation strategies are indicated to minimize the loss of ridge volume that typically follows tooth extraction. The aim of this systematic review was to determine the effect that socket filling with a bone grafting material has on the prevention of postextraction alveolar ridge volume loss as compared with tooth extraction alone in nonmolar teeth. Five electronic databases were searched to identify randomized clinical trials that fulfilled the eligibility criteria. Literature screening and article selection were conducted by 3 independent reviewers, while data extraction was performed by 2 independent reviewers. Outcome measures were mean horizontal ridge changes (buccolingual) and vertical ridge changes (midbuccal, midlingual, mesial, and distal). The influence of several variables of interest (i.e., flap elevation, membrane usage, and type of bone substitute employed) on the outcomes of ridge preservation therapy was explored via subgroup analyses. We found that alveolar ridge preservation is effective in limiting physiologic ridge reduction as compared with tooth extraction alone. The clinical magnitude of the effect was 1.89 mm (95% confidence interval [CI]: 1.41, 2.36; p < .001) in terms of buccolingual width, 2.07 mm (95% CI: 1.03, 3.12; p < .001) for midbuccal height, 1.18 mm (95% CI: 0.17, 2.19; p = .022) for midlingual height, 0.48 mm (95% CI: 0.18, 0.79; p = .002) for mesial height, and 0.24 mm (95% CI: -0.05, 0.53; p = .102) for distal height changes. Subgroup analyses revealed that flap elevation, the usage of a membrane, and the application of a xenograft or an allograft are associated with superior outcomes, particularly on midbuccal and midlingual height preservation.

Objectives: To (1) investigate effects of aerobic walking on motor function, cognition, and quality of life in Parkinson disease (PD), and (2) compare safety, tolerability, and fitness benefits of different forms of exercise intervention: continuous/moderate intensity vs interval/alternating between low and vigorous intensity, and individual/neighborhood vs group/facility setting. Methods:Initial design was a 6-month, 2 3 2 randomized trial of different exercise regimens in independently ambulatory patients with PD. All arms were required to exercise 3 times per week, 45 minutes per session.Results: Randomization to group/facility setting was not feasible because of logistical factors.Over the first 2 years, we randomized 43 participants to continuous or interval training. Because preliminary analyses suggested higher musculoskeletal adverse events in the interval group and lack of difference between training methods in improving fitness, the next 17 participants were allocated only to continuous training. Eighty-one percent of 60 participants completed the study with a mean attendance of 83.3% (95% confidence interval: 77.5%-89.0%), exercising at 46.8% (44.0%-49.7%) of their heart rate reserve. There were no serious adverse events. Across all completers, we observed improvements in maximum oxygen consumption, gait speed, Unified Parkinson's Disease Rating Scale sections I and III scores (particularly axial functions and rigidity), fatigue, depression, quality of life (e.g., psychological outlook), and flanker task scores (p , 0.05 to p , 0.001). Increase in maximum oxygen consumption correlated with improvements on the flanker task and quality of life (p , 0.05). Conclusions:Our preliminary study suggests that aerobic walking in a community setting is safe, well tolerated, and improves aerobic fitness, motor function, fatigue, mood, executive control, and quality of life in mild to moderate PD. Classification of evidence:This study provides Class IV evidence that in patients with PD, an aerobic exercise program improves aerobic fitness, motor function, fatigue, mood, and cognition. Figure Test; FSS 5 Fatigue Severity Scale; HR max 5 maximal heart rate; HRR 5 heart rate reserve; PD 5 Parkinson disease; PDQUALIF 5 Parkinson's Disease Quality of Life Scale; PIS 5 percent increase score; RT 5 reaction time; UPDRS 5 Unified Parkinson's Disease Rating Scale; Vȯ 2 5 maximum oxygen uptake.

The aim of this study was to evaluate the effect of digital tooth preparation imaging and evaluation technology on dental students' technical abilities, self-evaluation skills, and the assessment of their simulated clinical work. A total of 80 secondyear students at one U.S. dental school were assigned to one of three groups: control (n=40), E4D Compare (n=20), and Sirona prepCheck (n=20). Students in the control group were taught by traditional teaching methodologies, and the technology-assisted groups received both traditional training and supplementary feedback from the corresponding digital system. Three outcomes were measured: faculty technical score, self-evaluation score, and E4D Compare scores at 0.30 mm tolerance. Correlations were determined between the groups' scores from visual assessment and self-evaluation and between the visual assessment and digital scores. The results showed that the visual assessment and self-evaluation scores did not differ among groups (p>0.05). Overall, correlations between visual and digital assessment scores were modest though statistically signiicant (5% level of signiicance). These results suggest that the use of digital tooth preparation evaluation technology did not impact the students' prosthodontic technical and self-evaluation skills. Visual scores given by faculty and digital assessment scores correlated moderately in only two instances.

Sphingoid bases found in the outer layers of the skin exhibit antimicrobial activity against gram-positive and gram-negative bacteria. We investigated the uptake of several sphingoid bases by Escherichia coli and Staphylococcus aureus, and assessed subsequent ultrastructural damage. E. coli and S. aureus were incubated with d-sphingosine, dihydrosphingosine, or phytosphingosine at ten times their MIC for 0.5 and 4 h, respectively, to kill 50% of viable bacteria. Treated bacterial cells were immediately prepared for SEM, TEM, and analyzed for lipid content by QTLC. E. coli and S. aureus treated with sphingoid bases were distorted and their surfaces were concave and rugate. Significant differences were observed in the visual surface area relative to controls for both E. coli and S. aureus when treated with dihydrosphingosine and sphingosine (p < 0.0001) but not phytosphingosine. While sphingoid base-treated S. aureus exhibited disruption and loss of cell wall and membrane, E. coli cytoplasmic membranes appeared intact and the outer envelope uncompromised. Both E. coli and S. aureus cells contained unique internal inclusion bodies, likely associated with cell death. QTLC demonstrated extensive uptake of sphingoid bases by the bacteria. Hence, sphingoid bases induce both extracellular and intracellular damage and cause intracellular inclusions that may reflect lipid uptake.

Lauric acid (C12:0) and sapienic acid (C16:1Δ6) derived from human sebaceous triglycerides are potent antimicrobials found at the human skin surface. Long-chain bases (sphingosine, dihydrosphingosine and 6-hydroxysphingosine) are also potent and broad-acting antimicrobials normally present at the skin surface. These antimicrobials are generated through the action of ceramidases on ceramides from the stratum corneum. These natural antimicrobials are thought to be part of the innate immune system of the skin. Exogenously providing these lipids to the skin may provide a new therapeutic option, or could potentially provide prophylaxis in people at risk of infection.

Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria; however, little is known about their spectrum of antimicrobial activity or mechanisms of action against oral bacteria. In this study, we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Minimal inhibitory concentrations, minimal bactericidal concentrations, and kill kinetics revealed variable, but potent, activity of oral mucosal and salivary lipids against P. gingivalis, indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria, although specific components of bacterial membranes are also likely important. Electron micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma membrane. This information, coupled with the association of treatment lipids with P. gingivalis lipids revealed via thin layer chromatography, suggests that the plasma membrane is a likely target of lipid antibacterial activity. Utilizing a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique P. gingivalis stress response, including proteins important in fatty acid biosynthesis, metabolism and energy production, protein processing, cell adhesion and virulence. Prophylactic or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.

Conventional grading of dental students' projects in preclinical courses has mainly relied on visual evaluation by experienced instructors. The purpose of this study was to compare conventional visual grading in a dental anatomy course at one U.S. dental school to a novel digital assessment technique. A total of sixty samples comprised of two sets of faculty wax-ups (n=30), student wax-ups (n=15), and dentoform teeth of tooth #14 (n=15) were used for this study. Two additional faculty members visually graded the samples according to a checklist and then repeated the grading after one week. The sample wax-up with the highest score based on the visual grading was selected as the master model for the digital grading, which was also performed twice with an interim period of one week. Descriptive statistics and signed rank tests for systematic bias were used for intra-and interrater comparisons. The intraclass correlation (ICC) was used as a measure of intra-and interrater reliability. None of the faculty members achieved the minimum acceptable intrarater agreement of 0.8. Interrater agreement was substantially less than intrarater agreement for the visual grading, whereas all measures of intrarater agreement were greater than 0.9 and considered excellent for the digital assessment technique. These results suggest that visual grading is limited by modest intrarater reliability and low interrater agreement. Digital grading is a promising evaluation method showing excellent intrarater reliability and correlation. Correlation for visual and digital grading was consistently modest, partly supporting the potential use of digital technology in dental anatomy grading.