Monitoring silver diamine fluoride application with optical coherence tomography and thermal imaging: An in vitro proof of concept study.

OBJECTIVES: The purpose of this study was to show that optical coherence tomography (OCT) and thermal imaging can be used to monitor changes in the structure and activity of caries lesions over time after treatment with silver diamine fluoride (SDF). METHODS: Artificial caries lesions were formed on enamel and dentin bovine blocks. Each block was partitioned into five windows with the central three windows exposed to a demineralization solution to create lesions: one sound window served as a sound control (SC), one sound window was exposed to SDF to serve as a test control (SCT), one lesion window served as a lesion control (LC), one lesion window received one application of SDF (L1), while the other lesion window received two applications of SDF (L2). Each window was scanned using OCT before SDF application, and every week subsequently, for 12 weeks after initial SDF treatment. Changes in the mean intensity and the width of the peak of increased reflectivity due to the lesion and SDF along with the intensity at a depth of 180 µm from the surface representing optical penetration through the lesion were monitored. Changes in the heat lost, ΔQ (temperature integrated over time) of each window during drying with air were also monitored using a thermal imaging camera. Transverse microradiography (TMR), and high-resolution microscopy were also used for the analysis of selected samples. RESULTS: The reflectivity and optical penetration of sound and lesion areas of enamel and dentin manifested significant changes in OCT images after SDF application. Thermal imaging showed significant differences in ΔQ indicative of permeability changes in the sound and lesion areas of enamel and dentin after SDF application.

Treponema denticola dentilisin triggered TLR2/MyD88 activation upregulates a tissue destructive program involving MMPs via Sp1 in human oral cells.

Periodontal disease is driven by dysbiosis in the oral microbiome, resulting in over-representation of species that induce the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling matrix metalloproteinases (MMPs) in the periodontium. These chronic tissue-destructive inflammatory responses result in gradual loss of tooth-supporting alveolar bone. The oral spirochete Treponema denticola, is consistently found at significantly elevated levels in periodontal lesions. Host-expressed Toll-Like Receptor 2 (TLR2) senses a variety of bacterial ligands, including acylated lipopolysaccharides and lipoproteins. T. denticola dentilisin, a surface-expressed protease complex comprised of three lipoproteins has been implicated as a virulence factor in periodontal disease, primarily due to its proteolytic activity. While the role of acylated bacterial components in induction of inflammation is well-studied, little attention has been given to the potential role of the acylated nature of dentilisin. The purpose of this study was to test the hypothesis that T. denticola dentilisin activates a TLR2-dependent mechanism, leading to upregulation of tissue-destructive genes in periodontal tissue. RNA-sequencing of periodontal ligament cells challenged with T. denticola bacteria revealed significant upregulation of genes associated with extracellular matrix organization and degradation including potentially tissue-specific inducible MMPs that may play novel roles in modulating host immune responses that have yet to be characterized within the context of oral disease. The Gram-negative oral commensal, Veillonella parvula, failed to upregulate these same MMPs. Dentilisin-induced upregulation of MMPs was mediated via TLR2 and MyD88 activation, since knockdown of expression of either abrogated these effects. Challenge with purified dentilisin upregulated the same MMPs while a dentilisin-deficient T. denticola mutant had no effect. Finally, T. denticola-mediated activation of TLR2/MyD88 lead to the nuclear translocation of the transcription factor Sp1, which was shown to be a critical regulator of all T. denticola-dependent MMP expression. Taken together, these data suggest that T. denticola dentilisin stimulates tissue-destructive cellular processes in a TLR2/MyD88/Sp1-dependent fashion.

Vestibular perception and the vestibulo-ocular reflex in young and older adults.

OBJECTIVES: Quantification of the perceptual thresholds to vestibular stimuli may offer valuable complementary information to that provided by measures of the vestibulo-ocular reflex (VOR). Perceptual thresholds could be particularly important in evaluating some subjects, such as the elderly, who might have a greater potential of central as well as peripheral vestibular dysfunction. The authors hypothesized that perceptual detection and discrimination thresholds would worsen with aging, and that there would be a poor relation between thresholds and traditional measures of the angular VOR represented by gain and phase on rotational chair testing. DESIGN: The authors compared the detection and discrimination thresholds of 19 younger and 16 older adults in response to earth-vertical, 0.5 Hz rotations. Perceptual results of the older subjects were then compared with the gain and phase of their VOR in response to earth-vertical rotations over the frequency range from 0.025 to 0.5 Hz. RESULTS: Detection thresholds were found to be 0.69 ± 0.29 degree/sec (mean ± standard deviation) for the younger participants and 0.81 ± 0.42 degree/sec for older participants. Discrimination thresholds in younger and older adults were 4.83 ± 1.80 degree/sec and 4.33 ± 1.57 degree/sec, respectively. There was no difference in either measure between age groups. Perceptual thresholds were independent of the gain and phase of the VOR. CONCLUSIONS: These results indicate that there is no inevitable loss of vestibular perception with aging. Elevated thresholds among the elderly are therefore suggestive of pathology rather than normal consequences of aging. Furthermore, perceptual thresholds offer additional insight, beyond that supplied by the VOR alone, into vestibular function.

The role of heat shock protein 70 in mediating age-dependent mortality in sepsis.

Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6- to 12-wk-old) and aged (16- to 17-mo-old) HSP70(-/-) and wild-type (WT) mice to determine whether HSP70 modulated outcome in an age-dependent fashion. Young HSP70(-/-) and WT mice subjected to cecal ligation and puncture, Pseudomonas aeruginosa pneumonia, or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70(-/-) mice than aged WT mice subjected to cecal ligation and puncture (p = 0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared with WT mice, aged septic HSP70(-/-) mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70(-/-) mice had increased systemic levels of TNF-α, IL-6, IL-10, and IL-1ß compared with WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged, but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation.