The objectives of this dissertation were to: (1) investigate a bioactive nanocomposite with strong antibacterial and ion-recharge capabilities containing dimethylaminododecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP), and evaluate long-term Ca and P ion recharge by testing for 12 cycles of recharge and release; (2) develop a low-shrinkage-stress (LSS) nanocomposite with antibacterial and remineralization capabilities through the incorporation of DMAHDM and NACP to reduce marginal enamel and dentin demineralization under recurrent caries biofilm-model; (3) investigate the effects of the new composite on biofilm inhibition, mechanical properties, shrinkage stress, degree of conversion, and Ca and P ion releases; and (4) investigate the cytotoxicity of the new LSS composite and its monomers in vitro. For the antibacterial and rechargeable nanocomposite, biofilm lactic acid and colony-forming units (CFU) were measured. Ion recharge was tested for 12 cycles. For the LSS antibacterial and remineralizing nanocomposite, mechanical properties, shrinkage stress, and degree of conversion were evaluated. The growth of Streptococcus mutans and multi-species salivary biofilms was assessed using biofilm CFU, lactic acid production, and confocal laser scanning microscopy. Ca and P ion releases, and human gingival fibroblasts cytotoxicity were measured. The bioactive rechargeable nanocomposite reduced biofilm acid production and viability. High levels of ion releases were maintained throughout 12 cycles of recharge, maintaining steady-state releases without reduction in 6 months, representing long-term remineralization potential. The LSS composite with DMAHDM and NACP had flexural strength matching that of a commercial control composite. The bioactive low-shrinkage-stress composite substantially reduced the biofilm CFU and lactic acid production compared to control composite. The bioactive LSS composite exhibited no significant difference in antibacterial performance before and after three months of aging, demonstrating long-term antibacterial activity. The shrinkage stress of the bioactive low-shrinkage-stress nanocomposite was 36% lower than that of traditional control composite, with similar degrees of conversion. The new bioactive nanocomposite had a satisfactorily low cytotoxic effect toward human gingival fibroblasts and the new monomers had fibroblast viability similar to that of commercial control. The two developed nanocomposites are promising to inhibit recurrent caries and protect the teeth with an intended application for reducing recurrent caries.

It is desirable to use a minimally invasive approach in dentistry through conservative techniques in order to prevent destruction of the tooth structure. Since resin-based dental materials are increasingly used, the occurrence of re-infections is also increasing. Recurrent caries and secondary infections are major problems in the restorative dentistry field. The prevalence of recurrent caries associated with resin-based restorative materials was previously shown to reach 60%. It is the most common reason recognized for composite resin restorations replacement and failure. Many efforts have been made to incorporate antibacterial agents into restorative materials. However, the majority of these materials act by releasing these agents into the surrounding environment, leading to their depletion over time. There is a clinical need for durable bioactive composite restorations that resist the formation of secondary caries for an extended period of time. Dimethylaminohexadecyl methacrylate (DMAHDM) is an antibacterial agent that is immobilized in resin and not lost or released with time. Therefore, this dissertation aims to develop new composite resin formulations containing DMAHDM antibacterial, 2-methacryloyloxyethyl phosphorylcholine (MPC) protein repellent, and nanoparticles of calcium fluoride (nCaF2) remineralizing modalities which could be a promising approach for management of recurrent caries around or under restoration margins. This dissertation incorporated DMAHDM, MPC and nCaF2 into composite resin restorations to achieve potent, long-lasting antibacterial, protein repellent, and Ca and F ion release and recharge/re-release capabilities. Mechanical testing was performed for all composite formulations. To determine biofilm properties, a human salivary microcosm biofilm model was used. Biofilm colony-forming units (CFU), minimum inhibitory concentration, lactic acid production, and metabolic activity of biofilm were investigated. Fluoride (F) and calcium (Ca) initial ion releasing, recharging and re-releasing capabilities were tested. The majority of nCaF2 nanocomposites show matching mechanical properties to the commercial control composite. The nCaF2-DMAHDM nanocomposites have potent antibacterial effects that substantially reduce biofilm activities in all biofilm experiments. Similarly, all nCaF2 nanocomposites have higher values of F and Ca ion release- recharge, and re-release when compared to the commercial control composite. Therefore, these new composite resin formulations may potentially lead to a fundamental contribution in restorative techniques that can be used to fight this most common limitation of composite restorations - recurrent caries - and contribute to the longevity of composite restorations through long-lasting antibacterial and protein repellent properties and remineralization capabilities.

In the United States, nearly 1 million people suffer from burning mouth syndrome (BMS), a chronic orofacial pain condition that is largely unrecognized by the medical community and predominantly affects post- and peri-menopausal women. Relatively little in-depth research is available on the condition, and patients often give up seeking treatment. The pain in BMS arises spontaneously (i.e. in the absence of stimuli), but the mechanisms of this spontaneous pain is unclear, and there is limited research on structural and functional brain changes that may occur in a BMS sufferer. The goal of this dissertation was to investigate the central nervous system mechanisms of pain experienced in BMS. We collected: 8-day diaries, morning and afternoon quantitative sensory testing of both orofacial and forearm regions; afternoon structural and functional MRIs, and questionnaires from 27 BMS patients and 33 healthy post-menopausal women. Our hypotheses that, compared to healthy participants BMS patients have: higher pain sensitivity, especially in orofacial regions during the afternoon; lower grey matter volume and higher functional connectivity in nociceptive pathways associated with noxious heat during rest and evoked thermal pain, even after accounting for anxiety, were not supported. Instead, we found a time-of-day-dependent effect during warm detection and cold detection of face and forearm; lower grey matter volume of the dorsolateral prefrontal cortex (DLPFC), and higher grey matter volume of the inferior temporal gyrus and parabrachial nucleus (PBN); lower PBN connectivity with the DLPFC and primary somatosensory cortex (S1); higher connectivity of the right lateral hypothalamus (LH) with posterior insula during warm condition; connectivity of right medial hypothalamus and LH to left DLPFC and right PBN to bilateral S1 not associated with anxiety in BMS compared to healthy participants. Altogether, BMS showed abnormal responses to innocuous stimuli. This was supported by fMRI data, where connectivity differences were mostly present during innocuous stimulation. These altered sensory and brain responses could reflect heightened anticipation of thermal stimuli (both pain-specific and non-pain specific) associated with disruption of communication between regions associated with negative affect of pain (insula), attention modulation of pain (left DLPFC), somatosensation (S1), and thermoregulation (LH and PBN).

The main purpose of this systematic narrative review is to determine the difference in abundance of bacteria and bacterial genes of subgingival microflora of human periodontal pockets compared to healthy sites, via Metagenomic and Metatranscriptomic analyses. Databases EMBASE and MEDLINE were searched for articles, with earliest records from 1978. Main outcome measures included: 1) Bacterial genera and/or species significantly increased 2) Most prevalent or significantly upregulation of genes. Ten studies met selection criteria and were included in the study. Nine studies were cross-sectional, and one was longitudinal. Main results showed trends of specific bacteria and genes found in periodontal pockets. However, within the limitations of this narrative review, trends of abundant bacteria and genes does not imply these specific species or genes are actively participating in disease progression. Nine of ten included studies were cross-sectional in design with eight studies being metagenome based and not able to measure gene expression.

Tumors of the tongue are routinely removed by partial glossectomy surgery. This study examines the extent of anatomical asymmetries caused by the glossectomy surgery and its effects on the tongue’s resting position and motor symmetry. Magnetic resonance imaging (MRI) data of ten control subjects and ten glossectomy patients were obtained. 3D tongue volumes were extracted from high-resolution MRI data using Matlab. Using cine- and tagged-MRI data, shortening of the genioglossus, transverse, and verticalis muscles were calculated during a speech task involving /∫/ and /l/. Anatomical asymmetries were observed in the control subjects, although they were generally small and less than in glossectomy patients. Glossectomy patients aimed to distribute their tongue volume evenly in the oral cavity, irrespective of anatomical asymmetry, by posturing their tongue towards the resected side. Glossectomy patients shortened more muscles when executing the speech task. Muscle shortening asymmetry was observed in both control and patient groups.

Purpose: The purpose of this study is to support the position of the AAO by demonstrating that the oropharyngeal volume does not decrease as a result of premolar extractions and orthodontic treatment. Materials and Methods: Cone-beam CT’s were obtained for twenty-seven orthodontic patients before and after treatment. Nine patients were treated with four premolar extractions, and eighteen treated non-extraction. Total oropharyngeal airway volume and minimum area of constriction were measured using InVivo Anatomage Software. Results: The initial and final airway volumes of the non-extraction group were correlated (p = 0.61). The total airway volume in the non-extraction cases showed a significant increase (p = .037). Conclusion: There was no significant change in oropharyngeal volume in Class II patients that underwent orthodontic treatment with extractions, however; patients that were treated non-extraction had a significant increase in oropharyngeal volume. There was no significant change in area of minimum constriction in either group.

Transient receptor potential vanilloid subtype 1 (TRPV1) is a nonselective cation permeable channel activated by painful stimuli, such as capsaicin and noxious heat, and enriched in many primary afferent neurons of the pain pathway. During inflammation, chemical mediators activate protein kinases (such as PKC) that phosphorylate TRPV1 and thereby enhance its function, which results in nociceptor sensitization. And this can result in a lower threshold for pain. However, the causal relationships between TRPV1 phosphorylation and pathological pain remain unexplored. To directly investigate the roles of one specific TRPV1 phosphorylation event in vivo, we genetically altered a major PKC phosphorylation site, mouse TRPV1 S801, to alanine. The TRPV1 expression pattern in sensory neurons of S801A knock-in (KI) mice was comparable to that in wildtype (WT) controls. In sensory neurons from KI mice, following the activation of PKC, the usual increase of capsaicin-induced currents was substantially impaired. Thermal hyperalgesia induced by PMA or burn injury in KI was identical to WT. Thermal hyperalgesia was only marginally attenuated in KI mice duirng inflammation. In contrast, PMA-evoked nocifensive responses and hyperalgesia to capsaicin were significantly attenuated in the hindpaws of KI mice. Ongoing pain from inflamed masseter muscle was also reduced in KI mice, and the pain was further inhibited by the TRPV1 antagonist AMG9810. These results suggest that PKC-mediated phosphorylation of TRPV1 S801 contributes to inflammation-mediated sensitization of TRPV1 to ligand, but not heat, in vivo. Further, this suggests that interference with TRPV1 S801 phosphorylation might represent a potential way to reduce inflammatory pain in the clinic, yet spare basal sensitivity and produce fewer side effects than with a more general TRPV1 inhibition.

The goal of this study was to investigate the accuracy, over time, of computer-aided design and computer-aided manufactured (CAD/CAM) dental patterns in two different materials (resin and wax) using two different fabrication methods (subtractive and additive manufacturing). The intaglio surface of the patterns (n=48/time period) were evaluated at five predetermined time periods (zero minutes, 20 minutes, 24 hours, one week, and two weeks) relative to fabrication time. Intaglio surface scans of the generated samples were aligned with the Best Fit alignment to the design file (.stl) and compared with 3D Compare on Geomagic Control X to obtain the deviations as a root mean square (RMS). Trueness of the patterns were compared at all time points using three-way Analysis of Variance (ANOVA) (=.05). Accuracy of dental patterns deteriorated over time. When materials were considered, wax had better dimensional stability than resin. When fabrication method was considered, milled patterns had better dimensional stability than printed patterns. Time, material type, fabrication method, and all their interactions, showed a significant effect, however, the differences were very small (ranging from <1 m to 20 m). Thus, both resin and wax CAD/CAM patterns fabricated by additive and subtractive manufacturing can be used to produce dental restorations with acceptable accuracy.

Control of plaque biofilm is central to prevention of gingivitis. In addition to professional care, effective oral hygiene measures are known to improve gingival health. The objective of this study was to investigate the effect of chitosan/blackberry-extract, delivered in a chewing gum, as an adjunct to oral hygiene, on gingival inflammation and plaque biofilm accumulation. In this 12-week randomized controlled study, the use of chitosan/blackberry-extract gum was compared to placebo in 34 subjects (17/17). Plaque index(mPI) and gingival index(mGI) were the main outcome measures followed at baseline, week 2, 4, 8, and 12. Measured patient compliance and mPI had no significant difference between experimental and control at any interval during the study. mGI was significantly lower for the experimental group compared to control at 12 weeks(P<0.005). Chitosan/blackberry-extract chewing gum may be beneficial in reduction of clinical signs of gingival inflammation and has potential as an adjunct to routine oral hygiene.

Purpose: This study examines the tongue behavior of glossectomy (N = 8) and control (N =12) speakers using a combination of high-resolution and cine- MRI. The speech task “a geese” phonetically spelled /əgis/, was used to measure anterior tongue displacement, termed “anteriority”, for the /ə/, a neutral vowel, and the /s/. Effects on anteriority due to palate height, arch perimeter, inter-canine width and /s/ type were measured on controls and patients. There are two variants of /s/ in English: apical and laminal. The apical /s/ elevates the tongue tip to contact the palate, create a narrow, grooved constriction, and focus the jet stream of air onto the incisors. The laminal /s/ uses the tongue blade, just behind the tip, to create the grooved constriction, and the tip is kept lower in the mouth.[1, 2]