Microglia regulate central nervous system myelin growth and integrity.

Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have been implicated in myelin health1, it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFß1-TGFßR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease2,3.

The effect of gum chewing on xerostomia and salivary flow rate in elderly and medically compromised subjects: a systematic review and meta-analysis.

BACKGROUND: Xerostomia negatively affects quality of life. Symptoms include oral dryness; thirst; difficulty speaking, chewing, and swallowing food; oral discomfort; mouth soft tissue soreness and infections; and rampant tooth decay. The objective of this systematic review and meta-analysis was to investigate if gum chewing is an intervention that results in objective improvements in salivary flow rates and subjective relief from xerostomia. METHOD: We searched electronic databases including Medline, Scopus, Web of Science, Embase, Cochrane Library (CDSR and Central), Google Scholar and the citations of review papers (last searched 31/03/23). The study populations included: 1) elderly people with xerostomia (> 60 years old, any gender, and severity of xerostomia), and 2) medically compromised people with xerostomia. The intervention of interest was gum chewing. Comparisons included gum chewing vs. no gum chewing. The outcomes included salivary flow rate, self-reported xerostomia, and thirst. All settings and study designs were included. We conducted a meta-analysis on studies where measurements of unstimulated whole salivary flow rate for both a gum chewing, and no gum chewing intervention (daily chewing of gum for two weeks or longer) were reported. We assessed risk of bias using Cochrane's RoB 2 and ROBINS-I tools. RESULTS: Nine thousand six hundred and two studies were screened and 0.26% (n = 25) met the inclusion criteria for the systematic review. Two of the 25 papers had a high overall risk of bias. Of the 25 papers selected for the systematic review, six met the criteria to be included in the meta-analysis which confirmed a significant overall effect of gum on saliva flow outcomes compared to control (SMD = 0.44, 95% CI: 0.22-0.66; p = 0.00008; I2 = 46.53%). CONCLUSIONS: Chewing gum can increase unstimulated salivary flow rate in elderly and medically compromised people with xerostomia. Increasing the number of days over which gum is chewed increases the improvement in the rate of salivation. Gum chewing is linked with improvements in self-reported levels of xerostomia (although it is noted that no significant effects were detected in five of the studies reviewed). Future studies should eliminate sources of bias, standardise methods to measure salivary flow rate, and use a common instrument to measure subjective relief from xerostomia. STUDY REGISTRATION: PROSPERO CRD42021254485.

COVID-19 acute respiratory distress syndrome: A simulation study of the effects of combination therapy with tocilizumab and siltuximab.

AIMS: To assess the potential of interleukin-6 (IL-6) signalling blockade in the lung to treat SARS-CoV-2 infection via model-based simulation by exploring soluble IL-6 receptor (sIL-6R) sequestration by tocilizumab (TCZ) and IL-6 sequestration by siltuximab (SIL). METHODS: Literature values of IL-6, IL-6 antagonist SIL, sIL-6R, IL-6R antagonist TCZ and their respective binding constants were used to develop a model to predict the impact of treatment on IL-6 signalling. Models were used to generate simulated bronchoalveolar lavage fluid concentrations for normal subjects, subjects at risk of developing acute respiratory distress syndrome (ARDS), and subjects with ARDS under 4 conditions: without treatment; treatment with TCZ; treatment with SIL; and treatment with TCZ + SIL. RESULTS: With TCZ intervention, IL-6 levels are unaffected and sIL-6R is reduced somewhat below the Normal case. IL-6:sIL-6R complex only slightly decreased relative to the no-intervention case. With SIL intervention, sIL-6R levels are unaffected and IL-6 is greatly reduced below the Normal case. IL-6:sIL-6R complex is greatly decreased relative to the no-intervention case. With TCZ + SIL intervention, IL-6 and sIL-6R levels are reduced below the Normal case and achieve suppression equivalent to monotherapy results for their respective targets. IL-6:sIL-6R complex reduction is predicted to be greater than that achieved with monotherapy. This reflects sequestration of both components of the complex and the nonlinear binding equilibrium. CONCLUSION: Coadministration of both IL-6 and IL-6R sequestering products such as SIL and TCZ may be necessary to effectively treat COVID-19 patients who have or are at risk of developing ARDS.

Model-informed drug repurposing: Viral kinetic modelling to prioritize rational drug combinations for COVID-19.

AIM: We hypothesized that viral kinetic modelling could be helpful to prioritize rational drug combinations for COVID-19. The aim of this research was to use a viral cell cycle model of SARS-CoV-2 to explore the potential impact drugs, or combinations of drugs, that act at different stages in the viral life cycle might have on various metrics of infection outcome relevant in the early stages of COVID-19 disease. METHODS: Using a target-cell limited model structure that has been used to characterize viral load dynamics from COVID-19 patients, we performed simulations to inform on the combinations of therapeutics targeting specific rate constants. The endpoints and metrics included viral load area under the curve (AUC), duration of viral shedding and epithelial cells infected. Based on the known kinetics of the SARS-CoV-2 life cycle, we rank ordered potential targeted approaches involving repurposed, low-potency agents. RESULTS: Our simulations suggest that targeting multiple points central to viral replication within infected host cells or release from those cells is a viable strategy for reducing both viral load and host cell infection. In addition, we observed that the time-window opportunity for a therapeutic intervention to effect duration of viral shedding exceeds the effect on sparing epithelial cells from infection or impact on viral load AUC. Furthermore, the impact on reduction on duration of shedding may extend further in patients who exhibit a prolonged shedder phenotype. CONCLUSIONS: Our work highlights the use of model-informed drug repurposing approaches to better rationalize effective treatments for COVID-19.

Using in silico viral kinetic models to guide therapeutic strategies during a pandemic: An example in SARS-CoV-2.

AIMS: We propose the use of in silico mathematical models to provide insights that optimize therapeutic interventions designed to effectively treat respiratory infection during a pandemic. A modelling and simulation framework is provided using SARS-CoV-2 as an example, considering applications for both treatment and prophylaxis. METHODS: A target cell-limited model was used to quantify the viral infection dynamics of SARS-CoV-2 in a pooled population of 105 infected patients. Parameter estimates from the resulting model were used to simulate and compare the impact of various interventions against meaningful viral load endpoints. RESULTS: Robust parameter estimates were obtained for the basic reproduction number, viral release rate and infected-cell mortality from the infection model. These estimates were informed by the largest dataset currently available for SARS-CoV-2 viral time course. The utility of this model was demonstrated using simulations, which hypothetically introduced inhibitory or stimulatory drug mechanisms at various target sites within the viral life-cycle. We show that early intervention is crucial to achieving therapeutic benefit when monotherapy is administered. In contrast, combination regimens of two or three drugs may provide improved outcomes if treatment is initiated late. The latter is relevant to SARS-CoV-2, where the period between infection and symptom onset is relatively long. CONCLUSIONS: The use of in silico models can provide viral load predictions that can rationalize therapeutic strategies against an emerging viral pathogen.

Model-informed drug repurposing: A pharmacometric approach to novel pathogen preparedness, response and retrospection.

During a pandemic caused by a novel pathogen (NP), drug repurposing offers the potential of a rapid treatment response via a repurposed drug (RD) while more targeted treatments are developed. Five steps of model-informed drug repurposing (MIDR) are discussed: (i) utilize RD product label and in vitro NP data to determine initial proof of potential, (ii) optimize potential posology using clinical pharmacokinetics (PK) considering both efficacy and safety, (iii) link events in the viral life cycle to RD PK, (iv) link RD PK to clinical and virologic outcomes, and optimize clinical trial design, and (v) assess RD treatment effects from trials using model-based meta-analysis. Activities which fall under these five steps are categorized into three stages: what can be accomplished prior to an NP emergence (preparatory stage), during the NP pandemic (responsive stage) and once the crisis has subsided (retrospective stage). MIDR allows for extraction of a greater amount of information from emerging data and integration of disparate data into actionable insight.

Multimodal imaging of composite carbon fiber-based implants for orthopedic spinal fixation.

OBJECTIVE: As cancer treatments continue to improve, the incidence of spinal metastases and the need for surgical management of these with fixation procedures are growing rapidly. Traditionally metallic implants, composed of titanium alloy, have been used in surgical fixation of unstable or symptomatic vertebral metastases or traumatic injuries. Metallic implants, however, cause significant artifact on post-operative imaging, degrading image quality and limiting interpretation, and can also impair the planning and delivery of radiotherapy. Composite carbon fiber-based materials, such as carbon fiber-reinforced polyetheretherketone (PEEK), have been developed to overcome these issues and are now available for spinal fixation procedures. We aimed to review the multimodal imaging features of these new implants. MATERIALS AND METHODS: Current literature and a case example from our institution were used to describe the multimodal imaging characteristics and considerations of new carbon fiber-based spinal fixation implants. RESULTS: New carbon fiber-based spinal implants allow far greater visualization of surrounding structures on post-operative cross-sectional imaging, significantly improving diagnostic accuracy and precision of radiotherapy planning, and do not significantly absorb or scatter X-ray photons during radiotherapy delivery. There are, however, important surgical and radiologic considerations associated with the use of carbon fiber-based implants which radiologists must be aware of, such as implications for surgical planning and intra-operative fluoroscopic and post-operative plain radiographic imaging. CONCLUSION: The use of carbon fiber-based implants, rather than traditional metallic implants, for spinal fixation offers significant advantages for post-operative diagnostic imaging and radiotherapy planning and delivery.

The Use of Halo Gravity Traction in Severe, Stiff Scoliosis.

PURPOSE: The correction of severe, stiff scoliosis in children is challenging. One method used to reduce the risk is preoperative halo gravity traction (HGT). In this study, the authors sought to define the efficiency and safety of HGT and characterize the chronology of the correction seen. METHOD: A consecutive group of pediatric patients with severe spinal deformities was treated with HGT before definitive correction. A standard protocol with the daily addition of weight to 50% of body weight at 3 weeks was used. Traction remained in place until signs of impending neurological complication or 6 weeks, whichever was sooner. RESULTS: Twenty-four patients were included with a mean age of 11.8 years. The mean coronal deformity was 123 degrees, with a T1-L5 height of 234 mm. The mean duration of traction was 42 days with a mean improvement in height of 72 mm with 82% occurring over the first 3 weeks. Hundred percent of the angular and 98% of T1-L5 height correction was reached by 6 weeks.One patient showed early signs of a cranial nerve palsy prompting early surgery and 8 patients showed pin loosening, 1 of which required revision of their halo. One patient underwent a slower progression of traction because of transitory urinary disturbance. Following fusion, angular correction of the major curve was 49%. CONCLUSION: HGT is a safe treatment for severe, stiff scoliosis because it can respond to early signs of impending neurological impairment. The first 3 weeks of treatment, reaching 50% of body weight as a traction force accounts for 80% of correction, with the remaining 20% in the following 2 weeks. At least 4 weeks of traction is recommended when following this protocol.

Resistance and resilience to experimental gingivitis: a systematic scoping review.

BACKGROUND: This systematic scoping review aimed to identify changes in biomarkers of microbiological, immunological and biochemical origin during experimental gingivitis (EG) studies that might indicate resistance and resilience. METHODS: The term 'experimental gingivitis' was run in PubMed from inception to April 11th, 2018. From the 411 studies retrieved, 22 studies were included for this review. RESULTS: Studies reporting data on biomarker changes during and after full mouth EG trial were included. Two studies reported findings on changes in biomarkers of microbiological, 12 on immunological and eight on biochemical origin. Changes were reported in the induction phase, and occasionally in the resolution phase. The microbiological composition of both supragingival and subgingival dental plaque changed over the course of EG to a more pathogenic direction, but showed a shift back to a more normal composition. This indicates resilience of the oral microbiome. For immunological biomarkers, it was challenging to retrieve a robust pattern of changes across multiple studies. IL-1ß and IL-6 in saliva and in gingival crevicular fluid increased during induction phase and returned in the resolution phase below baseline values. The biochemical parameters cystatin-SN, cystatin-S and lactoferrin in saliva were increased at the end of induction phase, however also here no clear pattern emerged based on all available studies. CONCLUSIONS: More research is needed to investigate which microbiological, immunological, and biochemical biomarkers can be useful for future investigations into the resistance and resilience of the oral cavity to experimental gingivitis.

Self-perceived mouthfeel and physico-chemical surface effects after chewing gums containing sorbitol and Magnolia bark extract.

The European Food Safety Authority recognizes the contribution of sugar-free chewing gum to oral health through increased salivation, clearance of food debris, and neutralization of biofilm pH. Magnolia bark extract is a gum additive shown to reduce the prevalence of bad-breath bacteria but its effects on self-perceived mouthfeel are unknown. This paper aims to relate the effects of sorbitol-containing chewing gum, with and without Magnolia bark extract, on tooth-surface hydrophobicity and salivary-film composition with self-perceived mouthfeel. In a crossover clinical trial, volunteers chewed sorbitol-containing gum, with or without Magnolia bark extract added, three times daily during a 4-wk time period. A subset of volunteers also chewed Parafilm as a mastication control. Oral moistness and tooth smoothness were assessed using questionnaires, and intra-oral water-contact angles were measured before, immediately after, and 60 min after, chewing. Simultaneously, saliva samples were collected, placed on glass slides, and the compositions of the adsorbed film were measured using X-ray photoelectron spectroscopy. Chewing of gum, regardless of whether or not it contained Magnolia bark extract, improved self-perceived mouthfeel up to 60 min, concurrent with a more hydrophilic tooth surface and an increased amount of O1s electrons bound at 532.6 eV in salivary films. Chewing of Parafilm affected neither tooth-surface hydrophobicity nor salivary-film composition. Accordingly, adsorption of sorbitol, rather than the presence of Magnolia bark extract or increased salivation, is responsible for improved self-perceived mouthfeel.

An induced extrinsic tooth stain prevention model to investigate whitening potential of sugar-free chewing gums.

PURPOSE: To establish an accelerated clinical test method to evaluate the effectiveness of sugar-free gums in prevention of the formation of extrinsic stains when chewed over a 2-week period in conjunction with daily tooth brushing. A secondary objective was to compare three methods for measuring extrinsic stain. METHODS: 25 healthy adult volunteers were enrolled in a single center, examiner blind, randomized 4-way crossover clinical study. Starting with a stain-free baseline, subjects rinsed five times daily with freshly brewed black tea, followed either by chewing one of three different gums for 12 minutes or not chewing (negative control). Extrinsic stain was measured at 1 and 2 weeks by modified Lobene Stain Index (MLSI), digital imaging, and a Vita EasyShade spectrophotometer. RESULTS: At 2 weeks, MLSI scores showed a statistically significant mean reduction of 43% or greater versus no-gum control for all three gum treatments. Digital image analysis and Vita EasyShade measurement showed reductions of yellowness (measured by difference in ∆b* values between the three gums and the non-gum control treatment) ranging from 0.28 to 0.34 and 3.52 to 4.18 Δb* units, respectively, for subjects using the chewing gums versus no-gum control (P< 0.05) after 2 weeks. This clinical study demonstrated that sugar-free gum can effectively reduce new stain formation along with daily tooth brushing in as little as 2 weeks when used in conjunction with tea rinsing to help promote more rapid stain formation. All three test methods confirmed the results, albeit with different levels of statistical significance. A minor modification of gum base polymer, or change of flavors, did not significantly impact the prevention of new stain formation. CLINICAL SIGNIFICANCE: Regular consumption of sugar-free chewing gum helps prevent extrinsic dental stain accumulation and provides a simple and enjoyable means for consumers to maintain their natural tooth color.

Extracellular Glycoside Hydrolase Activities in the Human Oral Cavity.

Carbohydrate availability shifts when bacteria attach to a surface and form biofilm. When salivary planktonic bacteria form an oral biofilm, a variety of polysaccharides and glycoproteins are the primary carbon sources; however, simple sugar availabilities are limited due to low diffusion from saliva to biofilm. We hypothesized that bacterial glycoside hydrolase (GH) activities would be higher in a biofilm than in saliva in order to maintain metabolism in a low-sugar, high-glycoprotein environment. Salivary bacteria from 13 healthy individuals were used to grow in vitro biofilm using two separate media, one with sucrose and the other limiting carbon sources to a complex carbohydrate. All six GHs measured were higher in vitro when grown in the medium with complex carbohydrate as the sole carbon source. We then collected saliva and overnight dental plaque samples from the same individuals and measured ex vivo activities for the same six enzymes to determine how oral microbial utilization of glycoconjugates shifts between the planktonic phase in saliva and the biofilm phase in overnight dental plaque. Overall higher GH activities were observed in plaque samples, in agreement with in vitro observation. A similar pattern was observed in GH activity profiles between in vitro and ex vivo data. 16S rRNA gene analysis showed that plaque samples had a higher abundance of microorganisms with larger number of GH gene sequences. These results suggest differences in sugar catabolism between the oral bacteria located in the biofilm and those in saliva.

Crossover clinical investigation of a whitening chewing gum for inhibiting dental stain formation in conjunction with tooth brushing.

OBJECTIVE: The purpose of this clinical investigation was to evaluate the effectiveness of a marketed whitening chewing gum compared to a no-gum control in preventing the formation of extrinsic stains on the teeth of stain-forming subjects when chewed over a 12-week period of regular unsupervised use in conjunction with daily tooth brushing. METHODS: This was a single-center, examiner-blind, randomized, 12-week crossover clinical trial. Stain-forming (after smoking or drinking coffee or tea) adults, starting with a stain-free baseline, either chewed the test gum (Orbit White) unsupervised four times per day, 15 minutes/chew, or used no gum along with daily brushing with a commercially available toothbrush and dentifrice for 12 weeks. At the crossover, all procedures were repeated with subjects assigned the opposite treatment. Extrinsic stain was measured at six and 12 weeks by both the Lobene Stain Index (LSI) and the Modified Lobene Stain Index (MLSI) using separate experienced examiners. RESULTS: After 12 weeks, LSI stain scores showed a significant 25% reduction (p = 0.0008) in new stain formation for subjects using the test chewing gum along with tooth brushing versus tooth brushing alone (no-gum control). The corresponding MLSI stain scores demonstrated a 36% reduction (p < 0.0001) in the formation of extrinsic stain on the teeth. CONCLUSION: The overall findings of this clinical study demonstrated that regular use of Orbit White chewing gum, soon after smoking or drinking coffee or tea, will supplement daily tooth brushing in preventing unsightly stains from forming on the anterior teeth compared to brushing alone.

Sample efficient reinforcement learning with active learning for molecular design.

Reinforcement learning (RL) is a powerful and flexible paradigm for searching for solutions in high-dimensional action spaces. However, bridging the gap between playing computer games with thousands of simulated episodes and solving real scientific problems with complex and involved environments (up to actual laboratory experiments) requires improvements in terms of sample efficiency to make the most of expensive information. The discovery of new drugs is a major commercial application of RL, motivated by the very large nature of the chemical space and the need to perform multiparameter optimization (MPO) across different properties. In silico methods, such as virtual library screening (VS) and de novo molecular generation with RL, show great promise in accelerating this search. However, incorporation of increasingly complex computational models in these workflows requires increasing sample efficiency. Here, we introduce an active learning system linked with an RL model (RL-AL) for molecular design, which aims to improve the sample-efficiency of the optimization process. We identity and characterize unique challenges combining RL and AL, investigate the interplay between the systems, and develop a novel AL approach to solve the MPO problem. Our approach greatly expedites the search for novel solutions relative to baseline-RL for simple ligand- and structure-based oracle functions, with a 5-66-fold increase in hits generated for a fixed oracle budget and a 4-64-fold reduction in computational time to find a specific number of hits. Furthermore, compounds discovered through RL-AL display substantial enrichment of a multi-parameter scoring objective, indicating superior efficacy in curating high-scoring compounds, without a reduction in output diversity. This significant acceleration improves the feasibility of oracle functions that have largely been overlooked in RL due to high computational costs, for example free energy perturbation methods, and in principle is applicable to any RL domain.

Chewing gum containing allyl isothiocyanate from mustard seed extract is effective in reducing volatile sulfur compounds responsible for oral malodor.

PURPOSE: To evaluate the in vivo effect of chewing gum containing allyl isothiocyanate alone, and in combination with zinc salts on reduction of the level of volatile sulfur compounds responsible for oral malodor. METHODS: 15 healthy volunteers between the ages of 20-50 chewed either an experimental gum or a placebo gum for 12 minutes. Their mouth air was analyzed for volatile sulfur compounds by a gas chromatograph at baseline, immediately after chewing, and at 60, 120 and 180 minutes after treatment. RESULTS: The study revealed that allyl isothiocyanate, a constituent of mustard seed extract, can effectively reduce the concentration of volatile sulfur compounds in mouth air. Chewing gum containing 0.1% zinc lactate and 0.01% of allyl isothiocyanate eliminated 89%, 55.5%, 48% and 24% of the total VSC concentration immediately after chewing and at 1, 2, and 3 hours after chewing, respectively.

Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses.

Licensed rabies virus vaccines based on whole inactivated virus are effective in humans. However, there is a lack of detailed investigations of the elicited immune response, and whether responses can be improved using novel vaccine platforms. Here we show that two doses of a lipid nanoparticle-formulated unmodified mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) induces higher levels of RABV-G specific plasmablasts and T cells in blood, and plasma cells in the bone marrow compared to two doses of Rabipur in non-human primates. The mRNA vaccine also generates higher RABV-G binding and neutralizing antibody titers than Rabipur, while the degree of somatic hypermutation and clonal diversity of the response are similar for the two vaccines. The higher overall antibody titers induced by the mRNA vaccine translates into improved cross-neutralization of related lyssavirus strains, suggesting that this platform has potential for the development of a broadly protective vaccine against these viruses.

A tool for evaluating heterogeneity in avidity of polyclonal antibodies.

Diversity in specificity of polyclonal antibody (pAb) responses is extensively investigated in vaccine efficacy or immunological evaluations, but the heterogeneity in antibody avidity is rarely probed as convenient tools are lacking. Here we have developed a polyclonal antibodies avidity resolution tool (PAART) for use with label-free techniques, such as surface plasmon resonance and biolayer interferometry, that can monitor pAb-antigen interactions in real time to measure dissociation rate constant (kd ) for defining avidity. PAART utilizes a sum of exponentials model to fit the dissociation time-courses of pAb-antigens interactions and resolve multiple kd contributing to the overall dissociation. Each kd value of pAb dissociation resolved by PAART corresponds to a group of antibodies with similar avidity. PAART is designed to identify the minimum number of exponentials required to explain the dissociation course and guards against overfitting of data by parsimony selection of best model using Akaike information criterion. Validation of PAART was performed using binary mixtures of monoclonal antibodies of same specificity but differing in kd of the interaction with their epitope. We applied PAART to examine the heterogeneity in avidities of pAb from malaria and typhoid vaccinees, and individuals living with HIV-1 that naturally control the viral load. In many cases, two to three kd were dissected indicating the heterogeneity of pAb avidities. We showcase examples of affinity maturation of vaccine induced pAb responses at component level and enhanced resolution of heterogeneity in avidity when antigen-binding fragments (Fab) are used instead of polyclonal IgG antibodies. The utility of PAART can be manifold in examining circulating pAb characteristics and could inform vaccine strategies aimed to guide the host humoral immune response.

Assessment of chewing sugar-free gums for oral debris reduction: a randomized controlled crossover clinical trial.

PURPOSE: To assess the oral debris removal efficacy of two commercial sugar-free chewing gums, based on a newly developed oral debris scoring system. METHODS: A randomized, examiner-blinded, three-arm crossover study was conducted, with a 1-week washout period between the crossover phases. 42 healthy adults were randomly assigned to sugar-free stick gum (Wrigley's Extra Freshmint), sugar-free pellet gum (Wrigley's Extra Fruit) or no-gum chewing groups. Subjects consumed a single chocolate cookie, and were examined at baseline, and at 2-, 5-, and 10-minute time points with or without gum-chewing treatment. Primary outcome measures were oral debris scores on the occlusal surface, interproximal and gingival margin areas. The entire test procedure was repeated on two subsequent visits. RESULTS: The baseline conditions in the three groups did not differ significantly. Chewing either stick gum or pellet gum resulted in significantly lower oral debris scores (P < 0.0001) compared to the control (no-gum) treatment for all intraoral sites, while no significant difference was observed between the two chewing gum groups. Intra-examiner repeatability of the new scoring criteria was high throughout the study (Kappa > 0.90).

The oral health benefits of chewing gum.

The use of sugar-free gum provides a proven anti-caries benefit, but other oral health effects are less clearly elucidated. Chewing sugar-free chewing gum promotes a strong flow of stimulated saliva, which helps to provide a number of dental benefits: first, the higher flow rate promotes more rapid oral clearance of sugars; second, the high pH and buffering capacity of the stimulated saliva help to neutralise plaque pH after a sugar challenge; and, lastly, studies have shown enhanced remineralisation of early caries-like lesions and ultimately prospective clinical trials have shown reduced caries incidence in children chewing sugar-free gum. This paper reviews the scientific evidence for these functional claims and discusses other benefits, including plaque and extrinsic stain reduction, along with the possibility of adding specific active agents, including fluoride, antimicrobials, urea and calcium phosphates, to enhance these inherent effects. The evidence for a specific effect of xylitol as a caries-therapeutic agent is also discussed. In conclusion, it is asserted that chewing gum has a place as an additional mode of dental disease prevention to be used in conjunction with the more traditional preventive methods.