Salivary N1-Methyl-2-Pyridone-5-Carboxamide, a Biomarker for Uranium Uptake, in Kuwaiti Children Exhibiting Exceptional Weight Gain.

In a longitudinal study of 6,158 Kuwaiti children, we selected 94 for salivary metabolomic analysis who were neither obese (by waist circumference) nor metabolic syndrome (MetS) positive (<3 diagnostic features). Half (43) remained healthy for 2 years. The other half (51) were selected because they became obese and MetS positive 2 years later. In the half becoming obese, metabolomic analysis revealed that the level of salivary N1-Methyl-2-pyridone-5-carboxamide (2PY) had the highest positive association with obesity (p = 0.0003, AUC = 0.72) of 441 salivary biochemicals detected. 2PY is a recognized uremic toxin. Also, 2PY has been identified as a biomarker for uranium uptake. Considering that a relatively recent military conflict with documented uranium contamination of the area suggests that this weight gain could be a toxicological effect of long-time, low-level uranium ingestion. Comparison of salivary 2PY in samples from the USA and Kuwait found that only Kuwait samples were significantly related to obesity. Also, the geographic distribution of both reported soil radioactivity from 238U and measured salivary 2PY was highest in the area where military activity was highest. The prevalence pattern of adult diabetes in Kuwait suggests that a transient diabetogenic factor has been introduced into the Kuwaiti population. Although we did not measure uranium in our study, the presence of a salivary biomarker for uranium consumption suggests potential toxicity related to obesity in children.

Oral Cancer Knowledge, Attitudes and Practices among Primary Oral Health Care Dentists in Kuwait

Background: Oral cancer signifies a public health concern of international importance. Early detection of oral cancer can improve the prognosis and the 5-year survival rate. Objective: The aim of this study was to assess the level of oral cancer knowledge, opinion, attitudes and practices among dentists working at the primary oral health care centers in Kuwait. Methods: In this cross-sectional study, self-reported questionnaire was distributed to the dentists working at the primary oral health care centers in Kuwait. A total of 289 dentists participated in the present study. The questionnaire included 23- questions on oral cancer knowledge, opinion, attitudes and practices. Results: The mean age of the dentists was 35.2 ± 10.9 years. Approximately, all dentists (99.7%) were aware of the major risk factors that were most likely associated with oral cancer. Overall, majority of the participants knew the most common form of oral cancer (80.6%), most common site (80.3%) and the likely lesions associated with oral cancer occurrence (87.9%). A large number of dental practitioners (81%) would routinely refer a patient with a suspicious lesion to a specialist. Nearly one-third (32%) reviewed their patients' oral cancer risk factors. Approximately two-thirds (62%) assessed the use of tobacco in their practice. Almost, all (92.4%) were interested in attending continuing education courses on oral cancer. Conclusions: Majority of the participants presented good knowledge about various aspects of oral cancer. More continuing education programs on risk factors and diagnosis of oral cancer should be organized to train the dentists. Oral cancer screening should be a routine procedure for the high risk patients at the primary oral health care centers in Kuwait.

The salivary microbiome is altered in the presence of a high salivary glucose concentration.

BACKGROUND: Type II diabetes (T2D) has been associated with changes in oral bacterial diversity and frequency. It is not known whether these changes are part of the etiology of T2D, or one of its effects. METHODS: We measured the glucose concentration, bacterial counts, and relative frequencies of 42 bacterial species in whole saliva samples from 8,173 Kuwaiti adolescents (mean age 10.00 ± 0.67 years) using DNA probe analysis. In addition, clinical data related to obesity, dental caries, and gingivitis were collected. Data were compared between adolescents with high salivary glucose (HSG; glucose concentration ≥ 1.0 mg/d, n = 175) and those with low salivary glucose (LSG, glucose concentration < 0.1 mg/dL n = 2,537). RESULTS: HSG was associated with dental caries and gingivitis in the study population. The overall salivary bacterial load in saliva decreased with increasing salivary glucose concentration. Under HSG conditions, the bacterial count for 35 (83%) of 42 species was significantly reduced, and relative bacterial frequencies in 27 species (64%) were altered, as compared with LSG conditions. These alterations were stronger predictors of high salivary glucose than measures of oral disease, obesity, sleep or fitness. CONCLUSIONS: HSG was associated with a reduction in overall bacterial load and alterations to many relative bacterial frequencies in saliva when compared with LSG in samples from adolescents. We propose that hyperglycemia due to obesity and/or T2D results in HSG and subsequent acidification of the oral environment, leading to a generalized perturbation in the oral microbiome. This suggests a basis for the observation that hyperglycemia is associated with an increased risk of dental erosion, dental caries, and gingivitis. We conclude that HSG in adolescents may be predicted from salivary microbial diversity or frequency, and that the changes in the oral microbial composition seen in adolescents with developing metabolic disease may the consequence of hyperglycemia.

Unhealthy Phenotype as Indicated by Salivary Biomarkers: Glucose, Insulin, VEGF-A, and IL-12p70 in Obese Kuwaiti Adolescents.

OBJECTIVE: Here, we investigated the relationships between obesity and the salivary concentrations of insulin, glucose, and 20 metabolic biomarkers in Kuwaiti adolescents. Previously, we have shown that certain salivary metabolic markers can act as surrogates for blood concentrations. METHODS: Salivary samples of whole saliva were collected from 8,317 adolescents. Salivary glucose concentration was measured by a high-sensitivity glucose oxidase method implemented on a robotic chemical analyzer. The concentration of salivary insulin and 20 other metabolic biomarkers was assayed in 744 randomly selected saliva samples by multiplexed bead-based immunoassay. RESULTS: Obesity was seen in 26.5% of the adolescents. Salivary insulin predicting hyperinsulinemia occurred in 4.3% of normal-weight adolescents, 8.3% of overweight adolescents, and 25.7% of obese adolescents (p < 0.0001). Salivary glucose predicting hyperglycemia was found in only 3% of obese children and was not predictive (p = 0.89). Elevated salivary glucose and insulin occurring together was associated with elevated vascular endothelial growth factor and reduced salivary interleukin-12. CONCLUSION: Considering the surrogate nature of salivary insulin and glucose, this study suggests that elevated insulin may be a dominant sign of metabolic disease in adolescent populations. It also appears that a proangiogenic environment may accompany elevated glucose in obese adolescents.

Salivary Biomarkers in Pediatric Metabolic Disease Research.

The increasing prevalence of childhood obesity and obesity-related metabolic disorders is now considered a global pandemic. The main goal of the pediatric obesity research community is to identify children who are at risk of becoming obese before their body mass index rises above age norms. To do so, we must identify biomarkers of metabolic health and immunometabolism that can be used for large-scale screening and diagnosis initiatives among at-risk children. Because blood sampling is often unacceptable to both parents and children when there is no direct benefit to the child, as in a community-based research study, there is a clear need for a low-risk, non-invasive sampling strategy. Salivary analysis is now well recognized as a likely candidate for this purpose. In this review, we discuss the physiologic role of saliva and its strengths and limitations as a fluid for biomarker discovery, obesity screening, metabolic disease diagnosis, and response monitoring after interventions. We also describe the current state of the salivary biomarker field as it pertains to metabolic research, with a special emphasis on studies conducted in children and adolescents. Finally, we look forward to technological developments, such as salivary "omics" and point of service diagnostic devices, which have the potential to accelerate the pace of research and discovery in this vitally important field.

Five-year Sealant Retention and Efficacy in a Multi-operated School-based Oral Health Programme in Kuwait.

PURPOSE: To evaluate sealant retention in a multi-operator school-based oral health programme and sealant efficacy in preventing caries in a high caries-risk population. MATERIALS AND METHODS: Sealant retention and caries status in previously placed sealants on permanent first molars were evaluated in 503 children ages 6 to 8 years at 20 primary schools. A total of 2538 sealants were applied on 876 first permanent molars and evaluated for retention and efficacy in preventing caries from 2002 to 2007. These sealants were placed on occlusal and buccal or palatal surfaces using a standard protocol after isolation with rubber-dam or cotton roll. Caries was scored in teeth in which the sealants were partially or completely lost. RESULT: 1752 sealants (69%) were examined at the end of the fifth year, with 58.3% of the sealants completely retained, 7.4% partially lost, 19% completely lost, 6.2% resealed and 9.1% restored. Only 3.1% of the previously sealed teeth were carious and 87.8% of previously sealed teeth were caries free. In multivariate analysis, occlusal surfaces were 2.0 times more likely to retain a sealant than were the buccal and palatal pits (p < 0.0001). No differences in sealant retention vs caries by arch, or teeth isolated using rubber-dam vs cotton roll were seen. CONCLUSION: The present study shows the effectiveness of sealants in caries prevention in a multi-operator school sealant programme, and provides evidence supporting their use in such programmes for high-caries populations.

Continuous Metabolic Syndrome Scores for Children Using Salivary Biomarkers.

BACKGROUND: Binary definitions of the metabolic syndrome based on the presence of a particular number of individual risk factors are limited, particularly in the pediatric population. To address this limitation, we aimed at constructing composite and continuous metabolic syndrome scores (cmetS) to represent an overall measure of metabolic syndrome (MetS) in a large cohort of metabolically at-risk children, focusing on the use of the usual clinical parameters (waist circumference (WC) and systolic blood pressure (SBP), supplemented with two salivary surrogate variables (glucose and high density lipoprotein cholesterol (HDLC). Two different approaches used to create the scores were evaluated in comparison. METHODS: Data from 8,112 Kuwaiti children (10.00 ± 0.67 years) were used to construct two cmetS for each subject. The first cmetS (cmetS-Z) was created by summing standardized residuals of each variable regressed on age and gender; and the second cmetS (cmetS-PCA) was defined as the first principal component from gender-specific principal component analysis based on the four variables. RESULTS: There was a graded relationship between both scores and the number of adverse risk factors. The areas under the curve using cmetS-Z and cmetS-PCA as predictors for severe metabolic syndrome (defined as the presence of ≥3 metabolic risk factors) were 0.935 and 0.912, respectively. cmetS-Z was positively associated with WC, SBP, and glucose, but inversely associated with HDLC. Except for the lack of association with glucose, cmetS-PCA was similar to cmetS-Z in boys, but had minimum loading on HDLC in girls. Analysis using quantile regression showed an inverse association of fitness level with cmetS-PCA (p = 0.001 for boys; p = 0.002 for girls), and comparison of cmetS-Z and cmetS-PCA suggested that WC and SBP were main contributory components. Significant alterations in the relationship between cmetS and salivary adipocytokines were demonstrated in overweight and obese children as compared to underweight and normal-weight children. CONCLUSION: We have derived continuous summary scores for MetS from a large-scale pediatric study using two different approaches, incorporating salivary measures as surrogate for plasma measures. The derived scores were viable expressions of metabolic risk, and can be utilized to study the relationships of MetS with various aspects of the metabolic disease process.

Salivary glucose concentration exhibits threshold kinetics in normal-weight, overweight, and obese children.

BACKGROUND: Metabolic syndrome in childhood predicts the development of cardiovascular disease and type 2 diabetes (T2D) in adulthood. Testing for features of metabolic syndrome, such as fasting plasma glucose concentration, requires blood sampling which can be difficult in children. Here we evaluated salivary glucose concentration as a surrogate measurement for plasma glucose concentration in 11-year-old US children. METHODS: Children from Portland, Maine, and Cambridge, Massachusetts, with a mean age of 10.6±0.2 years provided 6-hour fasting samples of both blood and whole saliva. Salivary glucose levels were measured with a high-sensitivity assay (sensitivity =0.002 mg/dL). Plasma glucose levels were determined by a commercial clinical laboratory. Blood pressure, salivary flow rate, height, and weight were also measured. RESULTS: Of the 65 children enrolled, there were two underweight children (3.1%), 30 normal-weight children (46.2%), 12 overweight children (18.4%), and 21 obese children (32.3%). The mean overall glucose concentrations were 0.11±0.02 mg/dL in saliva and 86.3±0.8 mg/dL in plasma, and these did not differ significantly by body-weight groups. By regression analysis, the plasma concentration equaled 13.5 times the saliva concentration, with a threshold level of 84.8 mg/dL. Salivary glucose values less than threshold plasma concentration were essentially zero. Diagnostic analysis indicated a positive predictive value of 50%, a negative predictive value of 90%, and a sensitivity and specificity both of approximately 75%. The salivary glucose concentration did not vary with saliva flow rate. CONCLUSION: Taking into account the threshold response characteristics of the salivary glucose concentration response, these results suggest that testing salivary glucose levels may be useful as a screening assay for high fasting plasma glucose levels. The low false positive value is important to assure a low fraction of missed diagnoses.

Metabolic disease risk in children by salivary biomarker analysis.

OBJECTIVE: The study of obesity-related metabolic syndrome or Type 2 diabetes (T2D) in children is particularly difficult because of fear of needles. We tested a non-invasive approach to study inflammatory parameters in an at-risk population of children to provide proof-of-principle for future investigations of vulnerable subjects. DESIGN AND METHODS: We evaluated metabolic differences in 744, 11-year old children selected from underweight, normal healthy weight, overweight and obese categories by analyzing fasting saliva samples for 20 biomarkers. Saliva supernatants were obtained following centrifugation and used for analyses. RESULTS: Salivary C-reactive protein (CRP) was 6 times higher, salivary insulin and leptin were 3 times higher, and adiponectin was 30% lower in obese children compared to healthy normal weight children (all P<0.0001). Categorical analysis suggested that there might be three types of obesity in children. Distinctly inflammatory characteristics appeared in 76% of obese children while in 13%, salivary insulin was high but not associated with inflammatory mediators. The remaining 11% of obese children had high insulin and reduced adiponectin. Forty percent of the non-obese children were found in groups which, based on biomarker characteristics, may be at risk for becoming obese. CONCLUSIONS: Significantly altered levels of salivary biomarkers in obese children from a high-risk population, suggest the potential for developing non-invasive screening procedures to identify T2D-vulnerable individuals and a means to test preventative strategies.

Caries prevalence, oral hygiene, and oral health habits of Kuwaiti infants and toddlers.

OBJECTIVE: The purpose of this study was to describe the oral health, oral hygiene, and oral health habits of Kuwaiti infants and toddlers. SUBJECTS AND METHODS: This cross-sectional study of a convenience sample included 336 infants and toddlers (156 females and 180 males). The teeth of the infants and toddlers were examined using a mirror and a light source. Oral hygiene was recorded, and then all teeth were cleaned with gauze and examined for caries. Parents were interviewed regarding their children's feeding habits, brushing or tooth cleaning, and night feeding. The evaluation criteria for caries were sound teeth, noncavitated lesions, cavitated lesions, filled teeth, and missing teeth. RESULTS: The mean age was 11.1 ± 2.4 months (range 2-23). Of the 336 subjects, 247 (73%) had good oral hygiene, 64 (19%) had parents who brushed or cleaned their infants' and toddlers' teeth; 288 (86%) were bottle-fed, and 290 (86%) were also night fed. The mean number of teeth upon examination was 4.6 ± 2.7 (range 2-8). Three percent of the infants and toddlers had caries. Cavitated lesions were present in 6 patients (1.8%), while 4 (1.2%) had noncavitated lesions. The mean d1d2t (caries teeth: noncavitated lesions and cavitated lesions) was 0.03 ± 0.3, and the mean d1d2s (carious surfaces) was 0.07 ± 0.5. CONCLUSION: The caries prevalence and severity was low in infants and toddlers. However, poor oral health practices and habits as well as unhealthy feeding practices that could affect the future caries prevalence were noted.

Obesity and dental decay: inference on the role of dietary sugar.

OBJECTIVE: To evaluate the relationship of children's obesity and dental decay. METHODS: We measured parameters related to obesity and dental decay in 8,275 4(th) and 5(th) grade Kuwaiti children (average age = 11.36 years) in a cross-sectional study. First to determine body weight, height, age for computation of BMI . Second, to determine numbers of teeth, numbers of fillings and numbers of untreated decayed teeth to determine extent and severity of dental disease. From these measurements, we computed measures of dental decay in children from four body weight categories; obese, overweight, normal healthy weight and underweight children. RESULTS: The percentage of children with decayed or filled teeth varied inversely with the body weight category. The percentage of decayed or filled teeth decreased from 15.61% (n=193) in underweight children, to 13.03% (n=4,094) in normal healthy weight children, to 9.73% (n=1,786) in overweight children to 7.87% (n=2,202) in obese children. Differences between all groups were statistically significant. Male children in this population had more dental decay than female children but the reduction of tooth decay as a function of BMI was greater in male children. CONCLUSIONS: The finding of an inverse obesity-dental decay relationship contradicts the obesity-sugar and the obesity-dental decay relationship hypotheses. Sugar is well recognized as necessary and sufficient for dental decay. Sugar is also hypothesized to be a leading co-factor in obesity. If the later hypothesis is true, one would expect dental decay to increase with obesity. This was not found. The reasons for this inverse relationship are not currently clear.

Effectiveness of primer and bond in sealant retention and caries prevention.

PURPOSE: The purpose of this clinical trial was to test the use of a primer and bonding agent to increase the retention of a fissuresealant in a group of Kuwaiti children. METHODS: In 78 6- to 9-year-old children who required sealants in all 4 permanent frst molars, sealants were placed in 2 teeth using a primer and bond (3M Scotch Bond) and in 2 teeth without primer and bond. Sealant retention was evaluated 1 and 2 years later. Sealant retention was scored as: (1) complete retention; (2) partial loss of sealant; and (3) complete loss of sealant Caries was scored for those teeth in which the sealant was partially or completely lost RESULTS: At the 2-year examination, in teeth sealed with primer and bond (a) 64% of the sealants were completely retained; (b) 23% were partially lost; and (c) 13% were completely lost. In teeth sealed without primer and bond: (a) 68% of the sealants were completely retained; (b) 20% were partially lost; and (c) 12% were completely lost There was no difference in sealant retention (P=.22) and caries (P=.56) in teeth sealed with and without bond. In multivariate analyses after controlling for age, gender, tooth surface, and arch, no differences in sealant retention and caries were seen. CONCLUSION: If a proper technique is used in sealant placement, primer and bond does not enhance sealant retention.

Enhancement of plaque removal efficacy by tooth brushing with baking soda dentifrices: results of five clinical studies.

OBJECTIVE: An earlier clinical study demonstrated that brushing with a commercial Arm & Hammer dentifrice containing baking soda physically removed significantly more plaque than brushing with either of two commercial dentifrices which did not contain baking soda. However, little has been done to confirm these results and to compare baking soda-containing dentifrices with more recently commercialized non-baking soda dentifrice formulations. The objective of this study was to compare commercial dentifrices containing 20% to 65% baking soda and commercial dentifrices without baking soda in enhancing plaque removal efficacy of tooth brushing. METHODS: Five randomized, controlled, blinded, crossover clinical studies were performed among healthy adult volunteers who provided informed consent. After approximately 24 hours without oral hygiene, subjects with sufficient plaque were enrolled in the study phase. Plaque was scored before and after supervised brushing for one minute using the Turesky, et al. modification of the Quigley-Hein Plaque Index at six sites per tooth according to Soparkar's modification as described by Lobene, et al. In each study, wash-out periods with a regular dentifrice not evaluated in the study separated each product treatment. RESULTS: In all studies, every dentifrice exhibited a significant (p < 0.0001) reduction in 24-hour plaque scores. Between-group comparisons of whole mouth plaque scores in all five studies demonstrated that brushing with baking soda dentifrices resulted in statistically greater (p < 0.01) reductions in whole mouth mean plaque scores than brushing with dentifrices that did not contain baking soda. Results on other tooth surfaces, such as facial, lingual, proximal, and gingival surfaces also demonstrated statistically greater (p < 0.05) reductions in mean plaque scores for the baking soda-containing dentifrices as compared to the baking soda-free dentifrices. In three of the studies comparing different levels of baking soda, brushing with dentifrices with higher concentrations of baking soda consistently removed numerically more plaque than those containing lower levels. In one of these three studies, the difference in plaque removal between the baking soda dentifrices reached statistical significance. The results suggest a positive relationship between plaque removal efficiency and baking soda concentration. CONCLUSION: The collective results from the five controlled clinical studies on over 270 subjects reported in this paper, consistently demonstrate that Arm & Hammer baking soda dentifrices enhanced plaque removal effectiveness of tooth brushing to a significantly greater extent than the non-baking soda dentifrice products.

Dental caries experience of Kuwaiti schoolchildren.

OBJECTIVE: This study was designed to measure the dental caries experience of Kuwaiti schoolchildren. METHODS: A national epidemiologic survey of the 5-14 year old children (n = 4,588) was conducted in the 5 governorates of Kuwait in 2001. Eight trained and calibrated dentists examined the children. Dental caries was scored using WHO criteria. RESULTS: In the primary dentition, the percentage of 5- and 6-year-old children with dft = 0 was 12.6% and 14.4% respectively. The corresponding mean dft/dfs for 5- and 6-year-olds were 4.6/9.7 and 4.6/9.9. For the permanent dentition, the percentage of 12- and 14-year-old children with DMFT = 0 was 26.4% and 21.7% respectively. The corresponding mean DMFT/DFS figures for 12- and 14-year-olds were 2.6/3.4 and 3.9/4.2. The d/D component was the major contributor to these mean scores. Poor oral hygiene (OR = 2.0; 95% CI = 1.7 - 2.4) and increasing age (OR = 1.4; 95% CI = 1.3 - 1.5) were significantly associated with caries risk in the permanent dentition. CONCLUSIONS: Caries levels are similar to those in neighbouring and other Middle East countries. There is a clear need for expanding the national school oral health programme to reach those children who are not yet receiving systematic preventive and curative services. Further studies are required to monitor the effect of the extensive caries preventive programme now in place in Kuwait.

Comparative tooth whitening and extrinsic tooth stain removal efficacy of two tooth whitening dentifrices: six-week clinical trial.

OBJECTIVE: The objective of this six-week, examiner-blind clinical study was to assess the tooth whitening and extrinsic tooth stain removal efficacy of a new dentifrice delivering 1.0% hydrogen peroxide, 0.243% sodium fluoride, and sodium tripolyphosphate in a high-cleaning silica base (Test Dentifrice), relative to that of commercially available hexametaphosphate-containing whitening dentifrice (Positive Control Dentifrice). METHODOLOGY: Following a baseline oral soft tissue examination and scoring of extrinsic tooth stain and tooth shade, qualifying adult male and female subjects from the Harrisburg, Pennsylvania area were randomized into either the Test or Positive Control Dentifrice group. The two groups were balanced for gender, extrinsic tooth stain, and tooth shade scores. All subjects were provided their assigned dentifrice and a soft-bristled adult toothbrush for home use. Subjects were instructed to brush their teeth for two minutes twice daily (morning and evening) using only the dentifrice provided, and to refrain from using any other oral hygiene products for the entire six weeks of the study. There were no restrictions regarding diet or smoking habits during the course of the study. Oral soft tissue, extrinsic tooth stain, and tooth shade assessments for each subject were repeated after two and six weeks of product use. All statistical tests were two sided and employed a level of significance of alpha = 0.05. RESULTS: Fifty-six (56) subjects complied with the protocol and completed the entire study. Compared to baseline at both the two- and six-week examinations, the Test Dentifrice group had statistically significant reductions in extrinsic tooth stain area and intensity, and statistically significant mean shade rank reductions, with a six-week reduction of 4.81. In contrast, at six weeks, the Positive Control dentifrice had a statistically significant increase in tooth stain area, a non-significant increase in tooth stain intensity, and a statistically significant mean 1.40 shade rank score reduction. At both the two- and six-week examinations, the Test Dentifrice group had statistically significantly lighter tooth shades and statistically significantly lower levels of extrinsic tooth stain area and intensity than the Positive Control Dentifrice group. CONCLUSION: A new whitening dentifrice delivering 1.0% hydrogen peroxide, 0.243% sodium fluoride, and sodium tripolyphosphate in a high-cleaning silica base has significant efficacy in tooth whitening and extrinsic stain removal, and provides a statistically significantly greater level of efficacy for both tooth whitening and extrinsic tooth stain removal than the commercially available Positive Control Dentifrice.