Predicting Dental Caries in Young Children in Primary Health Care Settings.

Young children need increased access to dental prevention and care. Targeting high caries risk children first helps meet this need. The objective of this study was to develop a parent-completed, easy-to-score, short, accurate caries risk tool for screening in primary health care settings to identify children at increased risk for cavities. A longitudinal, prospective, multisite, cohort study enrolled (primarily through primary health care settings) and followed 985 (out of 1,326) 1-y-old children and their primary caregivers (PCGs) until age 4. The PCG completed a 52-item self-administered questionnaire, and children were examined using the International Caries Detection and Assessment Criteria (ICDAS) at 12 ± 3 mo (baseline), 30 ± 3 mo (80% retention), and 48 ± 3 mo of age (74% retention). Cavitated caries lesion (dmfs = decayed, missing, and filled surfaces; d = ICDAS ≥3) experience at 4 y of age was assessed and tested for associations with questionnaire items using generalized estimating equation models applied to logistic regression. Multivariable analysis used backward model selection, with a limit of 10 items. At age 4, 24% of children had cavitated-level caries experience; 49% were female; 14% were Hispanic, 41% were White, 33% were Black, 2% were other, and 10% were multiracial; 58% enrolled in Medicaid; and 95% lived in urban communities. The age 4 multivariable prediction model, using age 1 responses (area under the receiver operating characteristic curve = 0.73), included the following significant (P < 0.001) variables (odds ratios): child participating in public assistance programs such as Medicaid (1.74), being non-White (1.80-1.96), born premature (1.48), not born by caesarean section (1.28), snacking on sugary snacks (3 or more/d, 2.22; 1-2/d or weekly, 1.55), PCG cleaning the pacifier with juice/soda/honey or sweet drink (2.17), PCG daily sharing/tasting food with child using same spoon/fork/glass (1.32), PCG brushing their teeth less than daily (2.72), PCG's gums bleeding daily when brushing or PCG having no teeth (1.83-2.00), and PCG having cavities/fillings/extractions in past 2 y (1.55). A 10-item caries risk tool at age 1 shows good agreement with cavitated-level caries experience by age 4.

Microbial Indicators of Dental Health, Dysbiosis, and Early Childhood Caries.

Dental caries lesions are a clinical manifestation of disease, preceded by microbial dysbiosis, which is poorly characterized and thought to be associated with saccharolytic taxa. Here, we assessed the associations between the oral microbiome of children and various caries risk factors such as demographics and behavioral and clinical data across early childhood and characterized over time the salivary and dental plaque microbiome of children before clinical diagnosis of caries lesions. Children (N = 266) were examined clinically at ~1, 2.5, 4, and 6.5 y of age. The microbiome samples were collected at 1, 2.5, and 4 y. Caries groups consisted of children who remained caries free (International Caries Detection and Assessment System [ICDAS] = 0) at all time points (CFAT) (n = 50); children diagnosed with caries (ICDAS ≥ 1) at 6.5 y (C6.5), 4 y (C4), or 2.5 y of age (C2.5); and children with early caries or advanced caries lesions at specific time points. Microbial community analyses were performed on zero-radius operational taxonomic units (zOTUs) obtained from V4 of 16S ribosomal RNA gene amplicon sequences. The oral microbiome of the children was affected by various factors, including antibiotic use, demographics, and dietary habits of the children and their caregivers. At all time points, various risk factors explained more of the variation in the dental plaque microbiome than in saliva. At 1 y, composition of saliva of the C4 group differed from that of the CFAT group, while at 2.5 y, this difference was observed only in plaque. At 4 y, multiple salivary and plaque zOTUs of genera Prevotella and Leptotrichia were significantly higher in samples of the C6.5 group than those of the CFAT group. In conclusion, up to 3 y prior to clinical caries detection, the oral microbial communities were already in a state of dysbiosis that was dominated by proteolytic taxa. Plaque discriminated dysbiotic oral ecosystems from healthy ones better than saliva.

Therapeutic drug monitoring and TB treatment outcomes in patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) increases the risk of TB disease and poor treatment outcomes such as delayed sputum culture conversion due to inadequate drug exposure. Therapeutic drug monitoring (TDM) has improved these outcomes in some settings.METHODS: To compare treatment outcomes in programs with routine TDM vs. programs that did not use TDM, we conducted a retrospective study among people with DM and TB at health departments in four US states.RESULTS: A total of 170 patients were enrolled (73 patients in the non-TDM group and 97 patients in the TDM group). Days to sputum culture conversion and total treatment duration were significantly shorter in the TDM group vs. the non-TDM group. In adjusted analyses, patients who underwent TDM were significantly more likely to achieve sputum culture conversion at 2 months (P = 0.007).CONCLUSION: TDM hastened microbiological cure from TB among people with DM and a high risk for poor treatment outcomes in the programmatic setting.

Improving Caries Risk Prediction Modeling: A Call for Action.

Dentistry has entered an era of personalized/precision care in which targeting care to groups, individuals, or even tooth surfaces based on their caries risk has become a reality to address the skewed distribution of the disease. The best approach to determine a patient's prognosis relies on the development of caries risk prediction models (CRPMs). A desirable model should be derived and validated to appropriately discriminate between patients who will develop disease from those who will not, and it should provide an accurate estimation of the patient's absolute risk (i.e., calibration). However, evidence suggests there is a need to improve the methodological standards and increase consistency in the way CRPMs are developed and evaluated. In fact, although numerous caries risk assessment tools are available, most are not routinely used in practice or used to influence treatment decisions, and choice is not commonly based on high-quality evidence. Research will propose models that will become more complex, incorporating new factors with high prognostic value (e.g., human genetic markers, microbial biomarkers). Big data and predictive analytic methods will be part of the new approaches for the identification of promising predictors with the ability to monitor patients' risk in real time. Eventually, the implementation of validated, accurate CRPMs will have to follow a user-centered design respecting the patient-clinician dynamic, with no disruption to the clinical workflow, and needs to operate at low cost. The resulting predictive risk estimate needs to be presented to the patient in an understandable way so that it triggers behavior change and effectively informs health care decision making, to ultimately improve caries outcomes. However, research on these later aspects is largely missing and increasingly needed in dentistry.

Maturation of the Oral Microbiome in Caries-Free Toddlers: A Longitudinal Study.

Understanding the development of the oral microbiota in healthy children is of great importance to oral and general health. However, limited data exist on a healthy maturation of the oral microbial ecosystem in children. Moreover, the data are biased by mislabeling "caries-free" populations. Therefore, we aimed to characterize the healthy salivary and dental plaque microbiome in young children. Caries-free (ICDAS [International Caries Detection and Assessment System] score 0) children (n = 119) and their primary caregivers were followed from 1 until 4 y of child age. Salivary and dental plaque samples were collected from the children at 3 time points (T1, ~1 y old; T2, ~2.5 y old; and T3, ~4 y old). Only saliva samples were collected from the caregivers. Bacterial V4 16S ribosomal DNA amplicons were sequenced using Illumina MiSeq. The reads were denoised and mapped to the zero-radius operational taxonomic units (zOTUs). Taxonomy was assigned using HOMD. The microbial profiles of children showed significant differences (P = 0.0001) over time. Various taxa increased, including Fusobacterium, Actinomyces, and Corynebacterium, while others showed significant decreases (e.g., Alloprevotella and Capnocytophaga) in their relative abundances over time. Microbial diversity and child-caregiver similarity increased most between 1 and 2.5 y of age while still not reaching the complexity of the caregivers at 4 y of age. The microbiome at 1 y of age differed the most from those at later time points. A single zOTU (Streptococcus) was present in all samples (n = 925) of the study. A large variation in the proportion of shared zOTUs was observed within an individual child over time (2% to 42% of zOTUs in saliva; 2.5% to 38% in dental plaque). These findings indicate that the oral ecosystem of caries-free toddlers is highly heterogeneous and dynamic with substantial changes in microbial composition over time and only few taxa persisting across the 3 y of the study. The salivary microbiome of 4-y-old children is still distinct from that of their caregivers.

Predicting Caries in Medical Settings: Risk Factors in Diverse Infant Groups.

Expanded partnership with the medical community is a promising strategy for reducing disparities in dental caries among young children. However, no validated caries risk instrument exists for use in primary health care settings. To help resolve this gap, a 52-item caries risk questionnaire was developed and targeted to primary caregivers (PCGs) to test in a 3-y prospective study. To begin to understand the validity of the questionnaire items, the purpose of this study was to compare responses to the questionnaire based on key demographic characteristics known to be associated with disparities in caries experience (e.g., race/ethnicity and insurance status). A total of 1,323 one-year-old children were recruited primarily through 3 medical research networks. Baseline questionnaire responses were analyzed via logistic regression. The sample was 49% female. Its racial/ethnic makeup was as follows: 13% Hispanic, 37% White, 37% Black, and 13% other or multiracial. Sixty-one percent were enrolled in Medicaid, and 95% resided in urban communities. Mothers represented 94% of PCGs. There were significant differences ( P < 0.05) in baseline responses based on Medicaid status and race/ethnicity. As compared with those not enrolled in Medicaid, children in the Medicaid group were significantly more likely (after adjusting for race/ethnicity) to 1) go to sleep while nursing or drinking something other than water, 2) eat sugary snacks between meals, 3) consume sugary drinks between meals, 4) receive topical fluoride from a health professional, 5) visit the dentist, and 6) not have an employed adult in the household. PCGs of children enrolled in Medicaid were significantly more likely to be the mother, have bleeding gums, eat sugary snacks between meals, consume sugary drinks between meals, eat or drink something other than water before going to bed, and not get regular dental checkups. In conclusion, there are significant differences in caries risk questionnaire responses based on Medicaid status and race/ethnicity that provide construct and criterion validity to the developed caries risk tool (ClinicalTrials.gov NCT01707797).

Biomarkers of inflammation - LBP and TLR- predict progression of knee osteoarthritis in the DOXY clinical trial.

OBJECTIVE: To evaluate systemic inflammatory biomarkers in symptomatic knee osteoarthritis (OA) and their association with radiographic and biochemical OA progression. METHODS: Lipopolysaccharide (LPS) binding protein (LBP), soluble Toll-like receptor 4 (sTLR4) and interleukin 6 (IL-6) were measured in plasma of 431 knee OA patients from the doxycycline (DOXY) trial at baseline and 18 months. Plasma lipopolysaccharide and lipopolysaccharide binding protein (LBP) were also measured at 12 months. As a biochemical indicator of disease activity and OA progression, urinary (u) C-telopeptide of Type II collagen (uCTX-II) was measured in samples collected at baseline and 18 months. Change over 16 months in radiographic tibiofemoral joint space width (JSW in mm) and joint space narrowing (JSN≥0.5 mm) were used to indicate radiographic OA progression. Change over 18 months for uCTX-II was used as a secondary outcome. Both univariate and multivariable regression analyses were performed to test the association between Z-score transformed biomarkers and outcomes. RESULTS: Baseline LBP and time-integrated concentration (TIC) of LBP over 12 and 18 months were associated with worsening joint space width (JSW) (parameter estimates: -0.1 to -0.07) and JSN (OR: 1.32 to 1.42) adjusting for treatment group, age, body mass index (BMI) and corresponding baseline radiographic measures. Baseline sTLR4 and TIC over 18 months were associated with change in uCTX-II over 18 months (adjusted parameter estimates: 0.0017 to 0.0020). Results were not modified by treatment with doxycycline. CONCLUSION: Plasma LBP and sTLR4 were associated with knee OA progression over 16-18 months. These results lend further support for a role of systemic low-grade inflammation in the pathogenesis of knee OA progression.

Fluoride Use in Health Care Settings: Association with Children's Caries Risk.

Expanded partnership with the medical community is an important strategy for reducing dental caries disparities. The purpose of this study was to assess the relationship between fluoride (F) "in office" (drops/tablets and/or varnish), as prescribed or applied by a health care professional by age 1 y, and 1) caries development and 2) presence of other caries risk factors or mediators (e.g., socioeconomic status). Child-primary caregiver (PCG) pairs ( N = 1,325) were recruited in Indiana, Iowa, and North Carolina as part of a longitudinal cohort study to validate a caries risk tool for primary health care settings. PCGs completed a caries risk questionnaire, while children received caries examinations per the criteria of the International Caries Detection and Assessment System at ages 1, 2.5, and 4 y. Baseline responses regarding children's history of F in office were tested for association with other caries risk variables and caries experience at ages 2.5 and 4 y via generalized estimating equation models applied to logistic regression. The sample was 48% female, and many children (61%) were Medicaid enrolled. The prevalence of cavitated caries lesions increased from 7% at age 2.5 y to 25% by age 4 y. Children who received F in office were likely deemed at higher caries risk and indeed were significantly ( P < 0.01) more likely to develop cavitated caries lesions by ages 2.5 and 4 y, even after F application (odds ratios: 3.5 and 2.3, respectively). Factors significantly associated with receiving F included the following: child being Medicaid enrolled, not having an employed adult in the household, child and PCG often consuming sugary drinks and snacks, and PCG having recent caries experience. Increased F in office from a health care provider by age 1 y was associated with known caries risk factors. Most (69%) children had never been to the dentist, suggesting that risk factors could be alerting medical providers and/or parents, thereby affecting in-office F recommendations. Differences among states could also be related to state-specific F-varnish reimbursement policies (ClinicalTrials.gov NCT01707797).

Validation of a Metastatic Assay using biopsies to improve risk stratification in patients with prostate cancer treated with radical radiation therapy.

Background: Radiotherapy is an effective treatment of intermediate/high-risk locally advanced prostate cancer, however, >30% of patients relapse within 5 years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Patients and methods: A bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to enable optimization of the Metastatic Assay threshold before further independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis-free survival (MFS). Results: Gene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients [HR = 3.21 (1.35-7.67); P = 0.003]. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases [HR = 2.71 (1.11-6.63); P = 0.030]. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) [HR = 3.23 (1.22-8.59); P = 0.019] whilst CAPRA itself was not significant [HR = 1.88, (0.52-6.77); P = 0.332]. A high concordance [100% (61.5-100)] for the assay result was noted between two separate foci taken from 11 tumours, whilst Gleason score had low concordance. Conclusions: The Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients. Genomic and clinical data are available as a public resource.

Medical cannabis: Another piece in the mosaic of autoimmunity?

Legalization of cannabis' medicinal use is rapidly increasing worldwide, raising the need to evaluate medical implications of cannabis. Currently, evidence supports cannabis and its active ingredients as immune-modulating agents, affecting T-cells, B-cells, monocytes, and microglia cells, causing an overall reduction in pro-inflammatory cytokine expression and an increase in anti-inflammatory cytokines. Due to the supporting evidence of cannabinoids as an immune-modulating agent, research focusing on cannabinoids and autoimmunity has emerged. Several clinical trials in multiple sclerosis, inflammatory bowel disease, and fibromyalgia suggest cannabis' effectiveness as an immune-modulator. However, contradicting results and lack of large-scale clinical trials obscure these results. Although lacking clinical research, in vitro and in vivo experiments in rheumatoid arthritis, diabetes type 1, and systemic sclerosis demonstrate a correlation between disease activity and cannabinoids.

Early diagnosis of Alzheimer's disease using infrared spectroscopy of isolated blood samples followed by multivariate analyses.

Alzheimer's disease (AD) is the most common cause of dementia, particularly in the elderly. The disease is characterized by cognitive decline that typically starts with insidious memory loss and progresses relentlessly to produce global impairment of all higher cortical functions. Due to better living conditions and health facilities in developed countries, which result in higher overall life spans, these countries report upward trends of AD among their populations. There are, however, no specific diagnostic tests for AD and clinical diagnosis is especially difficult in the earliest stages of the disease. Early diagnosis of AD is frequently subjective and is determined by physicians (generally neurologists, geriatricians, and psychiatrists) depending on their experience. Diagnosing AD requires both medical history and mental status testing. Having trouble with memory does not mean you have AD. AD has no current cure, but treatments for symptoms are available and research continues. In this study, we investigated the potential of infrared microscopy to differentiate between AD patients and controls, using Fourier transform infrared (FTIR) spectroscopy of isolated blood components. FTIR is known as a quick, safe, and minimally invasive method to investigate biological samples. For this goal, we measured infrared spectra from white blood cells (WBCs) and plasma taken from AD patients and controls, with the consent of the patients or their guardians. Applying multivariate analysis, principal component analysis (PCA) followed by linear discriminant analysis (LDA), it was possible to differentiate among the different types of mild, moderate, and severe AD, and the controls, with 85% accuracy when using the WBC spectra and about 77% when using the plasma spectra. When only the moderate and severe stages were included, an 83% accuracy was obtained using the WBC spectra and about 89% when using the plasma spectra.

Differential protein expression in the midgut of Culex quinquefasciatus mosquitoes induced by the insecticide temephos.

Mosquitoes are vectors for pathogens of malaria, lymphatic filariasis, dengue, chikungunya, yellow fever and Japanese encephalitis. Culex quinquefasciatus Say, 1823 (Diptera: Culicidae) is a known vector of lymphatic filariasis. Its control in Brazil has been managed using the organophosphate temephos. Studies examining the proteins of Cx. quinquefasciatus that are differentially expressed in response to temephos further understanding of the modes of action of the insecticide and may potentially identify resistance factors in the mosquito. In the present study, a comparative proteomic analysis, using 2-dimensional electrophoresis coupled with matrix-assisted laser desorption/ionization (MALDI) time of flight (TOF)/TOF mass spectrometry, and bioinformatics analyses were performed to identify midgut proteins in Cx. quinquefasciatus larvae that were differentially expressed in response to exposure to temephos relative to those in untreated controls. A total of 91 protein spots were differentially expressed; 40 were upregulated and 51 were downregulated by temephos. A total of 22 proteins, predominantly upregulated, were identified as known to play a role in the immune response, whereas the downregulated proteins were involved in energy and protein catabolism. This is the first proteome study of the midgut of Cx. quinquefasciatus and it provides insights into the molecular mechanisms of insecticide-induced responses in the mosquito.

Documentation of the dietetic care process: developing a sectoral, tailored system.

Use of electronic health records necessitates a systematic approach for documentation of the Dietetic Care Process (DCP). However, no standardized system exists in Israel. The authors propose a novel documentation system developed by an expert advisory committee and tailored to a specific patient population. In this pilot study, 12 experienced Israeli Registered Dietitians (RDs) (median years of practice=23.0; s.d.=8.8; practice in geriatric populations median=13.0; s.d.=8.5) were recruited to evaluate the new tool for DCP documentation. Participants completed an explanatory short course online and evaluated the utility of the tool. There was full agreement that the proposed tool is necessary and an effective method for documenting the DCP within geriatric populations in clinical practice. In conclusion, a novel, tailored and sectoral tool designed for standardized documentation of dietetic care was recommended for implementation by an experienced group of RDs with substantive clinical experience in geriatric populations.

Survey of Australasian geriatricians' satisfaction with, and preferences for, continuing professional development.

BACKGROUND: Continuing professional development (CPD) is an obligation for all Australasian geriatricians; however, there are no systematic data regarding Australian and New Zealand geriatricians' satisfaction with, and preferences for, CPD. AIMS: To inform understanding of Australasian geriatricians' satisfaction with, and preferences for, CPD. METHODS: An electronic survey to collect data relating to demographics, current CPD activities, preferred CPD activities and perceived major barriers to CPD was distributed to 706 geriatricians in Australia and New Zealand. RESULTS: Two hundred and thirteen (30%) responses were received. Respondents commonly reported CPD through participation in conferences (n = 205 (96%)) and research/educational activity (n = 146 (70%)). Most respondents agreed that the annual scientific meeting (n = 168 (79%)) and state-based meetings (n = 135 (63%)) are valuable for their CPD. Respondents perceived their professional (n = 155 (73%)) and non-professional (n = 21 (57%)) commitments as the major barriers to quality CPD. Respondents supported additional electronic CPD resources being made available, improved integration of assessment in CPD activities and flexible methods of CPD participation to meet the diverse needs of geriatricians. CONCLUSIONS: Respondents perceived the face-to-face CPD opportunities currently available to them as valuable for their CPD but seek additional, flexible products to enable CPD participation based on individual needs and preferences.

Ferritin in the antiphospholipid syndrome and its catastrophic variant (cAPS).

BACKGROUND: Ferritin is an iron storage protein considered also as an acute phase reactant with high levels in various inflammatory conditions. Recently, a plausible role for ferritin in the pathogenesis of immune-mediated and especially autoimmune diseases has been suggested. However, the link between ferritin and the antiphospholipid syndrome (APS) has been rarely explored. Therefore, in the current study we evaluated ferritin levels and their correlation to clinical and serological manifestations in patients with APS. We further analyzed ferritin levels among patients with the catastrophic variant of APS (cAPS). METHODS: Ferritin levels were determined in serum samples of 176 APS patients and 98 matched healthy controls according to age and sex (LIAISON, DiaSorin, Italy). APS samples were further analyzed for antiphospholipid (anti-cardiolipin, anti- beta-2-glycoprotein, lupus anticoagulant) and anti-infectious antibodies (CMV, EBV, rubella, toxoplasma, HBV) (LIAISON, DiaSorin, Italy). Clinical, serological and demographic manifestations were recorded. An additional analysis of ferritin levels among 14 patients with cAPS was performed. RESULTS: Hyperferritinemia was present in 9% vs. 0% of APS patients and controls, respectively (p < 0.001). Among patients with APS, ferritin levels correlated with venous thrombosis, cardiac, neurological, and hematological manifestations and the presence of anti-CMV-IgM antibodies. Hyperferritinemia was present in 71% of cAPS patients, and ferritin levels among this subgroup were significantly higher compared with APS-non-cAPS patients (816 ± 847 ng/ml vs. 120 ± 230 ng/ml, p < 0.001). CONCLUSIONS: Herein, we found that hyperferritinemia correlates with the presence of APS, its clinical manifestations and specifically with the catastrophic variant of this disease. Hyperferritinemia was also linked with anti-CMV antibodies among patients with APS. These associations allude to a pathogenic role of ferritin in the pathogenesis of APS, and the plausible role of ferritin as a marker of ensuing cAPS, although further studies are needed to elucidate these associations.

Longitudinal analyses of early lesions by fluorescence: an observational study.

Previous caries experience correlates to future caries risk; thus, early identification of lesions has importance for risk assessment and management. In this study, we aimed to determine if Quantitative Light-induced Fluorescence (QLF) parameters--area (A [mm(2)]), fluorescence loss (F [%]), and Q [% × mm(2)]--obtained by image analyses can predict lesion progression. We secured consent from 565 children (from 5-13 years old) and their parents/guardians and examined them at baseline and regular intervals over 48 months according to the International Caries Detection Assessment System (ICDAS), yearly radiographs, and QLF. QLF images from surfaces with ICDAS 0/1/2/3/4 at baseline that progressed (N = 2,191) to cavitation (ICDAS 5/6) or fillings and surfaces that did not progress to cavitation/fillings (N = 4,141) were analyzed independently for A, F, and Q. Linear mixed-effects models were used to compare means and slopes (changes over time) between surfaces that progressed and those that did not. QLF A, F, and Q increased at a faster rate for surfaces that progressed than for surfaces that did not progress (p = .0001), regardless of type of surface or baseline ICDAS score. AUC for ICDAS ranged from 0.65 to 0.80, but adding QLF information improved AUC (0.82-0.87, p < .0005). We concluded that faster changes in QLF variables can indicate lesion progression toward cavitation and be more clinically relevant than actual QLF values.

The natural history of dental caries lesions: a 4-year observational study.

Dental caries is a ubiquitous disease affecting all age groups and segments of the population. It is known that not all caries lesions progress to cavitation, but little is known regarding the progression pattern of caries lesions. This study's purpose was to evaluate the natural history of dental caries using a standardized, visually based system, the International Caries Detection and Assessment System (ICDAS). The study population consisted of 565 consenting children, who were enrolled and examined at baseline and at regular intervals over 48 months with ICDAS and yearly bitewing radiographs. Of these, 338 children completed all examinations. Not all lesions cavitated at the same rate, differing by surface type and baseline ICDAS severity score and activity status. With increasing severity, the percentage of lesions progressing to cavitation increased: 19%, 32%, 68%, and 66% for ICDAS scores 1, 2, 3, and 4, respectively. Lesions on occlusal surfaces were more likely to cavitate, followed by buccal pits, lingual grooves, proximal surfaces, and buccal and lingual surfaces. Cavitation was more likely on molars, followed by pre-molars and anterior teeth. Predictors of cavitation included age, gender, surfaces and tooth types, and ICDAS severity/activity at baseline. In conclusion, characterization of lesion severity with ICDAS can be a strong predictor of lesion progression to cavitation.

Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression.

BACKGROUND AND AIMS: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thrombosis, obstetric complications and the presence of anti-phospholipid antibodies such as anti-ß2GPI-Abs. These antibodies may set off the coagulation cascade via several mechanisms, including the induction of tissue factor (TF) expression. Vitamin D has recently emerged as an immunomodulator that might exert an anti-thrombotic effect. Therefore, we studied serum vitamin D levels in a cohort of APS patients, as well as the effect of vitamin D in an in vitro model of APS-mediated thrombosis. METHODS: Serum vitamin D levels were measured in 179 European APS patients and 141 healthy controls using the LIAISON chemiluminescent immunoassay, and the levels were evaluated in conjunction with a wide spectrum of clinical manifestations. In an vitro model, anti-ß2GPI antibodies were purified from four patients with APS to evaluate the expression of TF in activated starved human umbilical vein endothelial cells. The effect of vitamin D (1,25-dihydroxyvitamin D, 10 nm) on anti-ß2GPI-Abs mediated TF expression was analysed by immunoblot. RESULTS: Vitamin D deficiency (serum level ≤15 ng/ml) was documented in 49.5% of our APS patients versus 30% of controls (p<0.001) and was significantly correlated with thrombosis (58% vs 42%; p<0.05), neurological and ophthalmic manifestations, pulmonary hypertension, livedo reticularis and skin ulcerations. In vitro vitamin D inhibited the expression of TF induced by anti-ß2GPI-antibodies. CONCLUSIONS: Vitamin D deficiency is common among APS patients and is associated with clinically defined thrombotic events. Vitamin D inhibits anti-ß2GPI-mediated TF expression in vitro. Thus, vitamin D deficiency might be associated with decreased inhibition of TF expression and increased coagulation in APS. Evaluation of vitamin D status and vitamin D supplementation in APS patients should be considered.

Development of gold standard ion-selective electrode-based methods for fluoride analysis.

BACKGROUND/AIMS: Currently available techniques for fluoride analysis are not standardized. Therefore, this study was designed to develop standardized methods for analyzing fluoride in biological and nonbiological samples used for dental research. METHODS: A group of nine laboratories analyzed a set of standardized samples for fluoride concentration using their own methods. The group then reviewed existing analytical techniques for fluoride analysis, identified inconsistencies in the use of these techniques and conducted testing to resolve differences. Based on the results of the testing undertaken to define the best approaches for the analysis, the group developed recommendations for direct and microdiffusion methods using the fluoride ion-selective electrode. RESULTS: Initial results demonstrated that there was no consensus regarding the choice of analytical techniques for different types of samples. Although for several types of samples, the results of the fluoride analyses were similar among some laboratories, greater differences were observed for saliva, food and beverage samples. In spite of these initial differences, precise and true values of fluoride concentration, as well as smaller differences between laboratories, were obtained once the standardized methodologies were used. Intraclass correlation coefficients ranged from 0.90 to 0.93, for the analysis of a certified reference material, using the standardized methodologies. CONCLUSION: The results of this study demonstrate that the development and use of standardized protocols for F analysis significantly decreased differences among laboratories and resulted in more precise and true values.