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    Dietary Fluoride Intake during Pregnancy and Neurodevelopment in Toddlers: A Prospective Study in the PROGRESS Cohort
    (Elsevier, 2021) Cantoral, Alejandra; Téllez-Rojo, Martha M.; Malin, Ashley J.; Schnaas, Lourdes; Osorio-Valencia, Erika; Mercado, Adriana; Martínez-Mier, E. Ángeles; Wright, Robert O.; Till, Christine; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Foods and beverages provide a source of fluoride exposure in Mexico. While high fluoride concentrations are neurotoxic, recent research suggests that exposures within the optimal range may also pose a risk to the developing brain. This prospective study examined whether dietary fluoride intake during pregnancy is associated with toddlers' neurodevelopment in 103 mother-child pairs from the PROGRESS cohort in Mexico City. Food and beverage fluoride intake was assessed in trimesters 2 and 3 using a food frequency questionnaire and Mexican tables of fluoride content. We used the Bayley-III to evaluate cognitive, motor, and language outcomes at 12 and 24 months of age. Adjusted linear regression models were generated for each neurodevelopment assessment time point (12 and 24 months). Mixed-effects models were used to consider a repeated measurement approach. Interactions between maternal fluoride intake and child sex on neurodevelopmental outcomes were tested. Median (IQR) dietary fluoride intake during pregnancy was 1.01 mg/d (0.73, 1.32). Maternal fluoride intake was not associated with cognitive, language, or motor outcomes collapsing across boys and girls. However, child sex modified the association between maternal fluoride intake and cognitive outcome (p interaction term = 0.06). A 0.5 mg/day increase in overall dietary fluoride intake was associated with a 3.50-point lower cognitive outcome in 24-month old boys (95 % CI: -6.58, -0.42); there was no statistical association with girls (β = 0.07, 95 % CI: -2.37, 2.51), nor on the cognitive outcome at 12-months of age. Averaging across the 12- and 24-month cognitive outcomes using mixed-effects models revealed a similar association: a 0.5 mg/day increase in overall dietary fluoride intake was associated with a 3.46-point lower cognitive outcome in boys (95 % CI: -6.23, -0.70). These findings suggest that the development of nonverbal abilities in males may be more vulnerable to prenatal fluoride exposure than language or motor abilities, even at levels within the recommended intake range.
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    Impact of curcumin loading on the physicochemical, mechanical and antimicrobial properties of a methacrylate-based experimental dental resin
    (Springer Nature, 2022-11-04) Comeau, Patricia; Panariello, Beatriz; Duarte, Simone; Manso, Adriana; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Oral biofilms are directly linked to one of the most common chronic human diseases, dental caries. Resin-based dental materials have significant potential to replace amalgam, however they lack sufficient antimicrobial power. This innovative study investigates a curcumin-loaded dental resin which can be utilized in an antimicrobial photodynamic therapy (aPDT) approach. The study evaluated the effects of curcumin loading on resin physicochemical, mechanical, and adhesive properties, as well as the antimicrobial response associated with blue light activation. Preliminary tests involving degree of conversion (DC) and sample integrity determined the optimal loading of curcumin to be restricted to 0.05 and 0.10 wt%. These optimal loadings were tested for flexural strength (FS), water sorption (WS) and solubility (SL), shear bond strength to dentin (SBS), and viability of Streptococcus mutans under 14.6 J/cm2 blue light or dark conditions, in 6 h and 24 h biofilms. The results demonstrated that 0.10 wt% curcumin had minimal impact on either FS or SBS, but detectably increased WS and SL. A 2 log10 (CFU/mL) reduction in S. mutans after light application in both 6 h and 24 h biofilms were corroborated by CLSM imaging and highlighted the significant potential of this novel aPDT approach with resin-based dental materials.
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    Interkingdom assemblages in human saliva display group-level surface mobility and disease-promoting emergent functions
    (National Academy of Science, 2022) Ren, Zhi; Jeckel, Hannah; Simon-Soro, Aurea; Xiang, Zhenting; Liu, Yuan; Cavalcanti, Indira M.; Xiao, Jin; Tin, Nyi-Nyi; Hara, Anderson; Drescher, Knut; Koo, Hyun; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Fungi and bacteria form multicellular biofilms causing many human infections. How such distinctive microbes act in concert spatiotemporally to coordinate disease-promoting functionality remains understudied. Using multiscale real-time microscopy and computational analysis, we investigate the dynamics of fungal and bacterial interactions in human saliva and their biofilm development on tooth surfaces. We discovered structured interkingdom assemblages displaying emergent functionalities to enhance collective surface colonization, survival, and growth. Further analyses revealed an unexpected group-level surface mobility with coordinated “leaping-like” and “walking-like” motions while continuously growing. These mobile groups of growing cells promote rapid spatial spreading of both species across surfaces, causing more extensive tooth decay. Our findings show multicellular interkingdom assemblages acting like supraorganisms with functionalities that cannot be achieved without coassembly.
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    Nutritional Assessment of Denture Wearers Using Matched Electronic Dental-Health Record Data
    (Wiley, 2022-08) Felix Gomez, Grace Gomez; Cho, Sopanis D.; Varghese, Roshan; Rajendran, Divya; Eckert, George J.; Bhamidipalli, Sruthi Surya; Gonzalez, Theresa; Khan, Babar Ali; Thyvalikakath, Thankam Paul; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Purpose To assess the nutritional profile of denture wearers through a retrospective cohort study using nutritional biomarkers from matched electronic dental and health record (EDR-EHR) data. Materials and methods The case group (denture wearers) included matched EDR-EHR data of patients who received removable partial, complete, and implant-supported prosthodontic treatments between January 1, 2010 and December 31, 2018, study time. The control (nondenture wearers) group did not have recorded denture treatments and included patient records within 1 year of the denture index date (first date of case patients’ receiving complete or partial denture) of the matching cases. The qualified patients’ EDR were matched with their EHR based on the availability of laboratory reports within 2 years of receiving the dentures (index date). Nutritional biomarkers were selected from laboratory reports for complete blood count, comprehensive and basic metabolic profile, lipid, and thyroid panels. Summary statistics were performed, and general linear mixed effect models were used to evaluate the rate of change over time (slope) of nutritional biomarkers before and after the index date. Likelihood ratio tests were performed to determine the differences between dentures and controls. Results The final cohort included 10,481 matched EDR-EHR data with 3,519 denture wearers and 6,962 controls that contained laboratory results within the study time. The denture wearers’ mean age was 57 ±10 years and the control group was 56 ±10 years with 55% females in both groups. Pre-post analysis among denture wearers revealed decreased serum albumin (p = 0.002), calcium (p = 0.039), creatinine (p < 0.001) during the post-index time. Hemoglobin (Hb) was higher pre-index, and was decreasing during the time period but did not change post-index (p < 0.001). Among denture wearers, completely edentulous patients had a significant decrease in serum albumin, creatinine, blood urea nitrogen (BUN), but increased estimated glomerular filtration rate (eGFR). In partially edentulous patients, total cholesterol decreased (p = 0.018) and TSH (p = 0.004), BUN (p < 0.001) increased post-index. Patients edentulous in either upper or lower arch had decreased BUN and eGFR during post-index. Compared to controls, denture wearers showed decreased serum albumin and protein (p = 0.008), serum calcium (p = 0.001), and controls showed increased Hb (p = 0.035) during post-index. Conclusions The study results indicate nutritional biomarker variations among denture wearers suggesting a risk for undernutrition and the potential of using selected nutritional biomarkers to monitor nutritional profile.
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    Cross-Polarization Optical Coherence Tomographic Assessment of In situ Simulated Erosive Tooth Wear
    (Wiley, 2021) Romero, Maria Jacinta Rosario H.; Bezerra, Savio J.C.; Fried, Daniel; Yang, Vincent; Lippert, Frank; Eckert, George J.; Zero, Domenick T.; Hara, Anderson Takeo; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    This clinical study tested cross-polarization optical coherence tomography (CP-OCT) monitoring of erosive tooth wear (ETW). Twenty participants completed a 14-day/arm, 3-arm crossover study simulating different ETW severities. Participants received two enamel specimens (per arm) and were randomized to: severe (s-ETW, lemon juice/pH:2.5/4.25%wt/vol citric acid), moderate (m-ETW, grapefruit juice/pH:3.5/1.03%wt/vol citric acid), and non-ETW (water). Enamel thickness was measured with CP-OCT (day[D] 0, 7, 14) and micro-computed tomography (μ-CT; D14). Enamel surface loss was determined with CP-OCT and optical profilometry (OP; D7, D14). CP-OCT showed higher enamel surface loss for D14 than D7 for m-ETW (P = .009) and s-ETW (P = .040) and differentiated severity at D14 (s-ETW > non-ETW, P = .027). OP was able to differentiate surface loss between days (D7 < D14, P < .001) for m-ETW and s-ETW, and ETW severity effect after 7 and 14 days (non-ETW < m-ETW < s-ETW, P < .001). At D14, CP-OCT and μ-CT were positively correlated (r = .87, ICC = .62). CP-OCT showed potential as a tool for clinical ETW monitoring.
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    Indirect caries‐preventive effect of silver diamine fluoride on adjacent dental substrate: A single‐section demineralization study
    (Wiley, 2021-02) Romero, Maria Jacinta Rosario H.; Lippert, Frank; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    This study assessed the indirect effect of 38% silver diamine fluoride (SDF) on demineralization of adjacent untreated sound and pre-demineralized enamel and dentine using a single-section model for digital transverse microradiography (TMR-D). Forty-eight bovine dentine single sections were demineralized, stratified (n = 12) according to integrated mineral loss (ΔZ), and treated with SDF or deionized water (DIW). Each “treated dentine” section was attached between untreated sound and pre-demineralized enamel or dentine and then subjected to demineralization. ΔZ and lesion depths (LD) of all specimens at baseline, 24 and 48 h demineralization, and after treatment of “treated dentine” were quantified using TMR-D. Fluoride in the demineralization solution of SDF clusters was determined using an ion-selective electrode. ΔZ and LD of sound and ΔZ of pre-demineralized enamel adjacent to SDF-treated dentine did not increase over time. All untreated dentine demineralized significantly; however, ΔZ of sound dentine adjacent to SDF-treated specimen was still significantly lower than control. SDF-treated dentine remineralized and released fluoride even after 48 h. Consistent with clinical findings, when applied only to demineralized teeth in this chemical model, 38% SDF completely inhibited demineralization in adjacent untreated sound enamel. Demineralization prevention was observed to a lesser extent in adjacent pre-demineralized enamel but not in dentine.
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    Ferumoxytol Nanoparticles Target Biofilms Causing Tooth Decay in the Human Mouth
    (American Chemical Society, 2021) Liu, Yuan; Huang, Yue; Kim, Dongyeop; Ren, Zhi; Oh, Min Jun; Cormode, David P.; Hara, Anderson T.; Zero, Domenick T.; Koo, Hyun; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Severe tooth decay has been associated with iron deficiency anemia that disproportionally burdens susceptible populations. Current modalities are insufficient in severe cases where pathogenic dental biofilms rapidly accumulate, requiring new antibiofilm approaches. Here, we show that ferumoxytol, a Food and Drug Administration-approved nanoparticle formulation for treating iron deficiency, exerts an alternative therapeutic activity via the catalytic activation of hydrogen peroxide, which targets bacterial pathogens in biofilms and suppresses tooth enamel decay in an intraoral human disease model. Data reveal the potent antimicrobial specificity of ferumoxytol iron oxide nanoparticles (FerIONP) against biofilms harboring Streptococcus mutans via preferential binding that promotes bacterial killing through in situ free-radical generation. Further analysis indicates that the targeting mechanism involves interactions of FerIONP with pathogen-specific glucan-binding proteins, which have a minimal effect on commensal streptococci. In addition, we demonstrate that FerIONP can detect pathogenic biofilms on natural teeth via a facile colorimetric reaction. Our findings provide clinical evidence and the theranostic potential of catalytic nanoparticles as a targeted anti-infective nanomedicine.
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    Iodine Status Modifies the Association between Fluoride Exposure in Pregnancy and Preschool Boys' Intelligence
    (MDPI, 2022-07-16) Goodman, Carly V.; Hall, Meaghan; Green, Rivka; Chevrier, Jonathan; Ayotte, Pierre; Martinez-Mier, Esperanza Angeles; McGuckin, Taylor; Krzeczkowski, John; Flora, David; Hornung, Richard; Lanphear, Bruce; Till, Christine; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    In animal studies, the combination of in utero fluoride exposure and low iodine has greater negative effects on offspring learning and memory than either alone, but this has not been studied in children. We evaluated whether the maternal urinary iodine concentration (MUIC) modifies the association between maternal urinary fluoride (MUF) and boys' and girls' intelligence. We used data from 366 mother-child dyads in the Maternal-Infant Research on Environmental Chemicals Study. We corrected trimester-specific MUF and MUIC for creatinine, and averaged them to yield our exposure variables (MUFCRE, mg/g; MUICCRE, µg/g). We assessed children's full-scale intelligence (FSIQ) at 3 to 4 years. Using multiple linear regression, we estimated a three-way interaction between MUFCRE, MUICCRE, and child sex on FSIQ, controlling for covariates. The MUICCRE by MUFCRE interaction was significant for boys (p = 0.042), but not girls (p = 0.190). For boys whose mothers had low iodine, a 0.5 mg/g increase in MUFCRE was associated with a 4.65-point lower FSIQ score (95% CI: -7.67, -1.62). For boys whose mothers had adequate iodine, a 0.5 mg/g increase in MUFCRE was associated with a 2.95-point lower FSIQ score (95% CI: -4.77, -1.13). These results suggest adequate iodine intake during pregnancy may minimize fluoride's neurotoxicity in boys.
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    How Do Dental Clinicians Obtain Up-To-Date Patient Medical Histories? Modeling Strengths, Drawbacks, and Proposals for Improvements
    (Frontiers, 2022-03) Li, Shuning; Rajapuri, Anushri Singh; Felix Gomez, Grace Gomez; Schleyer, Titus; Mendonca, Eneida A.; Thyvalikakath, Thankam P.; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Background: Access to up-to-date patient medical history is essential for dental clinicians (DCs) to avoid potential harm to patients and to improve dental treatment outcomes. The predominant approach for dental clinicians (DCs) to gather patients' medical history is through patient-reported medical histories and medical consults. However, studies reported varied concordance and reliability of patient-reported medical conditions and medication histories compared to the patient medical records and this process also places a significant burden on patients. Information technology tools/platforms such as an integrated electronic health record containing an electronic dental record module may address these issues. However, these integrated systems are expensive and technically complex and may not be easily adopted by DCs in solo and small group practice who provide the most dental care. The recent expansion of regional healthcare information exchange (HIE) provides another approach, but to date, studies on connecting DCs with HIE are very limited. Our study objectives were to model different aspects of the current approaches to identify the strengths and weaknesses, and then model the HIE approach that addresses the weaknesses and retain the strengths of current approaches. The models of current approaches identified the people, resources, organizational aspects, workflow, and areas for improvement; while models of the HIE approach identified system requirements, functions, and processes that may be shared with software developers and other stakeholders for future development. Methods: There are three phases in this study. In Phase 1, we retrieved peer-reviewed PubMed indexed manuscripts published between January 2013 and November 2020 and extracted modeling related data from selected manuscripts. In Phase 2, we built models for the current approaches by using the Integrated DEFinition Method 0 function modeling method (IDEF0), the Unified Modeling Language (UML) Use Case Diagram, and Business Process Model and Notation (BPMN) methods. In Phase 3, we created three conceptual models for the HIE approach. Results: From the 47 manuscripts identified, three themes emerged: 1) medical consult process following patient-reported medical history, 2) integrated electronic dental record-electronic health record (EDR-EHR), and 3) HIE. Three models were built for each of the three themes. The use case diagrams described the actions of the dental patients, DCs, medical providers and the use of information systems (EDR-EHR/HIE). The IDEF0 models presented the major functions involved. The BPMN models depicted the detailed steps of the process and showed how the patient's medical history information flowed through different steps. The strengths and weaknesses revealed by the models of the three approaches were also compared. Conclusions: We successfully modeled the DCs' current approaches of accessing patient medical history and designed an HIE approach that addressed the current approaches' weaknesses as well as leveraged their strengths. Organizational management and end-users can use this information to decide the optimum approach to integrate dental and medical care. The illustrated models are comprehensive and can also be adopted by EHR and EDR vendors to develop a connection between dental systems and HIEs.
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    Retrospective Study of the Reasons and Time Involved for Dental Providers' Medical Consults
    (Frontiers, 2022-05) Li, Shuning; Williams, Karmen S.; Medam, Jayanth Kumar; Patel, Jay S.; Gonzalez, Theresa; Thyvalikakath, Thankam P.; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Background: Patient-reported medical histories and medical consults are primary approaches to obtaining patients' medical histories in dental settings. While patient-reported medical histories are reported to have inconsistencies, sparse information exists regarding the completeness of medical providers' responses to dental providers' medical consults. This study examined records from a predoctoral dental student clinic to determine the reasons for medical consults; the medical information requested, the completeness of returned responses, and the time taken to receive answers for medical consult requests. Methods: A random sample of 240 medical consult requests for 179 distinct patients were selected from patient encounters between 1 January 2015 and 31 December 2017. Descriptive statistics and summaries were calculated to determine the reasons for the consult, the type of information requested and returned, and the time interval for each consult. Results: The top two reasons for medical consults were to obtain more information (46.1%) and seek medical approval to proceed with treatment (30.3%). Laboratory and diagnostic reports (56.3%), recommendations/medical clearances (39.6%), medication information (38.3%), and current medical conditions (19.2%) were the frequent requests. However, medical providers responded fewer times to dental providers' laboratory and diagnostic report requests (41.3%), recommendations/medical clearances (19.2%), and current medical conditions (13.3%). While 86% of consults were returned in 30 days and 14% were completed after 30 days. Conclusions: The primary reasons for dental providers' medical consults are to obtain patient information and seek recommendations for dental care. Laboratory/diagnostic reports, current medical conditions, medication history, or modifications constituted the frequently requested information. Precautions for dental procedures, antibiotic prophylaxis, and contraindications included reasons to seek medical providers' recommendations. The results also highlight the challenges they experience, such as requiring multiple attempts to contact medical providers, the incompleteness of information shared, and the delays experienced in completing at least 25% of the consults. Practical Implications: The study results call attention to the importance of interdisciplinary care to provide optimum dental care and the necessity to establish systems such as integrated electronic dental record-electronic health record systems and health information exchanges to improve information sharing and communication between dental and medical providers.