Deciduous teeth from the New Hampshire birth cohort study: Early life environmental and dietary predictors of dentin elements.

BACKGROUND: Sparse research exists on predictors of element concentrations measured in deciduous teeth. OBJECTIVE: To estimate associations between maternal/child characteristics, elements measured in home tap water during pregnancy and element concentrations in the dentin of shed deciduous teeth. METHODS: Our analysis included 152 pregnant person-infant dyads followed from the second trimester through the end of the first postnatal year from the New Hampshire Birth Cohort Study. During pregnancy and early infancy, we collected dietary and sociodemographic information via surveys, measured elements in home tap water, and later collected naturally exfoliated teeth from child participants. We measured longitudinal deposition of elements in dentin using LA-ICP-MS. Multivariable linear mixed models were used to estimate associations between predictors and dentin element concentrations. RESULTS: We measured 12 elements in dentin including those previously reported (Ba, Mn, Pb, Sr, Zn) and less frequently reported (Al, As, Cd, Cu, Hg, Li, and W). A doubling of Pb or Sr concentrations in water was associated with higher dentin Pb or Sr respectively in prenatally formed [9% (95%CI: 3%, 15%); 3% (1%, 6%)] and postnatally formed [10% (2%, 19%); 6% (2%, 10%)] dentin. Formula feeding from birth to 6 weeks or 6 weeks to 4 months was associated with higher element concentrations in postnatal dentin within the given time period as compared to exclusive human milk feeding: Sr: 6 weeks: 61% (36%, 90%) and 4 months: 85% (54%, 121%); Ba: 6 weeks: 35% (3.3%, 77%) and 4 months: 42% (10%, 83%); and Li: 6 weeks: 61% (33%, 95%) and 4 months: 58% (31%, 90%). SIGNIFICANCE: These findings offer insights into predictors of dentin elements and potential confounders in exposure-health outcome relationships during critical developmental periods.

Impact of exercise changes on body composition during the college years--a five year randomized controlled study.

BACKGROUND: Observational studies have consistently reported severe weight gains during the college years; information about the effect on body composition is scarce, however. Thus, the aim of the study was to determine the effect of exercise changes on body composition during 5 years at university. METHODS: Sixty-one randomly selected male and female dental (DES; 21 ± 3 years., 22 ± 2 kg/m(2)) and 53 sport (physical education) students (SPS; 20 ± 2 years., 22 ± 3 kg/m(2)) were accompanied over their 5-year study program. Body mass and body composition as determined via Dual-Energy x-ray-absorptiometry (DXA) at baseline and follow-up were selected as primary study endpoints. Confounding parameters (i.e., nutritional intake, diseases, medication) that may affect study endpoints were determined every two years. Endpoints were log-transformed to stabilize variance and achieve normal distributed values. Paired t-tests and unpaired Welch-t-tests were used to check intra and inter-group differences. RESULTS: Exercise volume decreased significantly by 33% (p < .001) in the DES and increased significantly (p < .001) in the SPS group. Both cohorts comparably (p = .214) gained body mass (SPS: 1.9%, 95%-CI: 0.3-3.5%, p = .019 vs. DES: 3.4%, 1.4-5.5%, p = .001). However, the increase in the SPS group can be completely attributed to changes in LBM (2.3%, 1.1-3.5%, p < 0.001) with no changes of total fat mass (0.6%, -5.0-6.5%, p = 0.823), while DES gained total FM and LBM in a proportion of 2:1. Corresponding changes were determined for appendicular skeletal muscle mass and abdominal body-fat. Maximum aerobic capacity increased (p = .076) in the SPS (1.6%, -0.2-3.3%) and significantly decreased (p = .004) in the DES (-3.3%, -5.4 to -1.2%). Group differences were significant (p < .001). With respect to nutritional intake or physical activity, no relevant changes or group differences were observed. CONCLUSION: We conclude that the most deleterious effect on fatness and fitness in young college students was the pronounced decreases in exercise volume and particularly exercise intensity. TRIAL REGISTRATION: NCT00521235; "Effect of Different Working Conditions on Risk Factors in Dentists Versus Trainers. A Combined Cross sectional and Longitudinal Trial with Student and Senior Employees."; August 24, 2007.

Quantified retrospective biomonitoring of fetal and infant elemental exposure using LA-ICP-MS analysis of deciduous dentin in three contrasting human cohorts.

BACKGROUND: Spatial elemental analysis of deciduous tooth dentin combined with odontochronological estimates can provide an early life (in utero to ~2 years of age) history of inorganic element exposure and status. OBJECTIVE: To demonstrate the importance of data normalization to a certified reference material to enable between-study comparisons, using populations with assumed contrasting elemental exposures. METHODS: We used laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) of dentin to derive a history of elemental composition from three distinct cohort studies: a present day rural cohort, (the New Hampshire Birth Cohort Study (NHBCS; N = 154)), an historical cohort from an urban area (1958-1970), (the St. Louis Baby Tooth Study (SLBT; N = 78)), and a present-day Nigerian cohort established to study maternal HIV transmission (Dental caries and its association with Oral Microbiomes and HIV in young children-Nigeria (DOMHaIN; N = 31)). RESULTS: We report Li, Al, Mn, Cu, Zn, Sr, Ba and Pb concentrations (µg/g) and qualitatively examine As, Cd and Hg across all three cohorts. Rates of detection were highest, both overall and for each cohort individually, for Zn, Sr, Ba and Li. Zinc was detected in 100% of samples and was stably present in teeth at a concentration range of 64 - 86 µg/g. Mercury, As and Cd detection rates were the lowest, and had high variability within individual ablated spots. We found the highest concentrations of Pb in the pre- and postnatal dentin of the SLBT cohort, consistent with the prevalent use of Pb as an additive to gasoline prior to 1975. The characteristic decline in Mn after the second trimester was observed in all cohorts. IMPACT: Spatially resolved elemental analysis of deciduous teeth combined with methods for estimating crown formation times can be used to reconstruct an early-life history of elemental exposure inaccessible via other biomarkers. Quantification of data into absolute values using an external standard reference material has not been conducted since 2012, preventing comparison between studies, a common and highly informative component of epidemiology. We demonstrate, with three contrasting populations, that absolute quantification produces data with the lowest variability, compares well with available data and recommends that future tooth biomarker studies report data in this way.

Early life manganese exposure and reported attention-related behaviors in Italian adolescents.

Background: Manganese (Mn) is an essential nutrient and neurotoxicant, and the neurodevelopmental effects of Mn may depend on exposure timing. Less research has quantitatively compared the impact of Mn exposure on neurodevelopment across exposure periods. Methods: We used data from 125 Italian adolescents (10-14 years) from the Public Health Impact of Metals Exposure Study to estimate prospective associations of Mn in three early life exposure periods with adolescent attention-related behaviors. Mn was quantified in deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry to represent prenatal (2nd trimester-birth), postnatal (birth ~1.5 years), and childhood (~1.5-6 years) exposure. Attention-related behavior was evaluated using the Conners Behavior Rating Scales in adolescence. We used multivariable linear regression models to quantify associations between Mn in each exposure period, and multiple informant models to compare associations across exposure periods. Results: Median tooth Mn levels (normalized to calcium) were 0.4 area under the curve (AUC) 55Mn:43Ca × 104, 0.1 AUC 55Mn:43Ca × 104, and 0.0006 55Mn:43Ca for the prenatal, postnatal, and childhood periods. A doubling in prenatal tooth Mn levels was associated with 5.3% (95% confidence intervals [CI] = -10.3%, 0.0%) lower (i.e., better) teacher-reported inattention scores, whereas a doubling in postnatal tooth Mn levels was associated with 4.5% (95% CI = -9.3%, 0.6%) and 4.6% (95% CI = -9.5%, 0.6%) lower parent-reported inattention and attention deficit/hyperactivity disorder index scores, respectively. Childhood Mn was not beneficially associated with reported attention-related behaviors. Conclusion: Protective associations in the prenatal and postnatal periods suggest Mn is beneficial for attention-related behavior, but not in the childhood period.

Early-life manganese exposure during multiple developmental periods and adolescent verbal learning and memory.

BACKGROUND: Manganese (Mn) is both an essential and toxic metal, and associations with neurodevelopment depend on exposure timing. Prospective data examining early life Mn with adolescent cognition are sparse. METHODS: We enrolled 140 Italian adolescents (10-14 years old) from the Public Health Impact of Metals Exposure study. Mn in deciduous teeth was measured using laser ablation-mass spectrometry to represent prenatal, postnatal and early childhood exposure. The California Verbal Learning Test for Children (CVLT-C) was administered to assess adolescent verbal learning and memory. Multivariable regression models estimated changes in CVLT-C scores and the odds of making an error per doubling in dentine Mn in each exposure period. Multiple informant models tested for differences in associations across exposure periods. RESULTS: A doubling in prenatal dentine Mn levels was associated with lower odds of making an intrusion error (OR = 0.23 [95% CI: 0.09, 0.61]). This beneficial association was not observed in other exposure periods. A doubling in childhood Mn was beneficially associated with short delay free recall: (ß = 0.47 [95% CI: -0.02, 0.97]), which was stronger in males (ß = 0.94 [95% CI: 0.05, 1.82]). Associations were null in the postnatal period. CONCLUSION: Exposure timing is critical for understanding Mn-associated changes in cognitive function.

Multiple metals in children's deciduous teeth: results from a community-initiated pilot study.

BACKGROUND: Characterizing retrospective exposure to toxicants during multiple early-life developmental periods is challenging, yet critical for understanding developmental effects. OBJECTIVE: To characterize early-life metal exposure using deciduous teeth in a community concerned about past exposures. METHODS: Naturally shed teeth were collected from 30 children ages 5-13 years who resided in Holliston, Massachusetts since conception. We estimated weekly prenatal and postnatal (up to 1 year of age) exposure to 12 metals by measuring dentine concentrations using laser ablation-inductively coupled plasma-mass spectrometry. Multivariable linear mixed models were used to explore sociodemographic, dietary, and behavioral correlates of dentine metal concentrations. RESULTS: Temporal trends in dentine levels differed by metal. Source of milk during the first year of life was associated with dentine barium (Ba) levels, where being fed predominantly breastmilk was associated with 39% (95% CI: -57%, -13%) lower dentine Ba compared to predominantly formula use. Females had higher prenatal and postnatal dentine Mn and Pb, compared to males (e.g., % difference, postnatal Mn: 122% (17%, 321%); postnatal Pb: 60% (95% CI: -8%, 178%)). SIGNIFICANCE: Deciduous teeth provide retrospective information on dose and timing of early-life metals exposure at high resolution. We demonstrate their utility in a community-based study with known past contamination of drinking water. IMPACT STATEMENT: We conducted a community-initiated pilot study in a community concerned with historical exposure to multiple metals. Using deciduous teeth, a novel noninvasive biomarker, we characterized early-life exposure to 12 metals in approximately weekly increments during sensitive developmental periods, thus demonstrating the utility of this biomarker in communities concerned with past exposures.

Topology and accessibility of the transmembrane helices and the sensory site in the bifunctional transporter DcuB of Escherichia coli.

C(4)-Dicarboxylate uptake transporter B (DcuB) of Escherichia coli is a bifunctional transporter that catalyzes fumarate/succinate antiport and serves as a cosensor of the sensor kinase DcuS. Sites and domains of DcuB were analyzed for their topology relative to the cytoplasmic or periplasmic side of the membrane and their accessibility to the water space. For the topology studies, DcuB was fused at 33 sites to the reporter enzymes PhoA and LacZ that are only active when located in the periplasm or the cytoplasm, respectively. The ratios of the PhoA and LacZ activities suggested the presence of 10 or 11 hydrophilic loops, and 11 or 12 α-helical transmembrane domains (TMDs). The central part of DcuB allowed no clear topology prediction with LacZ/PhoA fusions. The sites of DcuB accessible to the hydrophilic thiol reagent 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonate (AMS) were determined with variants of DcuB that carried single Cys residues. After intact cells were labeled with the membrane-impermeable AMS, denatured cells were differentially labeled with the thiol reagent polyethylene-glycol-maleimide (PEGmal) and analyzed for a mass shift. From 35 positions 17 were accessible to AMS in intact bacteria. The model derived from topology and accessibility suggests 12 TMDs for DcuB and a waterfilled cavity in its central part. The cavity ends with a cytoplasmic lid accessible to AMS from the periplasmic side. The sensory domain of DcuB is composed of cytoplasmic loop XI/XII and a membrane integral region with the regulatory residues Thr396/Asp398 and Lys353.

Critical windows of susceptibility in the association between manganese and neurocognition in Italian adolescents living near ferro-manganese industry.

INTRODUCTION: Understanding the neurodevelopmental effects of manganese (Mn) is complicated due to its essentiality for growth and development. While evidence exists for the harmful effects of excess Mn, pediatric epidemiologic studies have observed inconsistent associations between Mn and child cognition. OBJECTIVE: We sought to estimate prospective associations between Mn measured in three different early-life time windows with adolescent cognition using deciduous teeth biomarkers. METHODS: Deciduous teeth were collected from 195 participants (ages 10-14 years) of the Public Health Impact of Manganese Exposure (PHIME) study in Brescia, Italy. Measurements of tooth Mn represented prenatal (∼14 weeks gestation - birth), early postnatal (birth - 1.5 years) and childhood (∼1.5 - 6 years) time windows. Neuropsychologists administered the Wechsler Intelligence Scale for Children, 3rd edition (WISC-III), to obtain composite IQ and subtest scores. Associations between tooth Mn at each time window and adolescent WISC-III scores were estimated using multivariable linear regression. We tested differences in associations between Mn and outcomes across time windows using multiple informant models. Sex-specific associations were explored in stratified models. RESULTS: Adjusted associations between tooth Mn and composite IQ scores were positive in the prenatal period and negative in the childhood period. Associations were strongest for subtest scores that reflect working memory, problem solving, visuospatial ability and attention: prenatal Mn was positively associated with Digits backward [SD change in score per interquartile range increase in Mn: ß = 0.20 (95 % CI: 0.02, 0.38)] and Block design [ß = 0.21 (0.01, 0.41)] and early postnatal Mn was positively associated with Digits forward [ß = 0.24 (0.09, 0.40)], while childhood Mn was negatively associated with Coding [ß = -0.14 (-0.28, -0.001)]. Sex-stratified analyses suggested different Mn-cognition associations for boys and girls and was also dependent on the time window of exposure. CONCLUSION: Our results suggest that exposure timing is critical when evaluating Mn associations between Mn and cognition. Higher prenatal Mn was beneficial for adolescent cognition; however, these beneficial associations shifted towards harmful effects in later time windows. Cognitive domains most sensitive to Mn across time windows included visuospatial ability, working memory, attention and problem-solving.

Associations of metals and neurodevelopment: a review of recent evidence on susceptibility factors.

PURPOSE OF REVIEW: Epidemiologic evidence exists that many metals are associated with adverse neurobehavioral effects in young children, including lead (Pb), methylmercury (meHg), manganese (Mn) and arsenic (As)5-8. Importantly, chemical insult can vary depending on host factors and exposure circumstance. This systematic review summarizes the recent literature investigating modifying factors of the associations between metals and neurodevelopment, including immutable traits (sex or genetics) or exposure conditions (timing or co-exposures). RECENT FINDINGS: Of the 53 studies included in this review, the number investigating modification of exposure effects were: 30 for sex, 21 for co-exposures, 12 for timing of exposure, and six for genetic modifiers. Sex-specific effects of metal-neurobehavioral associations were inconclusive for all metals, likely due to the heterogeneity of outcome domains assessed and the exposure time points measured. Seven studies evaluated both sex and exposure timing as modifying factors using deciduous teeth or other biomarkers with repeated measures to characterize metals exposure over time. Only five studies used statistical methods for mixtures to evaluate associations of more than two metals with neurobehavioral domains. SUMMARY: Despite the expansion of research on susceptibility to the neurodevelopmental effects of metals exposure, considerable gaps remain. This work remains critical, as characterizing susceptible subpopulations can aid in identifying biological mechanisms and is fundamental for the protection of public health.

Manganese in teeth and neurobehavior: Sex-specific windows of susceptibility.

BACKGROUND: Manganese (Mn) is an essential element required for growth and development, but higher body burdens have been associated with neurobehavioral decrements in children. OBJECTIVES: We examined whether prenatal or postnatal Mn measured in deciduous teeth was associated with scores on a test of visuospatial learning and memory. METHODS: Deciduous teeth were collected from 142 participants (ages 10-14years) residing near varied ferro­manganese industry in Italy. Mn concentrations were measured in prenatal and postnatal tooth regions by laser ablation inductively coupled plasma mass spectrometry (ICP-MS). The Virtual Radial Arm Maze (VRAM), an animal-human analogue task, was used to assess visuospatial learning and memory. We used generalized additive, linear and zero-inflated Poisson mixed regression models to estimate associations between prenatal or postnatal Mn concentrations and repeated measures of all four VRAM outcomes: time, distance, working and reference memory errors. Effect measure modification by sex was examined in stratified models. RESULTS: U-shaped associations between prenatal Mn and VRAM outcomes were observed among girls only (pGAMM=0.001 to 0.02 in stratified models). Compared to the mid-tertile of prenatal Mn, girls in the highest tertile took 7.7s [95% CI: -6.1, 21.5] longer to complete the task, traveled 2.3 maze units [0.1, 4.4] farther, and committed more working and reference memory errors (ß for count ratio=1.33 [1.01, 1.83]; 1.10 [0.98, 1.24], respectively). This association was not observed among boys. In contrast, for postnatal Mn, no significant associations were found, and patterns were similar for boys and girls. CONCLUSIONS: The prenatal period may be a critical window for the impact of environmental Mn on visuospatial ability and executive function, especially for females.

Preclinical investigations towards the first spacer gel application in prostate cancer treatment during particle therapy at HIT.

BACKGROUND: The application of spacer gel represents a promising approach to reliably spare the rectal frontal wall during particle therapy (IJROBP 76:1251-1258, 2010). In order to qualify the spacer gel for the clinical use in particle therapy, a variety of measurements were performed in order to ensure the biological compatibility of the gel, its physical stability during and after the irradiation, and a proper definition of the gel in terms of the Hounsfield Unit (HU) values for the treatment planning system. The potential for the use of the spacer gel for particle therapy monitoring with off-line Positron Emission Tomography (PET) was also investigated. RESULTS: The spacer gel implanted to the prostate patient in direct neighbourhood to the clinical target volume does not interfere with the particle therapy treatment planning procedure applied at Heidelberg Ion Beam Therapy Centre (HIT). The performed measurements show that Bragg-peak position of the particles can be properly predicted on the basis of computed tomography imaging with the treatment planning system used at HIT (measured water equivalent path length of 1.011 ±0.011 (2σ), measured Hounsfield Unit of 28.9 ±6.1 (2σ)). The spacer gel samples remain physically unchanged after irradiation with a dose exceeding the therapeutic dose level. The independently measured Bragg-Peak position does not change within the time interval of 10 weeks. CONCLUSIONS: As a result of the presented experiments, the first clinical application of spacer gel implant during prostate cancer treatment with carbon ions and protons was possible at HIT in 2012. The reported pre-clinical investigations demonstrate that use of spacer gel is safe in particle therapy in presence of therapy target motion and patient positioning induced particle range variations. The spacer gel injected between prostate and rectum enlarge the distance between both organs, which is expected to clinically significantly decrease the undesirable exposure of the most critical organ at risk, i.e. rectal frontal wall. Further research on the composition of spacer gel material might lead to additional clinical benefits by validation of particle therapy of prostate via post-therapeutic PET-imaging or by patient positioning based on the gel as a radio-opaque marker.

Awareness and education of patients receiving bisphosphonates.

BACKGROUND: Bisphosphonates are used to fight osteoporosis and for treating malignancies. In 2003, the first case reports appeared that described bisphosphonate-induced osteonecrosis of the jaw (BONJ). The aim of this study was to assess patient awareness of the adverse effects of bisphosphonates in order to improve cooperation among doctors and between doctors and patients. METHODS: Patients with symptoms of osteoporosis, prostate cancer, or breast cancer were surveyed to determine their knowledge of bisphosphonates. The questionnaire comprised 12 questions that covered sociographic data, kind of medication, level of information, and side effects experienced. Out of 142 patients contacted, 55 participated in the study. RESULTS: 62% of patients received most of their knowledge about the prescribed drug from the package insert. Despite knowledge that the patient was under treatment with bisphosphonates, 80% of dental treatments were continued without modifications. Only 32% of patients that received intravenous bisphosphonate treatment were aware of the possible risks of developing BONJ. CONCLUSION: The level of information is poor concerning the side effects of bisphosphonates, particularly the risk of BONJ. Clinicians should aim to sensitize the relevant people about the risks before treatment.

Esthetics and psyche-part 1: assessment of the influence of patients' perceptions of body image and body experience on selection of existing natural tooth color.

PURPOSE: The aim of this research was to test the hypothesis that patients' attitudes toward their body affect their capacity to accurately select their existing natural tooth color. MATERIALS AND METHODS: Standard validated psychologic assessments were used to determine a person's perception of body image and experience. Oral images were compared with the patients' perceptions of their natural tooth color, which were then compared with the actual tooth color judged by a dental professional. RESULTS: For the vital body dynamic and disliking body experience subscales, women exhibited a significantly more negative attitude toward their bodies than men (P = .000). Patients with a negative attitude toward their body tended to choose a lighter tooth color. The correlation between patients' and the testing physician's choices of color was r = 0.540 for women and r = 0.746 for men. CONCLUSIONS: Unhappiness with body image and experience results in poor perception of a patient's own oral image, which in turn results in a patient perceiving that his or her natural tooth color is lighter than that judged by a dental professional. This has clinical implications when trying to achieve patient satisfaction with dental prostheses.

Clinical use of a novel audio pillow with recorded hypnotherapy instructions and music for anxiolysis during dental implant surgery: a prospective study.

A prospective, comparative study of a novel audio pillow with hypnosis text and relaxation music was conducted in 82 dental-implant surgery patients to relieve anxiety over a 6-month period. Visual analogue scales combined with the Aachen Dental Treatment Fear Inventory (AZI) questionnaire were used to quantify patients' subjective feelings of fear. Blood pressure, heart rate, and capillary oxygen partial pressure were measured before, during, and after surgery. The AZI scores decreased in the hypnotherapy group (n = 44) and increased slightly in the control group; scores were significantly different between the groups (p = .000). During surgery, the average diastolic blood pressure and heart rate decreased in the hypnotherapy group and increased in controls. Thus, this audio pillow with relaxation music showed anxiolytic effects in patients during dental implantation procedures.