Purpose: The purpose of this study was to asses fluoride varnish use by dental practitioners in Virginia. Methods: Using a cross sectional survey design, all dentists in Virginia who are members of the Virginia Dental Association (VDA) were sent an online survey about usage and knowledge of fluoride varnish. Results: The majority of the respondents were general dentists (79%) followed by pediatric dentists (12%). Fluoride varnish use increased with year of graduation from dental school. Dentists who thought fluoride varnish was more effective and less time consuming use it more than other topical fluorides. Dentists who thought their patients prefer fluoride varnish use it more than other topical fluorides.Conclusion: The majority of dentists are not aware of the advantages of fluoride varnish. However, those who are, choose to use it as opposed to foams and gels. Recent graduates, with more exposure to fluoride varnish, use it more frequently.

For the brain to construct a comprehensive percept of the sensory world, information from the different senses must converge onto individual neurons within the central nervous system. As a consequence, how these neurons convert convergent sensory input into multisensory information is an important question facing neuroscience today. Recent physiological studies have demonstrated the presence of a robust population of multisensory neurons in the lateral bank of the rostral suprasylvian sulcus (LRSS) in adult ferret (Keniston et al, 2008). The LRSS is a region situated between somatosensory and auditory cortices, where bimodal (somatosensory-auditory) neurons occupy the greatest percentage of the sensory-responsive cell population. The present study was designed to evaluate the anatomical connections that underlie these multisensory features. Injections of neuroanatomical tracer were first made into the LRSS. After transport and histological processing, microscopy revealed retrogradely-labeled cell bodies in identified regions of cortex and thalamus. The resultant analysis showed that the greatest number of projections to LRSS originated in auditory and somatosensory cortex. Of these, auditory cortex contributed a greater proportion of inputs. These anatomical data support the idea that LRSS is a multisensory cortex that receives primarily bimodal input from auditory and somatosensory sources.

Purpose: The objective of this study was to determine if regular volunteering during adolescence was associated with a delay in first pregnancy until adulthood. Method: Data for this analysis were drawn from Wave III of the National Longitudinal Study of Adolescent Health (Add Health). Logistic regression was used, controlling for demographic characteristics and pregnancy intention, to estimate the independent contribution of volunteering during adolescence to a delay in first pregnancy until after age 18. Results: One-third of respondents reported regularly volunteering during adolescence. Volunteering significantly differed among those who had a teen pregnancy compared to those who delayed pregnancy until adulthood (chi-square 6.52, p-value 0.012). In the adjusted analysis, respondents who reported regularly volunteering during adolescence were nearly 60% more likely to delay their first pregnancy until adulthood compared to those who did not volunteer. Conclusions: This analysis is the only one known to have examined volunteering alone, not as part of a multiple component prevention program. Its findings suggest that incorporating volunteering opportunities may make pregnancy prevention programs more successful. In addition, increasing the number of the kinds of volunteering opportunities that are already available may confer some protection against adolescent pregnancy.

The neisserial transferrin binding proteins (Tbps) comprise a bipartite system for iron acquisition from human transferrin. TbpA is a TonB-dependent outer membrane protein that forms the pore for iron internalization. TbpB is a surface-exposed lipoprotein that makes the iron-uptake process more efficient. Previous studies have shown that the genes encoding these proteins are arranged in a bicistronic operon, with the tbpB gene located upstream of tbpA. The operon is under the control of the ferric uptake regulator (Fur) protein. However, promoter elements necessary for the regulation of the operon have not been experimentally defined. In this study, putative regulatory motifs were confirmed by mutagenesis. Further examination of the sequence upstream of these promoter/operator motifs led to the identification of two direct repeats. We hypothesized that these repeats may be involved in further regulation of the operon. Insertional mutagenesis of the repeats resulted in altered transcript and protein levels. These results confirmed that the region upstream of the operon serves as an extended regulatory region. A comprehensive investigation of the expression of the operon in response to different environmental stimuli that gonococci might encounter upon infection was also conducted. Changes in osmolarity, carbon source, cAMP availability, and H2O2 stress did not alter expression of the operon at the transcript or protein levels. However, low oxygen levels resulted in decreased tbpBA transcript and protein. These results are biologically relevant, and provide new insights into the use of the transferrin binding proteins as vaccine candidates. Lastly, the role of G4 DNA sequences identified in the vicinity of the tbpBA operon was investigated. We hypothesized that G4 DNA structures could be involved in the regulation of the operon. Results presented here indicate that interference with these sequences appears to have no effect on expression of the operon. However, identification of potential G4-forming sequences in the non-coding regions upstream and downstream of the operon suggests their importance, perhaps in mediating recombination which could lead to increased antigenic diversity.

Empirical evidence exists directly relating forgiveness to physiological markers of cardiovascular health based on the manner in which individuals respond to interpersonal offenses. Extant literature has identified the harmful effects of stress in cardiovascular disease and health in general and unforgiveness has been identified as a stressor with potential implications for cardiac health. Understanding cardiac response to the stress of unforgiveness may have favorable implications for heart disease prevention and treatment in women and may prove to be beneficial in reducing allostatic load.

This study was conducted to characterize cellular changes occurring during the progression of status epilepticus (SE) that could lead to the maintenance of increased membrane excitability. SE was induced by injection of pilocarpine after which rats were monitored both electrographically and behaviorally. After various lengths of time in SE, specific brain regions were isolated for biochemical study. SE resulted in an early maintenance of PKA activity in both cortical homogenate and crude synaptoplasmic membrane (crude SPM) fractions. At subsequent stages of SE there was a significant increase in PKA activity in both homogenate and crude SPM fractions. Wester blot analysis showed that alteration of PKA protein expression was not responsible for the increase in PKA activity. These results show that SE has a significant duration-dependent effect on PKA activity. Combined with other cellular changes these findings, could represent a mechanism for the formation for potentiated seizure states like epilepsy.

The goal of this study was to determine safety, tolerability and pharmacokinetics of 2ME2 in patients with solid tumors and determine maximum tolerated dose (MTD). The following hypotheses were tested: 1) 2ME2 will be well tolerated in clinic when given orally and will have quantifiable effects on the ex vivo markers of angiogenesis and apoptosis; 2) 2ME2 will exhibit linear pharmacokinetics; 3) Plasma protein binding will be extensive and linear; 4) Sulfation will be the major metabolic pathway for 2ME2.This was a phase I dose escalation study. Twenty patients with refractory solid tumors were enrolled. 2ME2 was administered orally starting at 400 mg bid with dose escalation upto 3000 mg bid. Pharmacokinetic sampling was done up to 50 hours after single oral dose for characterization of pharmacokinetics and plasma drug concentrations which were determined by liquid chromatography tandem mass-spectrometry [LC/MS/MS, LOQ: 1ng/mL]. Circulating plasma concentrations were very low at all dose levels with high interindividual pharmacokinetic variability. Median plasma half-life was about 1-2 days. The unphysiologically high oral CL/F and Vd/F reflect low oral bioavailability of 2ME2. There was no dose proportional increase in Cmax or AUClast. There were no dose limiting toxicities at highest dose level, therefore MTD was not defined. The trial was closed due to extremely low plasma concentrations of 2ME2 achieved. Hepatic in vitro metabolism studies showed that 2ME2 was metabolized by CYP 450 enzymes (CYP 1A1, 1A2, 3A4, 3A5 and 2E1) to four major metabolites. Hepatic phase II metabolism studies revealed two major glucuronide metabolites of 2ME2. Sulfation did not play a major role in metabolism of 2ME2. Total in-vivo hepatic clearance was estimated as 862 mL/min, primarily due to glucuronidation. Less than 0.01 % of total administered dose of 2ME2 was excreted unchanged in urine, and about 1% was excreted as glucuronides. Plasma protein binding of 2ME2 was studied using equilibrium dialysis. Mean unbound fraction of 2ME2 (fu) in plasma of patients and healthy human volunteers was 0.019 ± 0.0043 and 0.027 ± 0.0019 respectively. Binding was concentration-independent and unaffected by presence of 2-methoxyestrone. 2ME2 binds to albumin, a1-acid glycoprotein (AAG) and sex-hormone binding globulin (SHBG).

The major purposes of this study were to determine the relationships among resilience, risk-taking behavior and personal characteristics of Thai adolescents living in Bangkok and to examine the differences in risk-taking behavior by school grades or gender. To accomplish these, a cross-sectional correlational research design was conducted. Resilience was measured by using the State-Trait Resilience Inventory developed by Hiew, Mori, Shirnizu and Torninaga.Risk-taking behavior was measured by the Risk-taking Behavior Questionnaire for Thai Adolescents which is a modified version of the 2003 Youth Risk Behavior Survey (YRBS) originally developed by the U.S. Centers for Disease Control and Prevention. In order to make it more applicable to the Thai setting, the author modified the 2003 YRBS. The modified instrument was then translated and back translated; equivalence testing was performed; a pilot study was conducted; and test-retest reliability was measured. Overall, these procedures indicated that the modified version of YRBS had evidence of equivalence (semantic, content, and conceptual), feasibility and acceptability as well as good reliability for use among Thai adolescents to measure risk behavior. Risk-taking behavior in this study includes six categories of behavior: (1) behavior that contributes to unintentional injuries and violence; (2) tobacco use; (3) alcohol and other drug use; (4) sexual behavior contributing to unintended pregnancy and sexually transmitted diseases, including HIV infection; (5) unhealthy dietary behavior; and (6) inadequate physical activity.In all, 1409 students, grades 7 to 12 from six secondary schools in Bangkok, Thailand, participated in the study. Their mean age was 14.9 ± 1.8 years, and 54% were female. Data sets were analyzed using the SPSS for Windows, version 14.0 statistical software program. Resilience scores ranged from 72 to 161 with a mean of 125.55 and standard deviation of 11.44. There were significant positive and negative relationships between resilience and various risk-taking behavior (p Overall findings from this study provided more understanding of risk-taking behavior and its relationship with resilience among Thai adolescents. The recommendations for implementation and further studies were discussed.

The purpose of this study was to determine the prevalence and demographic predictors of pulpal and/or periradicular disease in an urban population. A total of 210 subjects were recruited from a population of patients that were screened for acceptance to the dental school clinics. The diagnosis of pulpal and/or periradicular disease was made using the following data: radiographic interpretation, patient's history of previous pain and chief complaint, and objective pulpal testing. Objective pulpal testing included percussion, palpation, electric pulp test, and cold. The unit of observation was the individual, not the tooth. The overall prevalence of endodontic disease among the study sample of the screening patient population was 39.52%. Controlling for gender, patients in the 30-39 age group were 3.05 times more likely to have pulpal disease than patients in the 18-29 age group (OR=3.05, 95%CI 1.04-8.9). Controlling for age, men were 1.82 times more likely to have pulpal disease than women (OR=1.82, 95%CI 1.01-3.26). Non-white patients were 2.69 times more likely to have pulpal disease than white patients (OR=2.69, 95%CI 1.51-4.81). Patients who earned less than $25,000 were 2.06 times more likely to have pulpal disease compared to those who earned more than $25,000 (OR=2.06, 95% CI 1.15-3.69). Overall, this data provides valuable information for identifying vulnerable populations and addressing the policy goals of the U.S. Surgeon General.

Nicotine is one of the first and most commonly abused drugs in adolescence. According to The Center for Disease Control, every day more than 6000 adolescents try their first cigarette and over 3000 of them become daily smokers. Smoking among adolescents is a strong predictor of future drug abuse and dependence in adulthood. A number of studies has suggests that adolescents pre-exposed to nicotine may suffer permanent disruption of the brain’s reward systems through changes in dopamine receptor function. We hypothesize that nicotine exposure during adolescence causes long lasting neurobiological alterations that increase the likelihood of cocaine use in adulthood. Furthermore, it activates a neurobiological mechanism that is shared by many drugs of abuse, which will increase susceptibility to their rewarding effects. The work in this thesis contributes to the further understanding of this critical developmental period. Conditioned-place-preference, acute locomotor and locomotor sensitization pardigms were used to examine changes in cocaine sensitivity in adulthood. Testing was performed on adult ICR mice that were exposed to nicotine (0.1 or 0.5 mg/kg, S.C., b.i.d.) or saline during adolescence (postnatal days 28 or 46) or adult (postnatal day 70). Data showed that a 7-day exposure to the higher dose of nicotine (0.5 mg/kg) altered cocaine-induced responses. In contrast, neither 1 day exposure nor a low dose of nicotine (0.1 mg/kg) elicited this effect. A follow-up study was undertaken to determine if this enhancement generally applies to other drugs of abuse. Pre-exposure to 0.5mg/kg nicotine during early adolescence demonstrated significant enhancement to morphine reward, but it failed to increase d-amphetamine preference in a CPP model. Further research will be required in order to more fully examine the mechanisms of action for the observed changes in cocaine rewards. In summary, these findings suggest that early adolescent nicotine exposure leads to changes in cocaine reward and sensitivity during adulthood in both dose and duration matters. Indeed, the adolescent brain is uniquely vulnerable to the effects of nicotine on subsequent drug reward.