Objective: To determine if the prevalence of anti-diabetic and antilipidemic medication use among children treated with atypical antipsychotics is higher than those not treated with antipsychotics. Methods: Virginia Medicaid beneficiaries (2-17 years) continuously enrolled from August 1, 2010 to July 31, 2011 with at least two prescription claims for atypical antipsychotics were the exposed group. All other subjects during the study period were the non-exposed group. Prevalence of anti-diabetic and antilipidemic medication use in both groups were computed and compared using Chi-square test (α=0.05). Results: A total of 299,593 and 4,922 subjects were identified as the non-exposed and exposed groups, respectively. Prevalence of anti-diabetic medication use was 0.32% in the unexposed and 1.40% in the exposed group (p<0.0001). Prevalence of antilipidemic medication use was 0.09% in the unexposed and 0.35% in the exposed group (p<0.0001). Conclusion: Prevalence of anti-diabetic and antilipidemic medication use in the exposed group was significantly higher.

Proper T-cell activation and effector function are essential for effective immunity. T-cell antigen receptor (TCR) signals are known to regulate the outcome of differentiation, but the mechanisms remain unclear. Recent work from our lab demonstrates that the Src family protein tyrosine kinase, p56Lck, is able to specifically link TCR signals to activation of the Mitogen Activated Protein Kinase (MAPK) pathway through the function of its SH3 domain. The MAPK pathway is known to be involved in T-cell activation downstream of TCR ligation and has previously been implicated in T-helper type 2 (Th2) effector function. We have utilized an Lck SH3 mutant knock-in mouse line (Lck W97A) to investigate the potential role of this regulatory signaling mechanism in determining T-lymphocyte activation and effector function. Our results demonstrate that the Lck SH3 domain function is required for normal activation of T-lymphocytes following TCR stimulation as indicated by significantly reduced proliferation, IL-2 production, and CD69 induction in Lck W97A T-cells. Biochemical studies confirm that activation of the MAPK pathway is selectively altered in Lck W97A T-cells as P-ERK1/2 induction is significantly reduced but phospho-PLCg1 induction and calcium mobilization is unaffected. In vivo experiments demonstrate a specific and significantly impaired Th2 immunity in Lck W97A mice, with reduced serum levels of IgG1, IgE and IL-4 following immunization with DNP-KLH, or infection with the helminth Nippostrongylus brasiliensis. Th1 immunity does not appear differentially regulated in Lck W97A mice as serum levels of IgG3 and IgG2b are similar to WT following immunization with DNP-KLH, as well as serum levels of IFN-g1 following immunization with heat-killed Brucella abortus. In vitro differentiation studies confirm that Lck W97A T-lymphocytes are able to be directed to the Th2 phenotype, as indicated by intracellular staining for IL-4, with significantly increased levels of IFN-g under Th2 differentiating conditions compared to WT. These data indicate that the Lck SH3 domain regulates activation of T-lymphocytes by affecting MAPK pathway induction and demonstrate a novel and critical role for Lck in the regulation of Th2-type immunity. The Lck SH3 domain has also been implicated in the pathogenesis of Plasmodium, the causative agent of malaria. The role of the mosquito vector on malaria pathogenesis is not well understood. Initial studies examining the role of vector salivary gland proteins on cells of the innate immune system indicate that Anopheles stephensi saliva is able to enhance macrophage activation and phagocytosis as well as enhance macrophage Ag-presentation to T-lymphocytes in an in vitro model.

Background: Forty percent of all head and neck cancers occur in the oral cavity. According to ICD-O (International classification of diseases for oncology) C00-C14 includes cancers of the lip, oral cavity and pharynx. Studies have indicated that increased population density or Metro living have increased oral cancer incidence. The objectives of this study are to look at the distribution of Oral and Oro pharyngeal Cancers in Virginia from 2001-2005 The study aims to determine if there is an association between metro living (beale code 3) and advanced Oral Cancers. This study is also being done to determine if Metro living is a predictor of Oral Cancer after adjusting for gender. Methods: The data for this study was obtained from the Virginia Cancer Registry. Cancer counts were obtained based on gender, beale code distribution and stage at diagnosis. The counts were collected for the years 2001-2005 based on the ICD-O codes C00-C14. Analysis of this secondary data was done using SAS 9.1. Descriptive statistics presents the distribution of oral cancer according to the stage, gender and urbanity level of the patient. A log-linear model was done to look for association between metro living and Oral Cancers in Virginia after adjusting for gender and stage. This model was fit using a Poisson’s regression to observe if the cancer counts are influenced by the urban beale code 3. Results: During the five year period of 2001- 2005 the Virginia Cancer registry received a total of 3,390 reported cases of oral and pharyngeal cancers. Out of the 3,390 cases 67.35% (2283) of the cases were diagnosed in males and the rest 32.65% were females (1107). Based on the stage at diagnosis, 34.45% (1168) of Oro-pharyngeal cancers were diagnosed to have localized staging as compared to 50.18% (1701) regional and 11.03% (374) distant. 4.34% of the cancers were unstaged (N=147). 82% of all Oro-pharyngeal cancers were seen amongst whites. Majority of oral cancers were seen amongst age groups 35-74 years (78.41%). While looking at the distribution of oral cancers reported from the urban populations; 82.3% (2790) were reported from beale code1. Only 9.73% (330) cases were reported from beale code 2 and 7.96% (270) cases were reported from beale code 3 (population fewer than 250,000 people). More than 50% of cancers were diagnosed at an advanced stage in the urban populations; we did not see a significant relation between advanced oral cancers and metro living. (p =0.2878). After performing a scaled deviance Poisson regression model indicated that there was a stable trend in counts of advanced oral cancer after adjusting for race, age and gender.(θ=-0.04 p-value =0.617). Conclusions: With a linear trend between increased population density and advanced oral cancers, our study observed a stable trend within the metro populations. Due to lack of a clear understanding of all the possible contributing factors further research is recommended to observe the various etiological differences within the urban populations and advanced oral cancers.

Purpose: The purpose of this study was to determine the relationship of the CYP2B6 genotype to the clinical response to meperidine in pediatric dental patients. Methods: Forty-nine patients, ASA I/ II, 41–101 months old, received an oral sedative regimen containing meperidine for dental treatment. The North Carolina Behavior Rating Scale (NCBRS) and Overall Effectiveness of Sedation Scale (OESS) were used to assess their behavior and sedation outcome. Saliva DNA samples were genotyped by PCR-RFLP. Results: We found the following genotype distributions: homozygous wild-type 1*1 (n = 19, 39%), heterozygous 1*6 (n = 25, 51%), and homozygous variant 6*6 (n = 5, 10%). The genotypes showed a significant difference in the North Carolina Behavior Rating Scores and a trend towards significance of the Overall Effectiveness of Sedation Scale during meperidine oral sedations. Conclusion: This research concludes that variations of the CYP2B6 enzyme can be used in the prediction of successful behaviors for oral sedations that include meperidine in the drug regimen. Future research regarding the enzyme kinetics of meperidine is needed to determine the exact enzymatic function of CYP2B6 and its variants.

BACKGROUND: Increasing rates of hospital acquired Clostridium difficile (CDI), as well as mortality owing to CDI, warrants further exploration of risk factors. Clostridium difficile bacteria typically produce toxins which inactivate the Rho proteins found in the colonic epithelium. Statins also disrupt Rho protein cell signaling functions. The objective of this study was to estimate the extent to which use of statins increases the risk of healthcare-acquired CDI. METHODS: Patients over 18 years of age admitted to hospitals contributing data to the University HealthSystem Consortium between 2002 and 2009 were eligible. We identified 25, 111 incident cases of CDI and matched up to 5 controls, matched on hospital, year of admission date, and age +/- 10 years (N=68,259). Patients with ICD-9-CM code of 008.45 who initiated a minimum three day course of either metronidazole or oral vancomycin on/after day 5 of admission were considered incident cases of CDI. RESULTS: Compared to non-users, users of any drug within the statin class as monotherapy were 0.63 times less likely to be classified as a case (95% CI = 0.60-0.66) adjusting for potential confounders. CONCLUSIONS: Our data did not support the Rho protein hypothesis. Rather it was consistent with a growing body of literature demonstrating reduced risk of infections with statin use. Statins’ pleiotropic properties may provide protection against CDI.

Background: The American College of Surgeons guidelines suggest the use of intact gloves, double gloving, hands-free zone technique to pass sharp instruments, and blunt tip suture needles to protect patients, as well as the surgical team. This study estimates the extent to which these guidelines are followed in a large academic health system. Methods: Over a two-month period in the spring of 2010, 320 general surgical attendings, subspecialty surgical attendings, and surgical resident physicians practicing at a large academic health system, were approached during or after surgical conferences to participate in a cross-sectional study. Nearly 1/3rd completed an anonymous and voluntary self-administered survey. The survey included questions regarding knowledge of each technique, beliefs about effectiveness of each technique, and adherence to the guidelines. Responses were compared by surgeon rank. Results: Awareness of ACS recommendation guidelines was high among surgical attendings (68%) and residents (60%). While 60% of residents adhered to these recommendations, only 43% of attendings adhered. Both attendings (65%) and residents (64%) had similar negative perception toward double gloving in terms of tactile sensation and hand free zone hindrance during procedural operations during cases. Forty percent of residents and attendings agreed on unhindered concentration to hand free zone technique. Blunt tip suture needle use had low awareness and usage regardless of surgeon rank (~40%). Conclusion: Increased promotion of the ACS guidelines is warranted. Continuing medical education for surgical attendings may promote more widespread adoption of techniques to promote safety.

Enamel demineralization is a concern in orthodontic patients with poor oral hygiene. To curtail this problem, amorphous calcium phosphate (ACP) containing adhesives have been developed. The purpose of this in vitro study was to evaluate the cariostatic potential of an ACP containing orthodontic bonding agent adjacent to brackets. Sixty human molars were randomly distributed into: ACP adhesive, resin modified glass ionomer cement (RMGIC), and conventional composite resin groups (N=20 each). Brackets were bonded following the manufacturer’s instructions. Tooth enamel through a 2mm window around the brackets was cycled in demineralization (6 hrs) and remineralization (18 hrs) solutions. After 14 days, teeth embedded in resin and were sectioned. Knoop indentations were performed to determine enamel hardness. There were no statistically significant differences between the control and experimental groups. However, both Fuji Ortho LC (RMGIC), and Aegis Ortho (ACP) showed a trend toward a reduction in demineralization. In addition, it was also shown that the initial acid etching of the enamel significantly reduces enamel hardness.

Introduction: Within the past decade, significant developments, new designs, and numerous proposed advantages of self-ligating (SL) brackets have caused them to gain great popularity among practicing orthodontists. The purpose of this study was to determine if there are significant clinical differences between SL and conventional brackets on orthodontic treatment as perceived by practicing orthodontists, and more specifically, if the proposed advantages of SL brackets are evident in clinical practice. Methods: A survey was developed to evaluate how SL brackets compare to conventional brackets when perceived by practicing orthodontists (n=430). The initial series of questions focused on individual practitioner characteristics and the clinician’s experience with SL brackets, while the second part of the survey allowed the orthodontists to indicate a preference for either SL or conventional brackets in regard to a variety of treatment factors. Results: Most of the responding orthodontists (90%) had experience using SL brackets in clinical practice. SL brackets were preferred for the majority of orthodontic treatment factors, and were most significantly indicated as having shorter adjustment appointments (P <0.0001), providing faster initial treatment progress (P <0.0001), and were the most preferred bracket during the initial alignment stage of treatment (P <0.0001). On the other hand, practitioners reported a stronger preference for conventional brackets during the finishing and detailing stages of treatment (P <0.0001), and regarded conventional brackets as being significantly more cost effective than SL brackets (P <0.0001). Less emergency appointments were also reported with conventional brackets compared to SL brackets (P <0.0001). Despite the perceived overall preference for SL brackets, more than one-third of practitioners no longer use or are planning on discontinuing use of SL brackets. In many circumstances, the orthodontists’ bracket preference was significantly influenced by the proportion of patients they treated with SL brackets (P <0.0001), the number of cases it took them to become accustomed to SL brackets (P <0.0001), and their average appointment intervals for both SL brackets (P <0.0001) and conventional brackets (P = 0.0002). Conclusion: Overall, the orthodontists participating in this study reported a perceived difference between SL brackets and conventional brackets on orthodontic treatment. SL brackets were found to be preferred for the majority of the treatment factors, while there were a few situations in which conventional brackets were preferred. Ultimately, due to the lack of high-quality evidence supporting SL brackets, more objective, evidence-based research is essential in order to evaluate definitively the clinical differences of SL and conventional brackets on orthodontic treatment.

Purpose: The purpose of this study is to describe children’s dental disease status and functional health literacy of families enrolled in the Child Health Investment Partnership program in Roanoke Valley. Methods: This was a prospective cohort study of children (n=166) enrolled in the Child Health Investment Partnership of Roanoke Valley, Virginia (CHIP). The parents of the 166 children completed the Life Skills Progression (LSP) survey at enrollment between September 2004 and September 2008 to assess their functional health literacy levels. Their LSP scores were used to determine their subsequent health care literacy (HCL), personal health literacy (PHL), and dental-child utilization (LSP22) scores. Descriptive statistics were recorded and a paired t-test was used to determine a relationship between the three measures of functional health literacy at baseline and at their most recent literacy assessment. Dental disease status was determined by an epidemiological dental exam and evaluated using d1d2-3f criteria. This was a visual exam that measured the presence of frank (d2-3) and non-cavitated carious lesions (d1), as well as filled teeth. Results: Descriptive analysis of the cohort reveals: 58% of the children enrolled had no carious teeth at the dental screening exam. The average mean of LSP scores for all three scales: HCL, PHL, and LSP22 were significantly different from baseline: p<.0001, p<.0009, and p<.0001, respectively. Conclusion: An improvement of parental functional health literacy has been documented in a low-income pediatric dental population when preventative efforts and education is delivered within the context of a home-visitation health program. The population of high-risk children had low levels of dental disease.

The epidemiology of snakebite injury in the Amazonian regions of Ecuador Introduction: Morbidity and mortality from snakebite envenomations is a major public health issue in remote areas of under-developed countries. Several attempts have been made to approximate the impact of snakebites worldwide, however these are assumed to be underestimations due to the lack of documentation on the local level. Ecuador's Amazonian region lacks a comprehensive community-based surveillance system, however it is unique in that an aero-medical transport system is in place to transfer the patients requiring hospitalization to one of the five urban medical centers. Beginning in 1998, Servicio Aéreo Misional (SAM), one of the two transport companies serving three of the rural provinces, began documenting flight data including the demographics of patients and their diagnoses. Methods: The SAM database was used to conduct a retrospective study to describe the incidence, patient demographics and geographic location of snakebite injuries in three rural provinces of Ecuador. SPSS was used for frequencies and Chi squares analyses. Results: In the years 2003 to 2005 there were a total of 1,340 aero-medical transports in this region. Of those, snakebite injuries constituted 4.2% of all medical diagnoses. The majority of snakebites occurred in males (p=0.027) aged 10-29 (p<0.001) and were concentrated in the low-lying areas of the province of Morona-Santiago. Discussion: These results describe the distribution of snakebites; efforts are now underway to identify the risk factors involved in this patient population. This information would then be used to optimize prevention and treatment.