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.

With over 140 vitamin B6 (Pyridoxal 5’-phosphate, PLP) dependent enzymes, serving vital roles in various transamination, decarboxylation, retro-aldol cleavage and synthesis pathways these enzymes constitute the most versatile catalytic systems in nature. Enzymes of this group have an inherent reaction as well as substrate specificity. A single co-factor namely, PLP is used by specific enzymes of this group to serve distinct roles during the catalytic reaction. An ordered evolutionary adaptation in these enzymes has led to specialization achieved by each enzyme for catalyzing specific reactions. L-Threonine aldolase (L-TA) is one such PLP- dependent enzyme that catalyzes the retro-aldol cleavage of several β-hydroxy amino acids, although its natural substrates are L-threonine and L-allo-threonine with the enzyme having significant preference for L-allo-threonine. It also catalyzes racemization and transamination of D-alanine but not of the β-hydroxy amino acids. Thus, the enzyme exhibits both substrate and reaction specificity. Although, L-TA is frequently employed for stereoselective synthesis of pharmaceutically useful compounds, its reaction mechanism and associated specificity is still not clearly understood. L-TA from Escherichia coli (eTA) is being studied in our laboratory. Our objective is to elucidate the catalytic mechanism of eTA and its mode of substrate and reaction specificity using X-ray crystallography. Another objective is to establish evolutionary relationship of L-TA with other B6-dependent enzymes, such as serine hydroxymethyltransferase (SHMT) and Thermatoga maritima L-TA (TTA) that have the same fold and catalyze similar reactions. Our structural studies show that while the crystal structures of the two L-TAs are similar, they are significantly different from that of SHMT, especially at the active site. In the L-TA structures, a loop with proposed important active site residue, His126 is replaced by tetrahydrofolate (THF) in SHMT. The crystal structures of eTA in its native form and in complex with substrate or product have highlighted the importance of His126 in ensuring substrate specificity during retro-aldol cleavage of various β-hydroxy amino acids and His83 or a conserved water molecule to be active site base. Our study emphasizes the molecular level implications of the catalytic mechanism of eTA.

Background: Endothelial dysfunction (ED) is one of the earliest subclinical indicators of impaired cardiovascular health and several non-invasive tools have been developed to evaluate vascular function, including strain gauge plethysmography (SGP), brachial artery flow-mediated dilation (FMD) via ultrasound, and peripheral artery tonometry (PAT). While these tools have extensively been studied during a resting condition, the responses following acute exercise are not as well characterized. Purpose: The purpose of this study was to compare the pre- and post-exercise vascular function values obtained with SGP, FMD, and PAT. Relationships among the primary outcome variables obtained with each assessment tool were also evaluated. Methods: Vascular function was assessed in 17 sedentary, apparently healthy male subjects (24±4 yrs; 24.5±3.2 kg/m2) at rest and following an acute submaximal exercise bout with SGP, FMD, and PAT. Results: During rest, post-occlusion reactive hyperemia resulted in significant (p<0.05) increases in forearm blood flow (FBF; 2.13±1.03 vs 6.35 ± 2.90 mL/min/100 mL tissue) and area under the curve (AUC; 226.77 ± 111.20 vs 588.22 ±283.33 mL/min/100 mL) as determined by SGP. Brachial artery diameter (BAD) as assessed with FMD was increased by 5.3% (p<0.05). Resting reactive hyperemia index (RHI) as assessed by PAT was observed to be 1.73±0.34. Significant exercise-induced increases (p<0.05) were observed in baseline and post-occlusion FBF and baseline AUC values utilizing SGP. Additionally, FMD baseline blood velocity was significantly increased (91.8±11.1 vs 108.0±17.1 cm/sec, p<0.05) and the PAT augmentation index (AI) was significantly more negative (-8.8 ±9.4 vs -18.9±8.4%, p<0.05) after exercise. There were no significant correlations observed among the primary outcome measures obtained from each assessment technique. There was, however, a moderate correlation between pre-exercise vascular reactivity as assessed by SGP and change in blood velocity as assessed by FMD (r= 0.566, p= 0.035). Conclusions: The addition of an exercise stress to vascular function assessment may offer greater insight into the health of the vasculature. This initial study was undertaken to further evaluate the pre- to post-exercise responses obtained using three commonly employed vascular function assessment techniques in healthy individuals. Additional research as to the value of the addition of an exercise stress to vascular function assessment in individuals with traditional cardiovascular disease risk factors or known cardiovascular disease is warranted.

Introduction: Obese women are predisposed to greater risks of insulin resistance and compensatory hyperinsulinemia. Likewise, African-Americans, appear to be inherently insulin resistant and hyperinsulinemic even after controlling for obesity. Hyperinsulinemia has been attributed to insulin resistance and a compensatory insulin hyper-secretion by the pancreas, as well as decreased insulin clearance, notably in obesity. Pharmacological agents that may worsen insulin resistance/hyperinsulinemia in obese women is of clinical relevance. Previous data from our group suggested that combined oral contraceptives (COCs) may worsen insulin sensitivity particularly in obese women, but limited information on insulin clearance is available in obese women or African-American women. Objective: The objective of the study is to evaluate and compare the effect of a COC containing ethinyl estradiol and norgestimate on insulin clearance among lean and obese pre-menopausal women and among African-American obese vs. non African-American obese women. Method: Plasma insulin clearance was calculated from plasma insulin concentrations, following frequently sampled intravenous glucose tolerance test. Changes in insulin clearance, during six months of COC use were analyzed by repeated measures analysis. Result: Six months of COC use showed no significant change in insulin clearance in all women (p=0.3713). Furthermore, there were no divergent effects on insulin clearance among lean (n=13) and obese (n=14) women (p=0.6703) and among African-American obese (n=7) and non African-American obese (n=7) women (p=0.0957). Changes in insulin clearance, following six months of COC administration was found to be positively correlated with changes in insulin sensitivity (r=0.385, p=0.0099) and negatively correlated with changes in acute insulin response to glucose (r=-0.432, p=0.0034). Discussion: In the present study, COC administration did not show any differential effect on insulin clearance in lean vs. obese women. Future studies evaluating the effects of hormonal agents on insulin-glucose dynamics may focus on mechanisms of hormone-mediated insulin resistance and compensatory hyperinsulinemia rather than insulin clearance.

The discovery of heparin in 1916 resulted in a huge impact on the practice of medicine. Heparin has played a major role in alleviating thrombotic disorders and has also exhibited effects on almost every major system in the human body. Over the past few decades, more and more heparin-protein interactions have come to light. It is implicated to modulate several important processes such as cell growth and differentiation, inflammatory response, viral infection mechanism etc. More interesting is the observation that these interactions are considerably specific with regard to oligosaccharide sequences which have specific spatially oriented sulfate groups modulating the responses. However, due to the complex nature of these interactions and lack of effective computational capabilities, predicting these interactions is challenging.An alternative approach to modulating heparin-protein interactions would be to screen a library of molecules having a diverse distribution of the negative charges and screen them against various proteins of interest to obtain valuable information about the binding/selectivity requirements. This approach would not only yield molecules with potential clinical viability, but may also yield molecules that help decipher native mechanisms regulating proteins, which is called chemical biology in today's terms. Since the difficulties associated with carbohydrate synthesis are well known, well characterized highly sulfated oligosaccharide library screening is considered nearly impossible. Thus, the main aim of this project was to develop an effective method for the synthesis of a library of variably sulfated, non-carbohydrate molecules. The library would contain varying in the number of sulfate groups, offer positional variants of the sulfate groups and provide molecules of varying length so as to afford structural diversity necessary to mimic the heparin sequences. Previous attempts in our laboratory to synthesize such a library encountered two major problems: 1) dimerization of polyphenols due to difficult protection / deprotection strategies and 2) ineffective purification of highly water soluble sulfated molecules. To overcome the problem of protection-deprotection, “click” chemistry has been used in this work for dimerization of polyphenols without any protective groups. To overcome the second problem, a non-aqueous method of purification of highly sulfated molecules was developed, which is the first such report.As a proof of concept, a small library of 14 sulfated monomers and dimers and 8 non-sulfated dimers was generated. The protocol for dimerization of free polyphenolic molecules in has been established to use “click” chemistry for coupling the monomers without the need to protect the free hydroxyl groups. Thus by circumventing the inefficient protection-deprotection protocol, there is a tremendous improvement in yields, ease of purification and characterization and greater productivity allowing the synthesis of more number of molecules in a relatively shorter span of time. By masking the charge of the sulfate using an appropriate counter-ion and owing to the inherent lipophilicity of the aromatic scaffold, these highly charged molecules could be purified using normal phase silica gel chromatography. This method reduced the purification time from previous over 48 hours with the aqueous method to approximately 15 minutes. Further, this purification protocol may be possibly automated so as to truly generate a large library of variably sulfated non-carbohydrate molecules for the first time. Screening this library of 22 sulfated and unsulfated molecules against three enzymes of the coagulation cascade – factors IIa, Xa and XIa – has provided a wealth of information with regard to engineering specificity for recognition of these enzymes. The screening led to the identification of CS3 which inhibited factor XIa with an IC 50 of ~ 5 μM and other enzymes with an IC 50 of > 500 μM as a lead candidate with high selectivity. The success of this strategy bodes well for understanding the heparin-protein interactions at a molecular level. Previous attempts in our laboratory to synthesize such a library encountered two major problems: 1) dimerization of polyphenols due to difficult protection / deprotection strategies and 2) ineffective purification of highly water soluble sulfated molecules. To overcome the problem of protection-deprotection, “click” chemistry has been used in this work for dimerization of polyphenols without any protective groups. To overcome the second problem, a non-aqueous method of purification of highly sulfated molecules was developed, which is the first such report.As a proof of concept, a small library of 14 sulfated monomers and dimers and 8 non-sulfated dimers was generated. The protocol for dimerization of free polyphenolic molecules in has been established to use “click” chemistry for coupling the monomers without the need to protect the free hydroxyl groups. Thus by circumventing the inefficient protection-deprotection protocol, there is a tremendous improvement in yields, ease of purification and characterization and greater productivity allowing the synthesis of more number of molecules in a relatively shorter span of time. By masking the charge of the sulfate using an appropriate counter-ion and owing to the inherent lipophilicity of the aromatic scaffold, these highly charged molecules could be purified using normal phase silica gel chromatography. This method reduced the purification time from previous over 48 hours with the aqueous method to approximately 15 minutes. Further, this purification protocol may be possibly automated so as to truly generate a large library of variably sulfated non-carbohydrate molecules for the first time. Screening this library of 22 sulfated and unsulfated molecules against three enzymes of the coagulation cascade – factors IIa, Xa and XIa – has provided a wealth of information with regard to engineering specificity for recognition of these enzymes. The screening led to the identification of CS3 which inhibited factor XIa with an IC 50 of ~ 5 ?M and other enzymes with an IC 50 of > 500 ?M as a lead candidate with high selectivity. The success of this strategy bodes well for understanding the heparin-protein interactions at a molecular level.

Today, more than ever, there exists an overlap between hospitality and healthcare industries; with the impact being felt in the way hospital interiors are designed. This influence impacts the patient’s experience but focuses very little on the experience of the caregiver. Caring for a sick child takes an emotional, mental, and physical toll on a family. It is especially challenging to care for a sick family member when away from the comfort and security of the family’s private home. This project explores that challenge through the interior design of a space that, for both patient and family, is restorative, healing, and encouraging. It is a space that assists a family in caring for their loved one.