Increasing rates of overweight/obese adults, with corresponding increases in health risks, obesity-related illnesses, and health costs have not been significantly impacted despite research and commercial attempts to provide recommended weight loss strategies. Mindfulness Meditation (MM) teaches individuals to increase their awareness in the present moment which may offer an additional strategy to weight loss interventions. This study explored the effects of MM combined with standard behavioral weight loss intervention (SBWP) on short-term weight loss, physical activity, eating behaviors, food intake and mindfulness in overweight/obese adults. Additionally, adherence, feasibility and acceptability of MM were explored through retention, attendance, diary return rate, MM practice and qualitative interviewing. This exploratory mixed methods study was a 24 week randomized controlled trial that compared SBWP and Standard Behavioral Weight Loss Program plus Mindfulness Meditation (SBWP+MM) followed by a qualitative interview that explored the experiences of 12 SBWP+MM participants. The sample which was randomized between treatment groups included 46 overweight/obese, 87% female, mean age 45.2 years (SD=8.2), mean weight 91.9 kg. (SD=12.8), 21.7% African American, and 78% college-educated adults living in the Pittsburgh area. Outcome measures of weight, physical activity, eating behavior, food intake and mindfulness were explored at three time points. Data analysis was based on intention-to-treat with linear mixed effects modeling and general linear modeling. Thirty-five subjects (76%) completed the study. Mean total weight loss was 5.48 kg (SD=2.01) with a significant decrease in food intake (p<.00) and significant increase in physical activity and healthy eating behaviors (p<.000). There was a mean greater weight loss in the SBWP+MM group (6.89kg compared to 4.07kg). Only eating behaviors significantly improved in the SBWP+MM group based on the results of linear mixed effects modeling (p=.034). The SBWP+MM group had higher rates of retention (86.4%) and attendance (75%) and a difference in diary return (15 weeks versus 12 weeks). The overarching SBWP+MM qualitative theme of expanding mindfulness in personal life flowed from taking time intentionally for self to lifestyle changes. The exploratory results, eating behavior significance and other outcome differences in the SBWP+MM group suggest that a larger sample size over a longer period of time may find further statistical and clinical significance. In light of the current obesity epidemic, hypothesis testing of MM could lead to enhanced weight loss interventions for this overweight/obese population.

BACKGROUND: Neuroglobin (Ngb) is a protein that increases oxygen availability in ischemic neuronal tissues, but whether Ngb gene variants contribute to patient outcomes is unknown. PURPOSE: To identify functional or non-functional variants in the Ngb gene in severe traumatic brain injury (TBI) patients and determine whether variants impact patients injury severity and functional outcomes. Specific Aims: To identify Ngb variants (present/absent) in DNA extracted from the cerebral spinal fluid and blood of patients with severe TBI, and then: 1) determine the variant frequencies, 2) determine demographic and clinical patient characteristics based on Ngb variants, 3) determine the relationship between the variants and TBI severity as measured by admission Glasgow Coma Scale (GCS), and 4) determine differences in functional outcomes (Glasgow Outcome Scale [GOS]) at 3,6,12, and 24 months post TBI based on Ngb variants. METHODS: Prospective, descriptive, comparative design using DNA collected (NIH NR04801 and NS30318) from 196 Caucasian subjects (non-Caucasians excluded to eliminate confounding from ancestry). We generated Ngb genotype data for 2 tagging single nucleotide polymorphism (SNP) variants (captures all of Ngbs genetic variation) using TaqMan PCR technology. Data analysis: independent t-tests; Fisher Exact, Pearsons Chi-square, Exact tests; logistic and linear regression. RESULTS: For Ngb SNP1, 36.3% were CC/CT (non-wild typed or present variant [SNP1 Vpresent]), and 62.2% were TT (wild typed or absent variant [SNP1 Vabsent]). For Ngb SNP2, only 6.6% were TT/GT (SNP2 Vpresent), whereas 91.3% were GG (SNP2 Vabsent). There was no significant relationship between variants of SNP1 or SNP2 and either demographic or clinical characteristics. There was a trend toward significance between SNP1 Vabsent and better GCS (p = 0.061), but not between SNP2 variants and GCS (p = 0.109). Subjects with good outcome by GOS were more likely to be SNP1 Vabsent at 3, 6, 12, and 24 months (p = 0.023; p = 0.01; p = 0.002; p = 0.035 respectively). No significant relationship was found between SNP2 and GOS at any time point. Using logistic and linear regression controlling for age, gender, and GCS, SNP1 Vpresent was significantly associated with poorer GOS at 12 months (p = 0.028) only; SNP2 showed no significance in regression analysis. CONCLUSION: SNP1 Vabsent TBI patients were more likely to have good outcomes, whereas genetic variants of SNP2 did not impact outcomes; possibly because Ngb SNP1 Vabsent affects the quantity or quality of Ngb in severe TBI, producing better outcomes.

The purpose of this study is to describe patterns and relationships among the modifiable cardiovascular risk factors of smoking behavior, overweight, physical inactivity and poor dietary behaviors within a ninth grade population. Four modifiable cardiovascular risk factors; smoking behavior, overweight, physical inactivity and poor dietary behavior were analyzed from the 2003 Youth Risk Behavior Surveillance System (YRBS) to explore associations in early adolescents, a critical developmental time frame. The specific aims of this study were to: 1) conduct a factor analysis of questions selected from the 2003 YRBS to represent the constructs of smoking behavior, physical inactivity and poor dietary behaviors; 2) to describe the modifiable risk factors of the targeted variables; 3) to examine relationships among the risk behavior factors of smoking behavior, overweight, physical inactivity and poor dietary behavior for the total sample; and 4) to examine relationships among the risk factors for subgroups identified by race and gender. Specific items were identified from the 2003 YRBS that represented modifiable cardiovascular risk factors. For specific aim 1, factor analysis was performed on the targeted variables. Analysis of specific aim 2 was conducted using descriptive statistics for each of the factors identified in Specific Aim 1, and the additional risk factor of overweight. Specific aim 3 was analyzed using a Pearson r correlational model for relationships among the risk behavior factors of smoking behavior, physical inactivity and poor dietary behaviors. Logistic regression was used to explore relationships of factors with overweight. Specific aim 4 was analyzed using logistic regression and Pearson r correlation for relationships among the identified risk behavior factors within demographic subgroups. While each of the four behavioral cardiovascular risk factors were present only physical inactivity, poor dietary behavior, and overweight were common factors that emerged in the final conceptual model. Findings demonstrated that gender was not associated with being overweight, but race did contribute significantly to the logistic regression model with overweight as a dependent variable. It is suggested that future directions be aimed at enhancing physical activity, improving dietary behavior, and preventing overweight for students in the 9th grade.

Objective: To: 1)determine the prevalence and incidence of ED in males with T1D enrolled in the Pittsburgh Epidemiology of Diabetes Complication (EDC) study from 1986 to 2007; 2)identify risk factors for development of ED; 3)identify the development of ED in relation to other markers of neuropathy; and, 4) determine behavioral and cognitive risk factors associated with the development of ED. Design: The EDC was a cohort study of 333 males with T1D: mean age of 27.53years (SD±7.8, range 8.5-47.4); 331 Caucasians and 2 African Americans; and, duration of diabetes of 19.6years (SD±7.5, range 7.7-37.4). Age-specific ED prevalence was determined from baseline (1986-1988) while age-specific incidence was determined from longitudinal data (1988-2007). Results: Prevalence rate was 10.4 %. Thirty-one had ED: mean age of 35.8years (SD±5.3, range 22.9-44.8) and mean duration of diabetes 26.9years (SD±5.9, range 8.1-37.4). Males with prevalent ED did not statistically differ from males without ED in metabolic control (HbA1), education, income, or the current use of ACE or lipid lowering medications. Associated risk factors for the 31 prevalent cases included; CDSP, HDL and BDI score. Incidence rate was 17.78 % (n=54) from 1989-2007 with a mean age of 40.61years (SD±5.9, range 26.7-60.8) and mean duration of diabetes of 32.54years (SD±5.88, range 20.9-51-9). Mean HbA1 was 10.68% (SD±2.19). Associated risk factors for the 54 incident cases included; CDSP, nonHDL cholesterol, and BDI score. E/I Ratio was significant (p<.01) at the time of the event, but not in the preceding event cycle (p=.18). CDSP was significant (p<.01) in the preceding cycle to ED development and at the time of event (p<.01). For the repeated measure analysis, CDSP was significant in the preceding cycle to the ED development but not at the time of the event. The following differences were found between those with and without ED: knowledge of diabetes (p=.04); self-management (p=.10); and, perception of severity (p=.08). However no significant difference was found between the two groups for self-efficacy. CONCLUSION: CDSP, HDL, nonHDL and total BDI score were risk factors for development of ED in males with T1D. Therefore, these should be assessed for frequently in males with T1D.

Introduction: Each year potentially 1:270 children in the US are affected by the diagnosis of cancer in their mother. The diagnosis of cancer in a woman may cause changes in her behavior, emotions, and physical and family functioning (Lewis, 1996). In turn, these changes may impact her adolescents behavior, school performance, emotions, and physical functioning (Visser et al., 2004). Purpose: The purpose of this study was to elicit and understand the adolescents experience of having a mother with early stage cancer, the meaning that adolescents construct about having a mother with early stage cancer, and the processes that adolescents use in coping with having a mother with early stage cancer. Methods: This qualitative study used a grounded theory method to guide the exploration of the experience of male and female adolescents, ages 12-17 years, whose mother had been diagnosed with early stage cancer a minimum of 6 months and a maximum of 2 years ago. Each early stage cancer had a 5-year relative survival rate of 80% or greater. Adolescents responses were elicited by a semi-structured interview guide. Findings: Adolescents experienced a process after their mother was diagnosed with cancer. After they learned the diagnosis, the process became cyclical and at times simultaneous, as cancer changed the family, the adolescents coped, and demonstrated a sense of purpose. Conclusions: Having a mother with cancer is a significant life changing event for adolescents.

Background: Mortality and morbidity of patients following traumatic brain injury (TBI) remains extremely high. TBI sets into motion a cascade of apoptotic events that includes bcl-2, which inhibits apoptosis. Patients with higher levels of bcl-2 protein after TBI appear to have smaller areas of ischemia and better functional outcomes as measured by Glasgow Outcome Scores (GOS). Purpose: The purpose of this study was to examine the relationship between BCL-2 genotypes in patients with severe TBI and global functional outcomes, cognitive-behavioral outcomes, mortality, and biological/clinical data. Methods: This pilot study was an ancillary study that examined biological/clinical markers in TBI patients and global functional and cognitive-behavioral outcomes after severe TBI (n=230). Nuclear DNA was extracted from CSF or blood. Based on HapMap, the DNA was analyzed for the genotypes of 17 high priority tagging single nucleotide polymorphisms (tSNPs) with a minor allele frequency ≥0.3 via TaqMan® allele discrimination. Biological/clinical data (bcl-2 protein levels, neurometabolites (lactate, pyruvate, and lactate pyruvate (LP) ratio) and cerebral blood flow (CBF) were analyzed following the first five to six (protein only) days post injury. Mortality and global functional outcomes [GOS & Disability Rating Scale (DRS)], analyzed at 3, 6, 12, and 24 months. The cognitive behavioral outcomes [Neurobehavioral Rating Scale Revised (NRS-R), Trails A, and Trails B] were analyzed at 3, 6, and 12 months post injury. Statistical analysis for BCL-2s relationship with neuropsychological outcomes and biological/ clinical data overtime utilized was mixed modeling, (mortality utilized generalized mixed modeling). Results: There were 3 tSNPs of particular interest: Rs1801018: homozygous variant (GG) significant associated with decreased mortality (p=0.0055; OR=5.01), higher GOS (p=0.0004), lower DRS (p=0.0002), lower Global CBF (p=0.0031), [presence of the variant allele (G)] lower LP ratios (p=0.024); all better outcomes. Rs17756073: presence of variant allele (G) was associated with higher NRS-R (p=0.0331) and longer Trails B times (p=0.0516); both poorer outcomes. Rs7236090: homozygous wild type (CC) was associated with lower bcl-2 protein concentrations when analyzed without outliers (p=0.0056); the literature associates this with poor outcomes. Conclusion: BCL-2 genotypes had a significant relationship with global functional outcomes, cognitive behavioral outcomes, bcl-2 protein concentrations, neurometabolites, and CBF.

Diabetic retinopathy (DR) is a microvascular complication of diabetes and proliferative diabetic retinopathy (PDR) is the most vision threatening form of DR and the leading cause of blindness in individuals aged 20-74 years. Genetic endowment is thought to play a role in development of DR. The adenosine A2 receptor (ADORA2A) is associated with decreased tissue impairment caused by inflammation, hypoxia, and oxidative stress, while vascular endothelial growth factor (VEGF) is associated with hypertension, vascular permeability, and neoangiogenesis, and is elevated in those with DR. The aim of this study was to determine if the ADORA2A or the VEGF genes are associated with prevalent baseline PDR (PBPDR) or prospective incident PDR (PIPDR) in participants of the Epidemiology of Diabetes Complications (EDC) prospective study of childhood onset type 1 diabetes. Two tagging single nucleotide polymorphisms (tSNPs) of the ADORA2A gene (rs2236624 and rs4822489) and 4 SNPs of the VEGF gene (rs2146323, rs833069, rs699947, rs10434) were genotyped and assessed for association with prevalence and incidence of PDR, while controlling for traditional covariates. Univariate analysis of ADORA2A rs2236624 was associated with PBPDR [OR=1.68; (95%CI=1.11-2.54); p=0.03] and PIPDR [HR=0.17; (95%CI=0.04-0.69); p=0.01]. These associations were sustained in the multivariate analysis with rs2236624-CT being significantly associated with PBPDR [OR=2.17; (95%CI=1.24-3.81); p=0.03]. In the Cox analysis rs2236624-CT [HR= 1.54; (95%CI=1.08-2.18); p=0.02] and rs2236624-TT [HR=0.10; (95%CI=0.01-0.72); p= 0.02] were significantly associated with PIPDR. Analysis of the rs4822489 tSNP found an association between the GT genotype and PIPDR in the univariate analysis [HR=1.53 ;( 95%CI: =1.12-2.09); p=0.008], and in the multivariate analyses [HR=1.57 ;( 95%CI: =1.13-2.17); p=0.0067] after controlling for covariates. To determine if there was increased risk associated with the 4822489 genotypes and PBPDR participants were stratified into late onset (PDR ¡Ý25 years T1d duration), early onset (PDR<25 years T1D duration), and protected (No PDR during follow-up) groups. Those with the GT genotype had a significantly increased association [OR=1.93; (95%CI: =1.11-3.35); p=0.03] with early onset PDR compared to the protected group. The association between the GT genotype of the rs4822489 tSNP was only marginally significant [OR=1.73 ;( 95%CI: =0.89-3.36); p=0.12] in the multivariate analyses after controlling for covariates. Furthermore univariately, the GG genotype of VEGF rs10434 was marginally [OR=1.3; (95%CI=0.75-2.28); p=0.14) associated with PBPDR but, multivariately significantly [OR=2.47; (95%CI=1.15-5.3); p=0054] associated with baseline PBPDR. Hypertension status [OR=3.93 (95%CI=1.98-7.8); p =<0.0001] low density lipoprotein [OR=1.01 ;( 95%CI=1.004-1.02); p=0.0050] and duration [OR=1.21 (95%CI=1.12-1.3); p=<0.0001] were also significantly associated with PBPDR. None of the VEGF SNPs were associated with PIPDR. Additional analysis showed a significant (p=0.045) direct univariate association between the AG genotype of rs10434 and hypertension. In the EDC population heterozygosity for the rs2236624 tSNP of the ADORA2A gene is associated with susceptibility to PDR while homozygosity for the (T) allele of rs2236624 tSNP is associated with protection form development of incident PDR. While homozygosity of the VEGF rs10434 tSNP is associated with baseline prevalent PDR and heterozygosity for the rs10434 tSNP is associated with baseline prevalent hypertension.

Alternative approaches to evaluating critical thinking skills are needed, as pencil and paper assessments may not accurately predict simulated or actual clinical performance. To ensure patient safety, it is imperative to determine how to best promote and measure critical thinking skills. Few studies have examined how these skills are related to performance in a simulated or actual clinical setting. The purpose of this study was to examine the relationship between metrics of critical thinking skills and performance in simulated clinical scenarios and identify predictors of simulation-based performance of nursing students in their last term of academic preparation. A convenience sample of 36 student nurses prepared at the diploma (n=14), associate (n=12), and baccalaureate (n=10) level in their last term of academic preparation participated in a measurement of critical thinking skills and simulation-based performance using videotaped vignettes (VTV), high-fidelity human simulation (HFHS), and two standardized tests: the California Critical Thinking Disposition Inventory (CCTDI) and California Critical Thinking Skills Test (CCTST). Simulation-based performance on the VTV and HFHS assessment was rated as meeting or not meeting overall expectations and in six categories: problem recognition, reports essential data, initiates appropriate nursing interventions, anticipates medical orders, provides rationale, and prioritizes the situation. Student scores on the CCTDI and CCTST were categorized as strong, average, or weak critical thinking disposition or skills. A majority (75.0%) of students did not meet overall performance expectations when assessed using VTV and HFHS. Those not meeting expectations had difficulty recognizing the clinical problem and reporting the appropriate findings to the physician. There was no significant difference between overall performance based on the method of simulation (VTV or HFHS). However, more students met performance expectations for the category of initiating nursing interventions (p=0.0002) using HFHS. The relationships between VTV performance and CCTDI or CCTST scores were not significant except for the relationship between the category of problem recognition and overall CCTST scores (Cramers V = 0.444, p = 0.029). There was a statistically significant relationship between HFHS performance and overall CCTDI scores (Cramers V = .413, p = 0.047). Gender, educational preparation, internship/residency participation, prior nursing aide experience, and number of classes using HFHS as a teaching method were not related to overall VTV or HFHS performance or scores on the CCTDI or CCTST. However, there was a significant relationship between age and overall CCTST scores (Cramers V = .388, p = 0.029). The CCTDI, CCTST, and level of educational preparation were not statistically significant predictors of VTV performance. Student nurses performance reflected difficulty meeting expectations when tested in both simulated settings. HFHS appeared to best approximate scores on a standardized metric of critical thinking. Further research is needed to determine if results of simulated performance predicts application of critical thinking skills in a clinical setting.

Background: Gene expression profiling of human acute ischemic stroke (AIS) has the potential to identify a diagnostic panel for differential diagnosis of AIS early in the treatment phase. Purpose: The objective of this dissertation was to identify peripheral blood biomarkers that could be further explored for use in differential diagnosis of AIS and the design of stroke therapeutics. Methods: A prospective gene expression profiling study of 39 patients and 25 healthy controls was conducted. Peripheral blood samples were collected in Paxgene Blood RNA tubes from patients who were ≥18 years of age with MRI diagnosed AIS after differential diagnosis and controls who were Non-stroke neurologically healthy. In stroke patients, blood was redrawn 24 hours following onset of symptoms to determine changes in gene expression profiles over time. RNA was hybridized to Illumina humanRef-8v2 bead chips. Validation was performed using Taqman Gene expression polymerase chain reaction on significant targets. Results: A nine gene profile has been identified for AIS. Five of these nine genes were identified in the previously published whole blood gene expression profiling study of stroke and therefore play a likely role in the response to AIS in humans. One of these nine genes (s100A12) was significantly associated with increasing age and therefore may be non-specific for stroke. Three genes were identified as the whole blood expression profile change over time (LY96, IL8, and SDPR). Pathway analysis revealed a robust innate immune response, with toll like receptor (TLR) signaling as a highly significant pathway present in the peripheral whole blood of AIS patients. Conclusion: The findings of this study support the claim that gene expression profiling of peripheral whole blood can be used to identify diagnostic markers of AIS. A plausible case for innate immunity through the activation of TLR4 as a mediator of response to AIS has been made from the results of this study. This study and those conducted by Moore et al (2005) and Tang et al (2006) provide the foundation of data that support the use of peripheral whole blood for future blood profiling studies of neurological disease; which significantly opens the door of opportunity.

Specific Aims: The complex nature of pain, composed of both subjective and objective components, makes its proper and effective management difficult for every patient. In many instances factors such as race/ethnicity, which affect culture distort the objective nature of self-reported pain levels. Management is further compounded by opioid analgesics, which exert a range of adverse affects that vary in presentation and intensity between individuals. Therefore research in genetics, particularly the OPRM1 gene, may expose more reliable and successful methods for individual pain management. This study sought to accomplish this goal by evaluating the following specific aims: 1) Describe the distributions of genotypes and alleles for the variants, A118G and C17T, 2) Evaluate the distributions of the genotypes for A118G and C17T between races/ethnicities, 3) Evaluate the distribution of self-reported pain scores by genotype, and 4) Evaluate the distribution of opioid use by genotype. Methods: Eighty-three subjects were recruited from Presbyterian Hospital, University of Pittsburgh Medical Center. Variables such as race/ethnicity, pain report, and opioid use were collected from patient report or from the medical record. Genotypes were determined through DNA extraction from saliva samples. Results: The proportions of C17T variant genotypes, CT and TT, were significantly higher in the African-American group as compared to the Caucasian group (p<.001). The pain scores at 15 minutes post-operatively were significantly lower in participants with either the CT and TT genotypes than participants having the CC genotype (p=.039). No significant differences between the genotypes, A118G and C17T, were found for other categories of race/ethnicity, self-reported pain levels, or amount of opioid use Conclusions: The finding of higher proportions of the variant CT and TT genotypes in African-American patients relative to Caucasian patients is consistent with the literature. The findings of lower pain scores within the immediate post-operative time frame for those with CT and TT genotypes has not been as well documented in the literature and may support the need for further research in this area. Therefore this study does not support a change in practice for pain management, but it does provide the basis for further research into the SNPs of OPRM1, particularly C17T.