Genomic structure and alternative splicing of murine R2B receptor protein tyrosine phosphatases (PTPκ, μ, ρ and PCP-2)

BACKGROUND: Four genes designated as PTPRK (PTPκ), PTPRL/U (PCP-2), PTPRM (PTPμ) and PTPRT (PTPρ) code for a subfamily (type R2B) of receptor protein tyrosine phosphatases (RPTPs) uniquely characterized by the presence of an N-terminal MAM domain. These transmembrane molecules have been implicated in homophilic cell adhesion. In the human, the PTPRK gene is located on chromosome 6, PTPRL/U on 1, PTPRM on 18 and PTPRT on 20. In the mouse, the four genes ptprk, ptprl, ptprm and ptprt are located in syntenic regions of chromosomes 10, 4, 17 and 2, respectively. RESULTS: The genomic organization of murine R2B RPTP genes is described. The four genes varied greatly in size ranging from ~64 kb to ~1 Mb, primarily due to proportional differences in intron lengths. Although there were also minor variations in exon length, the number of exons and the phases of exon/intron junctions were highly conserved. In situ hybridization with digoxigenin-labeled cRNA probes was used to localize each of the four R2B transcripts to specific cell types within the murine central nervous system. Phylogenetic analysis of complete sequences indicated that PTPρ and PTPμ were most closely related, followed by PTPκ. The most distant family member was PCP-2. Alignment of RPTP polypeptide sequences predicted putative alternatively spliced exons. PCR experiments revealed that five of these exons were alternatively spliced, and that each of the four phosphatases incorporated them differently. The greatest variability in genomic organization and the majority of alternatively spliced exons were observed in the juxtamembrane domain, a region critical for the regulation of signal transduction. CONCLUSIONS: Comparison of the four R2B RPTP genes revealed virtually identical principles of genomic organization, despite great disparities in gene size due to variations in intron length. Although subtle differences in exon length were also observed, it is likely that functional differences among these genes arise from the specific combinations of exons generated by alternative splicing

In vivo measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients

© 2008 Garvin and Dabrosin; licensee BioMed Central Ltd

Validity of physical activity monitors for assessing lower intensity activity in adults

Background: Accelerometers can provide accurate estimates of moderate-to-vigorous physical activity (MVPA). However, one of the limitations of these instruments is the inability to capture light activity within an acceptable range of error. The purpose of the present study was to determine the validity of different activity monitors for estimating energy expenditure (EE) of light intensity, semi-structured activities. Methods: Forty healthy participants wore a SenseWear Pro3 Armband (SWA, v.6.1), the SenseWear Mini, the Actiheart, ActiGraph, and ActivPAL monitors, while being monitored with a portable indirect calorimetry (IC). Participants engaged in a variety of low intensity activities but no formalized scripts or protocols were used during these periods. Results: The Mini and SWA overestimated total EE on average by 1.0% and 4.0%, respectively, while the AH, the GT3X, and the AP underestimated total EE on average by 7.8%, 25.5%, and 22.2%, respectively. The pattern-recognition monitors yielded non-significant differences in EE estimates during the semi-structured period (p = 0.66, p = 0.27, and p = 0.21 for the Mini, SWA, and AH, respectively). Conclusions: The SenseWear Mini provided more accurate estimates of EE during light to moderate intensity semi-structured activities compared to other activity monitors. This monitor should be considered when there is interest in tracking low intensity activities in groups of individuals.This research was funded by a grant from Bodymedia Inc. awarded to Dr. Greg Welk

Finding the best glaucoma questionnaire: a qualitative and quantitative evaluation of glaucoma knowledge assessments

Jullia A Rosdahl,1 Kelly W Muir1,2 1Department of Ophthalmology, Duke University, Durham, NC, USA; 2Health Services Research and Development, Durham Veterans Affairs Medical Center, Durham, NC, USA Objective: The goal of the study was to determine which glaucoma quiz provides the best information about patient glaucoma knowledge to clinicians in clinical practice settings. Methods: Four glaucoma quizzes were identified from the literature and national eye education programs and were qualitatively analyzed to categorize questions by topic. Quizzes were assessed by 64 glaucoma specialists using an online survey, with descriptive statistics. Comments about the quizzes were analyzed qualitatively using themes and representative quotations. Results: Quizzes covered content that was important for glaucoma diagnosis and management. The National Eye Health Education Program (NEHEP) and Prevent Blindness America quizzes covered primarily diagnosis, screening, and risk factors, and the quizzes from the literature primarily covered causes of glaucoma, vision loss, eye drops, and systemic disease. Overall, the NEHEP quiz was ranked best for clinical practice, ranked first by 38%. Ranked second overall, the Gray quiz was ranked first by 34% and last by 34%. Conclusion: The NEHEP quiz was rated most useful for assessing baseline general glaucoma knowledge for a busy clinical practice. The Gray quiz appears to be more useful as part of a comprehensive education program, perhaps in combination with an ophthalmic educator. Keywords: patient education, quiz, clinical practic

Validation of a glaucoma knowledge assessment in glaucoma patients

Veena S Rao, Esteban A Peralta, Jullia A Rosdahl Department of Ophthalmology, Duke University, Durham, NC, USA Summary: To develop metrics to identify knowledge deficits and barriers to learning in glaucoma patients, this study seeks to validate a glaucoma knowledge assessment to use in the evaluation of knowledge in glaucoma patients.Purpose: Glaucoma treatment adherence appears to improve when patients demonstrate a greater knowledge of the disease and its treatment. This study seeks to validate a glaucoma knowledge assessment in a glaucoma patient population to assist in patient educational assessments and interventions.Patients and methods: The National Eye Health Education Program’s (NEHEP) glaucoma knowledge assessment has previously been suggested as a useful measure to assess glaucoma patient’s knowledge. This questionnaire was administered in glaucoma patients along with a more comprehensive 49-question examination. Demographic data and health literacy were assessed. Statistical analyses were performed to assess the validity of the assessments.Results: A total of 12 glaucoma patients completed the knowledge assessments. The mean ± standard deviation age of the patients was 69±14 years, and the duration of glaucoma was 14±13 years. The participants’ mean score on the NEHEP assessment was 7.3±0.8 (of 10, 73% correct) vs 29.3±7.3 (of 49, 60% correct) on the comprehensive assessment. The value of coefficient α was 0.592 for NEHEP and 0.872 for the cumulative assessment. The P-value (proportion of examinees answering correctly) ranged from 0 to 1 for individual questions. Item point–biserial correlation values for each question ranged from –0.402 to 0.813.Discussion: The NEHEP quiz may be a good starting point for the development of a reliable knowledge assessment tool to measure and monitor glaucoma knowledge, due to its concise nature and reasonable level of difficulty. This study suggests that questions included in the currently available questionnaires vary widely in difficulty and ability to differentiate knowledge level, which may ultimately compromise reliability and utility of existing examinations. Further examination of individual questions and teaching points included in the current assessments may help to construct increasingly reliable and useful knowledge assessments in the future. Keywords: ophthalmology, patient education, educational tools, knowledge questionnaire, knowledge qui

Patient education preferences in ophthalmic care

Jullia A Rosdahl, Lakshmi Swamy, Sandra Stinnett, Kelly W MuirDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC, USABackground: The learning preferences of ophthalmology patients were examined.Methods: Results from a voluntary survey of ophthalmology patients were analyzed for education preferences and for correlation with race, age, and ophthalmic topic.Results: To learn about eye disease, patients preferred one-on-one sessions with providers as well as printed materials and websites recommended by providers. Patients currently learning from the provider were older (average age 59 years), and patients learning from the Internet (average age 49 years) and family and friends (average age 51 years) were younger. Patients interested in cataracts, glaucoma, macular degeneration, and dry eye were older; patients interested in double vision and glasses were younger. There were racial differences regarding topic preferences, with Black patients most interested in glaucoma (46%), diabetic retinopathy (31%), and cataracts (28%) and White patients most interested in cataracts (22%), glaucoma (22%), and macular degeneration (19%).Conclusion: Most ophthalmology patients preferred personalized education: one-on-one with their provider or a health educator and materials (printed and electronic) recommended by their provider. Age-related topics were more popular with older patients, and diseases with racial risk factors were more popular with high risk racial groups.Keywords: patient education, eye disease, cataracts, macular degeneration, glaucoma, diabetic retinopath

Stress and burnout in residents: impact of mindfulness-based resilience training

Brian E Goldhagen,1 Karen Kingsolver,2 Sandra S Stinnett,1 Jullia A Rosdahl1 1Department of Ophthalmology, 2Department of Family and Community Medicine, Duke University Medical Center, Durham, NC, USABackground and objective: Stress and burnout impact resident physicians. This prospective study tests the hypothesis that a mindfulness-based resilience intervention would decrease stress and burnout in residents.Methods: Resident physicians from the Departments of Family Medicine, Psychiatry, and Anesthesia at Duke University, Durham, NC, USA, participated in two or three 1-hour sessions of mindfulness-based resilience activities, which introduced mindful-awareness and included practical exercises for nurturing resilience. Anonymous surveys were distributed before (completed by 47 residents) and after the intervention (both completed by 30 residents); a follow-up survey was distributed 1 month later (seven residents completed all three surveys). The survey included the Depression Anxiety Stress Scale, 21-question version (DASS-21), the Oldenburg Burnout Inventory, the Mindful Attention Awareness Scale, and ten questions from the Cognitive Failures Questionnaire.Results: At baseline, most residents’ scores were in the normal range with respect to stress; however, female residents had higher DASS-21 scores than male residents (31.7, females vs 18.4, males; P=0.002). Most residents’ burnout scores were in the abnormal range, both with respect to exhaustion (38/47 residents, subscore ≥2.25) and disengagement (37/47 residents, subscore ≥2.1). Higher perceived levels of stress correlated with the instruments. Analysis of the surveys before and after the intervention showed no significant short-term change in stress, burnout, mindful-awareness, or cognitive failure. There was a trend for females and post-medical school graduate year 1 and 2 (PGY1 and PGY2) residents to have a reduction in DASS-21 scores after intervention. There was also a trend of reduced stress and burnout in residents who perceived higher stress.Conclusion: Residents who are female, PGY1 and PGY2, and who perceive residency to be stressful may benefit most from a mindfulness-based resilience intervention. Keywords: physician, self-care, wellness, medical trainee