Detection of thiopurine s-methyltransferase mutations by template directed determinator in incorporation with fluorescence polarization （TDI-FP）

Objective: To develop a new method for the detection of TPMT gene mutations and determine the frequencies of four TPMT alleles, TPMT^*1,^*3A,^*3B and ^*3C in a healthy Chinese population. Methods:A TDI-FP assay system was set up in out lab. To evaluate this system, 220 healthy individuals were analyzed for the polymorphic sites at positions 460 (G→A)and 719 (A→G)of the TPMP gene using our new TDI FP method. Results:Three TPMP *3C(G^460→G^719) heterozygotes were identified, TPMP ^*3A and TPMP ^*3B were not found. All mutations were confirmed by conventional DNA sequencing analysis. Conclusion:TDI-FP method has proven to be very efficient as a rapid and accurate approach for TPMP genotyping. TPMP ^*3C was the only polymorphism identified in this clinical samples we have registered.     

Dual Pathology in a Patient with Right Lower Quadrant Pain

Meckel diverticula are remnants of the omphalomesenteric duct. They have 2% incidence in the general population, are usually asymptomatic, and tend to be diagnosed incidentally. The generally held principle had been that asymptomatic cases do not require resection, as exemplified by a 2008 systematic review of over 200 studies. However, a recent series reported an increased risk of malignancies, and recommended mandatory resection. We present a case of Meckel diverticulitis with concurrent infiltrative appendiceal carcinoid in a patient with right lower quadrant pain.     

Economic Analysis of a Multi-Site Prevention Program: Assessment of Program Costs and Characterizing Site-level Variability

Programmatic cost analyses of preventive interventions commonly have a number of methodological difficulties. To determine the mean total costs and properly characterize variability, one often has to deal with small sample sizes, skewed distributions, and especially missing data. Standard approaches for dealing with missing data such as multiple imputation may suffer from a small sample size, a lack of appropriate covariates, or too few details around the method used to handle the missing data. In this study, we estimate total programmatic costs for a prevention trial evaluating the Strong African American Families-Teen program. This intervention focuses on the prevention of substance abuse and risky sexual behavior. To account for missing data in the assessment of programmatic costs we compare multiple imputation to probabilistic sensitivity analysis. The latter approach uses collected cost data to create a distribution around each input parameter. We found that with the multiple imputation approach, the mean (95 % confidence interval) incremental difference was $2,149 ($397, $3,901). With the probabilistic sensitivity analysis approach, the incremental difference was $2,583 ($778, $4,346). Although the true cost of the program is unknown, probabilistic sensitivity analysis may be a more viable alternative for capturing variability in estimates of programmatic costs when dealing with missing data, particularly with small sample sizes and the lack of strong predictor variables. Further, the larger standard errors produced by the probabilistic sensitivity analysis method may signal its ability to capture more of the variability in the data, thus better informing policymakers on the potentially true cost of the intervention.     

The Effect of Left Ventricular Assist Device Therapy on Cardiac Biomarkers: Implications for the Identification of Myocardial Recovery

Purpose of Review

Left ventricular assist device (LVAD) therapy serves as mainstay therapy for bridge to transplantation and destination therapy. Evidence is now mounting on the role of LVAD therapy as bridge to recovery. In the current review, we will summarize the data on biomarkers of myocardial recovery following LVAD implantation.

Recent Findings

Myocardial recovery can occur spontaneously, following pharmacological intervention and in the setting of mechanical circulatory support such as LVAD. Several biomarkers such as B-type natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), ST2, etc. have been identified and are being used to guide medical therapy in heart failure (HF) patients. However, recent data raised concern that those biomarkers may not be helpful in managing heart failure patients in general, and as such questioned their use in the advanced heart failure population. At this point, the use of biomarker to identify patients with myocardial recovery during LVAD support has not been established, and LVAD explantation remains a decision driven by echocardiographic and hemodynamics improvement.

Summary

HF biomarkers in monitoring myocardial and neurohormonal activation response to mechanical unloading and medical therapy could be valuable. However, at this time, there is inadequate evidence to select a single or a set of HF biomarkers to reliably identify patients bridged to recovery for LVAD explantation.

     

Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment,Learning, and Social Behavior

Background

In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today.

Objectives

The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model.

Methods

We administered vaccines to six groups of infant male rhesus macaques (n = 12–16/group) using a standardized thimerosal dose where appropriate. Study groups included the recommended 1990s Pediatric vaccine schedule, an accelerated 1990s Primate schedule with or without the measles–mumps–rubella (MMR) vaccine, the MMR vaccine only, and the expanded 2008 schedule. We administered saline injections to age-matched control animals (n = 16). Infant development was assessed from birth to 12 months of age by examining the acquisition of neonatal reflexes, the development of object concept permanence (OCP), computerized tests of discrimination learning, and infant social behavior. Data were analyzed using analysis of variance, multilevel modeling, and survival analyses, where appropriate.

Results

We observed no group differences in the acquisition of OCP. During discrimination learning, animals receiving TCVs had improved performance on reversal testing, although some of these same animals showed poorer performance in subsequent learning-set testing. Analysis of social and nonsocial behaviors identified few instances of negative behaviors across the entire infancy period. Although some group differences in specific behaviors were reported at 2 months of age, by 12 months all infants, irrespective of vaccination status, had developed the typical repertoire of macaque behaviors.

Conclusions

This comprehensive 5-year case–control study, which closely examined the effects of pediatric vaccines on early primate development, provided no consistent evidence of neurodevelopmental deficits or aberrant behavior in vaccinated animals.

Citation

Curtis B, Liberato N, Rulien M, Morrisroe K, Kenney C, Yutuc V, Ferrier C, Marti CN, Mandell D, Burbacher TM, Sackett GP, Hewitson L. 2015. Examination of the safety of pediatric vaccine schedules in a non-human primate model: assessments of neurodevelopment, learning, and social behavior. Environ Health Perspect 123:579–589; http://dx.doi.org/10.1289/ehp.1408257     

Giant cell (cranial) arteritis: a clinical review

Giant cell arteritis is a disease of the elderly which is more common than previously recognized. It is important to be aware of this condition because treatment effectively relieves symptoms and prevents serious complications. The disease is suggested when an elderly patient complains of constitutional symptoms, headache, jaw claudication, or the musculoskeletal manifestations of polymyalgia rheumatica. Abnormalities in temporal arteries or other cranial arteries, or evidence of large vessel involvement may be detected by physical examination. A markedly elevated sedimentation rate in association with other clinical features of the disease strongly suggests giant cell arteritis, but a biopsy should be performed to confirm the diagnosis. Corticosteroid therapy should be started promptly in high doses in order to prevent blindness. Prolonged treatment with lower dose corticosteroids is generally necessary for up to 1 to 2 years, and sometimes longer, for continued symptomatic relief. Long-term follow-up of treated patients has demonstrated no detectable effect on survivorship.     

Reducing False-Positive Biopsies using Deep Neural Networks that Utilize both Local and Global Image Context of Screening Mammograms

Journal of Digital Imaging - Breast cancer is the most common cancer in women, and hundreds of thousands of unnecessary biopsies are done around the world at a tremendous cost. It is crucial to...