18F-3′-Deoxy-3′-Fluorothymidine Positron Emission Tomography Imaging for the Prediction of Acute Graft-Versus-Host Disease in Mouse Hematopoietic Stem Cell Transplant Models

Acute graft-versus-host disease (aGVHD) remains a barrier to the success of allogeneic hematopoietic stem cell transplantation. In mice, studies have demonstrated that donor conventional T cells traffic into host secondary lymphoid tissues early after transplant, and that this process is critical for the development of disease. As a result, the measurement of cellular proliferation within lymphoid sites early after transplant might be a useful approach for predicting aGVHD in humans. 18F-3′-deoxy-3′-fluorothymidine (FLT) positron emission tomography (PET) imaging has recently emerged as a functional imaging modality in oncology patients. FLT, a thymidine analog, is incorporated into replicating DNA and is thus an indirect marker of cellular proliferation. Here we report that FLT PET imaging can differentiate mice receiving alloreactive T cells and destined to develop lethal aGVHD from control mice. Mice receiving allogeneic T cells demonstrated a stronger FLT signal within the peripheral lymph nodes compared with control mice at all time points after transplant. In addition, allogeneic T cell recipients transiently demonstrated stronger FLT uptake within the spleen. Importantly, these differences were apparent before the development of clinical disease. In contrast, the FLT signal within the host bowel, an important aGVHD target organ, was more variable after transplant and was not consistently different between aGVHD mice and control mice. Collectively, these findings suggest that the imaging of patient lymphoid sites using existing FLT PET technology might be useful for predicting aGVHD in the clinical setting.     

Predictors of Job Satisfaction among Staff in Residential Settings for Persons with Intellectual Disabilities: A Comparison between Three Residential Models

Background This cross‐sectional study aims to assess whether there are differences in staff job satisfaction, including organizational and individual characteristics, between three residential models for adults with intellectual disabilities (small residential home, group home and institution) and to investigate the organizational and individual variables associated with staff job satisfaction. Methods A standardized self‐administered questionnaire (Job Satisfaction Survey) was distributed together with demographic questions between April 2007 and June 2007. In total, 1301 staff members completed the questionnaire. Results We found that staff working at small homes had a significantly higher level of job satisfaction than staff from the other two models. Logistic regression revealed that the characteristics of the organizations at which they were employed rather than the staff’s individual characteristics were strongly associated with job satisfaction. Conclusion This study suggests that the residential model and the provider sector of the residential setting are the factors of concern when ensuring staff job satisfaction.     

Identification and preliminary characterization of ubiquitin C terminal hydrolase 1 (UCHL1) as a biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage

By using two different approaches, ubiquitin C‐terminal hydrolase 1 (UCHL1) was identified as a potential cerebrospinal fluid (CSF) biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage (ASAH) and presumably other CNS damage and disease states. Appropriate antibodies and a sensitive ELISA were generated, and the release of UCHL1 into CSF was compared with that of pNF‐H and S100β in a cohort of 30 ASAH patients. Both UCHL1 and pNF‐H showed persistent release into CSF in almost all patients in the second week postaneurysmal rupture (AR), and S100β levels rapidly declined to baseline levels in 23 of 30 patients. Seven of thirty patients showed persistently elevated S100β levels over the first 5 days post‐AR and also had relatively higher levels of pNF‐H and UCHL1 higher compared with the rest. These patients proved to have very poor outcomes, with 6 of 7 expiring. Patients who did reduce S100β levels tended to have a better outcome if pNF‐H and UCHL1 levels were also lower, and elevated UCHL1 levels in the second week post‐AR were particularly predictive of poor outcome. Acute coordinated releases of large amounts of UCHL1, pNF‐H, and S100β in 16 of 30 patients were observed, suggesting sudden loss of brain tissues associated with secondary events. We conclude that measurement of the CSF levels of these proteins reveals details of ASAH progression and recovery and predicts patient outcome. © 2010 Wiley‐Liss, Inc.     

BOOK REVIEW

Heart to Heart is a computer-based decision aid for patients and providers that provides personalized, evidence-based information about coronary heart disease (CHD) risk and potential risk-reducing interventions. To develop Heart to Heart, the authors used Framingham risk equations and systematic reviews of risk-reducing interventions. The Web version was programmed using PHP: Hypertext Processor, a Web-based programming language, and has separate interfaces for providers and patients. The authors subsequently developed a modified version for personal digital assistants. Heart to Heart uses information about a patient's CHD risk factors (age, gender, total and high-density lipoprotein cholesterol levels, diabetes, smoking, systolic blood pressure, and left ventricular hypertrophy) to calculate risk of total CHD events over 5 or 10 years. Patients and providers can then examine the effect of introducing one or more risk-reducing interventions (aspirin, lipid-lowering drug therapy, antihypertensive medication, or smoking cessation) on the patient's CHD risk. Future research will be directed to determining whether Heart to Heart can improve utilization of effective CHD risk-reducing interventions.     

Profiles of gonadal development, sex steroids, aromatase activity, and gonadotropin II in the controlled sex change of protandrous black porgy, Acanthopagrus schlegeli Bleeker

The objectives of the present study were to investigate the effects of oral administration of estradiol-17 beta (E(2)) on the sex steroids and gonadotropin II (GTH II) in plasma, aromatase activity in gonad and brain, and sex change in protandrous black porgy, Acanthopagus schlegeli Bleeker. Two-year-old black porgy were divided into two groups, one fed a control diet and the other a diet mixed with E(2) (4.0 mg/kg feed) for 7 months. Significantly higher GSI was observed in the E(2) group. Fish treated with E(2) showed complete suppression of spermatogenesis and spermiation and induced sex change with vitellogenic oocytes and large primary oocytes. Lower levels of plasma 11-ketotestosterone and higher levels of plasma vitellogenin were shown in the E(2) group. Higher gonadal aromatase activity in concordance with elevated plasma levels of GTH II was observed in the E(2) group. The highest aromatase activity in the forebrain in the control group was observed in January. Higher aromatase activity in forebrain, midbrain, and hindbrain was also detected in the E(2) group than the control group. The change of aromatase activity in brain was more susceptible than that in gonad. The data showed that the increase of plasma GTH II levels and gonadal aromatase activity may be important to the controlled sex change by administration in black porgy.