Successful treatment of murine beta-thalassemia intermedia by transfer of the human beta-globin gene

The beta-thalassemias are caused by more than 200 mutations that reduce or abolish beta-globin production. The severity of the resulting anemia can lead to lifelong transfusion dependency. A genetic treatment based on globin gene transfer would require that transgene expression be erythroid specific, elevated, and sustained over time. We report here that long-term synthesis of chimeric hemoglobin (mualpha(2):hubeta(A)(2)) could be achieved in mice with beta-thalassemia intermedia following engraftment with bone marrow cells transduced with a lentiviral vector encoding the human beta-globin gene. In the absence of any posttransduction selection, the treated chimeras exhibit durably increased hemoglobin levels without diminution over 40 weeks. Ineffective erythropoiesis and extramedullary hematopoiesis (EMH) regress, as reflected by normalization of spleen size, architecture, hematopoietic colony formation, and disappearance of liver EMH. These findings establish that a sustained increase of 3 to 4 g/dL hemoglobin is sufficient to correct ineffective erythropoiesis. Hepatic iron accumulation is markedly decreased in 1-year-old chimeras, indicating persistent protection from secondary organ damage. These results demonstrate for the first time that viral-mediated globin gene transfer in hematopoietic stem cells effectively treats a severe hemoglobin disorder.     

Morinda Citrifolia (Noni) Reduces Cancer Risk in Current Smokers by Decreasing Aromatic DNA Adducts

Quantitative determination of aromatic DNA adducts in peripheral blood lymphocytes (PBLs) of current smokers is an useful surrogate biomarker for the evaluation of environmental carcinogen exposure or chemopreventive intervention. In this study, we examined the impact of Tahitian Noni Juice (TNJ) on the aromatic DNA adducts of PBLs, before and after a 1-mo intervention, using ³²P postlabeling assay. Of 283 enrolled, 203 smokers completed the trial. Aromatic DNA adducts levels in all participants were significantly reduced by 44.9% (P < 0.001) after drinking 1 to 4 oz of TNJ for 1 mo. Dose-dependent analyses of aromatic DNA adduct levels showed reductions of 49.7% (P < 0.001) in the 1-oz TNJ group and 37.6% (P < 0.001) in the 4-oz TNJ group. Gender-specific analyses resulted in no significant differences in the 4-oz TNJ groups. Interestingly, the 1-oz TNJ group showed a reduction of 43.1% (P < 0.001) in females compared with 56.1% (P < 0.001) in males. The results suggest that drinking 1 to 4 oz of TNJ daily may reduce the cancer risk in heavy cigarette smokers by blocking carcinogen-DNA binding or excising DNA adducts from genomic DNA.     

Transcatheter aortic valve replacement: History and current status

Despite the poor prognosis associated with severe, symptomatic aortic stenosis, treatment options were limited for a large subgroup of patients deemed high risk for surgical replacement. The introduction of transcatheter aortic valve replacement (TAVR) over the past 10 years marks a new and exciting era in the treatment of valvular disease in these high-risk and inoperable patients. In this review, we outline the historical development, key clinical trials, current outcomes and future directions of TAVR.     

Classifying highly imbalanced ICU data

Highly imbalanced data sets are those where the class of interest is rare. In this paper, we compare the performance of several common data mining methods, logistic regression, discriminant analysis, Classification and Regression Tree (CART) models, C5, and Support Vector Machines (SVM) in predicting the discharge status (alive or deceased, with “deceased” being the class of interest) of patients from an Intensive Care Unit (ICU). Using a variety of misclassification cost ratio (MCR) values and using specificity, recall, precision, the F-measure, and confusion entropy (CEN) as criteria for evaluating each method’s performance, C5 and SVM performed better than the other methods. At a MCR of 100, C5 had the highest recall and SVM the highest specificity and lowest CEN. We also used Hand’s measure to compare the five methods. According to Hand’s measure, logistic regression performed the best. This article makes several contributions. We show how the use of MCR for analyzing imbalanced medical data significantly improves the method’s classification performance. We also found that the F-measure and precision did not improve as the MCR was increased.     

Hypnotically induced emotional numbing

This study investigated the utility of a hypnotic suggestion to inhibit emotional response. High and low hypnotizable participants (N = 53) were administered a hypnotic induction, and half the participants were then administered a suggestion for emotional numbing. Participants were then presented with slides depicting neutral or disfigured faces. Participants who received the emotional numbing suggestion reported less responsivity to the disfigured faces than did those in the control condition, and this pattern was stronger for high than for low hypnotizable participants. Highs in the numbing condition displayed less overall distress in their facial expressions in response to the disfigured slides relative to those in the control condition. These findings suggest that hypnotic emotional numbing may be a useful paradigm in which to explore processes in emotion inhibition.