Cystathionine-ß-synthase X proteins negatively regulate NADPH-thioredoxin reductase C activity.

Redox regulation is a posttranslational modification based on the redox reaction of protein thiols. A small ubiquitous protein thioredoxin (Trx) plays a central role in redox regulation, but a unique redox-regulatory factor called NADPH-Trx reductase C (NTRC) is also found in plant chloroplasts and some cyanobacteria. Several important functions of NTRC have been suggested, but the mechanism for controlling NTRC activity remains undetermined. Cystathionine-ß-synthase X (CBSX) proteins have been previously shown to interact with NTRC physically. Based on these observations, this study biochemically investigated the functional interaction between CBSX proteins and NTRC from Arabidopsis thaliana in vitro. Consequently, we concluded that CBSX proteins act as negative regulators of NTRC in the presence of AMP.

Assessment of hemoglobin threshold for packed RBC transfusion in a medical-surgical PICU.

OBJECTIVE: Results of a large multicenter randomized clinical trial published in 2007 demonstrated no benefit in using a liberal versus conservative RBC transfusion threshold in stable critically ill children. Using the conservative threshold decreased the number of RBC transfusions without increasing adverse outcomes. We aimed to determine if wide dissemination of this evidence altered the hemoglobin threshold used for RBC transfusions in our pediatric medical-surgical ICU. DESIGN: Before-after retrospective cohort study using multiple administrative databases and chart review. SETTING: PICU serving medical and surgical patients. PATIENTS: All potentially stable children receiving a RBC transfusion in the PICU in 2006 (prepublication) and in 2009-2010 (postpublication). Children were considered unstable and excluded if they were severely hypoxic, receiving renal replacement therapy, hemodynamically unstable, or bleeding. INTERVENTIONS: Physician education on evidence supporting hemoglobin transfusion thresholds in teaching conferences, staff meetings, and via e-mail. MEASUREMENTS AND MAIN RESULTS: In 2006, 14.6% of patients (n = 285/1,940) received a RBC transfusion. In 2009-2010, 12.1% of patients (n = 551/4,542) received a RBC transfusion. We evaluated patients transfused when they were potentially clinically stable, including 145 children in 2006 (191 transfusion days) and 266 children in 2009-2010 (369 transfusion days). We found no significant differences in age, sex, race, diagnoses, postoperative status, illness severity scores, mortality, or length of stay between these two groups. The median hemoglobin transfusion threshold decreased significantly from 8.0 g/dL (interquartile range 7.3, 8.6 g/dL) in 2006 to 7.5 g/dL (interquartile range 6.9, 8.1 g/dL) in 2009-2010 (p = 0.001). The percentage of transfusion days using a hemoglobin threshold more than 7 g/dL decreased from 81% (n = 154) in 2006 to 71% (n = 261) in 2009-2010. CONCLUSION: Although transfusion thresholds in potentially stable critically ill children in our PICU significantly decreased after dissemination of best available evidence, 71% of patients were transfused at a hemoglobin threshold more than 7 g/dL.

Economic evaluation of cell salvage in pediatric surgery.

BACKGROUND: Red blood cells are a scarce resource with demand outstripping supply. Use of intraoperative red cell salvage (CS) - the process of collecting shed blood during surgery and reinfusing it to patients - is often used as an effective blood conservation strategy. However, little is known about the economic impact of CS during pediatric surgery. METHODS: A decision tree model was used to estimate the transfusion-related costs per patient (2010 USD) from a healthcare system perspective of four transfusion strategies among children undergoing elective orthopedic or cardiac surgery: (i) CS followed by allogeneic transfusion, (ii) CS followed by autologous transfusion, (iii) allogeneic transfusion alone, and (iv) autologous transfusion alone. RESULTS: Cell salvage and allogeneic transfusion was the least expensive strategy (USD 883.3) followed by CS and autologous blood transfusion (USD 1,269.7), allogeneic transfusion alone (USD 1,443.0), and autologous transfusion alone (USD 1,824.7). Savings associated with CS use persisted in separate analyses of orthopedic and cardiac surgery, as well as in one-way and probabilistic sensitivity analyses. CONCLUSIONS: Use of CS, particularly along with allogeneic blood transfusion, appears cost-saving and cost-effective in pediatric surgery.

Impact of a conservative red blood cell transfusion strategy in children undergoing hematopoietic stem cell transplantation.

A 2008 randomized trial of critically ill, but stable, children reported the safety of transfusing red blood cells at a hemoglobin threshold of 7 g/dL. In 2009, we adopted the same transfusion criteria in our hematopoietic stem cell transplantation patients. Regression modeling was used to compare data obtained during primary admission for hematopoietic stem cell transplantation in calendar years before and after our practice change. Sixty-six patients admitted in the preintervention year were compared with 75 postintervention. Pre- and postpatients were similar in diagnoses and type of transplantations. Postintervention, median hemoglobin pretransfusion significantly decreased from 8.8 g/dL to 6.8 g/dL (P < .0001). In addition, transfused red blood cell units received by patients dropped from 4 (interquartile range [IQR] 3, 8) to 3 (IQR, 2, 5), (P = .002), and number of transfusion days per patients decreased from 4 (IQR, 2,5) to 3 (IQR, 2, 5), (P = .01). There were no differences in length of stay, time to engraftment, or 100-day mortality. Median blood product charges per patient significantly decreased ($3,624 [IQR, $2,265, $6,040] to $2,185 [IQR, $1,812, $3,997], P = .004). Our initial experience suggests that implementation of a conservative transfusion strategy in otherwise stable children undergoing hematopoietic stem cell transplantation appears safe and lowers transfusion exposures.

Optimal release conditions for the free throw in men's basketball.

The purpose of this study was to determine the optimum release conditions for the free throw in men's basketball. The study used hundreds of thousands of three-dimensional simulations of basketball trajectories. Five release variables were studied: release height, release speed, launch angle, side angle, and back spin. The free throw shooter was assumed to shoot at 70% and to release the ball 2.134 m (7 ft) above the ground. We found that the shooter should place up to 3 Hz of back spin on the ball, should aim the ball towards the back of the ring, and should launch the ball at 52 degrees to the horizontal. We also found that it is desirable to release the ball as high above the ground as possible, as long as this does not adversely affect the player's launch consistency.