Inhibition of ATR Reverses a Mitochondrial Respiratory Insufficiency.

Diseases that affect the mitochondrial electron transport chain (ETC) often manifest as threshold effect disorders, meaning patients only become symptomatic once a certain level of ETC dysfunction is reached. Cells can invoke mechanisms to circumvent reaching their critical ETC threshold, but it is an ongoing challenge to identify such processes. In the nematode Caenorhabditis elegans, severe reduction of mitochondrial ETC activity shortens life, but mild reduction actually extends it, providing an opportunity to identify threshold circumvention mechanisms. Here, we show that removal of ATL-1, but not ATM-1, worm orthologs of ATR and ATM, respectively, key nuclear DNA damage checkpoint proteins in human cells, unexpectedly lessens the severity of ETC dysfunction. Multiple genetic and biochemical tests show no evidence for increased mutation or DNA breakage in animals exposed to ETC disruption. Reduced ETC function instead alters nucleotide ratios within both the ribo- and deoxyribo-nucleotide pools, and causes stalling of RNA polymerase, which is also known to activate ATR. Unexpectedly, atl-1 mutants confronted with mitochondrial ETC disruption maintain normal levels of oxygen consumption, and have an increased abundance of translating ribosomes. This suggests checkpoint signaling by ATL-1 normally dampens cytoplasmic translation. Taken together, our data suggest a model whereby ETC insufficiency in C. elegans results in nucleotide imbalances leading to the stalling of RNA polymerase, activation of ATL-1, dampening of global translation, and magnification of ETC dysfunction. The loss of ATL-1 effectively reverses the severity of ETC disruption so that animals become phenotypically closer to wild type.

Exposure from the large C-arm versus the mini C-arm using hand/wrist and elbow phantoms.

PURPOSE: This study tests the conventional wisdom that using fluoroscopy under identical geometrical conditions results in less radiation when using the mini C-arm relative to the large C-arm. METHODS: We evaluated the radiation dose for both direct exposure and scatter 2.54 cm outside the intensifier. We used 3 mini and 3 large C-arms in a vertical orientation with the image intensifier below the specimen and the source above. We used 2 specimens: a cadaver hand/wrist and a cadaver elbow. Specimens were tested both directly on the intensifier and on a hand table placed on the intensifier. RESULTS: For the same setup, use of the mini C-arm resulted in direct patient radiation exposure greater than the exposure delivered by the large C-arm. Specifically, exposure using the mini C-arm was 53% to 70% greater than that using the large C-arm. In addition, use of the hand table resulted in exposure 80% to 94% greater compared with placing the specimen directly on the intensifier. In all cases, scatter at 2.54 cm from the intensifier resulted in an average exposure of 1.5% (SD, 0.24%) of the direct beam. Tube current, and therefore machine radiation output, was approximately 13 to 14 times greater for the large C-arm. CONCLUSIONS: Direct radiation exposure to the patient and scatter to the surgeon are minimized when the C-arm is positioned with the intensifier below and the extremity is placed directly on the intensifier. Under identical geometrical conditions with the intensifier below the specimen, the large C-arm with its greater source to image intensifier distance is associated with less radiation exposure than the mini C-arm.

X-ray dose from pediatric cardiac catheterization: a comparison of materials and methods for measurement or calculation.

Pediatric cardiac catheterization procedures have the potential to transmit high X-ray doses, which may lead to acute effects or latent skin reactions. Direct measurement of radiation dose was facilitated using nanodot dosimeters and radiochromic film. Direct measurement results were compared with vendor-listed dosimetry and calculation using phantom data. Vendor-listed data demonstrated a wide discrepancy with measured data, whereas the calculation reproducibly overestimated the actual dose. A simple formula was derived to calculate the dose using fluoroscopy time, cine frame quantity and average cine mA in a biplane environment.

CT imaging for gynecological HDR: tools and tricks.

Computerized tomography (CT)-assisted treatment planning for high-dose-rate (HDR) gynecological cancer treatments allows for better structure visualization and dose-volume histogram analysis definition. Problems associated with CT imaging are addressed. These pitfalls include the potential for multiple patient transfers and movement between applicator insertion, simulation, and treatment. Applicator CT imaging artifacts are also discussed. A modified transport table and a machined connection for a commercially available non-CT-compatible tandem and a CT-compatible ring applicator are described. These 2 modifications provide a safe and reliable method to utilize the advantages of CT imaging for gynecological HDR treatments.