Intraoperative aberrometry versus standard preoperative biometry and a toric IOL calculator for bilateral toric IOL implantation with a femtosecond laser: One-month results.

PURPOSE: To compare astigmatic outcomes in patients with bilateral cataracts having toric intraocular lens (IOL) implantation with intraoperative aberrometry measurements in 1 eye and standard power calculation and a toric IOL calculator with inked axis marking in the contralateral eye. SETTING: Twelve sites in the United States. DESIGN: Prospective cohort study. METHODS: The eye with the more visually significant cataract was randomized to intraoperative aberrometry measurements (Ocular Response Analyzer with Verifeye) or standard preoperative biometry and use of a toric calculator with the contralateral eye automatically assigned to the other group. The primary effectiveness outcome was the proportion of eyes with a postoperative refractive astigmatism of 0.50 diopter (D) or less at 1 month. RESULTS: Of the 130 patients (260 eyes) enrolled, 124 (248 eyes) were randomized; 121 (242 eyes) completed the trial. The percentage of eyes with astigmatism of 0.50 D or less at 1 month was higher in the intraoperative aberrometry group than in the standard group (89.2% versus 76.6%) (P = .006). The mean postoperative refractive astigmatism was lower in the intraoperative aberrometry group (0.29 D ± 0.28 [SD] versus 0.36 ± 0.35 D) (P = .041). Secondary effectiveness endpoints, including manifest refraction spherical equivalent prediction error, uncorrected distance visual acuity, and corrected distance visual acuity, were similar. CONCLUSIONS: Compared with standard methods, the use of the intraoperative aberrometry system increased the proportion of eyes with postoperative refractive astigmatism of 0.50 D or less and reduced the mean postoperative refractive astigmatism at 1 month. Other efficacy outcomes were similar. FINANCIAL DISCLOSURES: Drs. Woodcock, Lehmann, and Cionni are consultants to Alcon Laboratories, Inc. Dr. Breen is an employee of Alcon Laboratories, Inc. Dr. Scott has no financial or proprietary interest in any material or method mentioned.

Micro-CT for anatomic referencing in PET and SPECT: radiation dose, biologic damage, and image quality.

UNLABELLED: CT is widely used for anatomic referencing of PET and SPECT images of small animals but requires sufficiently high radiation doses capable of causing significant DNA damage. Therefore, we described the relationship between radiation dose, biologic damage, and image quality to determine whether CT can be used without significantly compromising radiotherapy and tumor development studies. METHODS: The CT dose index generated by the nanoSPECT/CT system was compared with measurements using EBT2 gafchromic film. The effects of micro-CT were evaluated in 2 mouse strains that differ in sensitivity to radiation. γH2AX foci analysis to determine leukocyte, liver, and jejunum DNA damage and hematoxylin and eosin staining to investigate macroscopic jejunum damage were performed. Signal-to-noise ratio, contrast-to-noise ratio, and scanner linearity were determined to assess image quality. RESULTS: For the standard settings, that is, as set by the manufacturers, EBT2 gafchromic film dosimetry showed that the nanoSPECT/CT system underestimated the absorbed dose. Moreover, significant doses were obtained, resulting in a significant increase in γH2AX formation in leukocytes, liver, and jejunum 40 min after CT, using preset parameters when compared with nonimaged controls. The jejenum response was more pronounced for the more radiosensitive strain. In contrast to leukocytes, the liver and jejunum still showed evidence of DNA damage 3 d after CT. Contrast-to-noise ratio, signal-to-noise ratio, and scanner linearity were sufficient to allow for anatomic referencing for both imaging protocols tested. CONCLUSION: Anatomic reference images can be produced with no observable DNA damage or compromising image quality using low radiographic voltage, flux, and duration.

Cohesin phosphorylation and mobility of SMC1 at ionizing radiation-induced DNA double-strand breaks in human cells.

Cohesin, a hetero-tetrameric complex of SMC1, SMC3, Rad21 and Scc3, associates with chromatin after mitosis and holds sister chromatids together following DNA replication. Following DNA damage, cohesin accumulates at and promotes the repair of DNA double-strand breaks. In addition, phosphorylation of the SMC1/3 subunits contributes to DNA damage-induced cell cycle checkpoint regulation. The aim of this study was to determine the regulation and consequences of SMC1/3 phosphorylation as part of the cohesin complex. We show here that the ATM-dependent phosphorylation of SMC1 and SMC3 is mediated by H2AX, 53BP1 and MDC1. Depletion of RAD21 abolishes these phosphorylations, indicating that only the fully assembled complex is phosphorylated. Comparison of wild type SMC1 and SMC1S966A in fluorescence recovery after photo-bleaching experiments shows that phosphorylation of SMC1 is required for an increased mobility after DNA damage in G2-phase cells, suggesting that ATM-dependent phosphorylation facilitates mobilization of the cohesin complex after DNA damage.

Pattern of posterior capsule opacification models 2 years postoperatively with 2 single-piece acrylic intraocular lenses.

PURPOSE: To compare posterior capsule opacification (PCO) in eyes with 1 of 2 models of 1-piece acrylic intraocular lenses (IOLs). SETTING: Ambulatory surgery center. METHODS: This paired-eye study evaluated patients who had implantation of a Tecnis AAB00 IOL with a continuous optic edge in 1 eye and an AcrySof SA60AT or SN60AT IOL with an interrupted optic edge in the fellow eye. Exclusion criteria were anterior capsule overlap onto the IOL optic of fewer than 360 degrees, neodymium:YAG laser capsulotomy, postoperative time fewer than 24 months or more than 30 months, pseudoexfoliation, glaucoma, history of iritis, and surgical complications that would affect the assessment of PCO. Posterior capsule opacification was assessed using the Evaluation of Posterior Capsular Opacification (EPCO) system on a scale of 0 (none) to 4 (severe opacity with a darkening effect). RESULTS: In 13 of 14 patients, the eye with the interrupted-edge IOL had a higher EPCO score than the eye with the continuous-edge IOL. The mean EPCO score was 0.39 and 0.08, respectively; the difference was statistically significant (P = .012). The PCO density was greater in eyes with the interrupted-edge IOL, with 35% having an EPCO score of 3 or 4; no eye with a continuous-edge IOL had a score that high. CONCLUSION: Eyes with an IOL with a continuous 360-degree square edge had significantly less PCO than eyes with an IOL with a square edge that was interrupted at the optic-haptic junction.

Cohesin promotes the repair of ionizing radiation-induced DNA double-strand breaks in replicated chromatin.

The cohesin protein complex holds sister chromatids together after synthesis until mitosis. It also contributes to post-replicative DNA repair in yeast and higher eukaryotes and accumulates at sites of laser-induced damage in human cells. Our goal was to determine whether the cohesin subunits SMC1 and Rad21 contribute to DNA double-strand break repair in X-irradiated human cells in the G2 phase of the cell cycle. RNA interference-mediated depletion of SMC1 sensitized HeLa cells to X-rays. Repair of radiation-induced DNA double-strand breaks, measured by gammaH2AX/53BP1 foci analysis, was slower in SMC1- or Rad21-depleted cells than in controls in G2 but not in G1. Inhibition of the DNA damage kinase DNA-PK, but not ATM, further inhibited foci loss in cohesin-depleted cells in G2. SMC1 depletion had no effect on DNA single-strand break repair in either G1 or late S/G2. Rad21 and SMC1 were recruited to sites of X-ray-induced DNA damage in G2-phase cells, but not in G1, and only when DNA damage was concentrated in subnuclear stripes, generated by partially shielded ultrasoft X-rays. Our results suggest that the cohesin complex contributes to cell survival by promoting the repair of radiation-induced DNA double-strand breaks in G2-phase cells in an ATM-dependent pathway.

Representation of Clinical Nursing Protocols Using GEM II & GEM Cutter.

The machineable representation and execution of clinical guidelines has been the focus of research efforts for some time, however there is less examination of whether the methods and techniques for guidelines are sufficient for clinical protocols. The objective of this study was to test the feasibility of using the Guideline Elements Model II (GEM II) and GEM Cutter for the representation of clinical protocols, specifically clinical protocols commonly used by nurses. After downloading the GEM Cutter 2.5, we decomposed a set of clinical protocols and analyzed the completeness in which elemental protocol data was represented. One of the most complicated of these protocols (extravasations of infused medication) is presented as an example. While GEM II adequately represents core elements of clinical protocols at the high level, it was not possible to adequately represent sequence and associated role based permissions via use of conditional criteria at branching and procedural levels. Functionality of the tool would also be enhanced with more robust terminology management and support for multi-authoring.

Radiosensitization by nitric oxide at low radiation doses.

Nitric oxide was shown to radiosensitize anoxic V79 and CHO hamster cells and MCF7 and UT-SCC-14 human cells, measuring clonogenic survival and/or DNA damage in vitro at low radiation doses (0.1-5 Gy). Radiosensitization was easily detected after 2 Gy in anoxic V79 cells exposed to 40 ppm ( approximately 70 nM) nitric oxide, indicating that nitric oxide is a significantly more efficient radiosensitizer than oxygen. The yield of double-strand breaks (as gamma-H2AX foci) in V79 and MCF7 cells was doubled by irradiation in 1% v/v nitric oxide/N(2), and there was a longer repair time in cells irradiated in nitric oxide than in air or anoxia; single-strand breaks ("comet" assay) also appeared to be enhanced. Potent radiosensitization by nitric oxide is consistent with near diffusion-controlled reaction of nitric oxide with purine and pyrimidine radicals observed by pulse radiolysis, with nitric oxide reacting two to three times faster than oxygen with the 5-hydroxy-uracil-6-yl radical. Stable NO/base adducts were formed with uracil radicals. Effects on the radiosensitivity of cells exposed to as low as 40 ppm v/v nitric oxide after doses of 1-2 Gy suggest that variations in radiosensitivity in individual patients after radiotherapy might include a component reflecting differing levels of nitric oxide in tumors.

Low-dose reduction in transformation frequency compared to unirradiated controls: the role of hyper-radiosensitivity to cell death.

Calculations based on plausible parameters taken from the existing experimental database, and new measurements on the cell cycle dependence of low-dose hyper-radiosensitivity (HRS) of non-tumorigenic HeLa x skin fibroblast human hybrid cells, provide the first experimental evidence that the selective killing of a transformation-sensitive G(2)/M-phase subpopulation as a consequence of low-dose HRS could account in part for the observed reduction of induced transformation frequencies at low doses to values below that observed spontaneously. However, it is clear that other mechanisms associated with classical adaptive response, such as induced DNA repair, are also likely to be involved.