Knowledge and Perception of the Role of Targeted Ultrasound in Detecting Down Syndrome Among a High Risk Population

The purpose of this study was to determine the perception and knowledge of targeted ultrasound in women who screen positive for Down syndrome in the first or second trimester, and to assess the perceived detection rate of Down syndrome by targeted ultrasound in this population. While several studies have reported patient perceptions’ of routine ultrasound, no study has specifically examined knowledge regarding the targeted ultrasound and its role in detecting Down syndrome. A targeted ultrasound is a special ultrasound during the second trimester offered to women who may be at a higher-than-average risk of having a baby with some type of birth defect or complication. The purpose of the ultrasound is to evaluate the overall growth and development of the baby as well as screen for birth defects and genetic conditions. Women under the age of 35 referred for an abnormal first or second trimester maternal serum screen to several Houston area clinics were asked to complete a questionnaire to obtain demographic and ultrasound knowledge information as well as assess perceived detection rate of Down syndrome by ultrasound. Seventy-seven women completed the questionnaire and participated in the study. Our findings revealed that women have limited background knowledge about the targeted ultrasound and its role in detecting Down syndrome. These findings are consistent with other studies that have reported a lack of understanding about the purpose of ultrasound examinations. One factor that seems to increase background knowledge about the targeted ultrasound is individuals having a higher level of education. However, most participants regardless of race, education, income, and exposure to targeted ultrasound information did not know the capabilities of a targeted ultrasound. This study confirmed women lack background knowledge about the targeted ultrasound and do not know enough about the technology to form a perception regarding its ability to detect Down syndrome. Additional studies to identify appropriate education techniques are necessary to determine how to best inform our patient population about targeted ultrasound.

Evolutionarily conserved role of calcineurin in phosphodegron-dependent degradation of phosphodiesterase 4D.

Calcineurin is a widely expressed and highly conserved Ser/Thr phosphatase. Calcineurin is inhibited by the immunosuppressant drug cyclosporine A (CsA) or tacrolimus (FK506). The critical role of CsA/FK506 as an immunosuppressant following transplantation surgery provides a strong incentive to understand the phosphatase calcineurin. Here we uncover a novel regulatory pathway for cyclic AMP (cAMP) signaling by the phosphatase calcineurin which is also evolutionarily conserved in Caenorhabditis elegans. We found that calcineurin binds directly to and inhibits the proteosomal degradation of cAMP-hydrolyzing phosphodiesterase 4D (PDE4D). We show that ubiquitin conjugation and proteosomal degradation of PDE4D are controlled by a cullin 1-containing E(3) ubiquitin ligase complex upon dual phosphorylation by casein kinase 1 (CK1) and glycogen synthase kinase 3beta (GSK3beta) in a phosphodegron motif. Our findings identify a novel signaling process governing G-protein-coupled cAMP signal transduction-opposing actions of the phosphatase calcineurin and the CK1/GSK3beta protein kinases on the phosphodegron-dependent degradation of PDE4D. This novel signaling system also provides unique functional insights into the complications elicited by CsA in transplant patients.

Ultrasound feedback and motivational interviewing targeting smoking cessation in the second and third trimesters of pregnancy.

INTRODUCTION: Cigarette smoking during pregnancy is associated with poor maternal and child health outcomes. Effective interventions to increase smoking cessation rates are needed particularly for pregnant women unable to quit in their first trimester. Real-time ultrasound feedback focused on potential effects of smoking on the fetus may be an effective treatment adjunct, improving smoking outcomes. METHODS: A prospective randomized trial was conducted to evaluate the efficacy of a smoking cessation intervention consisting of personalized feedback during ultrasound plus motivational interviewing-based counseling sessions. Pregnant smokers (N = 360) between 16 and 26 weeks of gestation were randomly assigned to one of three groups: Best Practice (BP) only, Best Practice plus ultrasound feedback (BP+US), or Motivational Interviewing-based counseling plus ultrasound feedback (MI+US). Assessments were conducted at baseline and end of pregnancy (EOP). RESULTS: Analyses of cotinine-verified self-reported smoking status at EOP indicated that 10.8% of the BP group was not smoking at EOP; 14.2% in the BP+US condition and 18.3% who received MI+US were abstinent, but differences were not statistically significant. Intervention effects were found conditional upon level of baseline smoking, however. Nearly 34% of light smokers (< or =10 cigarettes/day) in the MI+US condition were abstinent at EOP, followed by 25.8% and 15.6% in the BP+US and BP conditions, respectively. Heavy smokers (>10 cigarettes/day) were notably unaffected by the intervention. DISCUSSION: Future research should confirm benefit of motivational interviewing plus ultrasound feedback for pregnant light smokers and explore mechanisms of action. Innovative interventions for pregnant women smoking at high levels are sorely needed.

Evaluation of deformable image registration for improved 4D CT-derived ventilation for image guided radiotherapy

Recent treatment planning studies have demonstrated the use of physiologic images in radiation therapy treatment planning to identify regions for functional avoidance. This image-guided radiotherapy (IGRT) strategy may reduce the injury and/or functional loss following thoracic radiotherapy. 4D computed tomography (CT), developed for radiotherapy treatment planning, is a relatively new imaging technique that allows the acquisition of a time-varying sequence of 3D CT images of the patient's lungs through the respiratory cycle. Guerrero et al. developed a method to calculate ventilation imaging from 4D CT, which is potentially better suited and more broadly available for IGRT than the current standard imaging methods. The key to extracting function information from 4D CT is the construction of a volumetric deformation field that accurately tracks the motion of the patient's lungs during the respiratory cycle. The spatial accuracy of the displacement field directly impacts the ventilation images; higher spatial registration accuracy will result in less ventilation image artifacts and physiologic inaccuracies. Presently, a consistent methodology for spatial accuracy evaluation of the DIR transformation is lacking. Evaluation of the 4D CT-derived ventilation images will be performed to assess correlation with global measurements of lung ventilation, as well as regional correlation of the distribution of ventilation with the current clinical standard SPECT. This requires a novel framework for both the detailed assessment of an image registration algorithm's performance characteristics as well as quality assurance for spatial accuracy assessment in routine application. Finally, we hypothesize that hypo-ventilated regions, identified on 4D CT ventilation images, will correlate with hypo-perfused regions in lung cancer patients who have obstructive lesions. A prospective imaging trial of patients with locally advanced non-small-cell lung cancer will allow this hypothesis to be tested. These advances are intended to contribute to the validation and clinical implementation of CT-based ventilation imaging in prospective clinical trials, in which the impact of this imaging method on patient outcomes may be tested.

Fast magnetic resonance temperature imaging for focused ultrasound thermal therapy

The current standard for temperature sensitive imaging using magnetic resonance (MR) is 2-D, spoiled, fast gradient-echo (fGRE) phase-difference imaging exploiting temperature dependent changes in the proton resonance frequency (PRF). The echo-time (TE) for optimal sensitivity is larger than the typical repetition time (TR) of an fGRE sequence. Since TE must be less than TR in the fGRE sequence, this limits the technique's achievable sensitivity, spatial, and temporal resolution. This adversely affects both accuracy and volume coverage of the measurements. Accurate measurement of the rapid temperature changes associated with pulsed thermal therapies, such as high-intensity focused ultrasound (FUS), at optimal temperature sensitivity requires faster acquisition times than those currently available. ^ Use of fast MR acquisition strategies, such as interleaved echo-planar and spiral imaging, can provide the necessary increase in temporal performance and sensitivity while maintaining adequate signal-to-noise and in-plane spatial resolution. This research explored the adaptation and optimization of several fast MR acquisition methods for thermal monitoring of pulsed FUS thermal therapy. Temperature sensitivity, phase-difference noise and phase-difference to phase-difference-to noise ratio for the different pulse sequences were evaluated under varying imaging parameters in an agar gel phantom to establish optimal sequence parameters for temperature monitoring. The temperature sensitivity coefficient of the gel phantom was measured, allowing quantitative temperature extrapolations. ^ Optimized fast sequences were compared based on the ability to accurately monitor temperature changes at the focus of a high-intensity focused ultrasound unit, volume coverage, and contrast-to-noise ratio in the temperature maps. Operating parameters, which minimize complex phase-difference measurement errors introduced by use of the fast-imaging methods, were established. ^