Purpose To compare the diagnostic performance of a short dual-pulse sequence magnetic resonance (MR) imaging protocol versus a standard six-pulse sequence multiparametric MR imaging protocol for ...detection of clinically significant prostate cancer. Materials and Methods This HIPAA-compliant study was approved by the regional ethics committee. Between July 2013 and March 2015, 63 patients from a prospectively accrued study population who underwent MR imaging of the prostate including transverse T1-weighted; transverse, coronal, and sagittal T2-weighted; diffusion-weighted; and dynamic contrast material-enhanced MR imaging with a 3-T imager at a single institution were included in this retrospective study. The short MR imaging protocol image set consisted of transverse T2-weighted and diffusion-weighted images only. The standard MR imaging protocol image set contained images from all six pulse sequences. Three expert readers from different institutions assessed the likelihood of prostate cancer on a five-point scale. Diagnostic performance on a quadrant basis was assessed by using areas under the receiver operating characteristic curves, and differences were evaluated by using 83.8% confidence intervals. Intra- and interreader agreement was assessed by using the intraclass correlation coefficient. Transperineal template saturation biopsy served as the standard of reference. Results At histopathologic evaluation, 84 of 252 (33%) quadrants were positive for cancer in 38 of 63 (60%) men. There was no significant difference in detection of tumors larger than or equal to 0.5 mL for any of the readers of the short MR imaging protocol, with areas under the curve in the range of 0.74-0.81 (83.8% confidence interval CI: 0.64, 0.89), and for readers of the standard MR imaging protocol, areas under the curve were 0.71-0.77 (83.8% CI: 0.62, 0.86). Ranges for sensitivity were 0.76-0.95 (95% CI: 0.53, 0.99) and 0.76-0.86 (95% CI: 0.53, 0.97) and those for specificity were 0.84-0.90 (95% CI: 0.79, 0.94) and 0.82-0.90 (95% CI: 0.77, 0.94) for the short and standard MR protocols, respectively. Ranges for interreader agreement were 0.48-0.60 (83.8% CI: 0.41, 0.66) and 0.49-0.63 (83.8% CI: 0.42, 0.68) for the short and standard MR imaging protocols. Conclusion For the detection of clinically significant prostate cancer, no difference was found in the diagnostic performance of the short MR imaging protocol consisting of only transverse T2-weighted and diffusion-weighted imaging pulse sequences compared with that of a standard multiparametric MR imaging protocol.
RSNA, 2017 Online supplemental material is available for this article.
The 413.d insertional mutation arrests mouse development shortly after gastrulation. nodal, a novel TGF beta-related gene, is closely associated with the locus. The present study provides direct ...evidence that the proviral insertion causes a loss of function mutation. nodal RNA is initially detected at day 5.5 in the primitive ectoderm. Concomitant with gastrulation, expression becomes restricted to the proximal posterior regions of the embryonic ectoderm. nodal RNA is also expressed in the primitive endoderm overlying the primitive streak. A few hours later, expression is strictly confined to the periphery of the mature node. Interestingly 413.d mutant embryos show no morphological evidence for the formation of a primitive streak. Nonetheless, about 25% of mutant embryos do form randomly positioned patches of cells of a posterior mesodermal character. Data presented in this report demonstrate the involvement of a TGF beta-related molecule in axis formation in mammals.
Decoration of tetrelchalcogenide T-E clusters with chelating donor ligands was achieved to capture transition metal ions on their surfaces. We demonstrate that by covalent linking of bispyridyl ...ligands to an Sn-S complex, ZnX(+) units can be trapped and incorporated into the cluster framework. Intermediates that were identified using spectroscopy and/or X-ray diffraction gave insight into the formation processes.
The aim of the study was to report the mental and physical health of a population-based cohort of Gulf War and Gulf Era veterans 20 years after the war.
A multimode (mail, Web, or computer-assisted ...telephone interviewing) heath survey of 14,252 Gulf War and Gulf Era veterans. The survey consisted of questions about general, physical, mental, reproductive, and functional health.
Gulf War veterans report a higher prevalence of almost all queried physical and mental health conditions. The population as a whole, however, has a significant burden of disease including high body mass index and multiple comorbid conditions.
Gulf War veterans continue to report poorer heath than Gulf Era veterans, 20 years after the war. Chronic disease management and interventions to improve health and wellness among both Gulf War and Gulf Era veterans are necessary.
At present the analysis of somatic cell count (SCC) used for the detection of intramammary infections (IMI) in bovine milk is also recommended for goat milk, but due to the various factors ...influencing SCC it allows only limited conclusions on the udder health of goats. The research on enzyme activity in milk appears to show promise in finding an approach with more suitable indicators of the early detection of IMI in goats. Therefore, the present study aimed to investigate the influence of goat udder infection status on different milk enzyme activities and SCC throughout early lactation. A total of 60 dairy goats were sampled at weekly intervals over a period of 6 weeks after kidding and the bacteriological status, milk SCC and the activity of N-acetyl-β-d-glucosaminidase (NAGase), β-glucuronidase and lactate dehydrogenase (LDH) of udder halves were analysed. Infections with minor or major pathogens were identified in 47% of all animals over the sampling period. Coagulase-negative staphylococci (CNS) represented the main group of pathogens in bacteria isolates (16.4%). Corynebacteria and major pathogens were detected in 7.2% and 5.7% of udder half samples. Excluding the first week after parturition, the study revealed a highly significant influence of lactation week on log10 SCC (F4,255=11.63, p<0.001) and log10 LDH (F4,285=5.02, p<0.01) and must be acknowledged as the most dominating predictor on NAGase activity (F4,250=29.62, p<0.001) in early lactation. Levels in β-glucuronidase activity were not influenced by the stage of lactation. The infection status of udder halves had a highly significant effect on log10 SCC (F3,528=18.88, p<0.001), log10 β-glucuronidase (F3,407=11.02, p<0.001) and log10 LDH (F3,534=12.39, p<0.001). We revealed no effect of different pathogenic groups on NAGase activity, thus this parameter proved not to be suitable as an indicator for udder infections in early lactation. The proposed milk enzymes β-glucuronidase and LDH might be indicative of inflammatory processes, but the influence of parity and lactation stage on the overall results should be considered in the assessment of udder health in dairy goats.
Abstract Purpose To compare prospectively, in patients undergoing chest computed tomography (CT) for pulmonary-nodules or infection, image-quality and accuracy of standard dose (SD) and reduced dose ...(RD) CT with tin-filtration. Material and methods This IRB-approved study included 100 consecutive patients (36 female;median age 56 years) referred for follow-up of pulmonary-nodules ( n = 43) or suspicion of infection ( n = 57) undergoing single-energy CT with SD and RD using tin-filtration at 100 kVp (CTDIvol 2.47 mGy and 0.07 mGy, respectively). Images were reconstructed with advanced modeled iterative reconstruction (ADMIRE) at strength 3 and 5. Image-noise was measured. Two independent readers evaluated nodules and pulmonary-infection. SD CT served as reference standard. Results No significant difference was found in noise between RD with ADMIRE5 and SD with ADMIRE3 (118HU ± 14 vs. 120HU ± 17; p = 0.08). Sensitivity for detection of atelectasis and interstitial lung changes was higher in images reconstructed with ADMIRE5 (93% and 88%; respectively) than in those reconstructed with ADIMRE3 (77% and 78%; respectively). Sensitivity for detection of consolidations was 90% for ADMIRE3 and 89% for ADMIRE5. Sensitivity for nodule detection was 71% for ADMIRE3 and 81% for ADMIRE5. Specificity for detection of atelectasis and interstitial lung changes was 99% and 96% with ADMIRE5 and 99% and 96% with ADMIRE3. Specificity for detection of consolidations was 99% for ADMIRE3 and 5. Specificity for detection of nodules was 87% for both ADMIRE3 and 5. Conclusion Chest CT with a radiation dose equivalent to conventional radiography is feasible and allows for detection of pulmonary infection with high sensitivity, whereas the accuracy for detecting nodules is only moderate.
Abstract
CRISPR-cas loci typically contain CRISPR arrays with unique spacers separating direct repeats. Spacers along with portions of adjacent repeats are transcribed and processed into CRISPR(cr) ...RNAs that target complementary sequences (protospacers) in mobile genetic elements, resulting in cleavage of the target DNA or RNA. Additional, standalone repeats in some CRISPR-cas loci produce distinct cr-like RNAs implicated in regulatory or other functions. We developed a computational pipeline to systematically predict crRNA-like elements by scanning for standalone repeat sequences that are conserved in closely related CRISPR-cas loci. Numerous crRNA-like elements were detected in diverse CRISPR-Cas systems, mostly, of type I, but also subtype V-A. Standalone repeats often form mini-arrays containing two repeat-like sequence separated by a spacer that is partially complementary to promoter regions of cas genes, in particular cas8, or cargo genes located within CRISPR-Cas loci, such as toxins-antitoxins. We show experimentally that a mini-array from a type I-F1 CRISPR-Cas system functions as a regulatory guide. We also identified mini-arrays in bacteriophages that could abrogate CRISPR immunity by inhibiting effector expression. Thus, recruitment of CRISPR effectors for regulatory functions via spacers with partial complementarity to the target is a common feature of diverse CRISPR-Cas systems.
Graphical Abstract
Graphical Abstract
The aims of this study were to implement a protocol for simultaneous multislice (SMS) accelerated diffusion-weighted imaging (DWI) of the kidneys and to perform a systematic analysis of image quality ...of the data sets.
Ten healthy subjects and 5 patients with renal masses underwent DWI of the kidney in this prospective institutional review board-approved study on a 3 T magnetic resonance scanner. Simultaneous multislice DWI echo-planar sequences (acceleration factors AFs 2 and 3) were compared with conventional echo-planar DWI as reference standard for each acquisition scheme. The following 3 acquisition schemes were applied: comparison A, with increased number of acquisitions at constant scan time; comparison B, with reduction of acquisition time; and comparison C, with increased slice resolution (constant acquisition time, increasing number of slices). Interreader reliability was analyzed by calculating the intraclass correlation coefficient (ICC). Qualitative image quality features were evaluated by 2 independent radiologists on a 5-point Likert scale. Quantification accuracy of the apparent diffusion coefficients (ADCs) and signal-to-noise ratios (SNRs) were assessed by region of interest analysis. Furthermore, lesion conspicuity in the 5 patients was assessed using a 5-point Likert scale by 2 independent radiologists.
Interreader agreement was substantial with an ICC of 0.68 for the overall image quality and an ICC of 0.73 for the analysis of artifacts. In comparison A, AF2 resulted in increased SNR (P < 0.05) by 21% at stable image quality scores (image quality: P = 0.76, artifacts: P = 0.21). In comparison B, applying AF2, the scan time could be reduced by 46% without significant reduction in qualitative image quality scores (P = 0.059) or SNR (P = 0.126). In comparison C, slice resolution could be improved by 28% using AF2 with stable image quality scores and SNR. In general, AF3 resulted in reduced image quality and SNR. Significantly reduced ADC values were observed for AF3 in comparison C (cortex: P = 0.003; medulla: P = 0.001) compared with the standard echo-planar imaging sequence. The conventional DWI and the SMS DWI with AF2 showed stable lesion conspicuity (AF1/AF2: reader 1 1.8/1.4 and reader 2 1.8/1.4). The lesion conspicuity was lower using AF3 (reader 1: 2.2 and reader 2: 1.8).
In conclusion, SMS DWI of the kidney is a potential tool to substantially reduce scan time without negative effects on SNR, ADC quantification accuracy, and image quality if an AF2 is used. Although AF3 results in even higher scan time reduction, a negative impact on image quality, SNR, ADC quantification accuracy, and lesion conspicuity must be considered.
Gulf War Illness (GWI) remains a significant health concern for many veterans. The relation of pre-war health conditions and symptoms to GWI could aid in developing a more accurate case definition of ...GWI. The objective of this study was to investigate pre-war predictors of GWI in a population-based sample of Gulf War veterans using two definitions of GWI.
Data come from the 1995–1997 National Health Survey of Persian Gulf War Era Veterans, a survey of a representative sample of deployed and non-deployed US veterans. Using two definitions of GWI (CDC/Kansas and a newly developed 3-domain definition), we conducted a series of multivariable logistic regression analyses to assess the associations of demographic, lifestyle factors, and pre-war medical conditions and symptoms to subsequent GWI.
All pre-war symptom predictor domains were significantly and positively associated with GWI using a new 3-domain definition with aORs for individual domains ranging from 2.17 (95% CI = 1.99–2.38) for dermatologic conditions to 3.06 (95% CI = 2.78–3.37) for neurological conditions. All symptom predictor domains were associated with significantly increased likelihood of GWI using the CDC/Kansas definition, with aORs ranging from 2.54 (95% CI = 2.31–2.81) for inflammatory conditions to 3.22 (95% CI = 2.94–3.55) for neurological conditions. These estimates were attenuated but remained significant after inclusion of all significant symptom predictor domains.
Results from this study suggest that demographic/lifestyle factors and pre-war medical conditions are strong predictors of GWI. Additional research is needed to confirm these findings, and to clarify the unique characteristics of this common, but still poorly understood illness.
Urokinase-type plasminogen activator receptor (uPAR) regulates pericellular proteolysis by binding the serine proteinase urokinase-type plasminogen activator (uPA) that promotes cell surface ...activating of plasminogen to plasmin. In addition, uPAR as a glycosylphosphatidylinositol (GPI)-anchored signaling receptor affects cell migration, differentiation, and proliferation. The aim of the present study was to monitor the occurrence and distribution pattern of uPAR in cells of the rat molar tooth germ. By means of immunocytochemistry moderate, uPAR immunoreactivity was detected in epithelial cells of the enamel organ and in ameloblasts and odontoblasts. RT-PCR and Western blotting experiments demonstrated the expression of uPAR in phorbol 12-myristate 13-acetate (PMA)-stimulated dental epithelial cells (HAT-7 cells). A substantial part of uPAR was detected in the detergent-insoluble caveolin-1-containing low-density raft membrane fraction of HAT-7 cells suggesting a partial localization within
lipid rafts
. However, co-immunoprecipitation experiments showed that uPAR and caveolin-1 do not associate with each other directly. Cell stimulation experiments with PMA indicated that protein kinase C (PKC)-mediated signaling pathways contribute to the expression of uPAR in cells of the enamel organ. The localization of uPAR in membrane rafts provides a basis for further investigations on the role of uPAR-mediated signaling cascades in ameloblasts.
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