Πέμπτη, 23 Νοεμβρίου 2017

Concerns about a New Preterm MR Imaging Scoring System [LETTERS]



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The Role of Hemodynamics in Intracranial Bifurcation Arteries after Aneurysm Treatment with Flow-Diverter Stents [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Treatment of intracranial bifurcation aneurysms with flow-diverter stents can lead to caliber changes of the distal vessels in a subacute phase. This study aims to evaluate whether local anatomy and flow disruption induced by flow-diverter stents are associated with vessel caliber changes in intracranial bifurcations.

MATERIALS AND METHODS:

Radiologic images and demographic data were acquired for 25 patients with bifurcation aneurysms treated with flow-diverter stents. Whisker plots and Mann-Whitney rank sum tests were used to evaluate if anatomic data and caliber changes could be linked. Symmetry/asymmetry were defined as diameter ratio 1 = symmetric and diameter ratio <1 = asymmetric. Computational fluid dynamics was performed on idealized and patient-specific anatomies to evaluate flow changes induced by flow-diverter stents in the jailed vessel.

RESULTS:

Statistical analysis identified a marked correspondence between asymmetric bifurcation and caliber change. Symmetry ratios were lower for cases showing narrowing or subacute occlusion (medium daughter vessel diameter ratio = 0.59) compared with cases with posttreatment caliber conservation (medium daughter vessel diameter ratio = 0.95). Computational fluid dynamics analysis in idealized and patient-specific anatomies showed that wall shear stress in the jailed vessel was more affected when flow-diverter stents were deployed in asymmetric bifurcations (diameter ratio <0.65) and less affected when deployed in symmetric anatomies (diameter ratio ~1.00).

CONCLUSIONS:

Anatomic data analysis showed statistically significant correspondence between caliber changes and bifurcation asymmetry characterized by diameter ratio <0.7 (P < .001). Similarly, computational fluid dynamics results showed the highest impact on hemodynamics when flow-diverter stents are deployed in asymmetric bifurcations (diameter ratio <0.65) with noticeable changes on wall sheer stress fields. Further research and clinical validation are necessary to identify all elements involved in vessel caliber changes after flow-diverter stent procedures.



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Temporal Lobe Malformations in Achondroplasia: Expanding the Brain Imaging Phenotype Associated with FGFR3-Related Skeletal Dysplasias [PEDIATRICS]

SUMMARY:

Thanatophoric dysplasia, achondroplasia, and hypochondroplasia belong to the fibroblast growth factor receptor 3 (FGFR3) group of genetic skeletal disorders. Temporal lobe abnormalities have been documented in thanatophoric dysplasia and hypochondroplasia, and in 1 case of achondroplasia. We retrospectively identified 13 children with achondroplasia who underwent MR imaging of the brain between 2002 and 2015. All children demonstrated a deep transverse temporal sulcus on MR imaging. Further common neuroimaging findings were incomplete hippocampal rotation (12 children), oversulcation of the mesial temporal lobe (11 children), loss of gray-white matter differentiation of the mesial temporal lobe (5 children), and a triangular shape of the temporal horn (6 children). These appearances are very similar to those described in hypochondroplasia, strengthening the association of temporal lobe malformations in FGFR3-associated skeletal dysplasias.



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Feasibility of Brain Atrophy Measurement in Clinical Routine without Prior Standardization of the MRI Protocol: Results from MS-MRIUS, a Longitudinal Observational, Multicenter Real-World Outcome Study in Patients with Relapsing-Remitting MS [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Feasibility of brain atrophy measurement in patients with MS in clinical routine, without prior standardization of the MRI protocol, is unknown. Our aim was to investigate the feasibility of brain atrophy measurement in patients with MS in clinical routine.

MATERIALS AND METHODS:

Multiple Sclerosis and Clinical Outcome and MR Imaging in the United States (MS-MRIUS) is a multicenter (33 sites), retrospective study that included patients with relapsing-remitting MS who began treatment with fingolimod. Brain MR imaging examinations previously acquired at the baseline and follow-up periods on 1.5T or 3T scanners with no prior standardization were used, to resemble a real-world situation. Brain atrophy outcomes included the percentage brain volume change measured by structural image evaluation with normalization of atrophy on 2D-T1-weighted imaging and 3D-T1WI and the percentage lateral ventricle volume change, measured by VIENA on 2D-T1WI and 3D-T1WI and NeuroSTREAM on T2-fluid-attenuated inversion recovery examinations.

RESULTS:

A total of 590 patients, followed for 16 months, were included. There were 585 (99.2%) T2-FLAIR, 425 (72%) 2D-T1WI, and 166 (28.2%) 3D-T1WI longitudinal pairs of examinations available. Excluding MR imaging examinations with scanner changes, the analyses were available on 388 (65.8%) patients on T2-FLAIR for the percentage lateral ventricle volume change, 259 and 257 (43.9% and 43.6%, respectively) on 2D-T1WI for the percentage brain volume change and the percentage lateral ventricle volume change, and 110 (18.6%) on 3D-T1WI for the percentage brain volume change and percentage lateral ventricle volume change. The median annualized percentage brain volume change was –0.31% on 2D-T1WI and –0.38% on 3D-T1WI. The median annualized percentage lateral ventricle volume change was 0.95% on 2D-T1WI, 1.47% on 3D-T1WI, and 0.90% on T2-FLAIR.

CONCLUSIONS:

Brain atrophy was more readily assessed by estimating the percentage lateral ventricle volume change on T2-FLAIR compared with the percentage brain volume change or percentage lateral ventricle volume change using 2D- or 3D-T1WI in this observational retrospective study. Although measurement of the percentage brain volume change on 3D-T1WI remains the criterion standard and should be encouraged in future prospective studies, T2-FLAIR–derived percentage lateral ventricle volume change may be a more feasible surrogate when historical or other practical constraints limit the availability of percentage brain volume change on 3D-T1WI.



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Vertebroplasty and Kyphoplasty for Osteoporotic Vertebral Fractures: What Are the Latest Data? [REVIEW ARTICLE]

SUMMARY:

Osteoporotic vertebral compression fractures frequently result in significant morbidity and health care resource use. For patients with severe and disabling pain, vertebral augmentation (vertebroplasty and kyphoplasty) is often considered. Although vertebroplasty was introduced >30 years ago, there are conflicting opinions regarding the role of these procedures in the treatment of osteoporotic vertebral compression fractures. This review article updates clinicians on the published prospective randomized controlled data, including the most recent positive trials that followed initial negative trials in 2009. Analysis of multiple national claim datasets has also provided further insight into the utility of these procedures. Finally, we considered the recent recommendations of national organizations and medical societies that advise on the use of vertebral augmentation procedures for osteoporotic vertebral compression fractures.



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Optimization of Quantitative Dynamic Postgadolinium MRI Technique Using Normalized Ratios for the Evaluation of Temporomandibular Joint Synovitis in Patients with Juvenile Idiopathic Arthritis [HEAD & NECK]

BACKGROUND AND PURPOSE:

MR imaging has been shown to be useful in the diagnosis of juvenile idiopathic arthritis of the temporomandibular joint. Prior MR imaging approaches have relied mainly on the subjective interpretation of synovial enhancement as a marker for synovial inflammation. Although, more recently, several attempts have been made to quantify synovial enhancement, these methods have not taken into account the dynamic enhancement characteristics of the temporomandibular joint and the effect of sampling time. Our aim was to develop a clinically feasible, reproducible, dynamic, contrast-enhanced MR imaging technique for the quantitative assessment of temporomandibular joint synovitis in patients with juvenile idiopathic arthritis and to study the effect of sampling time on the evaluation of synovitis.

MATERIALS AND METHODS:

This was a retrospective study of all patients who had dynamic, contrast-enhanced coronal T1 3T MR imaging through the temporomandibular joint at our institution between January 1, 2015, and July 8, 2016. Patients in this cohort included those with a history of juvenile idiopathic arthritis and control patients who underwent MR imaging for other routine, clinical purposes. Synovial enhancement was calculated for each temporomandibular joint using 3 different types of equations termed normalization ratios. The enhancement profiles generated by each equation were studied to determine which provided the best discrimination between affected and unaffected joints, was the least susceptible to sampling errors, and was the most clinically feasible.

RESULTS:

A ratio of synovial enhancement (defined as the difference between the postgadolinium and the pregadolinium T1 signal of the synovium) to the postgadolinium signal of the longus capitis provided the best discrimination between affected and unaffected joints, the least susceptibility to sampling error, and was thought to be the most clinically feasible method of quantification of synovial inflammation. Additional synovial enhancement ratios studied did not provide the same level rates of discrimination between the affected and unaffected joints and were thought to be too temporally variable to provide reliable clinical use.

CONCLUSIONS:

We provide a robust, reproducible, dynamic gadolinium-enhanced MR imaging technique for the quantitative assessment of temporomandibular joint synovitis in patients with juvenile idiopathic arthritis.



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Leukoaraiosis Attenuates Diagnostic Accuracy of Large-Vessel Occlusion Scales [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Prehospital stroke scales may help identify patients likely to have large-vessel occlusion to facilitate rapid triage to thrombectomy-capable stroke centers. Scale misclassification may result in inaccurate decisions and possible harm. Pre-existing leukoaraiosis has been shown to attenuate the association between deficit type and stroke severity. We sought to determine whether leukoaraiosis affects the predictive ability of 5 commonly used large-vessel occlusion scales.

MATERIALS AND METHODS:

We retrospectively analyzed 274 consecutive patients with stroke with available brain MR imaging and vessel imaging. We used the following large-vessel occlusion scales: the 3-Item Stroke Scale; Field Assessment Stroke Triage for Emergency Destination; Rapid Arterial Occlusion Evaluation; Vision, Aphasia, Neglect score; and Cincinnati Prehospital Stroke Severity Scale. For diagnostic scale accuracy, we assessed sensitivity, specificity, positive predictive value, negative predictive value, and . Multivariable logistic regression was used to determine the predictive ability of the scales after adjustment for leukoaraiosis and potential confounders.

RESULTS:

In unadjusted analyses, all scales predicted the presence of large-vessel occlusion (n = 46, P < .01 each), though diagnostic accuracy was attenuated among patients with moderate-to-severe leukoaraiosis. After adjustment, the Field Assessment Stroke Triage for Emergency Destination (OR = 3.2; 95% CI, 1.1–9.5; P = .033) and Rapid Arterial Occlusion Evaluation (OR = 3.7; 95% CI, 1.3–10.8; P = .015), but not the 3-Item Stroke Scale (OR = 5.4; 95% CI, 0.86–33.9; P = .073), Vision, Aphasia, Neglect score (OR = 2.5; 95% CI, 0.8–7.2), and Cincinnati Prehospital Stroke Severity Scale (OR = 2.8; 95% CI, 1.0–8.0), predicted large-vessel occlusion.

CONCLUSIONS:

The diagnostic accuracy of the tested large-vessel occlusion scales was attenuated in the presence of moderate-to-severe leukoaraiosis. This information that may aid the design of future studies that require large-vessel occlusion scale screening of patients who are likely to have concomitant leukoaraiosis.



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Posttreatment Infarct Volumes when Compared with 24-Hour and 90-Day Clinical Outcomes: Insights from the REVASCAT Randomized Controlled Trial [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Endovascular therapy has become the standard of care for patients with disabling anterior circulation ischemic stroke due to proximal intracranial thrombi. Our aim was to determine whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in posttreatment infarct volume in the Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours (REVASCAT) trial.

MATERIALS AND METHODS:

The REVASCAT trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 206 enrolled subjects (endovascular treatment, n = 103; control, n = 103), posttreatment infarct volume was measured in 204 subjects. Posttreatment infarct volumes were compared with treatment assignment and recanalization status. Appropriate statistical models were used to assess the relationship among baseline clinical and imaging variables, posttreatment infarct volume, the 24-hour NIHSS score, and functional status with the 90-day modified Rankin Scale score.

RESULTS:

The median posttreatment infarct volume in all subjects was 23.7 mL (interquartile range = 68.9 mL) and 16.3 mL (interquartile range = 50.2 mL) in the endovascular treatment arm and 38.6 mL (interquartile range = 74.9 mL) in the control arm (P = .02 for endovascular treatment versus control subjects). Baseline NIHSS (P < .01), site of occlusion (P < .03), baseline NCCT ASPECTS (P < .01), and recanalization status (P = .02) were independently associated with posttreatment infarct volume. Baseline NIHSS (P < .01), time from symptom onset to randomization (P = .02), treatment type (P = .04), and recanalization status (P < .01) were independently associated with the 24-hour NIHSS scores. The 24-hour NIHSS score strongly mediated the relationship between treatment type and 90-day mRS (P < .01 for indirect effect when adjusted for age), while posttreatment infarct volume did not (P = .26).

CONCLUSIONS:

Endovascular treatment saves brain and improves 90-day clinical outcomes primarily through a beneficial effect on the 24-hour stroke severity.



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Perivascular Spaces in Old Age: Assessment, Distribution, and Correlation with White Matter Hyperintensities [ADULT BRAIN]

BACKGROUND AND PURPOSE:

The visual rating scales for perivascular spaces vary considerably. We sought to develop a new scale for visual assessment of perivascular spaces and to further describe their distribution and association with white matter hyperintensities in old age.

MATERIALS AND METHODS:

This population-based study included 530 individuals who did not have dementia and were not institutionalized (age, ≥60 years or older; mean age, 70.7 years; 58.9% women) who were living in central Stockholm, Sweden. A semiquantitative visual rating scale was developed to score the number and size of visible perivascular spaces in 7 brain regions in each hemisphere. A modified Scheltens visual rating scale was used to assess white matter hyperintensities.

RESULTS:

The global scores for perivascular spaces ranged from 4–32 for number, 3–22 for size, and 7–54 for the combination of number and size. The weighted statistics for the intra- and interrater reliability both were 0.77. The global score for the number of perivascular spaces increased with advancing age (P < .001). The scores for the number of perivascular spaces in the basal ganglia and subinsular regions were significantly correlated with the load of white matter hyperintensities, especially in lobar and deep white matter regions (partial correlation coefficients, >0.223; P < .01).

CONCLUSIONS:

The new visual rating scale for perivascular spaces shows excellent intra- and interrater reliability. The number of perivascular spaces globally and, especially, in the basal ganglia, is correlated with the load of lobar and deep white matter hyperintensities, supporting the view that perivascular spaces are a marker for cerebral small-vessel disease.



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Diagnostic Accuracy of Digital Breast Tomosynthesis in the Evaluation of Palpable Breast Abnormalities

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Publication date: Available online 23 November 2017
Source:Academic Radiology
Author(s): Jeffrey R. Hawley, Justine K. Kang-Chapman, Sarah E. Bonnet, Amy L. Kerger, Clayton R. Taylor, Barbaros S. Erdal
Rationale and ObjectivesThe role of digital breast tomosynthesis (DBT) in evaluating palpable abnormalities has not been evaluated and its accuracy compared to 2D mammography is unknown. The purpose of this study was to evaluate combined 2D mammography, DBT, and ultrasound (US) at palpable sites.Materials and MethodsTwo breast imagers reviewed blinded consecutive cases with combined 2D mammograms and DBT examinations performed for palpable complaints. By consensus, 2D and DBT findings were recorded and compared to US. Patient characteristics, demographics, subsequent workup, and outcome were recorded.ResultsA total of 229 sites in 188 patients were included, with 50 biopsies performed identifying 18 cancers. All 18 cancers were identified on 2D and US, whereas 17 cancers were identified on DBT. Cancer detection sensitivities for 2D, DBT, and US were 100.0%, 94.4%, and 100.0%. The negative predictive value, when combined with US, was 100% for both. The sensitivity and the specificity for both benign and malignant findings with 2D and DBT were 70.5% versus 75.4% (P = 0.07) and 95.3% versus 99.1% (P = 0.125). Palpable findings not identified by 2D and DBT were smaller than those identified (11.5 ± 8.3 mm vs 23.9 ± 12.8 mm, P < 0.001). Patients with dense breasts were more likely to have mammographically occult findings than patients with nondense breasts (27.4% vs 8.3%).ConclusionsDBT did not improve cancer detection over 2D or US. Both mammographic modalities failed to identify sonographically confirmed findings primarily in dense breasts. The diagnostic use of DBT at palpable sites provided limited benefit over combined 2D and US. When utilizing DBT, US should be performed to adequately characterize palpable sites.



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Impact of Radiation Dose Reduction in Abdominal Computed Tomography on Diagnostic Accuracy and Diagnostic Performance in Patients with Suspected Appendicitis

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Publication date: Available online 23 November 2017
Source:Academic Radiology
Author(s): Corinna Storz, Manuel Kolb, Jong Hyo Kim, Jakob Weiss, Wolfgang G. Kunz, Konstantin Nikolaou, Fabian Bamberg, Ahmed E. Othman
Rationale and ObjectivesTo determine the intraindividual impact of radiation dose reduction in abdominal computed tomography (CT) on diagnostic performance in patients with suspected appendicitis.Materials and MethodsThis study was approved by the institutional review board. Seventy-five patients who underwent standard contrast-enhanced abdominal CT for suspected appendicitis between 2004 and 2009 were retrospectively included. Low-dose CT reconstructions with 75%, 50%, and 25% of the original radiation dose level were generated by applying realistic reduced-dose simulation. Two blinded, independent readers assessed image quality, signal-to-noise ratio, and diagnostic confidence on each dataset. Diagnostic accuracy for detection of appendicitis and complications were calculated for each reader. Paired univariate tests were used to determine intraindividual differences.ResultsAmong 75 subjects included in the analysis (57% female, mean age: 41 ± 18 years), the prevalence of histopathologically confirmed appendicitis was 59%. Signal-to-noise ratio and subjective image quality of 50% and 25% reduced-dose CTs were significantly lower than the reference datasets (all P < .005). Appendicitis was correctly identified in all reference and low-dose datasets (sensitivity: 100%, negative predictive value: 100%). Presence of complications was correctly detected in all reference, 75%, and 50% datasets, but was decreased in 25% datasets (sensitivity: 77.8% and negative predictive value: 97.4%). Diagnostic confidence was high for original and 75% datasets, but significantly lower for 50% and 25% datasets (P < .001).ConclusionsOur results indicate that diagnostic accuracy in abdominal CT acquisitions acquired at 75% and 50% of radiation dose is maintained in patients with suspected appendicitis, whereas further reduction of radiation exposition is associated with decreased diagnostic performance.



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Regional Heterogeneity of Lobar Ventilation in Asthma Using Hyperpolarized Helium-3 MRI

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Publication date: Available online 23 November 2017
Source:Academic Radiology
Author(s): Wei Zha, Stanley J. Kruger, Robert V. Cadman, David G. Mummy, Michael D. Evans, Scott K. Nagle, Loren C. Denlinger, Nizar N. Jarjour, Ronald L. Sorkness, Sean B. Fain
Rationale and ObjectivesTo determine lobar ventilation patterns in asthmatic lungs with hyperpolarized 3He magnetic resonance imaging (HP 3He MRI).Materials and MethodsEighty-two subjects (14 normal, 48 mild-to-moderate asthma, and 20 severe asthma) underwent HP 3He MRI, computed tomography (CT), and pulmonary function testing. After registering proton to 3He images, we segmented the lungs from proton MRI and further segmented the five lung lobes (right upper lobe [RUL], right middle lobe [RML], and right lower lobe [RLL]; left upper lobe and left lower lobe [LLL]) by referring to the lobar segmentation from CT. We classified the gas volume into four signal intensity levels as follows: ventilation defect percent (VDP), low ventilation percent, medium ventilation percent, and high ventilation percent. The local signal intensity variations in the ventilated volume were estimated using heterogeneity score (Hs). We compared each ventilation level and Hs measured in the whole lung and lobar regions across the three subject groups.ResultsIn mild-to-moderate asthma, the RML and RUL showed significantly greater VDP than the two lower lobes (RLL and LLL) (P ≤ .047). In severe asthma, the pattern was more variable with the VDP in the RUL significantly greater than in the RLL (P = .026). In both asthma groups, the lower lobes (RLL and LLL) showed significantly higher high ventilation percent and Hs compared to the three upper lobes (all P ≤ .015).ConclusionsIn asthma, the RML and RUL showed greater ventilation abnormalities, and the RLL and LLL were more highly ventilated with greater local heterogeneity. These findings may facilitate guided bronchoscopic sampling and localized airway treatment in future studies.



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Expanding the Definition of a Benign Renal Cyst on Contrast-enhanced CT

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Publication date: Available online 23 November 2017
Source:Academic Radiology
Author(s): Eric M. Hu, James H. Ellis, Stuart G. Silverman, Richard H. Cohan, Elaine M. Caoili, Matthew S. Davenport
Rationale and ObjectiveWe aimed to determine the frequency and clinical significance of homogeneous renal masses measuring 21–39 Hounsfield units on contrast-enhanced computed tomography (CT).MethodsSubjects 40–69 years old undergoing portal-venous-phase contrast-enhanced abdominal CT from January 1, 2006 to December 31, 2010 with slice thickness ≤5 mm and no prior CT or magnetic resonance imaging were identified (n = 1387) for this institutional review board-approved retrospective cohort study. Images were manually reviewed by three radiologists in consensus to identify all circumscribed homogeneous renal masses (maximum of three per subject) ≥10 mm with a measured attenuation of 21–39 Hounsfield units. Exclusion criteria were known renal cancer or imaging performed for a renal indication. The primary outcome was retrospective characterization as a clinically significant mass, defined as a solid mass, a Bosniak IIF/III/IV mass, or extirpative therapy or metastatic renal cancer within 5 years' follow-up.ResultsEligible masses (n = 74) were found in 5% (63/1387) of subjects. Of those with a reference standard (n = 42), none (0% [95% CI: 0.0%–8.4%]) were determined to be clinically significant.ConclusionIncidental renal masses on contrast-enhanced CT that are homogeneous and display an attenuation of 21–39 Hounsfield units are uncommon in patients 40–69 years of age, unlikely to be clinically significant, and may not need further imaging evaluation. If these results can be replicated in an independent and larger population, the practical definition of a benign cyst on imaging may be able to be expanded.



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Communicating Radiology Test Results

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Publication date: Available online 23 November 2017
Source:Academic Radiology
Author(s): Zeeshaan S. Bhatti, Richard K.J. Brown, Ella A. Kazerooni, Matthew S. Davenport
Rationale and ObjectivesThis study aimed to determine the preferences of radiology and referring provider residents regarding direct communication of radiology test results.MethodsThis Health Insurance Portability and Accountability Act-compliant quality improvement effort was exempt from institutional review board oversight. An anonymous survey was emailed to 44 radiology residents and 364 referring resident providers who routinely provide or receive direct communication of test results at our quaternary care medical center. The survey focused on the frequency, indication, clinical utility, and methods of direct communication of radiology results. Proportions were compared to chi-square or Fisher exact test.ResultsThe response rates were 86% (37 of 43) (radiology) and 41% (151 of 364) (referring providers). Approximately half of radiology residents (49% [18 of 37]) thought the frequency of direct verbal communication was excessive, and none (0 of 37) thought more communication was needed. In contrast, only 1.3% (2 of 151; P < .001) of referring providers felt the frequency was excessive, and 24% (36 of 151; P < .001) desired more. The majority (66% [100 of 151]) of referring providers felt phone calls from radiologists often or always added value beyond a timely radiology report, and 59% (44 of 74) felt it is the radiologist's responsibility to call about abnormal findings. Furthermore, 83% (125 of 151) of referring providers preferred to receive a phone call about non-emergent unexpected findings, although preferences varied for various example abnormalities. For outpatients with non-emergent unexpected findings, most providers (90% [64 of 71]) prefer written communication rather than a phone call.ConclusionsReferring providers prefer direct communication of radiology results, even for non-urgent unexpected findings, whereas radiology residents prefer less direct communication and are more likely to consider radiologist-to-provider communication superfluous.



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Optical Coherence Tomography

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Publication date: Available online 23 November 2017
Source:Academic Radiology
Author(s): Richard Ha, Lauren C. Friedlander, Hanina Hibshoosh, Christine Hendon, Sheldon Feldman, Soojin Ahn, Hank Schmidt, Margaret K. Akens, MaryAnn Fitzmaurice, Brian C. Wilson, Victoria L. Mango
Rationale and ObjectivesThis study aimed to assess whether different breast cancer subspecialty physicians can be trained to distinguish non-suspicious from suspicious areas of post-lumpectomy specimen margin in patients with breast cancer using optical coherence tomography (OCT) images (a near-infrared based imaging technique) with final histology as the reference standard.Materials and MethodsThis institutional review board-exempt, Health Insurance Portability and Accountability Act-compliant study was performed on 63 surgically excised breast specimens from 35 female patients, creating a 90-case atlas containing both non-suspicious and suspicious areas for cancer. OCT images of the specimens were performed, providing 6.5–15 µm resolution with tissue visualization 1–2 mm subsurface. From the 90-case atlas, 40 cases were chosen for training and 40 were randomly selected for reader assessment. Three breast imaging radiologists, two pathologists, two breast surgeons, and one non-clinical reader were trained and assessed for ability to distinguish non-suspicious from suspicious findings blinded to clinical data and corresponding histology slides. Duration of training and assessment, sensitivity, specificity, positive predictive value, negative predictive value, and the area under the curve for each reader were calculated as well as averages by subspecialty.ResultsThe average training time was 3.4 hours (standard deviation, 1.2). The average assessment time was 1.9 hours (standard deviation, 0.7). The overall average reader sensitivity, specificity, and accuracy for detecting suspicious findings with histologic confirmation of cancer at the surgical margin for all eight readers were 80%, 87%, and 87%, respectively. Radiologists demonstrated the highest average among the disciplines, 85%, 93%, and 94%, followed by pathologists, 79%, 90%, and 84%, and surgeons, 76%, 84%, and 82% respectively.ConclusionsWith relatively short training (3.4 hours), readers from different medical specialties were able to distinguish suspicious from non-suspicious OCT imaging findings in ex vivo breast tissue as confirmed by histology. These results support the potential of OCT as a real-time intraoperative tool for post-lumpectomy specimen margin assessment.



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Adjuvant breast radiotherapy: How to trade-off cost and effectiveness?

A series of health economic evaluations (HEE) has analysed the efficiency of new fractionation schedules and techniques for adjuvant breast radiotherapy. This overview assembles the available evidence and evaluates to what extent HEE-results can be compared.

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Imaging Features of Gadoxetic Acid-enhanced and Diffusion-weighted MR Imaging for Identifying Cytokeratin 19-positive Hepatocellular Carcinoma: A Retrospective Observational Study.

Imaging Features of Gadoxetic Acid-enhanced and Diffusion-weighted MR Imaging for Identifying Cytokeratin 19-positive Hepatocellular Carcinoma: A Retrospective Observational Study.

Radiology. 2017 Nov 21;:162846

Authors: Choi SY, Kim SH, Park CK, Min JH, Lee JE, Choi YH, Lee BR

Abstract
Purpose To determine the preoperative magnetic resonance (MR) imaging findings potentially most useful for predicting cytokeratin 19 (CK19)-positive hepatocellular carcinoma (HCC) and to evaluate the prognosis after curative resection in patients with a single HCC lesion positive for CK19 compared with patients with HCC who are negative for CK19. Materials and Methods The institutional review board approved this study and waived the requirement for informed consent. Two hundred four patients with CK19-negative HCC and 38 with CK19-positive HCC who underwent curative resection after gadoxetic acid-enhanced and diffusion-weighted MR imaging were retrospectively evaluated in a single institution. Two radiologists evaluated preoperative findings at MR imaging. Significant findings for differentiating the two groups were identified at univariate and multivariate analyses. By using receiver operating characteristic analysis, the optimal cut-off values for quantitative variables were determined. Recurrence-free survival rates after surgery were also compared between groups. Results At multivariate analysis, irregular tumor margin (P = .024), arterial rim enhancement (P < .001), lower tumor-to-liver signal intensity (SI) ratio on hepatobiliary phase (HBP) images (≤0.522; P = .01), and lower tumor-to-liver apparent diffusion coefficient (ADC) ratio (≤0.820; P < .001) were independent significant factors to predict CK19-positive HCC. When three of these four criteria were combined, 63.2% (24 of 38; 95% confidence interval: 46.0%, 78.2%) of CK19-positive HCCs were identified with a specificity of 90.7% (185 of 204; 95% confidence interval: 46.0%, 78.2%). When all four criteria were satisfied, specificity was 99.5% (203 of 204; 95% confidence interval: 97.3%, 100%). Recurrence-free survival rates were significantly lower in patients with CK19-positive HCCs compared with those with CK19-negative HCCs after curative resection (63.9% vs 90.0% at 1 year, 63.9% vs 79.9% at 2 years, and 54.8% vs 70.2% at 3 years, P = .001 by log-rank test). Conclusion At gadoxetic acid-enhanced and diffusion-weighted MR imaging, irregular margin, arterial phase rim enhancement, lower tumor-to-liver ADC ratio, and lower tumor-to-liver SI ratio at HBP imaging may be helpful to predict CK19-positive HCC with early recurrence (<2 years) after curative resection. (©) RSNA, 2017 Online supplemental material is available for this article.

PMID: 29166246 [PubMed - as supplied by publisher]



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Evidence Supporting LI-RADS Major Features for CT- and MR Imaging-based Diagnosis of Hepatocellular Carcinoma: A Systematic Review.

Evidence Supporting LI-RADS Major Features for CT- and MR Imaging-based Diagnosis of Hepatocellular Carcinoma: A Systematic Review.

Radiology. 2017 Nov 21;:170554

Authors: Tang A, Bashir MR, Corwin MT, Cruite I, Dietrich CF, Do RKG, Ehman EC, Fowler KJ, Hussain HK, Jha RC, Karam AR, Mamidipalli A, Marks RM, Mitchell DG, Morgan TA, Ohliger MA, Shah A, Vu KN, Sirlin CB, LI-RADS Evidence Working Group

Abstract
The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). It assigns category codes reflecting relative probability of HCC to imaging-detected liver observations based on major and ancillary imaging features. LI-RADS also includes imaging features suggesting malignancy other than HCC. Supported and endorsed by the American College of Radiology (ACR), the system has been developed by a committee of radiologists, hepatologists, pathologists, surgeons, lexicon experts, and ACR staff, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Development of LI-RADS has been based on literature review, expert opinion, rounds of testing and iteration, and feedback from users. This article summarizes and assesses the quality of evidence supporting each LI-RADS major feature for diagnosis of HCC, as well as of the LI-RADS imaging features suggesting malignancy other than HCC. Based on the evidence, recommendations are provided for or against their continued inclusion in LI-RADS. (©) RSNA, 2017 Online supplemental material is available for this article.

PMID: 29166245 [PubMed - as supplied by publisher]



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Psychoradiologic Utility of MR Imaging for Diagnosis of Attention Deficit Hyperactivity Disorder: A Radiomics Analysis.

Psychoradiologic Utility of MR Imaging for Diagnosis of Attention Deficit Hyperactivity Disorder: A Radiomics Analysis.

Radiology. 2017 Nov 22;:170226

Authors: Sun H, Chen Y, Huang Q, Lui S, Huang X, Shi Y, Xu X, Sweeney JA, Gong Q

Abstract
Purpose To identify cerebral radiomic features related to diagnosis and subtyping of attention deficit hyperactivity disorder (ADHD) and to build and evaluate classification models for ADHD diagnosis and subtyping on the basis of the identified features. Materials and Methods A consecutive cohort of 83 age- and sex-matched children with newly diagnosed and never-treated ADHD (mean age 10.83 years ± 2.30; range, 7-14 years; 71 boys, 40 with ADHD-inattentive [ADHD-I] and 43 with ADHD-combined [ADHD-C, or inattentive and hyperactive]) and 87 healthy control subjects (mean age, 11.21 years ± 2.51; range, 7-15 years; 72 boys) underwent anatomic and diffusion-tensor magnetic resonance (MR) imaging. Features representing the shape properties of gray matter and diffusion properties of white matter were extracted for each participant. The initial feature set was input into an all-relevant feature selection procedure within cross-validation loops to identify features with significant discriminative power for diagnosis and subtyping. Random forest classifiers were constructed and evaluated on the basis of identified features. Results No overall difference was found between children with ADHD and control subjects in total brain volume (1069830.00 mm(3) ± 90743.36 vs 1079 213.00 mm(3) ± 92742.25, respectively; P = .51) or total gray and white matter volume (611978.10 mm(3) ± 51622.81 vs 616960.20 mm(3) ± 51872.93, respectively; P = .53; 413532.00 mm(3) ± 41 114.33 vs 418173.60 mm(3) ± 42395.48, respectively; P = .47). The mean classification accuracy achieved with classifiers to discriminate patients with ADHD from control subjects was 73.7%. Alteration in cortical shape in the left temporal lobe, bilateral cuneus, and regions around the left central sulcus contributed significantly to group discrimination. The mean classification accuracy with classifiers to discriminate ADHD-I from ADHD-C was 80.1%, with significant discriminating features located in the default mode network and insular cortex. Conclusion The results of this study provide preliminary evidence that cerebral morphometric alterations can allow discrimination between patients with ADHD and control subjects and also between the most common ADHD subtypes. By identifying features relevant for diagnosis and subtyping, these findings may advance the understanding of neurodevelopmental alterations related to ADHD. (©) RSNA, 2017 Online supplemental material is available for this article.

PMID: 29165048 [PubMed - as supplied by publisher]



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NMR Concepts



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2017-2020 Editorial Board



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Issue Information



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DVD Review



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Mobile lung cancer testing in supermarket car parks is to be expanded

A successful pilot scheme to detect lung cancer at an early stage by offering smokers and former smokers computerised tomography scanning in shopping area car parks is to be rolled out more...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=9FTzG_1pUS0:wQ9qX6dMjAU:V_sGLiP recent?d=qj6IDK7rITs recent?i=9FTzG_1pUS0:wQ9qX6dMjAU:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=9FTzG_1pUS0:wQ9qX6dMjAU:F7zBnMy recent?i=9FTzG_1pUS0:wQ9qX6dMjAU:-BTjWOF


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Serum thyroid stimulating hormone in assessment of severity of tissue hypothyroidism in patients with overt primary thyroid failure: cross sectional survey



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Double cone dystrophy and RPE degeneration in the retina of the zebrafish gnn mutant

PURPOSE: To characterize morphologic alterations in the retina of the visual mutant zebrafish gantenbein (gnn) and to examine whether these alterations correlate with those present in human hereditary eye diseases. METHODS: The gnn mutant was isolated by behavioral and macroscopic screening. Retinas of gnn zebrafish larvae were examined at different developmental stages from 2 to 9 days postfertilization (dpf) by standard histologic staining techniques and by immunocytochemistry. Ultrastructural alterations were examined by electron microscopy. The genetic map position of the induced mutation was identified by mapping with two candidate primer pairs on single larvae. RESULTS: The gnn mutant exhibited shortened outer photoreceptor segments and altered RPE morphology. In the photoreceptor layer of the mutant, the total number of lectin-labeled cones was reduced in all developmental stages from 2 to 7 dpf, whereas the amount of rhodopsin-positive cells remained at the wild-type (WT) level. Labeling with zebrafish opsin antibodies revealed dystrophic red cones at 5 dpf, whereas the morphology of all other cone types was largely unaffected. Electron microscopy unveiled electron-dense deposits between the discs of the double cone outer segments. In addition, the onset of progressive RPE degeneration was observed at this stage of development. At later stages, all cone types and the RPE became degenerative. The morphology of distinct second-order neurons remained largely unaffected by the mutation. The gnn mutation was located approximately 4.3 cM from the simple sequence length polymorphism (SSLP) marker Z15453 on linkage group 16. CONCLUSIONS: In gnn mutant zebrafish, cones, and especially red cones, are dystrophic in early retinal development. Subsequent to this cone dystrophy, the RPE becomes dysfunctional and starts to degenerate in later stages of development. Thus, the early developmental morphology of gnn exhibits similarities to cone dystrophies most commonly seen in age-related macular degeneration (AMD) among humans, whereas the later stages of degeneration in gnn resemble RPE alterations in retinitis pigmentosa (RP) in humans. The gnn zebrafish mutant may therefore be a useful model for examining the possible interplay and connection between cone dystrophy and RPE degeneration.

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Assessment of cortisol response with low-dose and high-dose ACTH in patients with chronic fatigue syndrome and healthy comparison subjects

A reduced secretion of cortisol has been proposed as a possible explanation of the symptoms in chronic fatigue syndrome. However, the evidence of hypocortisolism in chronic fatigue syndrome is conflicting. In order to simultaneously assess possible alterations in adrenocortical sensitivity and secretory adrenal reserve, the authors administered both low-dose and high-dose ACTH to a group of 18 chronic fatigue syndrome patients and 18 age- and gender-matched healthy comparison subjects. No response differences for salivary and plasma cortisol were detectable after administration of either low-dose or high-dose ACTH, indicating that primary adrenal insufficiency is unlikely to play a significant role in the etiology of chronic fatigue syndrome.

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The future diagnostic role of procalcitonin levels: the need for improved sensitivity



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Replacing the pyrophosphate group of HMB-PP by a diphosphonate function abrogates Its potential to activate human gammadelta T cells but does not lead to competitive antagonism

The immunological characterization of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), and its methylenediphosphonate analogue, HMB-PCP, is described. With an EC(50) of 0.1-0.2 nM, HMB-PP is significantly more potent in stimulating human Vgamma9/Vdelta2 T cells than any other compound described so far. However, replacing the pyrophosphate by a P-CH(2)-P function abrogates the bioactivity drastically, with HMB-PCP having a EC(50) of only 5.3 microM.

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Glucocorticoid-induced impairment of declarative memory retrieval is associated with reduced blood flow in the medial temporal lobe

Previous work indicates that stress levels of circulating glucocorticoids can impair retrieval of declarative memory in human subjects. Several studies have reported that declarative memory retrieval relies on the medial temporal lobe. The present study used H(2)(15)O-positron emission tomography to investigate whether acutely elevated glucocorticoid levels affect regional cerebral blood flow in the medial temporal lobe, as well as in other brain regions, during declarative memory retrieval in healthy male human subjects. When measured over four different declarative memory retrieval tasks, a single, stress-level dose of cortisone (25 mg) administered orally 1 h before retention testing, induced a large decrease in regional cerebral blood flow in the right posterior medial temporal lobe, the left visual cortex and the cerebellum. The decrease in the right posterior medial temporal lobe was maximal in the parahippocampal gyrus, a region associated with successful verbal memory retrieval. Cortisone administration also significantly impaired cued recall of word pairs learned 24 h earlier, while drug effects on performance in the other tasks (verbal recognition, semantic generation and categorization) were not significant. The present results provide further evidence that acutely elevated glucocorticoid levels can impair declarative memory retrieval processes and suggest that such impairments may be related to a disturbance of medial temporal lobe function.

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Tamoxifen-inducible glia-specific Cre mice for somatic mutagenesis in oligodendrocytes and Schwann cells

Inducible transgenesis provides a valuable technique for the analysis of gene function in vivo. We report the generation and characterization of mouse lines carrying glia lineage-specific transgenes expressing an improved variant of the tamoxifen-inducible Cre recombinase, CreERT2, where the recombinase is fused to a mutated ligand binding domain of the human estrogen receptor. Using a PLP-CreERT2 transgene, we have generated mice that show specific inducible Cre function, as analyzed by cross-breeding experiments into the Rosa26 Cre-LacZ reporter line, in developing and adult Schwann cells, in mature myelinating oligodendrocytes, and in undifferentiated NG2-positive oligodendrocyte precursors in the adult. Using a P0Cx-CreERT2 transgene, we have also established mouse lines with inducible Cre function specifically in the Schwann cell lineage. These tamoxifen-inducible CreERT2 lines will allow detailed spatiotemporally controlled analysis of gene functions in loxP-based conditional mutant mice in both developing and adult Schwann cells and in the oligodendrocyte lineage.

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Shunting and controlled reinitiation: the encounter of cauliflower mosaic virus with the translational machinery



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Within- and across-channel processing in auditory masking: a physiological study in the songbird forebrain

Synchronous envelope fluctuations in different frequency ranges of an acoustic background enhance the detection of signals in background noise. This effect, termed comodulation masking release (CMR), is attributed to both processing within one frequency channel of the auditory system and comparisons across separate frequency channels. Here we present data on CMR from a study in field L2 of the auditory forebrain of the European starling (Sturnus vulgaris) using two 25-Hz-wide bands of masking noise that provide the opportunity to distinguish between within-channel and across-channel effects. Acoustically evoked responses were recorded from unrestrained birds via radio telemetry. The signal was a 800 msec pure tone presented at the most sensitive frequency of the units in a previously determined frequency-tuning curve (FTC). One band of masking noise was centered on the signal frequency while the flanking band of noise was presented either within the limits of the excitatory FTC (i.e., within the same frequency channel as the on-frequency masker) or in the suppression area of the FTC (i.e., in a separate channel). For flanking bands inside the excitatory FTC, signal detection thresholds based on the rate code were lower in noise maskers with identical envelope fluctuations (comodulated) than in maskers with uncorrelated envelopes resulting in a neural CMR of approximately 4-7 dB. For flanking bands inside the suppression areas, the neural CMR was reduced. Although the average neural CMR was below the behaviorally determined CMR, a subsample of between 11 and 26% of the recording sites resembled the behavioral performance.

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Universal sex differences in the desire for sexual variety: tests from 52 nations, 6 continents, and 13 islands

Evolutionary psychologists have hypothesized that men and women possess both long-term and short-term mating strategies, with men's short-term strategy differentially rooted in the desire for sexual variety. In this article, findings from a cross-cultural survey of 16,288 people across 10 major world regions (including North America, South America, Western Europe, Eastern Europe, Southern Europe, Middle East, Africa, Oceania, South/Southeast Asia, and East Asia) demonstrate that sex differences in the desire for sexual variety are culturally universal throughout these world regions. Sex differences were evident regardless of whether mean, median, distributional, or categorical indexes of sexual differentiation were evaluated. Sex differences were evident regardless of the measures used to evaluate them. Among contemporary theories of human mating, pluralistic approaches that hypothesize sex differences in the evolved design of short-term mating provide the most compelling account of these robust empirical findings.

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Specific Immunotherapy in LAR: a randomized, double-blind placebo controlled trial with Phleum pratense subcutaneous allergen immunotherapy

Abstract

Background

Allergen immunotherapy has been shown to be an effective treatment for local allergic rhinitis (LAR) to house dust mites. Studies with pollen allergen immunotherapy are limited to observational studies. The aim of this study was to evaluate the clinical efficacy and safety of Phleum pratense subcutaneous immunotherapy (Phl-SCIT) in LAR.

Methods

In a randomized double-blind placebo-controlled study, 56 patients with moderate-severe LAR to grass pollen received Phl-SCIT with a depigmented-polymerized pollen vaccine or placebo for the first year, and Phl-SCIT the second one. The blind was maintained throughout the study. Primary outcome was combined symptoms-medication score (CSMS) during grass pollen season (GPS). Secondary clinical outcomes included organ-specific symptoms, medication free days, rhinitis severity, and asthma control. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), nasal allergen provocation test (NAPT), skin testing, serum levels of specific-IgG4 and specific-IgE, and safety were also evaluated.

Results

SCIT had a short-term and sustained effect with significant improvements of all primary and secondary clinical outcomes and RQLQ score. SCIT significantly increased serum sIgG4 levels and allergen tolerance, from the 6th to 24th months of treatment. At the end of the study 83% of patients treated with ≥6 months of SCIT tolerated a concentration of Phl over 50 times higher than baseline, and 56% gave a negative NAPT. SCIT was well-tolerated; six mild local reactions occurred, and there were no serious adverse events related to the study medication.

Conclusions

Subcutaneous immunotherapy with depigmented-polymerized allergen extracts is a safe and clinically effective treatment for LAR to Phleum pratense.clinicaltrials. gov identifier: NCT02126111.

This article is protected by copyright. All rights reserved.



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Mesh Migration into the J-Pouch in a Patient with Post-Ulcerative Colitis Colectomy: A Case Report and Literature Review

Mesh repair offers advantages like lower postsurgical pain and earlier return to work. Thus, it has become a widely used treatment option. Here, we present the first case report of a mesh migration into a J-pouch in a patient with history of ulcerative colitis who underwent total abdominal colectomy with J-pouch and ileoanal anastomosis and a subsequent laparoscopic ventral hernia repair with mesh.

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Heterologous Secretory Expression and Characterization of Dimerized Bone Morphogenetic Protein 2 in Bacillus subtilis

Recombinant human Bone Morphogenetic Protein 2 (rhBMP2) has important applications in the spine fusion and ortho/maxillofacial surgeries. Here we first report the secretory expression of biological active dimerized rhBMP2 from Bacillus subtilis system. The mature domain of BMP2 gene was amplified from pTz57R/BMP2 plasmid. By using pHT43 expression vector two constructs, pHT43-BMP2-M (single BMP2 gene) and pHT43-BMP2-D (two BMP2 genes coupled with a linker to produce a dimer), were designed. After primary cloning (DH5α strain) and sequence analysis, constructs were transformed into Bacillus subtilis for secretory expression. Expression conditions like media (2xYT) and temperature (30°C) were optimized. Maximum 35% and 25% secretory expression of monomer (~13 kDa) and dimer (~25 kDa), respectively, were observed on SDS-PAGE in SCK6 strain. The expression and dimeric nature of rhBMP2 were confirmed by western blot and native PAGE analysis. For rhBMP2 purification, 200 ml culture supernatant was freeze dried to 10 ml and dialyzed (Tris-Cl, pH 8.5) and Fast Protein Liquid Chromatography (6 ml, Resource Q column) was performed. The rhBMP2 monomer and dimer were eluted at 0.9 M and 0.6 M NaCl, respectively. The alkaline phosphatase assay of rhBMP2 (0, 50, 100, 200, and 400 ng/ml) was analyzed on C2C12 cells and maximum 200 ng/ml activity was observed in dose dependent manner.

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Clinical Characteristics and Surgical Procedures for Children with Congenital Membranous Cataract

Objective. In a group case series, the clinical characteristics of congenital membranous cataract in children were studied to establish a system of classification and determine the surgical method suited for each type. Methods. Children (18 eyes) with congenital membranous cataract were examined by slit lamp, ultrasound biomicroscopy, and operating microscopy to classify cataracts. The clinical characteristics of congenital membranous cataract and its feature related to the surgical method were analyzed. Results. Five major types of congenital membranous cataracts were classified. All of the surgeries were successful. Anterior and posterior capsulorhexis was performed using Klöti RF capsulotomy tips. The capsular flap was removed, and anterior vitrectomy was performed using a vitrectomy cutter. Postoperative complications included posterior capsule opacification in 16.7% of the patients. Conclusion. Ultrasound biomicroscopy was used successfully to classify congenital membranous cataracts prior to surgery. Anterior and posterior capsulorhexis was performed using Klöti RF capsulotomy tips, and capsulectomy was performed using a vitrectomy cutter. These were effective techniques and should be considered for congenital membranous cataract removal surgery. This trial is registered with registration number chiCTR-OOC-17010913.

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Uniqueness of the Sum of Points of the Period-Five Cycle of Quadratic Polynomials

It is well known that the sum of points of the period-five cycle of the quadratic polynomial is generally not one-valued. In this paper we will show that the sum of cycle points of the curves of period five is at most three-valued on a new coordinate plane and that this result is essentially the best possible. The method of our proof relies on a implementing Gröbner-bases and especially extension theory from the theory of polynomial algebra.

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Intraperitoneal Granulomas Unexpectedly Found during a Cesarean Delivery: A Late Complication of Dropped Gallstones

Laparoscopic cholecystectomy is the treatment of choice for patients with symptomatic cholelithiasis. Spillage of gallstones into the abdominal cavity during laparoscopic cholecystectomy occurs in approximately one-third of cases. Although retained gallstones remain asymptomatic, few cases may develop complications. We report the case of a 29-year-old nulliparous woman presenting with several hard nodules in the omentum, raising the possibility of a metastatic disease. Histological examination demonstrated a bile-stained material and a foreign body-type granulomatous response without neoplastic tissue. Our case demonstrates an example of a complication resulting two years after a laparoscopic cholecystectomy that was unexpectedly found during a cesarean delivery. Pathologists should be aware of this entity to avoid interpretation errors.

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On the Output Controllability of Positive Discrete Linear Delay Systems

Necessary and sufficient conditions for output reachability and null output controllability of positive linear discrete systems with delays in state, input, and output are established. It is also shown that output reachability and null output controllability together imply output controllability.

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A Case of Segmental Arterial Mediolysis Presenting as Mucosal Gastric Hematoma

Background. Although segmental arterial mediolysis (SAM) has been increasingly recognized as arteriopathy and there are some case reports about SAM, it is still very rare. It is characterized clinically by aneurysm, dissection, stenosis, and occlusion within splanchnic arterial branches, causing intra-abdominal hemorrhage or bowel ischemia. Mortality is as high as 50% in acute events. Case Presentation. A 51-year-old man was referred to our hospital with hematemesis. Gastroscopy revealed a submucosal-like tumor on the posterior wall of gastric angle with ulceration. Computed tomography indicated a tumor measuring  mm in the stomach, which was suspected to have invaded into the pancreas. Significant hematemesis recurred; the patient developed shock and underwent emergency distal gastrectomy, distal pancreatectomy, and splenectomy. The pathology and the clinical course were compatible with SAM splenic artery rupture causing retroperitoneal hemorrhage that penetrated into the stomach. After that surgery, aneurysm of common hepatic artery ruptured and coil embolization was performed. Conclusion. SAM is an important cause of intra-abdominal or retroperitoneal hemorrhage in patients without underlying disease. SAM typically presents as intra-abdominal hemorrhage, but, in this case, the retroperitoneal hemorrhage penetrated into the stomach and it looked like a submucosal tumor.

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A Novel Image Encryption Algorithm Based on a Fractional-Order Hyperchaotic System and DNA Computing

In the era of the Internet, image encryption plays an important role in information security. Chaotic systems and DNA operations have been proven to be powerful for image encryption. To further enhance the security of image, in this paper, we propose a novel algorithm that combines the fractional-order hyperchaotic Lorenz system and DNA computing (FOHCLDNA) for image encryption. Specifically, the algorithm consists of four parts: firstly, we use a fractional-order hyperchaotic Lorenz system to generate a pseudorandom sequence that will be utilized during the whole encryption process; secondly, a simple but effective diffusion scheme is performed to spread the little change in one pixel to all the other pixels; thirdly, the plain image is encoded by DNA rules and corresponding DNA operations are performed; finally, global permutation and 2D and 3D permutation are performed on pixels, bits, and acid bases. The extensive experimental results on eight publicly available testing images demonstrate that the encryption algorithm can achieve state-of-the-art performance in terms of security and robustness when compared with some existing methods, showing that the FOHCLDNA is promising for image encryption.

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Retinal defects in the zebrafish bleached mutant

The recessive zebrafish mutant bleached has, apart from its defects in pigmentation, a heritable defect leading to larval blindness. Here, we analyze the retina of homozygous bleached larvae, employing morphological and electrophysiological methods. Electroretinography revealed a complete lack of electrical signals in response to light. Histological analysis of mutant retinae showed a severely affected outer retina with a hypopigmented pigment epithelium and a disorganized outer nuclear layer containing few or no intact photoreceptors. Using the TUNEL assay for cell death detection, we noticed a strong increase of apoptotic cells in all retinal cell layers, starting in young larvae even before retinal support of visual function. At later stages cell death is most pronounced at the marginal zone, where new cells are constantly added to the retina. At early stages increased apoptosis is mainly confined to the retina, while at later stages elevated cell death is al so apparent in extra-retinal tissues, particularly in the brain. Hence, the lack of visual responses in homozygous bleached larvae can be attributed to a severe defect of the outer retina, preceded by increased levels of apoptotic cell death in all retinal cell layers.

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Production of procalcitonin (PCT) in non-thyroidal tissue after LPS injection

Procalcitonin (PCT) is one of the precursors in the synthesis of calcitonin in thyroidal C-cells and other neuroendocrine cells. PCT, among other calcitonin precursors, is elevated in the serum of many conditions associated with a systemic inflammatory response syndrome, even in the absence of the thyroid gland. The aim of our study was to identify PCT-producing extrathyroidal tissues in primate sepsis. In order to induce PCT production, we treated four olive baboons ( papio cynocephalus anubis) with the endotoxin lipopolysaccharide (LPS) from s. typhimurium. We found an increase in serum PCT 3 to 5 hours after LPS injection to levels of 0.2 ng/ml, attaining a peak above 4 ng/ml PCT at 10 hours. In contrast, the untreated baboon had no detectable circulating PCT in the serum. In one animal, additional LPS boosting after 24 hours did not increase serum PCT further. Soluble proteins were extracted from different organs, fractionated by C18 extraction, and PCT was measured in an immunoluminometric assay (ILMA), which was specifically developed for this study. PCT concentrations above 0.2 ng/g of wet tissue were found in a variety of organs in LPS treated baboons, but not in the control baboon. Organs and tissues with the highest PCT concentration included liver, kidney, aorta, fat, ovaries, bladder and adrenal gland. RT-PCR confirmed an extrathyroidal origin of PCT. Importantly, CT-mRNA expression was found in liver, lung, kidney, adrenal, colon, skin, spleen, brain and pancreas. In conclusion, our data confirm previous findings in hamsters, indicating an extrathyroidal origin for PCT in sepsis. Our primate model offers a valuable tool for further investigation of PCT's pathophysiological role and its immunoneutralization as a therapy for sepsis.

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Small molecule-protein interactions exemplified on short-chain dehydrogenases/reductases

The short-chain dehydrogenase/reductase (SDRs) family represents one of the largest enzyme superfamilies, with over 80 members in the human genome. Even though the human genome project has sequenced and mapped the entire human genome, the physiological functions of more than 70% of all SDRs are currently unexplored or insufficiently characterized. To start to fill this gap, the present thesis aimed to employ a combination of molecular modeling approaches and biological assessments for the identification and characterization of novel inhibitors and/or potential substrates of different SDRs. Due to their involvement in steroid biosynthesis and metabolism, SDRs are potential targets of endocrine disrupting chemicals (EDCs). To test the use of pharmacophore-based virtual screening (VS) applications and subsequent in vitro evaluation of virtual hits for the identification and characterization of potential inhibitors, 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) was selected as an example. 11β-HSD2 has an important role in the placenta by inactivating cortisol and protecting the fetus from high maternal glucocorticoid levels. An impaired placental 11β-HSD2 function has been associated with altered fetal growth and angiogenesis as well as a higher risk for cardio-metabolic diseases in later life. Despite this vital function, 11β-HSD2 is not covered in common off-target screening approaches. Several azole fungicides were identified as 11β-HSD inhibitors amongst approved drugs by testing selected virtually retrieved hits for inhibition of cortisol to cortisone conversion in cell lysates expressing recombinant human 11β-HSD2. Moreover, a significant structure-activity relationship between azole scaffold size, 11β-HSD enzyme selectivity and potency was observed. The most potent 11β-HSD2 inhibition was obtained for itraconazole (IC50 139 ± 14 nM), for its active metabolite hydroxyitraconazole (IC50 223 ± 31 nM), and for posaconazole (IC50 460 ± 98 nM). Interestingly, substantially lower inhibitory 11β-HSD2 activity of these compounds was detected using mouse and rat kidney homogenate preparations, indicating species-specific differences. Impaired placental 11β-HSD2 function exerted by these compounds might, in addition to the known inhibition of P-glycoprotein efflux transport and cytochrome P450 enzymes, lead to locally elevated cortisol levels and thereby could affect fetal programming. Successful employment of pharmacophore-based VS applications requires suitable and reliable in vitro validation strategies. Therefore, the following study addressed the re-evaluation of a potential EDC, the widely used flame retardant tetrabromobisphenol A (TBBPA), on glucocorticoid receptor (GR) and androgen receptor (AR) function. TBBPA was reported earlier in yeast-based reporter assays to potently interfere with GR and moderately with AR function. Human HEK-293 cell-based reporter assays and cell-free receptor binding assays did not show any activity of TBBPA on GR function, which was supported by molecular docking calculations. The antiandrogenic effect, however, could be confirmed, although less pronounced than in the HEK-293 cell system. Nevertheless, the evaluation of the relevant concentrations of an EDC found in the human body is crucial for an appropriate safety assessment. Considering the rapid metabolism of TBBPA and the low concentrations observed in the human body, it is questionable whether relevant concentrations can be reached to cause harmful effects. Thus, it is vital to take the limitations of each testing system including the distinct sensitivities and specificities into account to avoid false positive or false negative results. To extend the applications of in silico tools with demonstrated proof-of-concept, they were further employed to investigate novel substrate specificities for three different SDR members: the two multi-functional enzymes, 11β-HSD1 and carbonyl reductase (CBR) 1 as well as the orphan enzyme DHRS7. A role for 11β-HSD1 in oxysterol metabolism by metabolizing 7-ketocholesterol (7kC) has already been described. However, in contrast to the known receptors for 7α,25-dihydroxycholesterol (7α25OHC), i.e. Epstein-Barr virus-induced gene 2 (EBI2), or 7β,27-dihydroxycholesterol (7β27OHC), i.e. retinoic acid related orphan receptor (ROR)γ, no endogenous receptor has been identified so far for 7kC or its metabolite 7β-hydroxycholesterol. To explore the underlying biosynthetic pathways of such dihydroxylated oxysterols, the role of 11β-HSD1 in the generation of dihydroxylated oxysterols was investigated. For the first time, the stereospecific and seemingly irreversible oxoreduction of 7-keto,25-hydroxycholesterol (7k25OHC) and 7-keto,27-hydroxycholesterol (7k27OHC) to their corresponding 7β-hydroxylated metabolites 7β25OHC and 7β27OHC by recombinant human 11β-HSD1 could be demonstrated in vitro in intact HEK-293 cells. Furthermore, 7k25OHC and 7k27OHC were found to be potently inhibited the 11β-HSD1-dependent oxoreduction of cortisone to cortisol. Molecular modeling experiments confirmed these results and suggested competition of 7k25OHC and 7k27OHC with cortisone in the enzyme binding pocket. For a more detailed enzyme characterization, 11β-HSD1 pharmacophore models were generated and employed for VS of the human metabolome database and the lipidmaps structure database. The VS yielded several hundred virtual hits, including the successful filtering of known substrates such as endogenous 11-ketoglucocorticoids, synthetic glucocorticoids, 7kC, and several bile acids known to inhibit the enzyme. Further hits comprised several eicosanoids including prostaglandins, leukotrienes, cyclopentenone isoprostanes, levuglandins or hydroxyeicosatetraenoic acids (HETEs) and compounds of the kynurenine pathway. The important role of these compounds as well as 11β-HSD1 in inflammation emphasizes a potential association. However, further biological validation is of utmost necessity to explore a potential link. The closest relative of 11β-HSD1 is the orphan enzyme DHRS7, which has been suggested to act as tumor suppressor. Among others, cortisone and 5α-dihydrotestosterone have been identified as substrates of DHRS7, although effects in functional assays could only be observed at high concentrations that may not be of physiological relevance. Hence, the existence of other yet unexplored substrates of DHRS7 can be assumed, and the generation of homology models to study the structural features of the substrate binding site of DHRS7 was employed. The predictivity of the constructed models is currently limited, due to a highly variable region comprising a part of the ligand binding site but particularly the entry of the binding pocket, and requires further optimizations. Nevertheless, the models generally displayed a cone-shaped binding site with a rather hydrophobic core. This may suggest larger metabolites to be converted by DHRS7. Moreover, the flexible loops surrounding the binding pocket may lead to the induction of an induced fit upon ligand binding. However, further studies are crucial to confirm these findings. CBR1 is well-known for its role in phase I metabolism of a variety of carbonyl containing xenobiotic compounds. Several endogenous substrates of CBR1 have been reported such as prostaglandins, S-nitrosoglutathione or lipid aldehydes. The physiological relevance of these endogenous substrates, however, is not fully understood. Thus, the physiological roles of CBR1 was further explored by identifying a novel function for CBR1 in the metabolism glucocorticoids. CBR1 was found to catalyze the conversion of cortisol into 20β-dihydrocortisol (20β-DHF), which was in turn detected as the major route of cortisol metabolism in horses and elevated in adipose tissue derived from obese horses, humans and mice. Additionally, 20β-DHF was demonstrated as weak endogenous agonist of the GR, suggesting a novel pathway to modulate GR activation by CBR1-depenent protection against excessive GR activation in obesity. In conclusion, this thesis emphasized the employment of molecular modeling approaches as an initial filter to identify toxicological relevant compound classes for the identification of potential EDCs and, moreover, as valuable tools to identify novel substrates of multifunctional SDRs and to unravel novel functions for the large majority of yet unexplored orphan SDR members, while carefully considering the limitations of this strategy.

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A niche for adult neural stem cells

The adult mammalian brain harbors multipotent stem cells, which reside and participate in specialized niches that support self-renewal and differentiation. The first cellular and molecular elements of the stem cell niche in the adult brain have been identified and include cell-cell interactions and somatic cell signaling, the vasculature, the extracellular matrix and basal lamina. Furthermore, regulation at the epigenetic level via chromatin modification and remodeling is an integral aspect of stem cell biology. Understanding the in vivo stem cell niche will provide a framework for the elucidation of stem cell function in the adult brain.

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The glial identity of neural stem cells

Glia are the most numerous cells in the brain, and their many diverse functions highlight their essential role in the nervous system. Recent studies have revealed an unexpected new role for glia in a wide variety of species, that of stem cells/progenitors in the adult and embryonic brain. Differentiation along the glial lineage may be a default state of development reflected in the progression of stem cells along the neuroepithelial-->radial glia-->astrocyte lineage.

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Hepatitis C virus proteins do not directly trigger fibrogenic events in cultured human liver myofibroblasts

Although liver fibrosis is the major complication of hepatitis C virus (HCV) infection, the mechanisms of fibrogenesis in this setting are not completely understood. The aim of this study was to test the direct effect of HCV proteins on signalling- and fibrosis-related events in cultured human liver myofibroblasts, the effector cells of liver fibrogenesis. Cultured myofibroblasts were exposed to recombinant HCV core, a structural protein, and nonstructural proteins (NS) 3, NS 4 and NS 5. HCV proteins did not significantly increase DNA synthesis in myofibroblasts. We then examined if these proteins affected early signalling events. None of the HCV proteins affected the phosphorylation of the mitogen activated protein kinases/extracellular regulated kinases 1 and 2, or of the phosphatidylinositol 3-kinase target, Akt. HCV proteins had also no effect on intracellular calcium concentration. In other experiments, fibrogenesis-related parameters were measured. None of the HCV proteins had any effect on the secretion of type I collagen, tissue inhibitor of matrix metalloproteinases type 1, gelatinase or urokinase. Alpha-smooth muscle actin expression was also not modified. In summary, our experiments do not support a direct effect of these HCV proteins on fibrogenic cells.

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Bisphosphonate in der onkologie



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Immunoneutralization of procalcitonin as therapy of sepsis

Prior studies have demonstrated that the prohormone, procalcitonin (ProCT), and its component calcitonin precursors (CTpr) are increased in the serum of septic patients, correlate with the severity of the illness, and persist for relatively long periods of time. Animal studies in septic hamsters have revealed that the administration of ProCT is toxic and that immunoneutralization with IgG that is reactive to this molecule significantly improves survival. A large animal model of a very rapidly lethal polymicrobial sepsis has been developed in the pig in order to measure continuous physiological and metabolic parameters and also to compare the effects in this animal of an immunoneutralization, which is performed late in the course of the disease, to an identical, but early, therapy. Based upon the physiological and metabolic parameters, the late therapy, which was initiated during the fourth hour at a time when pigs were nearly moribund, was found to be as beneficial as early therapy. In both late and early therapy, the only animals to survive at the predetermined time of euthanasia were those which had received immunoneutralization therapy.

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Brain damage and addictive behavior: a neuropsychological and electroencephalogram investigation with pathologic gamblers

BACKGROUND: Gambling is a form of nonsubstance addiction classified as an impulse control disorder. Pathologic gamblers are considered healthy with respect to their cognitive status. Lesions of the frontolimbic systems, mostly of the right hemisphere, are associated with addictive behavior. Because gamblers are not regarded as "brain-lesioned" and gambling is nontoxic, gambling is a model to test whether addicted "healthy" people are relatively impaired in frontolimbic neuropsychological functions. METHODS: Twenty-one nonsubstance dependent gamblers and nineteen healthy subjects underwent a behavioral neurologic interview centered on incidence, origin, and symptoms of possible brain damage, a neuropsychological examination, and an electroencephalogram. RESULTS: Seventeen gamblers (81%) had a positive medical history for brain damage (mainly traumatic head injury, pre- or perinatal complications). The gamblers, compared with the controls, were significantly more impaired in concentration, memory, and executive functions, and evidenced a higher prevalence of non-right-handedness (43%) and, non-left-hemisphere language dominance (52%). Electroencephalogram (EEG) revealed dysfunctional activity in 65% of the gamblers, compared with 26% of controls. CONCLUSIONS: This study shows that the "healthy" gamblers are indeed brain-damaged. Compared with a matched control population, pathologic gamblers evidenced more brain injuries, more fronto-temporo-limbic neuropsychological dysfunctions and more EEG abnormalities. The authors thus conjecture that addictive gambling may be a consequence of brain damage, especially of the frontolimbic systems, a finding that may well have medicolegal consequences.

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IJERPH, Vol. 14, Pages 1437: Dietary Intake of Cadmium, Lead and Mercury and Its Association with Bone Health in Healthy Premenopausal Women

IJERPH, Vol. 14, Pages 1437: Dietary Intake of Cadmium, Lead and Mercury and Its Association with Bone Health in Healthy Premenopausal Women

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph14121437

Authors: Jesus Lavado-García Luis Puerto-Parejo Raul Roncero-Martín Jose Moran Juan Pedrera-Zamorano Ignacio Aliaga Olga Leal-Hernández Maria Canal-Macias

The bone is one of the relevant target organs of heavy metals, and heavy metal toxicity is associated with several degenerative processes, such osteoporosis and bone mineral alterations, that could lead to fractures. We aimed to study a presumed relationship between bone density, evaluated by quantitative bone ultrasound (QUS), dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) and the dietary intake of cadmium, lead and mercury in healthy premenopausal women. A total of 158 healthy, non-smoking, premenopausal women were incorporated into the study. A validated food frequency questionnaire (FFQ) was administered to assess intake during the preceding seven days. The median predicted dietary cadmium intake among the 158 women studied was 25.29 μg/day (18.62–35.00) and 2.74 μg/kg body weight/week (b.w./w) (1.92–3.83). Dietary lead intake was 43.85 μg/day (35.09–51.45) and 4.82 μg/kg b.w./w (3.67–6.13). The observed dietary mercury intake was 9.55 μg/day (7.18–13.57) and 1.02 μg/kg b.w./w (0.71–1.48). Comparisons, in terms of heavy metal intake, showed no significant results after further adjusting for energy intake. No statistically significant correlations between heavy metal intake and the QUS, DXA and pQCT parameters were observed. Levels of dietary exposure of cadmium, lead and mercury were mostly within the recommendations. We did not find associations between the QUS, DXA and pQCT parameters and the dietary intake of the studied heavy metals in healthy premenopausal women.



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IJERPH, Vol. 14, Pages 1441: The Content of Structural and Trace Elements in the Knee Joint Tissues

IJERPH, Vol. 14, Pages 1441: The Content of Structural and Trace Elements in the Knee Joint Tissues

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph14121441

Authors: Wojciech Roczniak Barbara Brodziak-Dopierała Elżbieta Cipora Krzysztof Mitko Agata Jakóbik-Kolon Magdalena Konieczny Magdalena Babuśka-Roczniak

Many elements are responsible for the balance in bone tissue, including those which constitute a substantial proportion of bone mass, i.e., calcium, phosphorus and magnesium, as well as minor elements such as strontium. In addition, toxic elements acquired via occupational and environmental exposure, e.g., Pb, are included in the basic bone tissue composition. The study objective was to determine the content of strontium, lead, calcium, phosphorus, sodium and magnesium in chosen components of the knee joint, i.e., tibia, femur and meniscus. The levels of Sr, Pb, Ca, P, Na and Mg were the highest in the tibia in both men and women, whereas the lowest in the meniscus. It should be noted that the levels of these elements were by far higher in the tibia and femur as compared to the meniscus. In the components of the knee joint, the level of strontium showed the greatest variation. Significant statistical differences were found between men and women only in the content of lead.



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Herpes simplex type 1 pneumonitis and acute respiratory distress syndrome in a patient with chronic lymphatic leukemia: a case report

Pulmonary pathogenicity of herpes simplex virus type 1 in patients in intensive care without classic immunosuppression as well as the necessity of antiviral treatment in the case of herpes simplex virus detect...

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A systemically administered beta-adrenoceptor antagonist blocks corticosterone-induced impairment of contextual memory retrieval in rats

Several studies have reported that glucocorticoids impair memory retrieval. The present study examined in male Sprague-Dawley rats the effects of systemically administered corticosterone on retrieval of memory for inhibitory avoidance training. Corticosterone (3.0mg/kg, s.c.) injected 30min before retention testing, 48h after training, significantly impaired retention performance, as compared to vehicle treatment, of rats tested in the training context. In contrast, corticosterone administration did not impair retrieval when rats were tested for retention in a different context. Corticosterone did also not impair retention performance of rats given a mild-intensity footshock that resulted in only weak, non-contextual memory. These findings strongly suggest that corticosterone selectively impaired retrieval of contextual information associated with the training context. The centrally acting beta-adrenoceptor antagonist propranolol (2.0mg/kg), co-administered in a dose that did not affect retention performance alone, blocked the impairment in contextual memory retrieval induced by corticosterone. These findings provide evidence for the view that glucocorticoids interact with noradrenergic mechanisms in influencing memory retrieval.

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Rezeptor-tyrosinkinasen: Angriffspunkte für neue tumortherapien



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Stress doses of hydrocortisone, traumatic memories, and symptoms of posttraumatic stress disorder in patients after cardiac surgery: a randomized study

Traumatic experiences associated with cardiac surgery (CS) can result in traumatic memories and posttraumatic stress disorder (PTSD). Because it is known that subjects who develop PTSD often show sustained reductions in circulating cortisol concentrations, we performed a prospective, randomized study to examine whether exogenously administered stress doses of hydrocortisone during the perioperative period of CS reduces the long-term incidence of chronic stress and PTSD symptoms.; Patients (n = 91) were prospectively randomized to receive either stress doses of hydrocortisone or standard treatment during the perioperative period of CS. Of 48 available patients at 6 months after CS, 26 had received stress doses of hydrocortisone and 22 standard treatment. Traumatic memories and PTSD symptoms were diagnosed with previously validated questionnaires.; As compared with patients after standard therapy, patients from the hydrocortisone group had significantly lower chronic stress symptom scores (p <.05). There was no significant difference regarding the number or type of traumatic memories between the hydrocortisone and the standard treatment groups.; Stress doses of hydrocortisone in patients undergoing CS are associated with a lower intensity of chronic stress and PTSD symptoms at 6 months after CS.

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Patterns and universals of mate poaching across 53 nations: the effects of sex, culture, and personality on romantically attracting another person's partner

As part of the International Sexuality Description Project, 16,954 participants from 53 nations were administered an anonymous survey about experiences with romantic attraction. Mate poaching--romantically attracting someone who is already in a relationship--was most common in Southern Europe, South America, Western Europe, and Eastern Europe and was relatively infrequent in Africa, South/Southeast Asia, and East Asia. Evolutionary and social-role hypotheses received empirical support. Men were more likely than women to report having made and succumbed to short-term poaching across all regions, but differences between men and women were often smaller in more gender-egalitarian regions. People who try to steal another's mate possess similar personality traits across all regions, as do those who frequently receive and succumb to the poaching attempts by others. The authors conclude that human mate-poaching experiences are universally linked to sex, culture, and the robust influence of personal dispositions.

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Endocrine changes in critical illness

The homeostatic corrections that have emerged in the course of human evolution to cope with catastrophic events involve a complex multisystem endeavor, of which the endocrine contribution is an integral component. Although the repertoire of endocrine changes has been probed in some detail, discerning the vulnerabilities and failure of this system is far more challenging. The ensuing endocrine topics illustrate some of the current issues reflecting attempts to gain an improved insight and clinical outcome for critical illness.

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Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors



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Associations between neuroendocrine responses to the Insulin Tolerance Test and patient characteristics in chronic fatigue syndrome

Subtle dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis have been proposed as an underlying pathophysiological mechanism in chronic fatigue syndrome (CFS). This study attempted to assess the relationship between patient characteristics and HPA axis functioning using a neuroendocrine challenge test.; A test battery designed to assess different dimensions of CFS was given to 18 CFS patients and 17 controls. To evaluate the integrity of the HPA axis, the Insulin Tolerance Test (ITT), a centrally acting neuroendocrine challenge test, was performed on patients and controls. ACTH, salivary free cortisol and total plasma cortisol levels were assessed as a measure of the HPA axis stress response. Correlations of patient characteristics were calculated with integrated responses for all endocrine parameters.; CFS patients had a significantly reduced area under the ACTH response curve (AUC) in the ITT. The AUC was significantly associated with the duration of CFS symptoms (r = -.592, P = .005) and the severity of fatigue symptomatology (r = -.41, P = .045). In addition, duration of CFS was correlated with the severity of fatigue symptoms (r = .38, P = .045). Similar associations were not observed for cortisol parameters.; It has been postulated that neuroendocrine dysregulations observed in CFS are of an acquired nature. The results of a strong association between the integrated ACTH response and the duration of CFS emphasizes the need to consider factors known to be risk factors for the chronicity of CFS symptoms, such as profound inactivity, deconditioning and sleep abnormalities, as possible candidates for secondary causes of neuroendocrine dysregulations in CFS.

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Amplitude control of cell-cycle waves by nuclear import

Propagation of waves of biochemical activities through consecutive stages of the cell cycle is essential to execute the steps of cell division in a strict temporal order. Mechanisms that ensure the proper amplitude and timing of these waves are poorly understood. Using a synthetic gene circuit, we show that a transcriptional activator driven by yeast cell-cycle promoters propagates transcriptional oscillations with substantial damping. Although regulated nuclear translocation has been implicated in the timing of oscillatory events, mathematical analysis shows that increasing the rate of nuclear transport is an example of a general regulatory principle, which enhances the fidelity of wave propagation. Indeed, increasing the constitutive import rate of the activator counteracts the damping of waves and concurrently preserves the intensity of the signal. In contrast to the regulatory range of nuclear transport, the range of mRNA turnover considerably limits transcriptional wave propagation. This classification of cellular processes outlines potential regulatory mechanisms that can contribute to faithful transmission of oscillations at different stages of the cell cycle.

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Expression of the neurotrophin receptor trkB is regulated by the cAMP/CREB pathway in neurons

trkB as receptor for neurotrophins brain-derived neurotrophic factor (BDNF)/neurotrophin (NT)-4/5 plays a crucial role during development, maintenance of the adult brain, and its adaptation to injury or pathological conditions. In spite of this, very little is known about the mechanisms that regulate its expression. Here, we show that forskolin (Fk) rapidly stimulates the expression of both the full-length and truncated trkB isoforms in primary cultures of cortical neurons. Gel shift assays and transient transfection experiments demonstrate that this activation occurs via a protein kinase A (PKA)/cyclic AMP-responsive element-binding protein (CREB)-dependent mechanism. Activated CREB binds to the second cyclic AMP (cAMP)-responsive element (CRE) of the two CRE sites located within the P2 promoter of the trkB gene, which is able to confer cAMP responsiveness to a heterologous promoter. Our results illustrate that the trkB gene is a target for CREB regulation and explain the increase of trkB expression produced in different adaptative responses of the nervous system where CREB is participating.

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Antiangiogenic potency of various chemotherapeutic drugs for metronomic chemotherapy

From previous preclinical findings continuous low dose (metronomic) chemotherapy is thought to inhibit tumor angiogenesis. This suggests that activated endothelial cells may be more sensitive to chemotherapeutic drugs than tumor cells. Therefore, we assessed the IC50 for several relevant chemotherapeutic drugs in different endothelial and tumor cell lines to identify optimal compounds to be used for metronomic therapy in a murine renal cell carcinoma model. Adriamycin, idarubicin, 5-fluorouracil, paclitaxel and etoposide were chosen for our studies because of their oral availability in patients or previous reports on metronomic potential. IC50s were determined by BrdU cell growth assay after short time as well as long term exposure of the following cell lines: human endothelial cells (HdmVEC/HUVEC), human breast cancer (Mcf-7), melanoma (Skmel), liver cancer (Huh7/Alexander), lung cancer (A549/LXFL), colon cancer (Dld) and murine renal cell carcinoma (RENCA). In addition, FACS analysis was performed to determine the effect on cell cycle. In vivo, doses of 2x12 mg/kg, 2x1.2 mg/kg and 10x0.24 mg/kg adriamycin were applied to 12 RENCA mice each and antitumor as well as antiangiogenic effects were assessed 21 days after tumor cell application. Independent of the exposure time, all chemotherapeutic drugs were more active against the endothelial cell lines. IC50s were significantly lower in endothelial cells (4.02E-06 to 6.16E-14 M) as compared to tumor cells (7.44E-02 to 1.9E-11 M). Cell cycle analysis of all chemotherapeutic drugs revealed a G1-arrest in endothelial cells. Adriamycin applied in metronomic doses of 10x0.24 mg/kg showed significant antiangiogenic activity whereas, in contrast, the application of 2x12 mg/kg significantly increased the vessel density in primary tumors. In summary, all chemotherapeutic agents were more active against endothelial cells in comparison to tumor cells. The hypothesis of an antiangiogenic active metronomic therapy could be confirmed in vivo by the use of adriamycin in RENCA.

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The Effect of Prucalopride on Small Bowel Transit Time in Hospitalized Patients Undergoing Capsule Endoscopy

Background. The inpatient status is a well-known risk factor for incomplete video capsule endoscopy (VCE) examinations due to prolonged transit time. We aimed to evaluate the effect of prucalopride on small bowel transit time for hospitalized patients undergoing VCE. Methods. We included all hospitalized patients who underwent VCE at a tertiary academic center from October 2011 through September 2016. A single 2 mg dose of prucalopride was given exclusively for all patients who underwent VCE between March 2014 and December 2015. VCE studies were excluded if the capsule was retained or endoscopically placed, if other prokinetic agents were given, in cases with technical failure, or if patients had prior gastric or small bowel resection. Results. 442 VCE were identified, of which 68 were performed in hospitalized patients. 54 inpatients were included, of which 29 consecutive patients received prucalopride. The prucalopride group had a significantly shorter small bowel transit time compared to the control group (92 versus 275.5, ). There was a trend for a higher completion rate in the prucalopride group (93.1% versus 76%, ). Conclusions. Our results suggest that the administration of prucalopride prior to VCE is a simple and effective intervention to decrease small bowel transit time.

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Exponential Stability of Linear Discrete Systems with Variable Delays via Lyapunov Second Method

The paper investigates the exponential stability of a linear system of difference equations with variable delays , , where , is a constant square matrix, are square matrices, , and for an . New criteria for exponential stability are derived using the method of Lyapunov functions and formulated in terms of the norms of matrices of linear terms and matrices solving an auxiliary Lyapunov equation. An exponential-type estimate of the norm of solutions is given as well. The efficiency of the derived criteria is numerically demonstrated by examples and their relations to the well-known results are discussed.

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Potential Developmental and Reproductive Impacts of Triclocarban: A Scoping Review

Triclocarban (TCC) is an antimicrobial agent used in personal care products. Although frequently studied with another antimicrobial, triclosan, it is not as well researched, and there are very few reviews of the biological activity of TCC. TCC has been shown to be a possible endocrine disruptor, acting by enhancing the activity of endogenous hormones. TCC has been banned in the US for certain applications; however, many human populations, in and outside the US, exhibit exposure to TCC. Because of the concern of the health effects of TCC, we conducted a scoping review in order to map the current body of literature on the endocrine, reproductive, and developmental effects of TCC. The aim of this scoping review was to identify possible endpoints for future systematic review and to make recommendations for future research. A search of the literature until August 2017 yielded 32 relevant studies in humans, rodents, fish, invertebrates, and in vitro. Based on the robustness of the literature in all three evidence streams (human, animal, and in vitro), we identified three endpoints for possible systematic review: estrogenic activity, androgenic activity, and offspring growth. In this review, we describe the body of evidence and make recommendations for future research.

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Intravitreal Ziv-Aflibercept in Treatment of Naïve Chronic Central Serous Chorioretinopathy Related Choroidal Neovascular Membrane

Purpose. To study the effect and outcome of intravitreal Ziv-Aflibercept (IVZ) in treatment of Chronic Central Serous Chorioretinopathy (CSCR) related Choroidal Neovascular Membrane (CNVM). Methods. A case report of 48-year-old male patient treated with 1.25 mg/0.05 ml IVZ (total 3 doses at monthly intervals) in CSCR related CNVM. Pre- and posttreatment fundus fluorescein angiography (FFA) and Optical Coherence Tomography (OCT) were done to document response along with improvement in visual acuity. Patients. Single eye of a 48-year-old male patient. Results. Regression of CNVM was noted with improvement of macular contour and thickness on OCT and cessation of leakage on FFA. Visual acuity improved from 3/60,

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