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Κυριακή, 3 Δεκεμβρίου 2017

Validation of an imaging based cardiovascular risk score in a Scottish population

Publication date: Available online 23 November 2017
Source:European Journal of Radiology
Author(s): Remko Kockelkoren, Pushpa M Jairam, John T. Murchison, Thomas P.A. Debray, Saeed Mirsadraee, Yolanda van der Graaf, Pim A.de Jong, Edwin J.R. van Beek
ObjectivesA radiological risk score that determines 5-year cardiovascular disease (CVD) risk using routine care CT and patient information readily available to radiologists was previously developed. External validation in a Scottish population was performed to assess the applicability and validity of the risk score in other populations.Methods2915 subjects aged ≥40 years who underwent routine clinical chest CT scanning for non-cardiovascular diagnostic indications were followed up until first diagnosis of, or death from, CVD. Using a case-cohort approach, all cases and a random sample of 20% of the participant's CT examinations were visually graded for cardiovascular calcifications and cardiac diameter was measured. The radiological risk score was determined using imaging findings, age, gender, and CT indication.ResultsPerformance on 5-year CVD risk prediction was assessed. 384 events occurred in 2124 subjects during a mean follow-up of 4.25 years (0–6.4 years). The risk score demonstrated reasonable performance in the studied population. Calibration showed good agreement between actual and 5-year predicted risk of CVD. The c-statistic was 0.71 (95%CI:0.67-0.75).ConclusionsThe radiological CVD risk score performed adequately in the Scottish population offering a potential novel strategy for identifying patients at high risk for developing cardiovascular disease using routine care CT data.



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Effect of computed tomography window settings and reconstruction plane on 8th edition T-stage classification in patients with lung adenocarcinoma manifesting as a subsolid nodule

Publication date: January 2018
Source:European Journal of Radiology, Volume 98
Author(s): Hyungwoo Ahn, Kyung Won Lee, Kyung Hee Lee, Jihang Kim, Kwhanmien Kim, Jin-Haeng Chung, Choon-Taek Lee
PurposeTo assess the effect of window settings and reconstruction plane on clinical T-stage determined by solid portion size within subsolid nodules (SSNs), based on 8th-edition TNM standards.Materials and methodsThis retrospective study included 247 SSNs from 221 patients who underwent surgery for lung adenocarcinomas between Feb 2012 and Oct 2015. Two radiologists independently measured the diameter of the solid portion on axial, coronal, and sagittal planes using lung- and mediastinal-window. The largest diameter among the measurements on the three planes was referred to as multiplanar measurement. Inter-reader agreement as well as the correlation between the CT and pathologic measurements were calculated using intra-class correlation coefficients (ICCs). The proportions of disagreement in clinical T-stage on different measurement methods were measured. The κ values for agreement between clinical- and pathological T-stage were measured.ResultsInter-reader agreement was moderate-to-excellent (ICC confidence interval [CI] range, 0.51–0.92) in lung-window, while it was good-to-excellent (0.77–0.95) in mediastinal-window. The correlation between the CT and pathologic measurements was good-to-excellent (ICC CI range, 0.63–0.82) in lung-window and fair-to-good (0.25–0.78) in mediastinal-window. The proportions of disagreement between clinical T-stages using mediastinal- and lung-window were 32.0%–41.7% and 33.6%–49.0% with axial and multiplanar measurement, respectively. Multiplanar measurement resulted in upstaging in 12.6%–15.8% and 19.0%–24.3% of cases with mediastinal- and lung-window, respectively, when compared with axial measurement alone. The κ values for agreement between clinical T-stage and pathological T-stage ranged from 0.53 to 0.69.ConclusionsMediastinal-window was a more stable method in the aspect of the inter-reader agreement, but the correlation between the CT and pathologic measurement was better in lung-window. The clinical T-stage varied in up to one-half of the cases according to the window setting, and multiplanar measurement resulted in upstaging in up to one-fourth of the cases.



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Micro-CT in an ectopic pregnancy: new radiological and microscopical perspectives (and level) in the study of the Fallopian tube

Publication date: Available online 29 November 2017
Source:European Journal of Radiology
Author(s): Osvaldo Luiz Aranda, Pedro Teixeira Castro, Edson Marchiori, Ana Paula Pinho Matos, Heron Werner, Alessandra Silveira Machado, Ricardo Tadeu Lopes, Ricardo Tadeu Lopes, Edward Araujo




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3D hybrid profile order technique in a single breath-hold 3D T2-weighted fast spin-echo sequence: Usefulness in diagnosis of small liver lesions

Publication date: January 2018
Source:European Journal of Radiology, Volume 98
Author(s): Kenichiro Hirata, Takeshi Nakaura, Tomoyuki Okuaki, Noriko Tsuda, Narumi Taguchi, Seitaro Oda, Daisuke Utsunomiya, Yasuyuki Yamashita
PurposeWe compared the efficacy of three-dimensional (3D) isotropic T2-weighted fast spin-echo imaging using a 3D hybrid profile order technique with a single-breath-hold (3D-Hybrid BH) with a two-dimensional (2D) T2-weighted fast spin-echo conventional respiratory-gated (2D-Conventional RG) technique for visualising small liver lesions.Materials and methodsThis study was approved by our institutional review board. The requirement to obtain written informed consent was waived. Fifty patients with small (≤15mm) hepatocellular carcinomas (HCC) (n=26), or benign cysts (n=24), had undergone hepatic MRI including both 2D-Conventional RG and 3D-Hybrid BH. We calculated the signal-to-noise ratio (SNR) and tumour-to-liver contrast (TLC). The diagnostic performance of the two protocols was analysed.ResultsThe image acquisition time was 89% shorter with the 3D-Hybrid BH than with 2D-Conventional RG. There was no significant difference in the SNR between the two protocols. The area under the curve (AUC) of the TLC was significantly higher on 3D-Hybrid BH than on 2D-Conventional RG.ConclusionThe 3D-Hybrid BH sequence significantly improved diagnostic performance for small liver lesions with a shorter image acquisition time without sacrificing accuracy.



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Accuracy of Multiparametric MR Imaging with PI-RADS V2 Assessment in Detecting Infiltration of the Neurovascular Bundles prior to Prostatectomy

Publication date: Available online 27 November 2017
Source:European Journal of Radiology
Author(s): Markus Sauer, Julius M Weinrich, Christoph Fraune, Georg Salomon, Pierre Tennstedt, Gerhard Adam, Dirk Beyersdorff
OBJECTIVESTo evaluate the accuracy of assessment of neurovascular bundle (NVB) infiltration using multiparametric magnetic resonance imaging (mpMRI) and PI-RADS V2 prior to prostatectomy.METHODSThe ethics committee approved this retrospective study with waiver of informed consent. N=198 consecutive patients with biopsy proved cancer underwent standardized mpMRI at 3T prior to surgery. NVB infiltration was assessed for each side (a total of 396). Maximum PI-RADS V2 scores were determined for the posterolateral areas adjacent to the NVBs. Imaging results were correlated with postoperative pathology and standard descriptive statistics were calculated.RESULTSOverall T-staging sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of mpMRI were 64.4%, 89.2%, 82.4%, 76.2 % and 78.3%, respectively. In 396 cases NVB infiltration was predicted with 75.3 %, 94.0%, 80.2 %, 92.1 % and 89.4 % sensitivity, specificity, PPV, NPV and accuracy, respectively. Analyses of 396 NVB and their adjacent PI-RADS-V2 scores with pathology revealed significantly more NVB-infiltrations in suspect scores of 5 and 4 vs. uncertain scores of 3 to 1 (81/264 vs. 16/132, p=0.0001). Considering scores higher than 3 as a criterion of infiltration demonstrated moderate sensitivity and poor specificity (83.5% and 38.8%, respectively). Interobserver agreement of a second reading of a random sample was good (κ=0.64) for NVB infiltrations and moderate (κ=0.59) for PI-RADS V2.CONCLUSIONSAssessment of infiltration of the neurovascular bundles using mpMRI has valuable diagnostic performance, yet PI-RADS V2 Scores demonstrate limited eligibility. Combined findings offer crucial information for the planning of prostatectomy.



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Preoperative assessment of pleural adhesion by Four-Dimensional Ultra-Low-Dose Computed Tomography (4D-ULDCT) with Adaptive Iterative Dose Reduction using Three-Dimensional Processing (AIDR-3D)

Publication date: Available online 21 November 2017
Source:European Journal of Radiology
Author(s): Masayuki Hashimoto, Yukihiro Nagatani, Yasuhiko Oshio, Norihisa Nitta, Tsuneo Yamashiro, Shinsuke Tsukagoshi, Noritoshi Ushio, Masayuki Mayumi, Tatsuya Kimoto, Tomoyuki Igarashi, Makoto Yoshigoe, Kyohei Iwai, Koki Tanaka, Shigetaka Sato, Akinaga Sonoda, Hideji Otani, Kiyoshi Murata, Jun Hanaoka
PurposeTo assess the feasibility of Four-Dimensional Ultra-Low-Dose Computed Tomography (4D-ULDCT) for distinguishing pleural aspects with localized pleural adhesion (LPA) from those without.MethodsTwenty-seven patients underwent 4D-ULDCT during a single respiration with a 16cm-coverage of the body axis. The presence and severity of LPA was confirmed by their intraoperative thoracoscopic findings. A point on the pleura and a corresponding point on the outer edge of the costal bone were placed in identical axial planes at end-inspiration. The distance of the two points (PCD), traced by automatic tracking functions respectively, was calculated at each respiratory phase. The maximal and average change amounts in PCD (PCDMCA and PCDACA) were compared among 110 measurement points (MPs) without LPA, 16MPs with mild LPA and 10MPs with severe LPA in upper lung field cranial to the bronchial bifurcation (ULF), and 150MPs without LPA, 17MPs with mild LPA and 9MPs with severe LPA in lower lung field caudal to the bronchial bifurcation (LLF) using the Mann-Whitney U test.RESULTSIn the LLF, PCDACA as well as PCDMCA demonstrated a significant difference among non-LPA, mild LPA and severe LPA (18.1±9.2, 12.3±6.2 and 5.0±3.3mm) (p<0.05). Also in the ULF, PCDACA showed a significant difference among three conditions (9.2±5.5, 5.7±2.8 and 2.2±0.4mm, respectively) (p<0.05), whereas PCDMCA for mild LPA was similar to that for non-LPA (12.3±5.9 and 17.5±11.0mm).ConclusionsFour D-ULDCT could be a useful non-invasive preoperative assessment modality for the detection of the presence or severity of LPA.



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Qualitative and semi-quantitative assessment of temporomandibular joint MRI protocols for juvenile idiopathic arthritis at 1.5 and 3.0T

Publication date: January 2018
Source:European Journal of Radiology, Volume 98
Author(s): Emilio J. Inarejos Clemente, Mirkamal Tolend, Thitiporn Junhasavasdikul, Jennifer Stimec, Nikolay Tzaribachev, Bernd Koos, Lynn Spiegel, Rahim Moineddin, Andrea S. Doria
ObjectiveTemporomandibular joints (TMJs) frequently develop silent inflammatory and osteochondral changes in children with juvenile idiopathic arthritis. Data-driven recommendations for TMJ imaging protocol are needed to reduce measurement error and scanning time. This study compares the impact of different protocols, imaging coils, and magnet strength on the reliability of image assessment and the subjective quality of images.Materials and methodsThree groups of bilateral TMJ MR studies were retrospectively collected from two institutions, including 24 1.5T and 19 3.0T studies using dedicated TMJ surface coils, and 23 1.5T studies with head coil. Post-contrast sequences were re-compiled from the full protocol to create minimum protocol studies for the three groups. Two radiologists and two non-radiologists first scored the three minimum protocol images according to pre-specified definitions, then scored the full protocol images. Minimum-to-full protocol agreement, inter-reader agreement, and subjective item visibility scores were assessed.ResultsWith dedicated TMJ dual surface coils, minimum-vs-full protocol agreement was moderate to good (0.5–0.8 intraclass correlation coefficients or kappa) for most items, and was not influenced by the magnet strength. Inter-reader reliability was more significantly influenced by the imaging coil and reader's training background than by protocol length or magnet strength differences. Sagittal and coronal planes weighted on PD, T2 Fat Suppressed and T1 Fat Suppressed -postcontrast adequately visualized all the different features, whereas the axial plane was more limited to visualizing synovium.ConclusionInter-reader reliability and qualitative measure of image quality improved more consistently with the coil offering the higher resolution, rather than increased magnet strength.



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Serial magnetic resonance imaging evaluations of irradiated superior cervical sympathetic ganglia: Not every retropharyngeal enlarging mass is a sign of malignancy

Publication date: January 2018
Source:European Journal of Radiology, Volume 98
Author(s): Se Jin Cho, Jeong Hyun Lee, Ji Eun Park, Young Jun Choi, Jin Hee Kim, Hwa Jung Kim, Jung Hwan Baek
IntroductionTo describe serial changes in irradiated superior cervical sympathetic ganglia (SCSGs) on MRI (magnetic resonance imaging) evaluation in patients with head and neck squamous cell carcinoma (HNSCC) and to find the features differentiating them from the metastatic retropharyngeal lymph nodes.Materials and methodsThis retrospective study evaluated 52 consecutive patients with definitive radiotherapy with/without chemotherapy for pathologically confirmed HNSCC and pre- and postradiation MRI follow-up evaluations. MR images of SCSGs were analyzed including enhancement pattern, margin, and the presence of intraganglionic hypointensity.ResultsMRI evaluations were performed in 36 men and 16 women with HNSCC with an average age of 58 years, range 23–80 years before irradiation (n=52), and at 6 (n=21) and 13–18 (n=52)months follow-up. Mean total radiation dose was 6351±483 cGy (range, 5640–7000 cGy). Intraganglionic hypointensity, homogeneous enhancement pattern, and well-defined margins were observed in 96%, 97%, and 97% of ganglia on the last follow-up, which showed no difference between pretreatment and 6-month follow-up (P>0.05). Mixed linear model analysis revealed significant increases in diameter and normalized T2SI of SCSGs after irradiation (P< 0.05).ConclusionsDespite of the increase in diameter and normalized T2SI of SCSGs, preservation of intraganglionic hypointensity, well-defined margins and homogeneous enhancement might be helpful for radiologists to identify SCSGs during the follow-up of HNSCC patients.



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MRI features and score for differentiating borderline from malignant epithelial ovarian tumors

Publication date: January 2018
Source:European Journal of Radiology, Volume 98
Author(s): Yong Ai Li, Jin Wei Qiang, Feng Hua Ma, Hai Ming Li, Shu Hui Zhao
PurposeTo identify the MRI features of borderline epithelial ovarian tumors (BEOTs) and to differentiate BEOTs from malignant epithelial ovarian tumors (MEOTs).Materials and methodsThe clinical and MRI data of 89 patients with a BEOT and 109 patients with a MEOT proven by surgery and histopathology were retrospectively reviewed. MRI features, including bilaterality, size, shape, margin, cystic-solid interface, configuration, papillae or nodules, signal intensity, enhancement, presence of an ipsilateral ovary, peritoneal implants and ascites were analyzed and compared. Based on the odds ratio (OR) values, the significant risk features for BEOTs were scored as 3 (OR≈∞), 2 (5≤OR<∞) or 1 (OR<5).ResultsThere were 89 BEOT patients with 113 tumors [mean size of (13±6.7)cm], with bilateral ovary involvement in 24 cases. There were 109 MEOT patients with 142 tumors [(9.3±4.2)cm] with bilateral ovary involvement in 33 cases. There were eight significant risk factors for BEOTs, including round or oval shape (OR=2.714), well-defined margins (OR=3.318), clear cystic-solid interfaces (OR=5.593), purely cystic (OR=15.206), predominantly cystic with papillae or nodules (OR=2.579), exophytic papillae or nodules (OR=5.351), branching papilla (OR≈∞) and the presence of an ipsilateral ovary (OR≈∞). Based on the scoring of the eight risk factors, a cut-off score of 3.5 yielded a differential sensitivity, specificity, and accuracy of 82%, 85% and 84%, respectively.ConclusionIn contrast to MEOTs, BEOTs frequently had the following features on MRI: round or oval, with well-defined margins and clear cystic-solid interfaces, purely cystic or predominantly cystic with papillae or nodules, branching or exophytic papillae, with the presence of an ipsilateral ovary. MRI can reveal the distinct morphological features of BEOTs and MEOTs and facilitate their discrimination.



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The impact of axillary ultrasound with biopsy in overtreatment of early breast cancer

Publication date: January 2018
Source:European Journal of Radiology, Volume 98
Author(s): Javier del Riego, María Jesús Diaz-Ruiz, Milagros Teixidó, Judit Ribé, Mariona Vilagran, Lydia Canales, Melcior Sentís
Purpose(a) To compare the axillary tumor burden detected by fine-needle aspiration cytology (FNAC) versus sentinel lymph node biopsy (SLNB). (b) To evaluate the relationship between axillary tumor burden and the number of suspicious lymph nodes detected by axillary ultrasonography (US). (c) To calculate the false-positive and false-negative rates for FNAC in patients fulfilling ACOSOG Z0011 criteria.MethodsRetrospective multicenter cross-sectional study of 355 pT1 breast cancers. SLNB and axillary lymph node dissection (ALND) were gold standards. Low axillary burden (≤2 positive lymph nodes); high burden (>2 positive lymph nodes). Patients ACOSOG Z0011: false-positive (positive FNAC+low burden), false-negative (negative FNAC+high burden).ResultsHigh axillary burden: in entire series 38.5% FNAC+ vs. 5.7% SLNB+ (p<0.0001). In subgroup fulfilling ACOSOG Z0011 criteria: 45.5% vs 6.7%, respectively (p<0.001).61 positive axillary US. With 1 suspicious node on axillary US: 95.6% had ≤2 involved nodes (including pN0); with 2 suspicious nodes: 60% had >2 involved nodes. In ACOSOG Z0011 patients, with 1 suspicious node, 93.7% had ≤2 involved nodes. Of the 37 FNAC in ACOSOG Z0011patients: 54.5% false-positives for high burden; 3.8% false-negatives.ConclusionsFNAC-positive tumors have greater axillary burden, even in patients fulfilling ACOSOG Z0011 criteria. Using axillary US/FNAC to triage patients meeting Z0011 criteria may result in axillary overtreatment. The number of suspicious nodes seen in axillary US is related with the final axillary burden and should be taken into account when deciding to do FNAC in patients fulfilling ACOSOG Z0011 criteria.



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Clinical application of Half Fourier Acquisition Single Shot Turbo Spin Echo (HASTE) imaging accelerated by simultaneous multi-slice acquisition

Publication date: Available online 2 December 2017
Source:European Journal of Radiology
Author(s): Jenni Schulz, Jose P. Marques, Annemieke ter Telgte, Anouk van Dorst, Frank-Erik de Leeuw, Frederick J.A. Meijer, David G. Norris
PurposeAs a single-shot sequence with a long train of refocusing pulses, Half-Fourier Acquisition Single-Shot Turbo-Spin-Echo (HASTE) suffers from high power deposition limiting use at high resolutions and high field strengths, particularly if combined with acceleration techniques such as simultaneous multi-slice (SMS) imaging. Using a combination of multiband (MB)-excitation and PINS-refocusing pulses will effectively accelerate the acquisition time while staying within the SAR limitations. In particular, uncooperative and young patients will profit from the speed of the MB-PINS HASTE sequence, as clinical diagnosis can be possible without sedation.Materials and methodsMB-excitation and PINS-refocusing pulses were incorporated into a HASTE-sequence with blipped CAIPIRINHA and TRAPS including an internal FLASH reference scan for online reconstruction. Whole brain MB-PINS HASTE data were acquired on a Siemens 3T-Prisma system from 10 individuals and compared to a clinical HASTE protocol.ResultsThe proposed MB-PINS HASTE protocol accelerates the acquisition by about a factor 2 compared to the clinical HASTE. The diagnostic image quality proved to be comparable for both sequences for the evaluation of the overall aspect of the brain, the detection of white matter changes and areas of tissue loss, and for the evaluation of the CSF spaces although artifacts were more frequently encountered with MB-PINS HASTE.ConclusionsMB-PINS HASTE enables acquisition of slice accelerated highly T2-weighted images and provides good diagnostic image quality while reducing acquisition time.



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Do Modic Changes, Disc Degeneration, Translation and Angular Motion Affect Facet Osteoarthritis of the Lumbar Spine

Publication date: Available online 2 December 2017
Source:European Journal of Radiology
Author(s): Permsak Paholpak, Emin Dedeogulllari, Christopher Lee, Koji Tamai, Kaku Barkoh, Kittipong Sessumpun, Jeffrey C. Wang, Zorica Buser
The objective of the study is to identified the correlation between Modic changes (MCs), disc degeneration, motions (translation and angulation) and facet osteoarthritis in lumbar spine. 425 patients who underwent multi-positional lumbar MRI were reviewed. A total of 2,250 lumbar spinal segments in neutral position were evaluated for MCs, disc degeneration grading, translation and angulation motion, and facet osteoarthritis. The chi-square test, Kruskal-Wallis, Mann-Whitney U test, Pearson's correlation and linear regression were used to test for statistically significant difference between parameters. MCs type 2 showed the most translational motion. The presence of MCs was significantly correlated with advanced disc degeneration (grade 4–5, Odds ratio 6.29, 95% CI 4.48–8.83) and the presence of facet osteoarthritis (Odds ratio 9.50, 95% CI 6.18–14.62). The presence of facet osteoarthritis had significantly more translation motion than non-osteoarthritis facet (p=0.04). The facet osteoarthritis grade was positively correlated with disc degeneration grade (r=0.309, p-value <0.001). Conclusion, the facet osteoarthritis correlated with the presence of MCs and more translation motion. The severity of facet osteoarthritis was correlated with the advanced disc degeneration. The MCs, translation motion, and disc degeneration were the significant parameters which affected lumbar facet osteoarthritis.



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Clinical-radiological Scoring System for Enhanced Diagnosis of Acute Appendicitis

Publication date: Available online 28 November 2017
Source:European Journal of Radiology
Author(s): Manoj Mannil, Christos Polysopoulos, Dominik Weishaupt, Anika Hansmann
IntroductionAcute appendicitis is the most common surgical condition in industrialized countries. However, diagnosis in borderline cases is often cumbersome and requires follow-up examinations, and/or a Computed Tomography examination. Therefore, our aim was to develop a combined clinical and sonographic score to enhance prediction of acute appendicitis.Patients and MethodsThe modified Alvarado score and various established sonographic criteria were investigated in 132 patients with suspected acute appendicitis. Two models were computed accounting for missing values. After analysis of sensitivity and specificity for the modified Alvarado score, logistic regression analysis was performed to identify significantly contributing sonographic features.ResultsThe threshold of the logistic regression analysis of the two models resulted in the formula: modified Alvarado score+axial Appendix diameter [mm]. When the Appendix diameter is >8mm, 1 point/mm is added, while for a diameter <8mm, 1 point/mm is subtracted. The cut-off value is ≥13 for acute appendicitis with a sensitivity 91.4% and a specificity of 100%, compared to a sensitivity of 90% and a specificity of 84.4% for the modified Alvarado score in our cohort.ConclusionThe established modified Alvarado score for diagnosis of acute Appendicitis can be improved by adding the axial diameter of the Appendix in a sonographic examination.



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Image quality and radiation dose of low-tube-voltage CT with reduced contrast media for right adrenal vein imaging

Publication date: Available online 26 November 2017
Source:European Journal of Radiology
Author(s): Yuki Takahashi, Hideki Ota, Kensuke Omura, Yutaka Dendo, Katharina Otani, Tomonori Matsuura, Masahiro Kitami, Kazumasa Seiji, Yuta Tezuka, Masahiro Nezu, Yoshikiyo Ono, Ryo Morimoto, Fumitoshi Satoh, Kei Takase
ObjectivesTo compare image quality and radiation dose of right adrenal vein (RAV) imaging computed tomography (CT) among conventional, low kV, and low kV with reduced contrast medium protocols.MethodsOne-hundred-and-twenty patients undergoing adrenal CT were randomly assigned to one of three protocols: contrast dose of 600mgI/kg at 120-kV tube voltage setting (600-120 group), 600mgI/kg at 80kV (600-80 group), and 360mgI/kg at 80kV (360-80 group). Iterative reconstruction was used for 80-kV groups. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the RAV and size-specific dose estimates (SSDE) were measured. Three radiologists evaluated 4-point visualisation scores of RAV by consensus reading.ResultsThe RAV detectability was 95%, 97.2%, and 97.3% for 600-120, 600-80, and 360-80 groups, respectively (p=1.000). Visualisation scores were not significantly different among the groups (p=0.152). There were no significant differences in CNR or SNR between the 600-120 and 360-80 groups. SSDE of the 360-80 group was significantly lower than that of the 600-120 group (5.86mGy±1.44 vs. 7.27mGy±1.81, p<0.001).Conclusions80-kV scans with 360 mgI/kg contrast media showed comparable detectability of RAV to conventional scans, while reducing 19% of SSDE.



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Seminal vesicle invasion on multi-parametric magnetic resonance imaging: correlation with histopathology

Publication date: Available online 21 November 2017
Source:European Journal of Radiology
Author(s): Nikolaos Grivas, Karel Hinnen, Jeroen de Jong, Wilma Heemsbergen, Luc Moonen, Thelma Witteveen, Henk van der Poel, Stijn Heijmink
ObjectivesThe pre-treatment risk of seminal vesicle (SV) invasion (SVI) from prostate cancer is currently based on nomograms which include clinical stage (cT), Gleason score (GS) and prostate-specific antigen (PSA). The aim of our study was to evaluate the staging accuracy of 3tesla (3T) multi-parametric (mp) Magnetic Resonance Imaging (MRI) by comparing the imaging report of SVI with the tissue histopathology. The additional value in the existing prediction models and the role of radiologists' experience were also examined.MethodsAfter obtaining institutional review board approval, we retrospectively reviewed clinico-pathological data from 527 patients who underwent a robot-assisted radical prostatectomy (RARP) between January 2012 and March 2015. Preoperative prostate imaging with an endorectal 3T-mp-MRI was performed in all patients. Sequences consisted of an axial pre-contrast T1 sequence, three orthogonally-oriented T2 sequences, axial diffusion weighted and dynamic contrast-enhanced sequences. We considered SVI in case of low-signal intensity in the SV on T2-weighted sequences or apparent mass while diffusion-weighted and DCE sequences were used to confirm findings on T2. Whole-mount section pathology was performed in all patients. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI (index test) for the prediction of histological SVI (reference standard) were calculated. We developed logistic multivariable regression models including: clinical variables (PSA, cT, percentage of involved cores/total cores, primary GS 4–5) and Partin table estimates. MRI results (negative/positive exam) were then added in the models and the multivariate modeling was reassessed. In order to assess the extent of SVI and the reason for mismatch with pathology an MRI-review from an expert genitourinary radiologist was performed in a subgroup of 379 patients.ResultsA total of 54 patients (10%) were found to have SVI on RARP-histopathology. In the overall cohort sensitivity, specificity, PPV and NPV for SVI detection on MRI were 75.9%, 94.7%, 62% and 97% respectively. Based on our sub-analysis, the radiologist's expertise improved the accuracy demonstrating a sensitivity, specificity, PPV and NPV of 85.4%, 95.6%, 70.0% and 98.2%, respectively. In the multivariate analysis PSA (odds ratio [OR] 1.07, p=0.008), primary GS 4 or 5 (OR 3.671, p=0.007) and Partin estimates (OR 1.07, p=0.023) were significant predictors of SVI. When MRI results were added to the analysis, a highly significant prediction of SVI was observed (OR 45.9, p < 0.0001). Comparing Partin, MRI and Partin with MRI predictive models, the areas under the curve were 0.837, 0.884 and 0.929, respectively.ConclusionsMRI had high diagnostic accuracy for SVI on histopathology. It provided added diagnostic value to clinical/Partin based SVI-prediction models alone. A key factor is radiologist's experience, though no inter-observer variability could be examined due to the availability of a single expert radiologist.



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Imaging manifestations of Behcet’s disease: Key considerations and major features

Publication date: Available online 21 November 2017
Source:European Journal of Radiology
Author(s): Ghazaleh Mehdipoor, Fereydoun Davatchi, Hadi Ghoreishian, Abbas Arjmand Shabestari
Behcet's disease is an autoimmune disease most commonly seen in the Middle East. Although primarily known with painful oral and genital ulcers, it can lead to vasculitis. Therefore, several associated complications such as thrombotic syndromes, aneurysmal arterial disease may arise. In many cases, it might be difficult to make the diagnosis purely based on clinical grounds; however, imaging plays an important role for both diagnosis and assessment of the disease's complications. We provide a comprehensive review of the most notable imaging findings of Behcet's disease.



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Computed Tomography–Based Imaging of Voxel-Wise Lesion Water Uptake in Ischemic Brain: Relationship Between Density and Direct Volumetry

Objectives Net water uptake per volume of brain tissue may be calculated by computed tomography (CT) density, and this imaging biomarker has recently been investigated as a predictor of lesion age in acute stroke. However, the hypothesis that measurements of CT density may be used to quantify net water uptake per volume of infarct lesion has not been validated by direct volumetric measurements so far. The purpose of this study was to (1) develop a theoretical relationship between CT density reduction and net water uptake per volume of ischemic lesions and (2) confirm this relationship by quantitative in vitro and in vivo CT image analysis using direct volumetric measurements. Materials and Methods We developed a theoretical rationale for a linear relationship between net water uptake per volume of ischemic lesions and CT attenuation. The derived relationship between water uptake and CT density was tested in vitro in a set of increasingly diluted iodine solutions with successive CT measurements. Furthermore, the consistency of this relationship was evaluated using human in vivo CT images in a retrospective multicentric cohort. In 50 edematous infarct lesions, net water uptake was determined by direct measurement of the volumetric difference between the ischemic and normal hemisphere and was correlated with net water uptake calculated by ischemic density measurements. Results With regard to in vitro data, water uptake by density measurement was equivalent to direct volumetric measurement (r = 0.99, P

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Increased Delay Between Gadolinium Chelate Administration and T1-Weighted Magnetic Resonance Imaging Acquisition Increases Contrast-Enhancing Tumor Volumes and T1 Intensities in Brain Tumor Patients

Objectives The aim of this study was to evaluate the impact of delayed T1-weighted (T1-w) MRI acquisition after gadolinium chelate administration on brain tumor volumes and T1-w intensities. Materials and Methods Fifty-five patients with histologically confirmed, contrast-enhancing intra-axial brain tumors were analyzed in this prospective test-retest study. Patients underwent 2 consecutive 3 T MRI scans (separated by a 1-minute break) during routine follow-up with contrast-enhanced T1 (ceT1-w), T2, and FLAIR acquisition. Macrocyclic gadolinium chelate–based contrast agent was only administered before the first ceT1-w acquisition; median latency to ceT1-w acquisition was 6.72 minutes (IQR, 6.53–6.92) in the first and 16.27 minutes (IQR, 15.49–17.26) in the second scan. Changes in tumor volumes and relative ceT1-w intensities between the 2 acquisitions were quantitatively assessed following semiautomated tumor segmentation (separately for contrast-enhancement [CE], necrosis [NEC], and nonenhancing [NE] tumor). Results Semiautomatically segmented CE tumor volumes were significantly larger in the second acquisition (median +32% [1.2 cm3]; IQR, 16%–62%; P

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Potential of Noncontrast Magnetic Resonance Imaging With Diffusion-Weighted Imaging in Characterization of Breast Lesions: Intraindividual Comparison With Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Objectives The aim of this study was to assess the potential of noncontrast magnetic resonance imaging (NC-MRI) with diffusion-weighted imaging (DWI) in characterization of breast lesions in comparison to dynamic contrast-enhanced MRI (DCE-MRI) at 3 T. Materials and Methods Consecutive patients with conventional imaging (mammography, ultrasound) BI-RADS 4/5 findings were included in this institutional review board–approved single-center study. All underwent 3 T breast MRI including readout-segmented DWI, DCE, and T2-weighted sequences. Final diagnosis was defined by histopathology or follow-up (>24 months). Two experienced radiologists (R1, R2) independently assigned lesion conspicuity (0 = minimal to 3 = excellent) and BI-RADS scores to NC-MRI (readout-segmented DWI including apparent diffusion coefficient maps) and DCE-MRI (DCE and T2-weighted). Receiver operating characteristics, κ statistics, and visual grading characteristics analysis were applied. Results Sixty-seven malignant and 56 benign lesions were identified in 113 patients (mean age, 54 ± 14 years). Areas under the receiver operating characteristics curves were similar: DCE-MRI: 0.901 (R1), 0.905 (R2); NC-MRI: 0.882 (R1), 0.854 (R2); P > 0.05, respectively. The κ agreement was 0.968 (DCE-MRI) and 0.893 (NC-MRI). Visual grading characteristics analysis revealed superior lesion conspicuity by DCE-MRI (0.661, P

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Computed Tomography–Based Imaging of Voxel-Wise Lesion Water Uptake in Ischemic Brain: Relationship Between Density and Direct Volumetry

Objectives Net water uptake per volume of brain tissue may be calculated by computed tomography (CT) density, and this imaging biomarker has recently been investigated as a predictor of lesion age in acute stroke. However, the hypothesis that measurements of CT density may be used to quantify net water uptake per volume of infarct lesion has not been validated by direct volumetric measurements so far. The purpose of this study was to (1) develop a theoretical relationship between CT density reduction and net water uptake per volume of ischemic lesions and (2) confirm this relationship by quantitative in vitro and in vivo CT image analysis using direct volumetric measurements. Materials and Methods We developed a theoretical rationale for a linear relationship between net water uptake per volume of ischemic lesions and CT attenuation. The derived relationship between water uptake and CT density was tested in vitro in a set of increasingly diluted iodine solutions with successive CT measurements. Furthermore, the consistency of this relationship was evaluated using human in vivo CT images in a retrospective multicentric cohort. In 50 edematous infarct lesions, net water uptake was determined by direct measurement of the volumetric difference between the ischemic and normal hemisphere and was correlated with net water uptake calculated by ischemic density measurements. Results With regard to in vitro data, water uptake by density measurement was equivalent to direct volumetric measurement (r = 0.99, P

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Increased Delay Between Gadolinium Chelate Administration and T1-Weighted Magnetic Resonance Imaging Acquisition Increases Contrast-Enhancing Tumor Volumes and T1 Intensities in Brain Tumor Patients

Objectives The aim of this study was to evaluate the impact of delayed T1-weighted (T1-w) MRI acquisition after gadolinium chelate administration on brain tumor volumes and T1-w intensities. Materials and Methods Fifty-five patients with histologically confirmed, contrast-enhancing intra-axial brain tumors were analyzed in this prospective test-retest study. Patients underwent 2 consecutive 3 T MRI scans (separated by a 1-minute break) during routine follow-up with contrast-enhanced T1 (ceT1-w), T2, and FLAIR acquisition. Macrocyclic gadolinium chelate–based contrast agent was only administered before the first ceT1-w acquisition; median latency to ceT1-w acquisition was 6.72 minutes (IQR, 6.53–6.92) in the first and 16.27 minutes (IQR, 15.49–17.26) in the second scan. Changes in tumor volumes and relative ceT1-w intensities between the 2 acquisitions were quantitatively assessed following semiautomated tumor segmentation (separately for contrast-enhancement [CE], necrosis [NEC], and nonenhancing [NE] tumor). Results Semiautomatically segmented CE tumor volumes were significantly larger in the second acquisition (median +32% [1.2 cm3]; IQR, 16%–62%; P

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Potential of Noncontrast Magnetic Resonance Imaging With Diffusion-Weighted Imaging in Characterization of Breast Lesions: Intraindividual Comparison With Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Objectives The aim of this study was to assess the potential of noncontrast magnetic resonance imaging (NC-MRI) with diffusion-weighted imaging (DWI) in characterization of breast lesions in comparison to dynamic contrast-enhanced MRI (DCE-MRI) at 3 T. Materials and Methods Consecutive patients with conventional imaging (mammography, ultrasound) BI-RADS 4/5 findings were included in this institutional review board–approved single-center study. All underwent 3 T breast MRI including readout-segmented DWI, DCE, and T2-weighted sequences. Final diagnosis was defined by histopathology or follow-up (>24 months). Two experienced radiologists (R1, R2) independently assigned lesion conspicuity (0 = minimal to 3 = excellent) and BI-RADS scores to NC-MRI (readout-segmented DWI including apparent diffusion coefficient maps) and DCE-MRI (DCE and T2-weighted). Receiver operating characteristics, κ statistics, and visual grading characteristics analysis were applied. Results Sixty-seven malignant and 56 benign lesions were identified in 113 patients (mean age, 54 ± 14 years). Areas under the receiver operating characteristics curves were similar: DCE-MRI: 0.901 (R1), 0.905 (R2); NC-MRI: 0.882 (R1), 0.854 (R2); P > 0.05, respectively. The κ agreement was 0.968 (DCE-MRI) and 0.893 (NC-MRI). Visual grading characteristics analysis revealed superior lesion conspicuity by DCE-MRI (0.661, P

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Modeling and Analysis of Integrated Pest Control Strategies via Impulsive Differential Equations

The paper is concerned with the development and numerical analysis of mathematical models used to describe complex biological systems in the framework of Integrated Pest Management (IPM). Established in the late 1950s, IPM is a pest management paradigm that involves the combination of different pest control methods in ways that complement one another, so as to reduce excessive use of pesticides and minimize environmental impact. Since the introduction of the IPM concept, a rich set of mathematical models has emerged, and the present work discusses the development in this area in recent years. Furthermore, a comprehensive parametric study of an IPM-based impulsive control scheme is carried out via path-following techniques. The analysis addresses practical questions, such as how to determine the parameter values of the system yielding an optimal pest control, in terms of operation costs and environmental damage. The numerical study concludes with an exploration of the dynamical features of the impulsive model, which reveals the presence of codimension-1 bifurcations of limit cycles, hysteretic effects, and period-doubling cascades, which is a precursor to the onset of chaos.

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IJMS, Vol. 18, Pages 2604: Preparation of A Spaceflight: Apoptosis Search in Sutured Wound Healing Models

IJMS, Vol. 18, Pages 2604: Preparation of A Spaceflight: Apoptosis Search in Sutured Wound Healing Models

International Journal of Molecular Sciences doi: 10.3390/ijms18122604

Authors: Stefan Riwaldt Monica Monici Asbjørn Graver Petersen Uffe Birk Jensen Katja Evert Desiré Pantalone Kirsten Utpatel Matthias Evert Markus Wehland Marcus Krüger Sascha Kopp Sofie Frandsen Thomas Corydon Jayashree Sahana Johann Bauer Ronald Lützenberg Manfred Infanger Daniela Grimm

To prepare the ESA (European Space Agency) spaceflight project “Wound healing and Sutures in Unloading Conditions”, we studied mechanisms of apoptosis in wound healing models based on ex vivo skin tissue cultures, kept for 10 days alive in serum-free DMEM/F12 medium supplemented with bovine serum albumin, hydrocortisone, insulin, ascorbic acid and antibiotics at 32 °C. The overall goal is to test: (i) the viability of tissue specimens; (ii) the gene expression of activators and inhibitors of apoptosis and extracellular matrix components in wound and suture models; and (iii) to design analytical protocols for future tissue specimens after post-spaceflight download. Hematoxylin-Eosin and Elastica-van-Gieson staining showed a normal skin histology with no signs of necrosis in controls and showed a normal wound suture. TdT-mediated dUTP-biotin nick end labeling for detecting DNA fragmentation revealed no significant apoptosis. No activation of caspase-3 protein was detectable. FASL, FADD, CASP3, CASP8, CASP10, BAX, BCL2, CYC1, APAF1, LAMA3 and SPP1 mRNAs were not altered in epidermis and dermis samples with and without a wound compared to 0 day samples (specimens investigated directly post-surgery). BIRC5, CASP9, and FN1 mRNAs were downregulated in epidermis/dermis samples with and/or without a wound compared to 0 day samples. BIRC2, BIRC3 were upregulated in 10 day wound samples compared to 0 day samples in epidermis/dermis. RELA/FAS mRNAs were elevated in 10 day wound and no wound samples compared to 0 day samples in dermis. In conclusion, we demonstrate that it is possible to maintain live skin tissue cultures for 10 days. The viability analysis showed no significant signs of cell death in wound and suture models. The gene expression analysis demonstrated the interplay of activators and inhibitors of apoptosis and extracellular matrix components, thereby describing important features in ex vivo sutured wound healing models. Collectively, the performed methods defining analytical protocols proved to be applicable for post-flight analyzes of tissue specimens after sample return.



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Viruses, Vol. 9, Pages 370: Subcellular Trafficking of the Papillomavirus Genome during Initial Infection: The Remarkable Abilities of Minor Capsid Protein L2

Viruses, Vol. 9, Pages 370: Subcellular Trafficking of the Papillomavirus Genome during Initial Infection: The Remarkable Abilities of Minor Capsid Protein L2

Viruses doi: 10.3390/v9120370

Authors: Samuel Campos

Since 2012, our understanding of human papillomavirus (HPV) subcellular trafficking has undergone a drastic paradigm shift. Work from multiple laboratories has revealed that HPV has evolved a unique means to deliver its viral genome (vDNA) to the cell nucleus, relying on myriad host cell proteins and processes. The major breakthrough finding from these recent endeavors has been the realization of L2-dependent utilization of cellular sorting factors for the retrograde transport of vDNA away from degradative endo/lysosomal compartments to the Golgi, prior to mitosis-dependent nuclear accumulation of L2/vDNA. An overview of current models of HPV entry, subcellular trafficking, and the role of L2 during initial infection is provided below, highlighting unresolved questions and gaps in knowledge.



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Testosterone: Relationships with Metabolic Disorders in Men—An Observational Study from SPECT-China

Background. The strength of associations between total testosterone (TT) and metabolic parameters may vary in different nature of population structure; however, no study has ever given this information in Chinese population, especially those without metabolic syndrome (MS). We aimed to analyze the association magnitudes between TT and multiple metabolic parameters in general Chinese men. Methods. 4309 men were recruited from SPECT-China study in 2014-2015, which was performed in 22 sites in East China. TT, weight status, and various metabolic parameters were measured. Linear and logistic regressions were used to analyze the associations. Results. Men in lower TT quartiles had worse metabolic parameters including body mass index, triglycerides, HbA1c, and HOMA-IR (all for trend

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Improving EEG-Based Motor Imagery Classification for Real-Time Applications Using the QSA Method

We present an improvement to the quaternion-based signal analysis (QSA) technique to extract electroencephalography (EEG) signal features with a view to developing real-time applications, particularly in motor imagery (IM) cognitive processes. The proposed methodology (iQSA, improved QSA) extracts features such as the average, variance, homogeneity, and contrast of EEG signals related to motor imagery in a more efficient manner (i.e., by reducing the number of samples needed to classify the signal and improving the classification percentage) compared to the original QSA technique. Specifically, we can sample the signal in variable time periods (from 0.5 s to 3 s, in half-a-second intervals) to determine the relationship between the number of samples and their effectiveness in classifying signals. In addition, to strengthen the classification process a number of boosting-technique-based decision trees were implemented. The results show an 82.30% accuracy rate for 0.5 s samples and 73.16% for 3 s samples. This is a significant improvement compared to the original QSA technique that offered results from 33.31% to 40.82% without sampling window and from 33.44% to 41.07% with sampling window, respectively. We can thus conclude that iQSA is better suited to develop real-time applications.

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An Aggressive Form of Langerhan Cell Histiocytosis in an Adult: Therapeutic Challenges

Langerhans cell histiocytosis (LCH) is rare in adults. Regular follow-up is mandatory due to reoccurrence. A 35-year-old male with an incidental left iliac bone lesion was diagnosed with LCH. He later became symptomatic with hip pain and spread of the disease. Despite excision of the symptomatic iliac lesion, he had progression while on cytarabine and nivolumab, evidenced by increased bone pain and involvement of other bones on imaging. He underwent excision of the jaw lesion followed by vinblastine; he was pain free and had stable disease on PET imaging after 3 months. LCH is an uncommon neoplasia. Treatment is reserved for symptomatic patients while asymptomatic patients are observed. Follow-up is imperative due to the risk of reoccurrence. Despite surgical treatment together with one of the front-line agents for refractory disease, in this case cytarabine, he still had progression of the disease. Furthermore, the trial of nivolumab was of no benefit. This case highlights good response to vinblastine which is previously reported to have good success. No trials are published, and the optimal strategy has yet to be defined. LCH with multiple bony involvement can be aggressive and therapeutically challenging.

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Pathogens, Vol. 6, Pages 64: Longitudinal Surveillance of Porcine Rotavirus B Strains from the United States and Canada and In Silico Identification of Antigenically Important Sites

Pathogens, Vol. 6, Pages 64: Longitudinal Surveillance of Porcine Rotavirus B Strains from the United States and Canada and In Silico Identification of Antigenically Important Sites

Pathogens doi: 10.3390/pathogens6040064

Authors: Frances K. Shepherd Fangzhou Chen Marie R. Culhane Michael P. Murtaugh Douglas G. Marthaler

Rotavirus B (RVB) is an important swine pathogen, but control and prevention strategies are limited without an available vaccine. To develop a subunit RVB vaccine with maximal effect, we characterized the amino acid sequence variability and predicted antigenicity of RVB viral protein 7 (VP7), a major neutralizing antibody target, from clinically infected pigs in the United States and Canada. We identified genotype-specific antigenic sites that may be antibody neutralization targets. While some antigenic sites had high amino acid functional group diversity, nine antigenic sites were completely conserved. Analysis of nucleotide substitution rates at amino acid sites (dN/dS) suggested that negative selection appeared to be playing a larger role in the evolution of the identified antigenic sites when compared to positive selection, and was identified in six of the nine conserved antigenic sites. These results identified important characteristics of RVB VP7 variability and evolution and suggest antigenic residues on RVB VP7 that are negatively selected and highly conserved may be good candidate regions to include in a subunit vaccine design due to their tendency to remain stable.



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An Uncommon Case of Bilateral Breast Enlargement Diagnosed as Tumoral Pseudoangiomatous Stromal Hyperplasia: Imaging and Pathological Findings

The incidence of reported pseudoangiomatous stromal hyperplasia (PASH), as well as the variability and severity of clinical presentations, is increasing in the literature. In parallel, several authors posit the need for an improved classification of PASH to avoid possible variables associated with this diagnosis. Here, we present a 25-year-old woman with PASH accompanied by severe bilateral and symmetrical breasts enlargement, highlighting an uncommon clinical presentation of PASH as much as the careful interdisciplinary review and correlation of histology and all available imaging studies to confirm the definitive diagnosis.

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Complex Segregation Analysis Provides Evidence for Autosomal Dominant Transmission in the Chinese Han Families with Ankylosing Spondylitis

Introduction. Familial aggregation of ankylosing spondylitis (AS) has been frequently noticed. However, the mode of inheritance in AS remains poorly understood. Our aim was to determine the mode of inheritance best fitting the observed transmission pattern of AS families. Methods. Families with 5 or more AS patients diagnosed with 1984 modified New York criteria were recruited. We performed complex segregation analysis for a binary trait in regressive multivariate logistic models. The inheritance models, including sporadic, major gene, environmental, general, and other 9 models, were compared by likelihood ratio tests and Akaike’s Information Criterion. Results. This research included 9 Chinese Han AS families with a total number of 315 persons, including 74 patients. First, familial association was determined. Sporadic with familial association model was rejected when compared with either the general model or the homogeneous general model (). The environmental model was also rejected when compared with general models (). Mendelian dominate mode fitted best in 5 AS families, while Tau AB free model best explained the mode of inheritance in these AS families. Conclusion. This study provided evidence in support of Mendelian dominant mode and firstly discovered a non-Mendelian mode called tau AB free inheritance mode in AS.

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Using Novel Technology within a School-Based Setting to Increase Physical Activity: A Pilot Study in School-Age Children from a Low-Income, Urban Community

Background. Less than half of American children meet national physical activity (PA) recommendations. This study tested the feasibility, acceptability, and preliminary effectiveness of using wearable PA monitors to increase PA in school-age children. Methods. In Phase 1 of this study, conducted in 2014, 32 fifth-grade students enrolled in a low-resource middle school were given a waist-worn Fitbit Zip monitor for 4 weeks to test its feasibility (adherence) and acceptability. Adherence, wear time of ≥8 hours per day, was examined. Feedback was solicited from parents through structured interviews. In Phase 2, conducted in 2015, 42 sixth-grade students were assigned, by classroom, to one of three conditions (Fitbit + goal and incentive-based intervention, Fitbit only, or control) to test the feasibility of the wrist-worn Fitbit Charge and its preliminary effectiveness in increasing PA over 6 weeks. Results. In Phase 1, average adherence was 64.1%. In Phase 2, it was 73.4% and 80.2% for participants in the Fitbit + intervention and Fitbit only groups, respectively (). After controlling for baseline values, weight status, and sex, there were no significant group differences in changes in MVPA or steps from baseline to follow-up. Conclusions. While moderately acceptable, wearable PA monitors did not increase PA levels in this sample. They may be more effective within a coordinated school-based physical activity program.

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Fault Detection of High-Speed Train Wheelset Bearing Based on Impulse-Envelope Manifold

A novel fault detection method employing the impulse-envelope manifold is proposed in this paper which is based on the combination of convolution sparse representation (CSR) and Hilbert transform manifold learning. The impulses with different sparse characteristics are extracted by the CSR with different penalty parameters. The impulse-envelope space is constructed through Hilbert transform on the extracted impulses. The manifold based on impulse-envelope space (impulse-envelope manifold) is executed to learn the low-dimensionality intrinsic envelope of vibration signals for fault detection. The analyzed results based on simulations, experimental tests, and practical applications show that the impulse-envelope manifold with both isometric mapping (Isomap) and locally linear coordination (LLC) can be successfully used to extract the intrinsic envelope of the impulses where local tangent space analysis (LTSA) fails to perform and the impulse-envelope manifold with Isomap outperforms those with LLC in terms of strengthening envelopes and the number of extracted harmonics. The proposed impulse-envelope manifold with Isomap is superior in extracting the intrinsic envelope, strengthening the amplitude of intrinsic envelope spectra, and enlarging the harmonic number of fault-characteristic frequency. The proposed technique is highly suitable for extracting intrinsic envelopes for bearing fault detection.

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Surgical Management of Pilocytic Astrocytoma of the Optic Nerve: A Case Report and Review of the Literature

Optic nerve astrocytomas (ONAs) are frequent types of optic nerve gliomas (ONGs), which can affect the visual pathway. An 18-year-old male patient was admitted to our department with right-sided intraorbital/retrobulbar swelling, which progressively grew over several months. Clinical examination showed right-sided diplopia, mydriasis, low visual acuity (0.4), exophthalmus (3 cm), epiphora, and severe retrobulbar pain. There was a family history of high-grade (IV) astrocytomas in which two of the family members died due to the disease. Preoperative MRI scan revealed a soft tissue mass around the retrobulbar area of the right eye with intact orbital bony walls. Surgery was performed whereby it was dissected freely from the muscles and was separated from the optic nerve and the globe. Histopathologic analysis confirmed a benign astrocytoma. The follow-up examination revealed no recurrent or residual tumor. A systemic review of the literature indicates that early diagnosis and experienced multidisciplinary management are required in case of unilateral, resectable forms of ONAs with no distant metastasis, in order to provide a long-time survival of patients. Surgical intervention of unilateral ONAs is a relatively safe procedure, allowing complete or partial tumor removal with minimal morbidity and low recurrence rate.

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A New Robust Classifier on Noise Domains: Bagging of Credal C4.5 Trees

The knowledge extraction from data with noise or outliers is a complex problem in the data mining area. Normally, it is not easy to eliminate those problematic instances. To obtain information from this type of data, robust classifiers are the best option to use. One of them is the application of bagging scheme on weak single classifiers. The Credal C4.5 (CC4.5) model is a new classification tree procedure based on the classical C4.5 algorithm and imprecise probabilities. It represents a type of the so-called credal trees. It has been proven that CC4.5 is more robust to noise than C4.5 method and even than other previous credal tree models. In this paper, the performance of the CC4.5 model in bagging schemes on noisy domains is shown. An experimental study on data sets with added noise is carried out in order to compare results where bagging schemes are applied on credal trees and C4.5 procedure. As a benchmark point, the known Random Forest (RF) classification method is also used. It will be shown that the bagging ensemble using pruned credal trees outperforms the successful bagging C4.5 and RF when data sets with medium-to-high noise level are classified.

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Numerical Analysis of Fractional Order Epidemic Model of Childhood Diseases

The fractional order Susceptible-Infected-Recovered (SIR) epidemic model of childhood disease is considered. Laplace–Adomian Decomposition Method is used to compute an approximate solution of the system of nonlinear fractional differential equations. We obtain the solutions of fractional differential equations in the form of infinite series. The series solution of the proposed model converges rapidly to its exact value. The obtained results are compared with the classical case.

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Dispersed Two-Phase Flow Modelling for Nuclear Safety in the NEPTUNE_CFD Code

The objective of this paper is to give an overview of the capabilities of Eulerian bifluid approach to meet the needs of studies for nuclear safety regarding hydrogen risk, boiling crisis, and pipes and valves maintenance. The Eulerian bifluid approach has been implemented in a CFD code named NEPTUNE_CFD. NEPTUNE_CFD is a three-dimensional multifluid code developed especially for nuclear reactor applications by EDF, CEA, AREVA, and IRSN. The first set of models is dedicated to wall vapor condensation and spray modelling. Moreover, boiling crisis remains a major limiting phenomenon for the analysis of operation and safety of both nuclear reactors and conventional thermal power systems. The paper aims at presenting the generalization of the previous DNB model and its validation against 1500 validation cases. The modelling and the numerical simulation of cavitation phenomena are of relevant interest in many industrial applications, especially regarding pipes and valves maintenance where cavitating flows are responsible for harmful acoustics effects. In the last section, models are validated against experimental data of pressure profiles and void fraction visualisations obtained downstream of an orifice with the EPOCA facility (EDF R&D). Finally, a multifield approach is presented as an efficient tool to run all models together.

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MicroRNA-374b reduces the proliferation and invasion of colon cancer cells by regulation of LRH-1/Wnt signaling

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Rongfeng Qu, Shuhong Hao, Xianmei Jin, Guang Shi, Qiong Yu, Xianshuang Tong, Dongrui Guo
Deregulation of microRNA (miRNA) has been suggested as a critical event in colon cancer development and progression. Recent studies have suggested that miR-374b is a novel cancer-related miRNA involved in several cancer types. Thus far, very little is known about the role of miR-374b in colon cancer; therefore, the goal of this study was to investigate the potential role of miR-374b in colon cancer. Here, we showed that miR-374b expression was significantly downregulated in colon cancer tissues and cell lines. Overexpression of miR-374b inhibited the proliferation and invasion of colon cancer cells, while miR-374b suppression promoted colon cancer cell proliferation and invasion. Liver receptor homolog-1 (LRH-1) was identified as a target of miR-374b in colon cancer cells. Both the mRNA and protein expression of LRH-1 were regulated by miR-374b. In addition, an inverse correlation between LRH-1 mRNA and miR-374b expression was evidenced in colon cancer specimens. Notably, overexpression of miR-374b also downregulated the Wnt signaling in colon cancer cells. Furthermore, restoration of LRH-1 expression significantly abolished the antitumor effect of miR-374b in colon cancer cells. These findings suggest that miR-374b inhibits colon cancer cell proliferation and invasion through downregulation of LRH-1 expression. Inhibiting LRH-1 by miR-374b may represent a novel therapeutic strategy for the treatment of colon cancer.



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Adiponectin gene variants and decreased adiponectin plasma levels are associated with the risk of myocardial infarction in young age

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Michał Ambroziak, Monika Kolanowska, Zbigniew Bartoszewicz, Andrzej Budaj
The aim of the study was to investigate the role of adiponectin and 5 variants of its gene in the risk of premature myocardial infarction (MI).The studied group (MI<50) consisted of 158 young patients (125 men) aged <50 with MI. The control groups consisted of 155 healthy people (97 men), aged <50 and 202 patients (130 men) aged ≥50 with MI (MI≥50).There were statistically significant differences between MI<50 patients and healthy control group in the prevalence of rs17300539:G>A (AA genotype: 19.3% vs. 0%, p<0.0001) and rs72563731:C>T variants (CC genotype: 81.5% vs. 15.9%, p<0.0001) and between MI<50 and MI≥50 patients in variants: rs17300539:G>A (AA genotype: 19.3% vs. 0.5%, p<0.0001), rs72563731:C>T (CC genotype: 82.1% vs. 60.8%, p<0.0001), rs1501299:G>T (TT genotype: 6.8% vs. 14.9%, p=0.019) and rs822387:T>C (genotype CC: 1.5% vs. 0%, p=0.017). Multivariate analysis showed a significantly higher risk of MI in young CC carriers of rs72563731:C>T and in young AA carriers of rs17300539:G>A. Total and HMW adiponectin plasma levels have been significantly lower in MI<50 patients in comparison to MI≥50 patients (p=0.001 and p=0.001, respectively) and to healthy subjects (p=0.009 and p=0.01, respectively).Our study indicates the possible role of adiponectin and its genetic variants in MI in young age.



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Medaka igf1 identifies somatic cells and meiotic germ cells of both sexes

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Cancan Yuan, Kerang Chen, Yefei Zhu, Yongming Yuan, Mingyou Li
Insulin-like growth factors (IGFs) play significant roles in regulating cell proliferation, differentiation and reproduction in diverse organisms. Here, we report the identification of medaka igf1 and the expression pattern of igf1 RNA in adult medaka gonads. Using RT-PCR, igf1 RNA was easily detected in several somatic organs and adult gonads of both sexes. Using chromogenic in situ hybridization, igf1 RNA in the ovary was found in stage I-IV oocytes and in the somatic cells throughout oogenesis. In the testis, igf1 RNA was present in meiotic products and the somatic cells surrounding male germ cells throughout spermatogenesis. We performed fluorescent in situ hybridization and immunostaining for the Vasa protein as a germ cell marker on gonadal cryosections. We showed that igf1 RNA in the ovary was most abundant in theca cells and meiotic oocytes at stage I-IV, which was detectable in granulosa cells and infrequently occurred in the mature oocytes at stage V but was absent in oogonia. The igf1 RNA in the testis was most prominent in Leydig cells and Sertoli cells and meiotic spermatids and sperm as well as detectable in spermaotgonia and spermatocytes. We conclude that differential igf1 RNA expression identifies medaka somatic cells and meiotic germ cells of both sexes.



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Unusual features of the large linear plasmid pSA3239 from Streptomyces aureofaciens CCM 3239

Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Erik Mingyar, Renata Novakova, Renata Knirschova, Lubomira Feckova, Carmen Bekeova, Jan Kormanec
We previously identified the aur1 gene cluster, responsible for the production of the angucycline antibiotic auricin in Streptomyces aureofaciens CCM 3239. Pulse-field gel electrophoresis showed a single, 241kb linear plasmid, pSA3239, in this strain, and several approaches confirmed the presence of the aur1 cluster in this plasmid. We report here the nucleotide sequence of this 241,076-bp plasmid. pSA3239 contains an unprecedentedly small (13bp) telomeric sequence CCCGCGGAGCGGG, which is identical to the conserved Palindrome I sequence involved in the priming of end-patching replication. A bioinformatics analysis revealed 234 open reading frames with high number (28) of regulatory genes from various families. In contrast to most other linear plasmids, pSA3239 contains a pair of replication initiation genes (sa76 and sa75) located at its extreme left end, adjacent to the telomere. Together with similar proteins from several other linear plasmids (pFRL2, pSLA2-M, pSV2, pSDA1, and SAP1), they constitute a new family of replication initiation proteins. This left end also contains two genes, tpgSa and tapSa, encoding the terminal protein and the telomere associated-protein involved in telomere end-patching replication. pSA3239 also contains two genes homologous to the parAB partitioning system, and deletion of the parA homologue (sa43) affects structural stability of the plasmid. pSA3239 carries five potential secondary metabolite gene clusters. In addition to aur1 and a non-ribosomal peptide synthase (NRPS) gene cluster for the blue pigment indigoidine, it also contains a partial type II polyketide synthase (PKS) gene cluster, a partial type I PKS gene cluster, and a NRPS/PKSI gene cluster for unknown secondary metabolites. The last gene cluster contains a subcluster of seven genes (sa91–sa97), highly similar to part of the valanimycin biosynthetic cluster vlm. A S. aureofaciens strain lacking pSA3239 was prepared. This deletion did not substantially affect growth and differentiation. A comparative analysis of secondary metabolites between both strains did not identify any product, except auricin and indigoidine, which is dependent upon pSA3239. Thus, the other three identified gene clusters are likely silent under these conditions.



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Expression profiles of the p38 MAPK signaling pathway from Chinese shrimp Fenneropenaeus chinensis in response to viral and bacterial infections

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Yuying He, Wanlong Yao, Ping Liu, Jian Li, Qingyin Wang
Mitogen-activated protein kinase (MAPK) signaling pathway plays an important role in cellular response to inflammatory cytokines, environmental stress and pathogenic infection, However, compared with mammals and insects, the potential function of p38 MAPK from Chinese shrimp (Fenneropenaeus chinensis) in response to viruses and bacterial infection is limited. In the study, the immune responses of four genes MKK3, MKK4, p38 and ATF-2 from F. chinensis were investigated in defending against white spot syndrome virus (WSSV), Vibrio anguillarum (V. anguillarum) and Staphylococcus aureus (S. aureus) infection. Results demonstrated that the expression levels of these four genes were apparently modulated in hemocytes and gills when shrimp were stimulated by WSSV or bacteria, particularly at 3–24h after infection. MKK3, p38 and ATF-2 were most sensitive to V. anguillarum (Gram-negative bacteria), followed by WSSV and S. aureus (Gram-positive bacteria), while MKK4 gene was most sensitive to S. aureus, followed by WSSV and V. anguillarum. Knockdown of Fcp38 by RNA interference (RNAi) resulted in a reduction in the expression of FcMKK3 and FcATF-2. The results indicate that p38MAPK signaling pathway plays a role in defending against viral and bacterial infections in F. chinensis.



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Expression pattern and functional analysis of R-spondin1 in tongue sole Cynoglossus semilaevis

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Jinxiang Liu, Tiantian Liu, Jingjing Niu, Xiaolong Wu, Jieming Zhai, Quanqi Zhang, Jie Qi
R-spondin 1 (Rspo1) is a potential female-determining gene in mammals that could regulate the Wnt/β-catenin signaling pathway. The deletion of Rspo1 causes sex reversal in females. To investigate sexual determination and differentiation, we cloned and analyzed the Rspo1 gene in Cynoglossus semilaevis. Phylogenetic and gene structure analyses revealed that Rspo1 gene exhibited high sequence conservation and contained an N-terminal signal peptide, two furin-like cysteine-rich domains (FU1 and FU2), a thrombospondin type 1 repeat, and a C-terminal region enriched with basic charged amino acids. qRT-PCR revealed that Rspo1 expressed sexual dimorphism in gonad, with higher expression levels in the ovary than in the testis, thus, suggesting the involvement of Rspo1 in gonad differentiation. In situ hybridization results demonstrated that Rspo1 was expressed in premature germ cells, including spermatogonia and spermatocytes in the testis and stage II and stage III oocytes in the ovary. The methylation levels in two CpG sites of Rspo1 promoter significantly differed among females, males, and pseudomales. After 30days of exposure to high temperature, the expression of Rspo1 significantly decreased in female individuals, some of which were prone to males. However, no difference of Rspo1 gene expression was observed between the control group and high-temperature group in males. These preliminary findings suggested that Rspo1 played a crucial role in sex determination and development. This study laid the groundwork for further sex control breeding techniques in C. semilaevis.



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ClC-3 chloride channel is involved in isoprenaline-induced cardiac hypertrophy

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Chunmei Li, Dan Huang, Jing Tang, Mengqing Chen, Qun Lu, He Li, Mengzhen Zhang, Bin Xu, Jianwen Mao
Isoprenaline, an activator of β-adrenergic receptor, has been found to induce cardiac hypertrophy in vivo and in vitro, but the exact mechanism is still unclear. ClC-3 is a member of the chloride channel family and is highly expressed in mammalian myocardium. In the present study, the role of ClC-3 in isopronaline-induced cardiac hypertrophy was investigated. We found that ClC-3 expression was reduced in isoprenaline-induced hypertrophic H9c2 cells, primary rat neonatal cardiomyocytes and myocardium of C57/BL/6 mice, and this reduction was prevented by the pretreatment of propranolol. Adeno-associated virus 9 (AAV9)-mediated ClC-3 expression in myocardium decreased heart mass index, thinned interventricular septum and left ventricular wall and lowered the mRNA expression of natriuretic peptide type A (ANF) and β-myosin heavy chain (β-MHC). Our results showed that ClC-3 played an important role in β-adrenergic cardiac hypertrophy which could be associated with ANF and β-MHC, and all these findings suggested that ClC-3 may be a novel therapeutic target for the prevention or treatment of myocardiac hypertrophy.



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Cloning and characterization of two novel β-glucosidase genes encoding isoenzymes of the cellobiase complex from Cellulomonas biazotea

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Anthony K.N. Chan, Alan K.L. Ng, Kate K.Y. Ng, W.K.R. Wong
Enzymatic degradation of cellulosic waste to generate renewable biofuels has offered an attractive solution to the energy problem. Synergistic hydrolysis of cellulose residues requires the participation of three different types of cellulases – endoglucanases, exoglucanases, and β-glucosidases (Bgl). Our group has been interested in using Bgl of Cellulomonas biazotea in studies designed to investigate cooperative action among different cellulases. We previously have cloned bgl genes encoding Cba and Cba3, which are C. biazotea Bgl isozymes representing two different Bgl families, respectively; specifically, Glycoside Hydrolase Family 3 (GH3) and Glycoside Hydrolase Family 1 (GH1). To gain an understanding of the complexity of Bgl in C. biazotea, we analyzed E. coli clones containing plasmids into which C. biazotea DNA had been inserted; these clones could hydrolyze 4-methylumbelliferyl β-d-glucopyranoside (MUG) supplemented in solid agar media, suggesting they might contain bgl genes. Through restriction analysis and DNA sequencing, two novel bgl genes, designated cba4 and cba5 and encoding Cba4 (484 amino acids) and Cba5 (758 amino acids) were identified. Cba4 and Cba5 appear to be members of GH1 and GH3, respectively. Both Cba4 and Cba5 were concluded to be genuine cellobiases as each was found to enable their E. coli hosts to survive on media in which cellobiose was the sole carbon source. Despite lacking a typical secretory signal sequence, Cba4 and Cba5 are secretory proteins. Although they are isoenzymes, Cba, Cba3, Cba4, and Cba5 were shown to possess distinct substrate specificities. These four Bgl members may play important roles in hydrolyzing a wide variety of β-glucosides including cellobiose and non-cellulosic substrates.



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Mucolipidosis type III gamma: Three novel mutation and genotype-phenotype study in eleven patients

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Beyhan Tüysüz, Özgür Kasapçopur, Dilek Uludağ Alkaya, Sezgin Şahin, Betül Sözeri, Gözde Yeşil
Mucolipidosis type III gamma (MLIII gamma) is a lysosomal storage disease characterized by joint stiffness, mild coarse face and corneal clouding, which becomes recognizable usually in childhood. Biallelic mutations in the GNPTG gene, which encode the γ subunit of the N-acetylglucosamine-1-phosphotransferase enzyme, are the underlying cause of MLIII gamma. The aim of this study is to evaluate the longitudinal findings and genotype of eleven patients from eight families with MLIII gamma and to establish a genotype-phenotype correlation. The most frequently observed initial finding was stiffness of finger joints, which detected in patients between 18month-olds and five year-olds. However, in four patients presented here, initial finding was knee pain or waddling gait, which started between six-16years of age. All patients also had variable degrees of stiffness on large joints. The longest follow up period was 16years while the shortest was three years and six months. We observed that the patients who had an early onset disease and severe joint stiffness had also rapidly progressive joint involvement mostly localized in hands, shoulders, and hip. However; the patients with late onset and/or mild joint stiffness experienced slowly progressive symptoms. Most patients dropped in their growth curve in time and the ones who were severely affected reached the final height below the third centile. Seven disease-causing mutations, three of them novel, were detected in GNPTG gene. According to our clinical observations c.493_494insC and c.283_284insC mutations lead to a severe phenotype and c.196C>T, c.347_349del, c.652_655delTACT and c.445delG/c.367A>G mutations seemed to generate a milder phenotype.



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Unravelling the link between embryogenesis and cancer metastasis

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Kanisha Shah, Shanaya Patel, Sheefa Mirza, Rakesh M. Rawal
PurposeCancer as opposed to embryonic development is characterized by dysregulated, uncontrolled and clonal growth of cells. Inspite of that they share certain commonality in gene expression patterns and a number of cellular & molecular features. Consequently, in the present study we aimed to evaluate the role of a definite set of genes in fetal liver, primary liver cancers and metastatic liver tissue.MethodsThe relative expression of fourteen candidate genes obtained by data mining and manual curation of published data (CXCL12, CXCR4, CK7, CDH1, CTNNB1, CLDN4, VEGFA, HIF1A, MMP9, p53, OPN, CDKN2A, TGFBR2, MUC16, β-actin) were performed on 62 tissues (32 liver metastasis tissues and 30 primary Liver cancer tissues), Fetal liver tissues (below and above 20weeks of gestation) and 2 sets of control samples by real-time quantitative reverse transcription PCR (qRT-PCR).ResultsResults showed significant down-regulation of MMP9 and TP53 in Fetal liver above 20weeks of gestation whereas it was up-regulated in fetal liver below 20weeks of gestation, primary liver cancers and liver metastasis. Contradictory to that OPN and CDKN2A were significantly up-regulated in primary liver cancer, liver metastasis; down-regulated in fetal liver above 20weeks of gestation but were not expressed during early embryo development (below 20weeks of gestation). Moreover, MMP9 and TP53 demonstrated a strong correlation with MUC16 whereas CDKN2A and OPN showed correlation with CXCL12/CXCR4 signifying that MUC16, CXCL12/CXCR4 might be involved in the complex process of cancer metastasis.ConclusionMMP9, OPN, TP53 and CDKN2A were the identified markers that were expressed in a similar pattern in early embryonic development and cancer development & invasion suggesting that these genes are activated during embryogenesis and might be re-expressed in cancer metastasis. Moreover, these genes govern a pathway that might be activated during cancer metastasis. Thus, targeting these molecules may provide better treatment for metastatic liver cancers.



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Role of tumor necrosis factor-α in epithelial-to-mesenchymal transition in transplanted kidney cells in recipients with chronic allograft dysfunction

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Chunchun Zhao, Zhen Xu, Zijie Wang, Chuanjian Suo, Jun Tao, Zhijian Han, Min Gu, Ruoyun Tan
BackgroundChronic allograft dysfunction (CAD) is characterized by allograft kidney interstitial fibrosis, the underlying mechanism of which is unclear. Our aim was to elucidate the role and mechanism of TNF-α-induced epithelial-to-mesenchymal transition (EMT) in transplant kidney tubular interstitial fibrosis.MethodsHuman kidney tissues from normal volunteers and CAD patients were assessed using periodic acid-Schiff, Masson trichrome and immunohistochemical staining. mRNA and protein expression of E-cadherin, α-smooth muscle actin (SMA) and fibronectin(FN) in renal proximal tubule epithelial (HK-2) cells after treatment with TNF-α under different conditions were assessed using western blot and qRT-PCR analysis. Cell motility and migration were assessed using wound healing and transwell assays. Expression of Smurf2 and TNF-α-signaling pathway-related proteins in HK-2 cells treated with TNF-α was detected by western blotting. E-cadherin and α-SMA expression was also assessed in Smurf2 plasmid-transfected or Smurf2 siRNA-treated HK-2 cells.ResultsThe expression of TNF-α, Smurf2, α-SMA, and fibronectin was significantly upregulated, while the expression of E-cad was downregulated in the CAD group compared with the normal group. The in vitro results showed that TNF-α remarkably upregulated the expression of Smurf2, α-SMA and fibronectin and downregulated the expression of E-cadherin in HK-2 cells and enhanced motility and migration in HK-2 cells. Overexpression of Smurf2 could promote the expression of α-SMA and inhibit the expression of E-cad, whereas knockdown of Smurf2 expression reversed TNF-α-induced upregulation of α-SMA and prohibited the reduction of E-cad expression. Furthermore, TNF-α-induced Smurf2 expression promoted EMT through the Akt signaling pathway.ConclusionsTNF-α induced EMT via the TNF-α/Akt/Smurf2 signaling pathways, and it may play a role in aggravating allograft kidney interstitial fibrosis in CAD patients.



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The association between caspase-5 gene polymorphisms and rheumatoid arthritis in a Chinese population

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Huan Rui, Ting Yan, Zhiyong Hu, Ruiping Liu, Liqun Wang
Genetic factors are widely recognized to have a substantial effect on the susceptibility to rheumatoid arthritis (RA). We examined the contribution of caspase-5 (CASP5) gene polymorphisms to RA risk in a Chinese population. We conducted a case-control study involving 500 RA patients and 500 controls and performed co-expression analysis to identify genes associated with CASP5. We attempted to analyze the functions of these genes by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. We carried out genotyping using a custom-by-design 48-Plex SNP (single nucleotide polymorphism) Scan™ Kit. The independent effects of these genetic loci were evaluated by creating genetic risk scores (GRS). Bioinformatics analysis confirmed that CASP5 was related to the development of inflammation, which is the main feature of RA. In addition, the CASP5 rs9651713 polymorphism was associated with an increased risk of RA, but there was no significant association between any other tested polymorphism (rs2276414, rs2282657, rs3181171, rs3181318, rs3181175, rs3181337, and rs552217) and RA risk. In addition, a high GRS was positively correlated with the risk of RA. In conclusion, CASP5 may contribute to the development of RA by mediating inflammation. Larger studies with more diverse ethnic populations are needed to confirm these results.



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Insights into the multifunctional role of natural killer enhancing factor-A (NKEF-A/Prx1) in big-belly seahorse (Hippocampus abdominalis): DNA protection, insulin reduction, H2O2 scavenging, and immune modulation activity

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): G.I. Godahewa, N.C.N. Perera, Jehee Lee
Natural killer enhancing factor A (NKEF-A), also known as peroxiredoxin 1 (Prx1), is a well-known antioxidant involved in innate immunity. Although NKEF-A/Prx1 has been studied in different fish species, the present study broadens the knowledge of NKEF-A gene in terms of molecular structure, function, and immune responses in fish species. Hippocampus abdominalis NKEF-A (HaNKEF-A) cDNA encoded a putative protein of 198 amino acids containing a thioredoxin_2 domain, VCP motifs, and three conserved cysteine residues including peroxidatic and resolving cysteines. Amino acid sequence comparison and phylogenetic breakdown showed the higher sequence identity and closer evolutionary position of HaNKEF-A to those of other fish counterparts. A recombinant protein of HaNKEF-A was shown to i) protect supercoiled DNA against mixed catalyzed oxidation, ii) reduce insulin disulfide bonds, and iii) scavenge extracellular H2O2. Results of in vitro assays demonstrated the concentration dependent antioxidant function of recombinant HaNKEF-A. In addition, qPCR assessments revealed that the HaNKEF-A transcripts were constitutively expressed in fourteen tissues with the highest expression in liver. As an innate immune response, HaNKEF-A transcripts were up-regulated in liver post injection of LPS, Edwardsiella tarda, Streptococcus iniae, and polyinosinic-polycytidylic acid. Thus, HaNKEF-A can safeguards big-belly seahorse from oxidative damage and pathogenic infections. This study provides insight into the functions of NKEF-A/Prx1 in fish species.



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Evolution of vomeronasal receptor 1 (V1R) genes in the common marmoset (Callithrix jacchus)

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Keiko Moriya-Ito, Takashi Hayakawa, Hikoyu Suzuki, Kimiko Hagino-Yamagishi, Masato Nikaido
Pheromones are crucial for eliciting innate responses and inducing social and sexual behaviors in mammals. The vomeronasal receptor 1 genes, V1Rs, encode members of a pheromone receptor family that are mainly expressed in the vomeronasal organ (VNO). The V1R family shows extraordinary variety in gene number among vertebrates owing to successive gene gains and losses during evolution. Such diversity is believed to reflect a degree of dependence on the VNO. We investigated V1R evolution in primate lineages closely related to humans because these VNOs show a trend toward degeneration. We performed extensive phylogenetic analyses for V1Rs from a broad range of primate species. Although the decline of intact genes was evident in anthropoids (hominoids, Old World monkeys and New World monkeys), we found that a certain number of intact genes persist in New World monkeys. In one New World monkey species, the common marmoset (Callithrix jacchus), we examined seven putatively functional V1Rs using in situ hybridization and reverse transcription-PCR. Based on their mRNA expression patterns in the VNO and other organs, two types of V1Rs emerged: the canonical class with VNO-specific expression, and a second group having more ubiquitous expression in various organs as well as VNO. Furthermore, phylogenetic analysis revealed that the class with the more widespread expression had been retained longer in evolution than the VNO-specific type. We propose that the acquisition of a novel non-VNO–related function(s) may have led to the survival of a small but persistent number of V1Rs in anthropoid primates.



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Association of genetic polymorphisms with erythrocyte traits: Verification of SNPs reported in a previous GWAS in a Japanese population

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Toshio Seiki, Mariko Naito, Asahi Hishida, Sahoko Takagi, Takashi Matsunaga, Tae Sasakabe, Yuta Hattori, Sayo Kawai, Rieko Okada, Guang Yin, Nobuyuki Hamajima, Kenji Wakai
Erythrocyte count and volume are the commonly used hematological indices for anemia that change in various diseases. To date, however, only one study ever exists that addressed erythrocyte trait-associated single nucleotide polymorphisms (SNPs) in a Japanese population. Because that study was performed in patients with various diseases, we confirmed the reported associations in a general population. Participants in the current study were from the Shizuoka component of the Japan Multi-Institutional Collaborative Cohort Study, which included 4971 men and women aged 35 to 69years who were recruited between 2006 and 2007. We analyzed the association of seven selected SNPs with the following erythrocyte traits: red blood cell count, hemoglobin (Hb) and hematocrit (Ht) levels, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. The erythrocyte traits were regressed on a number of minor alleles of selected SNPs. Then we compared our findings with those from a genome-wide association study performed in a Japanese population. We replicated the association of ABO rs495828, PDGFRA-KIT rs218237, USP49-MED20-BSYL-CCND3 rs3218097, C6orf182-CD164 rs11966072, TERT rs2736100, and TMPRSS6 rs5756504 with erythrocyte traits in our independent Japanese population. In addition, we found a significant interaction between TERT rs2736100 and smoking habit that affected Hb and Ht levels.



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Identification and functional analysis of a novel mutation in the PAX3 gene associated with Waardenburg syndrome type I

Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Zhijie Niu, Jiada Li, Fen Tang, Jie Sun, Xueping Wang, Lu Jiang, Lingyun Mei, Hongsheng Chen, Yalan Liu, Xinzhang Cai, Yong Feng, Chufeng He
Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant genetic disorder of neural crest cells (NCC) characterized by congenital sensorineural hearing loss, dystopia canthorum, and abnormal iris pigmentation. WS1 is due to loss-of-function mutations in paired box gene 3 (PAX3). Here, we identified a novel PAX3 mutation (c.808C>G, p.R270G) in a three-generation Chinese family with WS1, and then analyzed its in vitro activities. The R270G PAX3 retained nuclear distribution and normal DNA-binding ability; however, it failed to activate MITF promoter, suggesting that haploinsufficiency may be the underlying mechanism for the mild WS1 phenotype of the study family.

Graphical abstract

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Identification of key microRNAs associated with diffuse large B-cell lymphoma by analyzing serum microRNA expressions

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Yuanyuan Meng, Lina Quan, Aichun Liu
PurposeThis study aimed to investigate the molecular mechanism underlying diffuse large B-cell lymphoma (DLBCL).MethodsSerum miRNA expression analysis for the serum samples of patients with DLBCL and those of controls was performed using the Illumina sequencing technology. Differentially expressed miRNAs (DEMs) were identified on the basis of the sequencing data. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and protein–protein interaction (PPI) network construction for the target genes of DEMs were also conducted. Moreover, the selected DEMs were verified using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsFifty-one DEMs were identified between DLBCL disease and control groups, of which two were upregulated and 49 were downregulated. In total, 3631 target genes of DEMs were obtained, and hsa-miR-34a-5p had the most target genes. Among the 51 DEMs, 19 were significantly enriched in 41 KEGG pathways. hsa-miR-34a-5p was enriched in 15 pathways such as the p53 signaling pathway. hsa-miR-323b-3p was enriched in four pathways such as pathways in cancer. The PPI network revealed that hsa-miR-34a-5p had the most target genes such as tumor protein p53 (TP53), and hsa-miR-431-5p regulated tyrosine protein kinase Fyn (FYN). Furthermore, qRT-PCR results showed that hsa-miR-34a-5p was upregulated, whereas hsa-miR-323b-3p and hsa-miR-431-5p were downregulated.Conclusionhsa-miR-34a-5p may be directly regulated by TP53 and may be involved in DLBCL development via the p53 signaling pathway. Furthermore, hsa-miR-323b-3p may be related to DLBCL by participating in pathways in cancer. hsa-miR-431-5p may also play a role in DLBCL by regulating FYN.



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The thymidylate synthase enhancer region (TSER) polymorphism increases the risk of thymic lymphoid hyperplasia in patients with Myasthenia Gravis

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Angela Lopomo, Roberta Ricciardi, Anna De Rosa, Melania Guida, Michelangelo Maestri, Marco Lucchi, Franca Melfi, Alfredo Mussi, Lucia Migliore, Fabio Coppedè
BackgroundMyasthenia Gravis (MG) is caused, in approximately 80% of the patients, by autoantibodies against the nicotinic acetylcholine receptor (AChR). The disease is often associated with pathological changes of the thymus: thymic epithelial tumours are present in about 10–20% of the patients, while up to 80% of the patients with early disease onset have thymic hyperplasia. Folate metabolism is required for the production of DNA precursors and for proper DNA methylation reactions, and impaired folate metabolism has been often associated with cellular growth and cancer.MethodsWe investigated if major polymorphisms of folate-related genes, namely MTHFR c.677C>T, MTR c.2756A>G, MTRR c.66A>G and TYMS TSER (a 28-bp tandem repeat in the 5′ promoter enhancer region of TYMS) increase the risk of pathological changes of the thymus in AChR+ MG patients. A total of 526 AChR+ MG patients, including 132 patients with normal (involuted) thymus, 146 patients with thymic hyperplasia, and 248 patients with a thymoma were included in the study. Allele and genotype comparisons were performed among the three study groups, after correcting for multiple testing.ResultsThe frequency of the TYMS TSER 3R allele was significantly higher in MG patients with thymic hyperplasia (P=0.004), and the TYMS TSER 3R3R genotype was significantly associated with increased risk of thymic hyperplasia [OR 2.71 (95% CI: 1.34–5.47)].ConclusionsThe 3R allele in the thymidylate synthase promoter enhancer region results in increased protein production, required for the synthesis of DNA precursors. The present study suggests that the TYMS TSER 3R allele increases the risk of thymic lymphoid hyperplasia in AChR+ MG patients.



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Recombinant latcripin 11 of Lentinula edodes C91-3 suppresses the proliferation of various cancer cells

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Yifan Gao, Arshad Ahmed Padhiar, Jia Wang, Wei Zhang, Mintao Zhong, Ben Liu, Zhijie Kang, Xiaoli Wang, Xingyun Li, Min Huang
Lentinula edodes C91-3 is an edible mushroom that has demonstrated a remarkable anti-tumor effect in various cancer cells both in vitro and in vivo. In the present study, we report the ability of recombinant thioredoxin-like latcripin 11 (LP-11) of Lentinula edodes C91-3 to suppress the proliferation of various cancer cells. The LP-11 gene of Lentinula edodes C91-3 was cloned in the pET-32a(+) expression vector and expressed in a prokaryotic system. The expressed protein was refolded by gradual dialysis and purified by affinity gel filtration chromatography. The antioxidant activity of LP-11 was tested by 1,1-dipheny l-2-picrylhydrazyl (DPPH) assay. The anti-tumor activity of recombinant LP-11 was tested in eight kinds of tumor cell lines by CCK-8 assay. Recombinant LP-11 significantly suppressed the proliferation of various cancer cells, but not normal human umbilical vein endothelial cells. Human lymphoma U937 cells exhibited the most sensitivity to LP-11 protein. U937 cell apoptosis was assessed by Annexin V staining coupled with flow cytometry, and mitochondrial morphology was analyzed by light and electron microscopy. It was revealed that recombinant LP-11 induced apoptosis in human leukemic monocyte lymphoma U937 cells. Our findings suggest that recombinant LP-11 is a promising agent for the treatment of lymphoma.



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Contrasting the microbiomes from forest rhizosphere and deeper bulk soil from an Amazon rainforest reserve

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Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Jose Pedro Fonseca, Luisa Hoffmann, Bianca Catarina Azeredo Cabral, Victor Hugo Giordano Dias, Marcio Rodrigues Miranda, Allan Cezar de Azevedo Martins, Clarissa Boschiero, Wanderley Rodrigues Bastos, Rosane Silva
Pristine forest ecosystems provide a unique perspective for the study of plant-associated microbiota since they host a great microbial diversity. Although the Amazon forest is one of the hotspots of biodiversity around the world, few metagenomic studies described its microbial community diversity thus far. Understanding the environmental factors that can cause shifts in microbial profiles is key to improving soil health and biogeochemical cycles. Here we report a taxonomic and functional characterization of the microbiome from the rhizosphere of Brosimum guianense (Snakewood), a native tree, and bulk soil samples from a pristine Brazilian Amazon forest reserve (Cuniã), for the first time by the shotgun approach. We identified several fungi and bacteria taxon significantly enriched in forest rhizosphere compared to bulk soil samples. For archaea, the trend was the opposite, with many archaeal phylum and families being considerably more enriched in bulk soil compared to forest rhizosphere. Several fungal and bacterial decomposers like Postia placenta and Catenulispora acidiphila which help maintain healthy forest ecosystems were found enriched in our samples. Other bacterial species involved in nitrogen (Nitrobacter hamburgensis and Rhodopseudomonas palustris) and carbon cycling (Oligotropha carboxidovorans) were overrepresented in our samples indicating the importance of these metabolic pathways for the Amazon rainforest reserve soil health. Hierarchical clustering based on taxonomic similar microbial profiles grouped the forest rhizosphere samples in a distinct clade separated from bulk soil samples. Principal coordinate analysis of our samples with publicly available metagenomes from the Amazon region showed grouping into specific rhizosphere and bulk soil clusters, further indicating distinct microbial community profiles. In this work, we reported significant shifts in microbial community structure between forest rhizosphere and bulk soil samples from an Amazon forest reserve that are probably caused by more than one environmental factors such as rhizosphere and soil depth.



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