Eukaryotic Initiation Factor 2B (eIF2B) GEF Activity as a Diagnostic Tool for EIF2B-Related Disorders

BACKGROUND:In recent years, the phenotypes of leukodystrophies linked to mutations in the eukaryotic initiation factor 2B genes have been extended, classically called CACH/VWM (Childhood ataxia with cntral hypomyélination/vanishing white matter disorder). The large clinical spectrum observed from the more severe antenatal forms responsible for fetal death to milder adult forms with an onset after 16 years old and restricted to slow cognitive impairment have lead to the concept of eIF2B-related disorders. The typical MRI pattern with a diffuse CSF-like aspect of the cerebral white matter can lack particularly in the adult forms whereas an increasing number of patients with clinical and MRI criteria for CACH/VWM disease but without eIF2B mutations are found. Then we propose the use of biochemical markers to help in this difficult diagnosis. The biochemical diagnosis of eIF2B-related disorder is difficult as no marker, except the recently described asialotransferrin/transferrin ratio measured in cerebrospinal fluid, has been proposed and validated until now. Decreased eIF2B GEF activity has been previously reported in lymphoblastoid cell lines from 30 eIF2B-mutated patients. Our objective was to evaluate further the utility of this marker and to validate eIF2B GEF activity in a larger cohort as a specific diagnostic test for eIF2B-related disorders. METHODOLOGY/PRINCIPAL FINDINGS:We performed eIF2B GEF activity assays in cells from 63 patients presenting with different clinical forms and eIF2B mutations in comparison to controls but also to patients with defined leukodystrophies or CACH/VWM-like diseases without eIF2B mutations. We found a significant decrease of GEF activity in cells from eIF2B-mutated patients with 100% specificity and 89% sensitivity when the activity threshold was set at < or =77.5%. CONCLUSION:These results validate the measurement of eIF2B GEF activity in patients' transformed-lymphocytes as an important tool for the diagnosis of eIF2B-related disorders

The apex of the aortic arch backshifts with aging

BACKGROUND: Only a few studies, involving small numbers of patients, have globally assessed the curvature of the thoracic aorta but without any details concerning the location of the supra-aortic trunks. OBJECTIVES: Using CT to describe normal aortic-arch morphology and its changes with age and sex. METHODS: 344 CT scans were studied. We measured the distances from the apex to the ascending and descending aorta, the curvilinear length of the entire arch, that of the segment, including bifurcations of supra-aortic vessels, and the angle, height, and shift of the arch. RESULTS: In men, the arch was significantly longer (146.2 vs 122.8 mm; p < 0.001), higher (49.3 vs 40.1 mm, p < 0.001), and wider transversely (83.6 vs 73.3 mm; p < 0.001) than in women. The average men's arch also had a more acute angle at the apex (79.7 degrees vs 83.7 degrees p < 0.001). Neither morphology nor age influenced the winding angle around the mediastinum. Aging was accompanied by deflection and extension of the aortic arch, which grew more anteroposteriorly (6.1 mm/10 years in men) than vertically (2.5 mm/10 years in men), while the apex moved towards the rear of the arch. The ascending aorta was the only curvilinear length unaffected by age, whereas the supra-aortic trunks parted from each other. CONCLUSION: We believe that all these original observations could lead to a better assessment of normal aging of the aorta and guide technical choices during surgical or hybrid procedure

Can the SCD test and terminal uridine nick-end labeling by flow cytometry technique (TUNEL/FCM) be used interchangeably to measure sperm DNA damage in routine laboratory practice?

Background: Numerous tests have been proposed to evaluate sperm DNA integrity. To assess the sperm chromatin dispersion (SCD) test in an andrology laboratory, twenty-five men attending Clermont-Ferrand (France) University Hospital's Center for Reproductive Medicine were recruited. Sperm DNA damage was measured in the same semen samples using the SCD test and the Terminal Uridine Nick-end Labeling by flow cytometry technique (TUNEL/FCM) after density gradient centrifugation. Results: SCD test reliability between readings, readers or slides was clearly established with very high agreement between measurements (Intraclass correlation coefficient (ICC) at 0.97, 0.95 and 0.98 respectively). Despite very good agreement between the SCD test and TUNEL/FCM (ICC at 0.94), the SCD test tended to slightly but significantly underestimate DNA damage compared with TUNEL (p = 0.0127). This systematic difference between the two techniques was - 3.39 +/- 1.45% (mean +/- SE). Conclusions: Andrology laboratories using the SCD test to measure sperm DNA damage need to know that it appears to give slightly underestimated measurements compared to TUNEL/FCM. However, this systematic underestimation is very small in amplitude. Both techniques give almost perfectly congruent results. Our study underlines the importance for each laboratory to validate its method to assess sperm DNA damage before implementing it in routine andrology lab practice

Preliminary results for the supervised detection of lumen and stent from OCT pullbacks

International audienceIn cardiology, optical coherence tomography (OCT) has been established as a reference for in vivo intravascular image. OCT provides high-resolution and enables us to visualize accurately vessel intimal layers and stents. The drawback is the time necessary to manually select stent struts and lumen boundary. We developed and evaluated an automatic stent strut detection method to apply to intravascular OCT images. The proposed approach innovates the strut shadow detection, which can be considered as an independent processing step that helps discriminating struts by using a profile map. The paper will be presented as a complete process, explaining the necessary steps in order of appearance

Improving image quality of mid trimester fetal sonography in obese: the role the ultrasound propagation velocity

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Un entraînement excentrique excessif chez des souris carencées en vitamine D conduit à une perte de capacités physiques, une atrophie musculaire et une inflammation systémique

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