Manifestation of epilepsy in a patient with EED-related overgrowth (Cohen-Gibson syndrome).

Cohen-Gibson syndrome is a rare genetic disorder, characterized by fetal or early childhood overgrowth and mild to severe intellectual disability. It is caused by heterozygous aberrations in EED, which encodes an evolutionary conserved polycomb group (PcG) protein that forms the polycomb repressive complex-2 (PRC2) together with EZH2, SUZ12, and RBBP7/4. In total, 11 affected individuals with heterozygous pathogenic variants in EED were reported, so far. All variants affect a few key residues within the EED WD40 repeat domain. By trio exome sequencing, we identified the heterozygous missense variant c.581A > G, p.(Asn194Ser) in exon 6 of the EED-gene in an individual with moderate intellectual disability, overgrowth, and epilepsy. The same pathogenic variant was detected in 2 of the 11 previously reported cases. Epilepsy, however, was only diagnosed in one other individual with Cohen-Gibson syndrome before. Our findings further confirm that the WD40 repeat domain represents a mutational hotspot; they also expand the clinical spectrum of Cohen-Gibson syndrome and highlight the clinical variability even in individuals with the same pathogenic variant. Furthermore, they indicate a possible association between Cohen-Gibson syndrome and epilepsy

Spaltstoffrueckfuehrung in Druckwasserreaktoren Weiterentwicklung der Auslegung und Verifikation an Anwendungsfaellen. Abschlussbericht

This study is an important step to verify and to establish the fuel recycling in PWR's. The design methods have been extended and the handling has been improved. No new cross-section librairy was established, because the JEF-2 data have been not yet available. The MOX-FA design was adapted to the modified boundary conditions (changed Pu-composition, increased content of fissile material, other carrier material). Insertion studies have been performed with FA of these designs up to an amount of 50% MOX-FA in low-leakage cores. Using the results of the inservice cycle monitoring it was possible to verify the design method and results related to U- and Pu-recycling. (orig.)Mit dem Vorhaben erfolgte ein wichtiger Schritt in Richtung Absicherung und Etablierung der Spaltstoffrueckfuehrung in DWR. Die Auslegungsmethoden wurden erweitert und die Anwendung vereinfacht. Die Einfuehrung neuer Wirkungsquerschnittsbibliotheken wurde zurueckgestellt, da JEF-2 noch nicht verfuegbar war. Die Auslegung der MOX-BE wurde an geaenderte Randbedingungen angepasst (geaenderte Pu-Zusammensetzung, hoeherer Spaltstoffgehalt, anderes Traegermaterial). Brennelemente dieser Auslegungen wurden im Rahmen von Beladestudien bis zu einem hohen Anteil (50%) in low-leakage-Kerne eingesetzt. Anhand von Ergebnissen aus der Betriebsverfolgung konnten die Auslegungsmethoden und die konkreten Brennelementauslegungen zur Plutonium- und Uranrueckfuehrung abgesichert werden. (orig.)SIGLEAvailable from TIB Hannover: RR 2707(1990,410) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections

Background: Human Ebola infection is characterized by a paralysis of the immune system. A signature of αβ T cells in fatal Ebola infection has been recently proposed, while the involvement of innate immune cells in the protection/pathogenesis of Ebola infection is unknown. Aim of this study was to analyze γδ T and NK cells in patients from the Ebola outbreak of 2014–2015 occurred in West Africa, and to assess their association with the clinical outcome. Methodology/Principal findings: Nineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Centre in Guinea. Patients were divided in two groups on the basis of the clinical outcome. The analysis was performed by using multiparametric flow cytometry established by the European Mobile Laboratory in the field. A low frequency of Vδ2 T-cells was observed during Ebola infection, independently from the clinical outcome. Moreover, Vδ2 T-cells from Ebola patients massively expressed CD95 apoptotic marker, suggesting the involvement of apoptotic mechanisms in Vδ2 T-cell loss. Interestingly, Vδ2 T-cells from survivors expressed an effector phenotype and presented a lower expression of the CTLA-4 exhaustion marker than fatalities, suggesting a role of effector Vδ2 T-cells in the protection. Furthermore, patients with fatal Ebola infection were characterized by a lower NK cell frequency than patients with non fatal infection. In particular, both CD56brightand CD56dimNK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56negNK cells was associated to non-fatal infections. Finally, NK activation and expression of NKp46 and CD158a were independent from clinical outcome. Conclusions/Significances: Altogether, the data suggest that both effector Vδ2 T-cells and NK cells may play a role in the complex network of protective response to EBOV infection. Further studies are required to characterize the protective effector functions of Vδ2 and NK cells

J Infect Dis

BACKGROUND: In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. Cycle threshold (Ct) in the Ebola virus RT-PCR and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to EVD patients on compassionate use basis. METHODS: To reduce biases in the raw field data, we carefully selected 163 of the 286 EVD patients for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry, favipiravir treatment, and outcome. RESULTS: The case fatality rate in favipiravir-treated patients was lower than in untreated patients (31/73 [42.5%] vs. 52/90 [57.8%], p = 0.053 in univariate analysis). In the multivariate regression analysis, higher Ct value and younger age were associated with survival (p <0.001), while favipiravir treatment showed no statistically significant effect (p = 0.11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (p = 0.015). The study also showed characteristic changes in blood chemistry in fatal cases vs. survivors. CONCLUSIONS: Consistent with the JIKI trial, this retrospective study reveals a trend toward improved survival in favipiravir-treated patients; however, the effect was not statistically significant except for survival time

Visual mismatch negativity to vanishing parts of objects in younger and older adults.

We investigated visual mismatch negativity (vMMN) to vanishing parts of continuously present objects by comparing the event-related potentials (ERPs) to infrequently (deviant) and frequently (standard) disappearing parts of the objects. This paradigm both excludes low-level stimulus-specific adaptation differences between the responses to deviants and standards, and increases the ecological validity of the stimuli. In comparison to frequently disappearing parts of the stimulus objects, infrequently vanishing parts elicited posterior negative event-related brain activity (vMMN). However, no vMMN emerged to the reappearance of the same parts of the objects. We compared the ERPs of an older and a younger sample of participants. In the 120-180 ms time period vMMN was similar in the two age groups, but in the 180-220 ms time period vMMN emerged only in the younger participants. We consider this difference as an index of more elaborate automatic processing of infrequent stimulus changes in younger adults