The mechanistic basis of gliogenesis, which occurs late in human development, is poorly understood. Here we identify nuclear factor IA (NFIA) as a molecular switch for inducing human glial competency. Transient expression of NFIA is sufficient to trigger glial competency of human pluripotent stem cell-derived neural stem cells within 5 days and to convert these cells into astrocytes in the presence of glial-promoting factors, compared to 3–6 months using current protocols. NFIA-induced astrocytes promote synaptogenesis, exhibit neuroprotective properties, display calcium transients in response to appropriate stimuli, and engraft in the adult mouse brain. Differentiation involves rapid but reversible chromatin remodeling, GFAP promoter demethylation, and a striking lengthening of the G1 cell cycle phase. Genetic or pharmacological manipulation of G1 length partially mimics NFIA function. We use the approach to generate astrocytes with region-specific or reactive features. Our study defines key mechanisms of the gliogenic switch and enables the rapid production of human astrocytes for disease modeling and regenerative medicine.

BackgroundSmall bowel obstruction (SBO) is characterized by a high rate of recurrence. In the present study, we aimed to compare the outcomes of patients managed either by conservative treatment or surgical operation for an episode of SBO.MethodsThe outcomes of all patients hospitalized at a single center for acute SBO between 2004 and 2007 were assessed. The occurrence of recurrent hospitalization, surgery, SBO symptoms at home, and mortality was determined.ResultsAmong 221 patients admitted with SBO, 136 underwent a surgical procedure (surgical group) and 85 were managed conservatively (conservative group). Baseline characteristics were similar between treatment groups. The median follow-up time (interquartile range) was 4.7 (3.7–5.8) years. Nineteen patients (14.0 %) of the surgical group were hospitalized for recurrent SBO versus 25 (29.4 %) of the conservative group [hazard ratio (HR), 0.5; 95 % CI, 0.3–0.9]. The need for a surgical management of a new SBO episode was similar between the two groups, ten patients (7.4 %) in the surgical group and six patients (7.1 %) in the conservative group (HR, 1.1; 95 % CI, 0.4–3.1). Five-year mortality from the date of hospital discharge was not significantly different between the two groups (age- and sex-adjusted HR, 1.1; 95 % CI, 0.6–2.1). A follow-up evaluation was obtained for 130 patients. Among them, 24 patients (34.8 %) of the surgical group and 35 patients (57.4 %) of the conservative group had recurrent SBO symptoms (odds ratio, 0.4; 95 % CI, 0.2–0.8).ConclusionsThe recurrence of SBO symptoms and new hospitalizations were significantly lower after surgical management of SBO compared with conservative treatment.Electronic supplementary materialThe online version of this article (doi:10.1007/s00268-014-2733-6) contains supplementary material, which is available to authorized users.

OBJECTIVEThe goal of this study was to determine the performance of intraoperative visual evoked potentials (VEPs) in detecting visual field changes.METHODSAssessments of VEPs were performed with simultaneous retinal responses by using white light-emitting diodes protected from scialytic microscope lights. The alarm criterion was a reproducible decrease in amplitude of the VEP P100 wave of 20% or more. Visual fields were assessed preoperatively and 1 month postsurgery (Goldmann perimetry).RESULTSThe VEPs were analyzed for 29 patients undergoing resection of a brain lesion. In 89.7% of patients, steady VEP and retinal responses were obtained for monitoring. The absence of alarm was associated in 94.4% of cases with the absence of postoperative visual changes (specificity). The alarms correctly identified 66.7% of cases with any postoperative changes and 100% of cases with changes more severe than just a discrete quadrantanopia or deterioration of an existing quadrantanopia (sensitivity, new diffuse deterioration < 2 dB). In 11.5% of patients, a transitory VEP decrease with subsequent recovery was observed without postoperative defects.CONCLUSIONSIntraoperative VEPs were performed with simultaneous recording of electroretinograms, with protection from lights of the operating room and with white light-emitting diodes. Intraoperative VEPs were shown to be reliable in predicting postoperative visual field changes. In this series of intraaxial brain procedures, reliable intraoperative VEP monitoring was achieved, allowing at minimum the detection of new quadrantanopia. The standardization of this technique appears to be a valuable effort in regard to the functional risks of homonymous hemianopia.

Pluripotent stem cell (PSC)-based cell therapy is an attractive concept for neurodegenerative diseases, but can lead to tumor formation. This is particularly relevant as proliferating neural precursors rather than postmitotic mature neurons need to be transplanted. Thus, safety mechanisms to eliminate proliferating cells are needed. Here, we propose a suicide gene approach, based on cell cycle-dependent promoter Ki67-driven expression of herpes simplex virus thymidine kinase (HSV-TK). We generated a PSC line expressing this construct and induced neural differentiation. In vitro, proliferating PSC and early neural precursor cells (NPC) were killed by exposure to ganciclovir. In vivo, transplantation of PSC led to tumor formation, which was prevented by early ganciclovir treatment. Transplanted NPC did not lead to tumor formation and their survival and neural maturation were not affected by ganciclovir. In conclusion, the cell cycle promoter-driven suicide gene approach described in this study allows killing of proliferating undifferentiated precursor cells without expression of the suicide gene in mature neurons. This approach could also be of use for other stem cell-based therapies where the final target consists of postmitotic cells.