No abstract

Hyper-reactivity and anxiety to sensory stimuli have been described in patients with fragile X syndrome (FXS), and may be related to abnormal processing in afferent sensory pathways. We used magnetoencephalography (MEG) to measure auditory responses to pure tones in 11 adults with FXS and 11 non-FXS subjects. The amplitude for the N100m auditory evoked field component was significantly higher for patients with FXS than for subjects. FXS subjects also had less lateralized N100m anterior-posterior dipole locations. These data may suggest that more neurons are activated by acoustic stimuli in FXS, consistent with subjective experience of increased stimulus intensity. Anomalous cerebral lateralization may suggest an early critical window for effects on neocortical development of the fragile X mental retardation protein (FMRP) produced by the FMR1 gene in individuals with FXS.

No abstract

Background Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. Methods This pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS). Results Enrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91–1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3–5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction. Conclusions In this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results. Clinical trials registration NCT02511405

Cerebral lateralization and localization of the M50 distinguished patients with schizophrenia from normal subjects. These findings suggest the possibility of anatomical displacement and/or disturbed organization of the primary sensory cortex in schizophrenia.