Glioblastoma (GBM) is the most common primary brain tumor and carries a grave prognosis. Despite years of research investigating potentially new therapies for GBM, the median survival rate of individuals with this disease has remained fairly stagnant. Delivery of drugs to the tumor site is hampered by various barriers posed by the GBM pathological process and by the complex physiology of the blood-brain and blood–cerebrospinal fluid barriers. These anatomical and physiological barriers serve as a natural protection for the brain and preserve brain homeostasis, but they also have significantly limited the reach of intraparenchymal treatments in patients with GBM.In this article, the authors review the functional capabilities of the physical and physiological barriers that impede chemotherapy for GBM, with a specific focus on the pathological alterations of the blood-brain barrier (BBB) in this disease. They also provide an overview of current and future methods for circumventing these barriers in therapeutic interventions. Although ongoing research has yielded some potential options for future GBM therapies, delivery of chemotherapy medications across the BBB remains elusive and has limited the efficacy of these medications.
Background-Fatigue and sleep deprivation are important safety issues for long-haul truck drivers. Methods-We conducted round-the-clock electrophysiologic and performance monitoring of four groups of 20 male truck drivers who were carrying revenue-producing loads. We compared four driving schedules, two in the United States (five 10-hour trips of day driving beginning about the same time each day or of night driving beginning about 2 hours earlier each day) and two in Canada (four 13-hour trips of late-night-to-morning driving beginning at about the same time each evening or of afternoon-tonight driving beginning 1 hour later each day). Results-Drivers averaged 5.18 hours in bed per day and 4.78 hours of electrophysiologically verified sleep per day over the five-day study (range, 3.83 hours of sleep for those on the steady 13hour night schedule to 5.38 hours of sleep for those on the steady 10-hour day schedule). These values compared with a mean (±SD) self-reported ideal amount of sleep of 7.1±1 hours a day. For 35 drivers (44 percent), naps augmented the sleep obtained by an average of 0.45±0.31 hour. No crashes or other vehicle mishaps occurred. Two drivers had undiagnosed sleep apnea, as detected by polysomnography. Two other drivers had one episode each of stage 1 sleep while driving, as detected by electroencephalography. Forty-five drivers (56 percent) had at least 1 six-minute interval of drowsiness while driving, as judged by analysis of video recordings of their faces; 1067 of the 1989 six-minute segments (54 percent) showing drowsy drivers involved just eight drivers. Conclusions-Long-haul truck drivers in this study obtained less sleep than is required for alertness on the job. The greatest vulnerability to sleep or sleep-like states is in the late night and early morning.
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