OBJECTIVEBased on a null hypothesis that the use of short-term lumbar drainage (LD) after endoscopic endonasal surgery (EES) for intradural pathology does not prevent postoperative CSF leaks, a trial was conducted to assess the effect of postoperative LD on postoperative CSF leak following standard reconstruction.METHODSA prospective, randomized controlled trial of lumbar drain placement after endoscopic endonasal skull base surgery was performed from February 2011 to March 2015. All patients had 3-month follow-up data. Surgeons were blinded to which patients would or would not receive the drain until after closure was completed. An a priori power analysis calculation assuming 80% of power, 5% postoperative CSF leak rate in the no-LD group, and 16% in the LD group determined a planned sample size of 186 patients. A routine data and safety check was performed with every 50 patients being recruited to ensure the efficacy of randomization and safety. These interim tests were run by a statistician who was not blinded to the arms they were evaluating. This study accrued 230 consecutive adult patients with skull base pathology who were eligible for endoscopic endonasal resection. Inclusion criteria (high-flow leak) were dural defect greater than 1 cm2 (mandatory), extensive arachnoid dissection, and/or dissection into a ventricle or cistern. Sixty patients were excluded because they did not meet the inclusion criteria. One hundred seventy patients were randomized to either receive or not receive a lumbar drain.RESULTSOne hundred seventy patients were randomized, with a mean age of 51.6 years (range 19–86 years) and 38% were male. The mean BMI for the entire cohort was 28.1 kg/m2. The experimental cohort with postoperative LD had an 8.2% rate of CSF leak compared to a 21.2% rate in the control group (odds ratio 3.0, 95% confidence interval 1.2–7.6, p = 0.017). In 106 patients in whom defect size was measured intraoperatively, a larger defect was associated with postoperative CSF leak (6.2 vs 2.9 cm2, p = 0.03). No significant difference was identified in BMI between those with (mean 28.4 ± 4.3 kg/m2) and without (mean 28.1 ± 5.6 kg/m2) postoperative CSF leak (p = 0.79). Furthermore, when patients were grouped based on BMI < 25, 25–29.9, and > 30 kg/m2, no difference was noted in the rates of CSF fistula (p = 0.97).CONCLUSIONSAmong patients undergoing intradural EES judged to be at high risk for CSF leak as defined by the study’s inclusion criteria, perioperative LD used in the context of vascularized nasoseptal flap closure significantly reduced the rate of postoperative CSF leaks.Clinical trial registration no.: NCT03163134 (clinicaltrials.gov).

We evaluated gamma-irradiated Listeria monocytogenes as a killed bacterial vaccine, testing the hypothesis that irradiation preserves antigenic and adjuvant structures destroyed by traditional heat or chemical inactivation. Irradiated Listeria monocytogenes (LM), unlike heat-killed LM, efficiently activated dendritic cells via Toll-like receptors and induced protective T cell responses in mice. Like live LM, irradiated LM induced Toll-like-receptor-independent T cell priming. Cross-presentation of irradiated listerial antigens to CD8(+) T cells involved TAP- and proteasome-dependent cytosolic antigen processing. These results establish that killed LM can induce protective T cell responses, previously thought to require live infection. gamma-irradiation may be potentially applied to numerous bacterial vaccine candidates, and irradiated bacteria could serve as a vaccine platform for recombinant antigens derived from other pathogens, allergens, or tumors.

The Kryptopterus bicirrhis (glass catfish) is known to respond to electromagnetic fields (EMF). Here we tested its avoidance behavior in response to static and alternating magnetic fields stimulation. Using expression cloning we identified an electromagnetic perceptive gene (EPG) from the K. bicirrhis encoding a protein that responds to EMF. This EPG gene was cloned and expressed in mammalian cells, neuronal cultures and in rat’s brain. Immunohistochemistry showed that the expression of EPG is confined to the mammalian cell membrane. Calcium imaging in mammalian cells and cultured neurons expressing EPG demonstrated that remote activation by EMF significantly increases intracellular calcium concentrations, indicative of cellular excitability. Moreover, wireless magnetic activation of EPG in rat motor cortex induced motor evoked responses of the contralateral forelimb in vivo. Here we report on the development of a new technology for remote, non-invasive modulation of cell function.

Explosive blast-induced traumatic brain injury (TBI) is the signature insult in modern combat casualty care and has been linked to post-traumatic stress disorder, memory loss, and chronic traumatic encephalopathy. In this article we report on blast-induced mild TBI (mTBI) characterized by fiber-tract degeneration and axonal injury revealed by cupric silver staining in adult male rats after head-only exposure to 35 psi in a helium-driven shock tube with head restraint. We now explore pathways of secondary injury and repair using biochemical/molecular strategies. Injury produced *25% mortality from apnea. Shams received identical anesthesia exposure. Rats were sacrificed at 2 or 24 h, and brain was sampled in the hippocampus and prefrontal cortex. Hippocampal samples were used to assess gene array (RatRef-12 Expression BeadChip; Illumina, Inc., San Diego, CA) and oxidative stress (OS; ascorbate, glutathione, low-molecular-weight thiols [LMWT], protein thiols, and 4-hydroxynonenal [HNE]). Cortical samples were used to assess neuroinflammation (cytokines, chemokines, and growth factors; Luminex Corporation, Austin, TX) and purines (adenosine triphosphate [ATP], adenosine diphosphate, adenosine, inosine, 2¢-AMP [adenosine monophosphate], and 5¢-AMP). Gene array revealed marked increases in astrocyte and neuroinflammatory markers at 24 h (glial fibrillary acidic protein, vimentin, and complement component 1) with expression patterns bioinformatically consistent with those noted in Alzheimer's disease and long-term potentiation. Ascorbate, LMWT, and protein thiols were reduced at 2 and 24 h; by 24 h, HNE was increased. At 2 h, multiple cytokines and chemokines (interleukin [IL]-1a, IL-6, IL-10, and macrophage inflammatory protein 1 alpha ) were increased; by 24 h, only MIP-1a remained elevated. ATP was not depleted, and adenosine correlated with 2¢-cyclic AMP (cAMP), and not 5¢-cAMP. Our data reveal (1) gene-array alterations similar to disorders of memory processing and a marked astrocyte response, (2) OS, (3) neuroinflammation with a sustained chemokine response, and (4) adenosine production despite lack of energy failure-possibly resulting from metabolism of 2¢-3¢-cAMP. A robust biochemical/molecular response occurs after blast-induced mTBI, with the body protected from blast and the head constrained to limit motion.