Contribution of edema and cerebral blood volume to traumatic brain swelling in head-injured patients

OBJECT: The pathogenesis of traumatic brain swelling remains unclear. The generally held view is that brain swelling is caused primarily by vascular engorgement and that edema plays a relatively minor role in the swelling process. The goal of this study was to examine the roles of cerebral blood volume (CBV) and edema in traumatic brain swelling. METHODS: Both brain-tissue water and CBV were measured in 76 head-injured patients, and the relative contribution of edema and blood to total brain swelling was determined. Comparable measures of brain-tissue water were obtained in 30 healthy volunteers and CBV in seven volunteers. Brain edema was measured using magnetic resonance imaging, implementing a new technique for accurate measurement of total tissue water. Measurements of CBV in a subgroup of 31 head-injured patients were based on consecutive measures of cerebral blood flow (CBF) obtained using stable xenon and calculation of mean transit time by dynamic computerized tomography scanning after a rapid bolus injection of iodinated contrast material. The mean (+/- standard deviation) percentage of swelling due to water was 9.37+/-8.7%, whereas that due to blood was -0.8+/-1.32%. CONCLUSIONS: The results of this study showed that brain edema is the major fluid component contributing to traumatic brain swelling. Moreover, CBV is reduced in proportion to CBF reduction following severe brain injury.     

Trans-scleral cyclophotocoagulation: a tale of two probes

To compare the histological effects of trans-scleral cyclophotocoagulation (TCP) performed with two different probes, the G-probe (IRIDEX Medical Instruments, Mountain View, CA, USA) and the Ciliprobe (Katalyst Surgical, Chesterfield, MO, USA). TCP was performed on two human cadaver eyes from the same corpse. The vertical meridian was marked and opposite sides were treated using either the G-probe or Ciliprobe. The first eye was treated with each probe at 2000ms/2000 mW and the second eye at 3000ms/1500 mW. Histological examination revealed separation and loss of the non-pigmented ciliary epithelium as well as vacuolization in all sections for both probes and settings. Changes to the non-pigmented ciliary epithelium treated at 3000ms/1500 mW were similar between the two probes. A slightly more complete separation of the non-pigmented epithelium was noted on the Ciliprobe treated sections as compared to the G-probe treated sections in the eye treated at 2000ms/2000 mW. Therefore, in human cadaver eyes, both the G-probe and Ciliprobe produced separation, vacuolization, and loss of the non-pigmented ciliary epithelium at two different, clinically utilized settings.     

Abrupt visual loss during anti-vascular endothelial growth factor treatment for type 3 neovascularization

AIM: To investigate the incidence of abrupt visual loss and its associated factors, during anti-vascular endothelial growth factor (VEGF) treatment for type 3 neovascularization. METHODS: This retrospective study included 137 eyes that were newly diagnosed with type 3 neovascularization. All eyes were treated with anti-VEGF therapy. Abrupt visual loss was defined as loss of 5 or more lines in best-corrected visual acuity (BCVA) in comparison to the previous visit. The incidence and timing of abrupt visual loss as well as the factors associated with it, were determined. In addition, the BCVA at the final follow-up was compared between the eyes with and those without abrupt visual loss. RESULTS: The mean follow-up period was 42.4±18.9mo after diagnosis, and abrupt visual loss was noted in 22 eyes (16.1%) at a mean of 19.6±13.9mo. Abrupt visual loss was found to be associated with subretinal hemorrhage in 11 eyes (50.0%), development of or increase in the height of pigment epithelial detachment with fluid in 8 eyes (36.4%), and tears in the retinal pigment epithelium in 3 eyes (13.6%). The logarithm of minimum angle of resolution (logMAR) mean BCVA at the final follow-up was 2.07±0.67 (Snellen equivalents: 20/2349) and 1.00±0.55 (20/200) in eyes with and without abrupt visual loss, respectively. BCVA was significantly worse in the eyes with abrupt visual loss (P<0.001). CONCLUSION: Abrupt visual loss is noted in 16.1% of patients with type 3 neovascularization and is associated with poor visual outcome. Additional studies are needed to determine how abrupt visual loss can be prevented.     

Expression and Role of Voltage-Gated Sodium Channels in Human Dorsal Root Ganglion Neurons with Special Focus on Nav1.7, Species Differences,and Regulation by Paclitaxel

Voltage-gated sodium channels(Navs) play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion(hDRG) tissues from healthy donors. PCR analysis of seven DRG-expressed Nav subtypes revealed that the hDRG has higher expression of Nav1.7(~50% of total Nav expression) and lower expression of Nav1.8(~12%), whereas the mouse DRG has higher expression of Nav1.8(~45%) and lower expression of Nav1.7(~18%). To mimic Nav regulation in chronic pain, we treated hDRG neurons in primary cultures with paclitaxel(0.1-1 μmol/L) for 24 h. Paclitaxel increased the Nav 1.7 but not Nav1.8 expression and also increased the transient Na~+ currents and action potential firing frequency in small-diameter(50 μm) hDRG neurons. Thus, the hDRG provides a translational model in which to study"human pain in a dish" and test new pain therapeutics.     

Use of the Ion AmpliSeq Cancer Hotspot Panel in clinical molecular pathology laboratories for analysis of solid tumours: With emphasis on validation with relevant single molecular pathology tests and the Oncomine Focus Assay

Targeted application of next-generation sequencing (NGS) technology allows detection of specific mutations that can provide treatment opportunities for cancer patients. We evaluated the applicability of the Ion AmpliSeq Cancer Hotspot Panel V2 (CHV2) using formalin-fixed, paraffin-embedded (FFPE) tissue of clinical specimens.Thirty-five FFPE tumour samples with known mutational status were collected from four different hospitals and sequenced with CHV2 using an Ion Chef System and Ion S5 XL system. Out of 35 cases, seven were sequenced with Oncomine focus Assay Panel for comparison. For the limit of detection test, we used an FFPE reference standard, a cell line that included an engineered 50% EGFR T790?M in an RKO cell line background. Coverage analysis results including number of mapped reads, on target percent, mean depth, and uniformity were not different according to hospitals. Sensitivity for mutation detection down to 3% was demonstrated. NGS results showed 100% concordance with the results from single molecular pathology tests Assay in 30 cases with 24 known positive mutations and 14 known negative mutations, and another NGS panel of the Oncomine focus in seven cases.The CHV2 NGS test for solid tumours using Ion chef system and S5 XL system in clinical molecular pathology laboratories for analysis of solid tumours could be routinely used and could replace some single molecular pathology tests after a stringent and thorough validation process.     

Autism Spectrum Disorder and School Bullying: Who is the Victim? Who is the Perpetrator?

While a growing number of studies indicate associations between experiences of bullying and autism spectrum disorder (ASD), it is not clear what roles comorbid behavioral problems may play. We investigated the experiences of children with ASD as victims and/or perpetrators of bullying. Children with ASD epidemiologically ascertained participated in a cross-sectional study. Although children with ASD showed significantly increased risk for bullying involvement compared to community children, after controlling for comorbid psychopathology and other demographic factors, increased risks for being perpetrators or victim-perpetrators disappeared while risk for being bullied/teased continued to be significantly elevated. This finding will help guide medical, educational and community personnel to effectively identify children with ASD at risk for school bullying and develop interventions.     

Structure-based pharmacophore modeling and virtual screening to identify novel inhibitors for anthrax lethal factor

Inhibition of anthrax lethal factor (LF) has been reported to be a potent strategy for the treatment of anthrax; however, no effective LF inhibitors are currently available. In this study, a structure-based pharmacophore model was developed based on the co-crystallized structure of anthrax LF with the active inhibitor GM6001. The best pharmacophore model (denoted as SB_Hypo1), consisting of two hydrogen bond acceptors, one hydrogen bond donor and one hydrophobic, was further validated using Gunner-Henry score method. The well-validated SB_Hypo1 was then used as a 3D-query in virtual screening to identify potential hits from NCI database. These hits were subsequently filtered by ADMET and validated by molecular docking experiments, and their binding stabilities were validated by 10-ns MD simulations. Finally, three hits were identified as potential leads based on their favorable binding interactions.