Serum long non-coding RNAs as potential noninvasive biomarkers for glioblastoma diagnosis, prognosis, and chemoresistance.

Gliomas are common brain tumors with a variable prognosis based on their tumor grade. With glioblastomas, the prognosis is usually unfavorable. Thus, having accurate and rapid methods for their diagnosis and follow-up are essential for rapid discovery of the tumor and to protect patients from unnecessary procedures. Some glioma cases are challenging since there is a limited ability to differentiate between gliomas, recurrent glioblastomas, and single metastatic lesions. Monitoring treatment responses and follow-ups can also be challenging. While both radiological and serological markers have been identified that can aid diagnosis and assess therapies, a particularly promising new class of serological markers are long non-coding RNAs. Long non-coding RNAs are a relatively recently discovered class of regulatory RNA molecules that play critical roles in many cellular and physiological processes. The potential role that long non-coding RNAs play with glioma pathogenic processes is not fully understood. In this literature review, we highlight the potential for long non-coding RNAs to be used as serum biomarkers in glioblastoma patients, including their potential to serve as non-invasive, easy to use, and rapid diagnostic or prognostic indicators.

Grapefruit Training Model for Distal Anterior Cerebral Artery Side-to-Side Bypass.

OBJECTIVE: Simulation models enable trainees to master microsurgical skills before performing surgeries. Vascular bypass is a critical component of cerebrovascular and many nonneurologic procedures. However, most available bypass training models lack important spatial, tactile, and physiologic aspects of real surgery. Animal and placental models provide true physiology but are expensive. While some models adequately simulate superficial temporal artery-middle cerebral artery bypass, there is no model for side-to-side distal anterior cerebral artery bypass. The objective is to create a realistic and inexpensive training model for this important procedure. METHODS: The depth of interhemispheric fissures in cadaver brains was compared with the grapefruit radii. Grapefruits were dissected to simulate the operative field within the deep and narrow interhemispheric fissure. Pericallosal arteries were mimicked with chicken wing vessels or synthetic tubing, with an aquarium pump providing closed circulation. Twelve board-certified neurosurgeons who were given bypass training using the grapefruit model were blindly surveyed on model realism and training suitability. RESULTS: Grapefruit depths from pith to central column were comparable with interhemispheric cadaveric fissure depths. Approximate preparation time of grapefruit training models was 5-10 minutes. Surveyed neurosurgeons rated the model a better replicate for cerebral artery bypass (P < 0.02) and more challenging than common training models (P < 0.01). They also rated the grapefruit model as likely to be superior for improving surgical skills before surgery (P < 0.05). CONCLUSIONS: This grapefruit model provides a realistic simulation of side-to-side distal anterior cerebral artery bypass procedure that can be inexpensively and easily implemented in nearly any resource environment.

Effect of perioperative aspirin use on hemorrhagic complications in elective craniotomy for brain tumors: results of a single-center, retrospective cohort study.

OBJECTIVE: In daily practice, neurosurgeons face increasing numbers of patients using aspirin (acetylsalicylic acid, ASA). While many of these patients discontinue ASA 7-10 days prior to elective intracranial surgery, there are limited data to support whether or not perioperative ASA use heightens the risk of hemorrhagic complications. In this study the authors retrospectively evaluated the safety of perioperative ASA use in patients undergoing craniotomy for brain tumors in the largest elective cranial surgery cohort reported to date. METHODS: The authors retrospectively analyzed the medical records of 1291 patients who underwent elective intracranial tumor surgery by a single surgeon from 2007 to 2017. The patients were divided into three groups based on their perioperative ASA status: 1) group 1, no ASA; 2) group 2, stopped ASA (low cardiovascular risk); and 3) group 3, continued ASA (high cardiovascular risk). Data collected included demographic information, perioperative ASA status, tumor characteristics, extent of resection (EOR), operative blood loss, any hemorrhagic and thromboembolic complications, and any other complications. RESULTS: A total of 1291 patients underwent 1346 operations. The no-ASA group included 1068 patients (1112 operations), the stopped-ASA group had 104 patients (108 operations), and the continued-ASA group had 119 patients (126 operations). The no-ASA patients were significantly younger (mean age 53.3 years) than those in the stopped- and continued-ASA groups (mean 64.8 and 64.0 years, respectively; p < 0.001). Sex distribution was similar across all groups (p = 0.272). Tumor locations and pathologies were also similar across the groups, except for deep tumors and schwannomas that were relatively less frequent in the continued-ASA group. There were no differences in the EOR between groups. Operative blood loss was not significantly different between the stopped- (186 ml) and continued- (220 ml) ASA groups (p = 0.183). Most importantly, neither hemorrhagic (0.6%, 0.9%, and 0.8%, respectively; p = 0.921) nor thromboembolic (1.3%, 1.9%, and 0.8%; p = 0.779) complication rates were significantly different between the groups, respectively. In addition, the multivariate model revealed no statistically significant predictor of hemorrhagic complications, whereas male sex (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.7-20.5, p = 0.005) and deep-extraaxial-benign ("skull base") tumors (OR 3.6, 95% CI 1.3-9.7, p = 0.011) were found to be independent predictors of thromboembolic complications. CONCLUSIONS: In this cohort, perioperative ASA use was not associated with the increased rate of hemorrhagic complications following intracranial tumor surgery. In patients at high cardiovascular risk, ASA can safely be continued during elective brain tumor surgery to prevent potential life-threatening thromboembolic complications. Randomized clinical trials with larger sample sizes are warranted to achieve a greater statistical power.

Platelet responses to silicon-alloyed pyrolytic carbons.

Pyrolytic carbon (PYC) containing approximately 7 wt % silicon is used in most clinical mechanical heart valves where it has demonstrated a high level of blood compatibility. The Si, present as SiC, is included since it is believed to enhance durability. However, it has been suggested that SiC reduces PYC blood compatibility. In the present study, PYC valve leaflets were prepared with low, conventional, and high levels of Si. The in vitro responses of human platelets to these materials were then quantified. Platelet responses were consistent with previous reports: Adherent platelets were extremely well spread, closely followed submicron contours, and formed very few aggregates or microthrombi-like structures. No significant differences with respect to the Si concentrations were observed for platelets adherent per unit area and the numbers of thrombi-like structures. Some differences were observed with platelet morphologies and the material surface covered with platelets, although these did not vary consistently with respect to Si concentration. These results indicate that lowering (or raising) the Si alloy concentration in PYC over a reasonable range (0.54-13.5 wt % as examined here) is unlikely to improve or otherwise alter the in vivo blood compatibility of this important clinical material.

Utilization of Capsules for Negative Staining of Viral Samples within Biocontainment.

Transmission electron microscopy (TEM) is used to observe the ultrastructure of viruses and other microbial pathogens with nanometer resolution. Most biological materials do not contain dense elements capable of scattering electrons to create an image; therefore, a negative stain, which places dense heavy metal salts around the sample, is required. In order to visualize viruses in suspension under the TEM they must be applied to small grids coated with a transparent surface only nanometers thick. Due to their small size and fragility, these grids are difficult to handle and easily moved by air currents. The thin surface is easily damaged, leaving the sample difficult or impossible to image. Infectious viruses must be handled in a biosafety cabinet (BSC) and some require a biocontainment laboratory environment. Staining viruses in biosafety levels (BSL)-3 and -4 is especially challenging because these environments are more turbulent and technicians are required to wear personal protective equipment (PPE), which decreases dexterity. In this study, we evaluated a new device to assist in negative staining viruses in biocontainment. The device is a capsule that works as a specialized pipette tip. Once grids are loaded into the capsule, the user simply aspirates reagents into the capsule to deliver the virus and stains to the encapsulated grid, thus eliminating user handling of grids. Although this technique was designed specifically for use in BSL-3 or -4 biocontainment, it can ease sample preparation in any lab environment by enabling easy negative staining of virus. This same method can also be applied to prepare negative stained TEM specimens of nanoparticles, macromolecules and similar specimens.

Preparation of viral samples within biocontainment for ultrastructural analysis: Utilization of an innovative processing capsule for negative staining.

Transmission electron microscopy can be used to observe the ultrastructure of viruses and other microbial pathogens with nanometer resolution. In a transmission electron microscope (TEM), the image is created by passing an electron beam through a specimen with contrast generated by electron scattering from dense elements in the specimen. Viruses do not normally contain dense elements, so a negative stain that places dense heavy metal salts around the sample is added to create a dark border. To prepare a virus sample for a negative stain transmission electron microscopy, a virus suspension is applied to a TEM grid specimen support, which is a 3mm diameter fragile specimen screen coated with a few nanometers of plastic film. Then, deionized (dI) water rinses and a negative stain solution are applied to the grid. All infectious viruses must be handled in a biosafety cabinet (BSC) and many require a biocontainment laboratory environment. Staining viruses in biosafety levels (BSL) 3 and 4 is especially challenging because the support grids are small, fragile, and easily moved by air currents. In this study we evaluated a new device for negative staining viruses called mPrep/g capsule. It is a capsule that holds up to two TEM grids during all processing steps and for storage after staining is complete. This study reports that the mPrep/g capsule method is valid and effective to negative stain virus specimens, especially in high containment laboratory environments.

New photoactivators for multiphoton excited three-dimensional submicron cross-linking of proteins: bovine serum albumin and type 1 collagen.

We report the synthesis and optical characterization of two new photoactivators and demonstrate their use for multiphoton excited three-dimensional free-form fabrication with proteins. These reagents were developed with the goal of cross-linking Type 1 collagen. This cross-linking process produces structures on the micron and submicron size scales. A rose bengal diisopropyl amine derivative combines the classic photoactivator and co-initiator system into one molecule, reducing the reaction kinetics and increasing cross-linking efficiency. This derivative was successful at producing stable structures from collagen, whereas rose bengal alone was not effective. A benzophenone dimer connected by a flexible diamine tether was also synthesized. This activator has two photochemically reactive groups and is highly efficient in cross-linking bovine serum albumin and Type 1 collagen to form stable, robust structures. This approach is more flexible in terms of cross-linking a variety of proteins than by traditional benzophenone photochemistry. The photophysical properties vary greatly from that of benzophenone, with the appearance of a new, lower energy absorption band (lambda max approximately 370 nm in water) and broad, visible emission band (approximately 500 nm maximum). This absorption band is highly solvatochromic, suggesting it arises, at least in part, from a charge transfer interaction. Collagens are typically difficult to cross-link photochemically, and the results here suggest that these two new activators will be suitable for cross-linking other forms of collagen and additional proteins for biomedical applications such as the de novo assembly of biomimetic tissue scaffolds.