Nucleobase and Linker Modification for Triple-Helical Recognition of Pyrimidines in RNA Using Peptide Nucleic Acids.

Triple-helical recognition of any sequence of double-stranded RNA requires high affinity Hoogsteen hydrogen binding to pyrimidine interruptions of polypurine tracts. Because pyrimidines have only one hydrogen bond donor/acceptor on Hoogsteen face, their triple-helical recognition is a formidable problem. The present study explored various five-membered heterocycles and linkers that connect nucleobases to backbone of peptide nucleic acid (PNA) to optimize formation of X•C-G and Y•U-A triplets. Molecular modeling and biophysical (UV melting and isothermal titration calorimetry) results revealed a complex interplay between the heterocyclic nucleobase and linker to PNA backbone. While the five-membered heterocycles did not improve pyrimidine recognition, increasing the linker length by four atoms provided promising gains in binding affinity and selectivity. The results suggest that further optimization of heterocyclic bases with extended linkers to PNA backbone may be a promising approach to triple-helical recognition of RNA.

Asynchronous magnetic resonance elastography: Shear wave speed reconstruction using noise correlation of incoherent waves.

PURPOSE: The noninvasive measurement of biological tissue elasticity is an evolving technology that enables the robust characterization of soft tissue mechanics for a wide array of biomedical engineering and clinical applications. We propose, design, and implement here a new MRI technique termed asynchronous magnetic resonance elastography (aMRE) that pushes the measurement technology toward a driverless implementation. This technique can be added to clinical MRI scanners without any additional specialized hardware. THEORY: Asynchronous MRE is founded on the theory of diffuse wavefields and noise correlation previously developed in ultrasound to reconstruct shear wave speeds using seemingly incoherent wavefields. Unlike conventional elastography methods that solve an inverse problem, aMRE directly reconstructs a pixel-wise mapping of wave speed using the spatial-temporal statistics of the measured wavefield. METHODS: Incoherent finger tapping served as the wave-generating source for all aMRE measurements. Asynchronous MRE was performed on a phantom using a Siemens Prismafit as an experimental validation of the theory. It was further performed on thigh muscles as a proof-of-concept implementation of in vivo imaging using a Siemens Skyra scanner. RESULTS: Numerical and phantom experiments show an accurate reconstruction of wave speeds from seemingly noisy wavefields. The proof-of-concept thigh experiments also show that the aMRE protocol can reconstruct a pixel-wise mapping of wave speeds. CONCLUSION: Asynchronous MRE is shown to accurately reconstruct shear wave speeds in phantom experiments and remains at the proof-of-concept stage for in vivo imaging. After further validation and improvements, it has the potential to lower both the technical and monetary barriers of entry to measuring tissue elasticity.

Series of M-MOF-184 (M = Mg, Co, Ni, Zn, Cu, Fe) Metal-Organic Frameworks for Catalysis Cycloaddition of CO2.

In light of the chemical exploitation of CO2, new reusable materials for efficiently catalyzing the cycloaddition of CO2 and epoxides under moderate conditions are needed. Herein, a new series of isostructural metal-organic frameworks (MOFs) M2(EDOB) [EDOB4- = 4,4'-(ethyne-1,2-diyl)bis(2-oxidobenzoate), M = Mg, Ni, Co, Zn, Cu, Fe], known as M-MOF-184, analogous to a well-studied MOF-74 structure, were synthesized and fully characterized. The M-MOF-184 (M = Mg, Co, Ni, Zn) frameworks exhibit accessible mesopore channels (24 Å) and high porosity. Among them, Mg-MOF-184 demonstrated the most upper surface area (>4000 m2 g-1) in any reported MOF-74-type frameworks. Furthermore, Co-MOF-184 revealed the highest CO2 uptake (73 cm3 g-1, at 298 K), and Zn-MOF-184 showed the highest catalytic activity upon the cycloaddition of CO2 (96% conversion, 86% selectivity, and 82% yield) under mild conditions (1 atm CO2, 80 °C, 6 h, and solvent-free). Notably, the catalytic performance of Zn-MOF-184 outperformed that of the original M-MOF-74 (M = Mg, Co, Zn) materials and various Zn-based MOFs. To evaluate the acidity and basicity of a series of M-MOF-184 (M = Mg, Co, Ni, Zn) frameworks, the interaction of these MOFs with acetonitrile vapor was investigated by vapor adsorption and ATR-FTIR spectroscopy measurements. As such, Zn-MOF-184 showed the strongest Lewis acidity derived by Zn cations, which was correlated to the highest catalytic activity upon the cycloaddition of CO2. Interestingly, the 2-oxidobenzoate anions from Co-MOF-184 showed the strongest basicity among the series, which was associated with the highest saturated acetonitrile uptake (544 cm3 g-1 at 298 K). Our findings suggest that the integration of Lewis acidic and basic sites, high surface area, and large accessible pores into the framework can facilitate the CO2 fixation reaction.

Contrast-Enhanced Cardiac Magnetic Resonance Imaging With a Manganese-Based Alternative to Gadolinium for Tissue Characterization of Acute Myocardial Infarction.

Background Late gadolinium enhancement cardiac magnetic resonance imaging is an effective and reproducible method for characterizing myocardial infarction. However, gadolinium-based contrast agents are contraindicated in patients with acute and chronic renal insufficiency. In addition, several recent studies have noted tissue deposition of free gadolinium in patients who have undergone serial contrast-enhanced magnetic resonance imaging. There is a clinical need for alternative forms of magnetic resonance imaging contrast agents that are acceptable in the setting of renal insufficiency. Methods and Results Three days after 80 minutes of ischemia/reperfusion of the left anterior descending coronary artery, cardiac magnetic resonance imaging was performed to assess myocardial lesion burden using both contrast agents. Late gadolinium enhancement cardiac magnetic resonance imaging was examined 10 and 15 minutes after contrast injection. Contrast agents were administered in alternating manner with a 2- to 3-hour washout period between contrast agent injections. Lesion evaluation and image processing were performed using Segment Medviso software. Mean infarct size and transmurality, measured using RVP-001, were not different compared with those measured using late gadolinium enhancement images. Bland-Altman analysis demonstrated a nominal bias of 0.13 mL (<1% of average total lesion volume) for RVP-001 in terms of gross infarct size measurement. Conclusions The experimental manganese-based contrast agent RVP-001 appears to be an effective agent for assessment of myocardial infarction location, size, and transmurality, and it may be useful as an alternative to gadolinium-based agents.

A simple and cost-effective model for ventricular catheter placement training: technical note.

OBJECTIVE: External ventricular drain (EVD) placement is one of first cranial procedures neurosurgery residents are expected to perform independently. While proper training improves patient outcomes, there are few options for practicing EVD placement prior to placing the EVD in patients in a clinical setting. Proposed solutions to this include using cadaveric models and virtual simulations, but barriers exist with these as well in regard to authenticity. EVD simulators using virtual reality technologies are a promising new technique for training, but the cost of these devices poses a barrier to general/widespread accessibility among smaller programs or underserved hospitals. The authors desribe a novel, yet simple, and cost-effective technique (less than $5 per mold) for developing a brain model constructed of homemade ballistics gelatin that can be used for teaching and practicing the placement of EVD. METHODS: A brain model is made with ballistics gelatin using an anatomically correct skull model as a mold. A 3D-printed ventricular system model is used to create a mold of an anatomically correct ventricular system in the brain model. A group of medical students (n = 10) were given a basic presentation about EVD placement, including standard landmarks and placement techniques, and were also shown a demonstration of EVD placement on the brain model. They were then allowed to perform an EVD placement using the brain model. The students were surveyed on their experience with using the brain model, including usability and practicality of the model. Accuracy of EVD placement by each student was also assessed, with adequate position of catheter tip being in the ipsilateral frontal horn. RESULTS: The final product is fairly inexpensive and easy to make. It is soft enough to pass a catheter through, but it is also firm enough to maintain its shape, including a cavity representing the lateral ventricles. The dense gelatin holds the catheter in its final resting position, while the two halves are separated and inspected. All participants in the test group of medical students reported that the brain model was easy to use, helped them understand the steps and technique of EVD placement, and provided good feedback on the ideal position of ventricular catheters. All of the participants in the group had adequate positioning of their ventricular catheters after one attempt. CONCLUSIONS: The presented brain model is easy to replicate, inexpensive, anatomically accurate, and provides a medium for neurosurgeons to teach and practice ventricular catheter placement in a risk-free environment.

Sellar/Suprasellar Ganglioglioma: Clinical Image.

BACKGROUND: This report presents a rare presentation of a ganglioglioma in the sellar/suprasellar region. On the basis of the patient's presentation and imaging characteristics, the initial diagnosis was craniopharyngioma. While gangliogliomas are already rare brain tumors that are usually found in the frontal and temporal lobes of young patients, the presentation of this tumor in the sellar region is exceedingly rare. CASE DESCRIPTION: A 25-year-old male presented to the emergency department with headache, agitation, and combativeness. A head computed tomography scan showed a sellar/suprasellar mass with mixed solid and cystic components and peripheral calcifications. The mass compressed the third ventricle and cerebral aqueduct, resulting in obstructive hydrocephalus. The patient was intubated for decline in mental status and combativeness. A ventricular drain was placed emergently. A pituitary function panel did not show endocrine dysfunction. Magnetic resonance imaging showed a 3.6 cm × 4.2 cm solid mass in the sellar/suprasellar region with a cystic component. The mass displaced the adenohypophysis and extended into the prepontine and interpedicular cisterns. The clinical presentation and radiologic characteristics led to an initial diagnosis of craniopharyngioma. The patient underwent a right pterional craniotomy and transsylvian approach for resection of mass without complication, although a subtotal resection was achieved due to adherence of the tumor to optic nerves and carotid arteries. The resected specimen was diagnosed as ganglioglioma. CONCLUSIONS: This case is a reminder of how much the field of neurosurgery relies on imaging modalities but also emphasizes the importance of histopathology in the field of brain tumors.

Dural Sandwich Technique for Hemicraniectomy and Benefits During Cranioplasty.

OBJECTIVE: Hemicraniectomy is a commonly performed neurosurgical procedure used in the setting of medically refractory malignant intracranial hypertension. Complications from cranioplasty after hemicraniectomy can be significant, including infection and wound issues. Difficulty with scar tissue during exposure for cranioplasty can be challenging and can lead to prolonged surgical time and increased bleeding. We describe a surgical technique, termed the "dural sandwich," that could provide a significant benefit during cranioplasty as compared with traditional single-layered dural closure. METHODS: A retrospective analysis was conducted that included 14 patients who underwent a hemicraniectomy procedure over a 4-year period. Seven patients were identified who received a cranioplasty after dural sandwich technique during craniectomy. They were compared with a similar patient group of 7 patients who received a cranioplasty after conventional hemicraniectomy with single-layered dural closure. Surgical time, estimated blood loss, and complication rates were compared between the 2 groups. Analysis of variance measures were performed to assess for statistically significant differences in blood loss and operative time between the dural sandwich and control groups. Statistical significance was defined as P < 0.05. RESULTS: The mean estimated blood loss was 82.1 mL in the dural sandwich craniectomy group versus 150 mL in the conventional hemicraniectomy group (P < 0.05). The mean estimated surgical time was 91.7 minutes in the dural sandwich craniectomy group versus 127.5 minutes in the conventional craniectomy group (P < 0.05). There was no evidence of neurologic deterioration, cerebral spinal fluid leak, or postoperative hematoma requiring evacuation in either group. In the conventional craniectomy group, a single report of a wound infection was noted that was treated conservatively with antibiotics. CONCLUSIONS: By layering bovine pericardium above and below the dura during initial hemicraniectomy, an artificial plane is created that improves ease of exposure during cranioplasty. This technique could reduce surgical time and blood loss during subsequent cranioplasty, and potentially reduce recovery time and postoperative complications.

Pediatric occipital condyle morphometric analysis using computed tomography with evaluation for occipital condyle screw placement.

OBJECTIVEOccipitocervical fusions in the pediatric population are rare but can be challenging because of the smaller anatomy. The procedure is even more exacting in patients with prior suboccipital craniectomy. A proposed method for occipitocervical fusion in such patients is the use of occipital condyle screws. There is very limited literature evaluating the pediatric occipital condyle for screw placement. The authors examined the occipital condyle in pediatric patients to determine if there was an age cutoff at which condylar screw placement is contraindicated.METHODSThe authors performed a retrospective morphometric analysis of the occipital condyle in 518 pediatric patients aged 1 week-9 years old. Patients in their first decade of life whose occipital condyle was demonstrated on CT imaging in the period from 2009 to 2013 at the Augusta University Medical Center and Children's Hospital of Georgia were eligible for inclusion in this study. Exclusion criteria were an age older than 10 years; traumatic, inflammatory, congenital, or neoplastic lesions of the occipital condyles; and any previous surgery of the occipitocervical junction. Descriptive statistical analysis was performed including calculation of the mean, standard deviation, and confidence intervals for all measurements. Probability values were calculated using the Student t-test with statistical significance determined by p < 0.05.RESULTSOverall, male patients had statistically significantly larger occipital condyles than the female patients, but this difference was not clinically significant. There was no significant difference in left versus right occipital condyles. There were statistically significant differences between age groups with a general trend toward older children having larger occipital condyles. Overall, 20.65% of all patients evaluated had at least one measurement that would prevent occipital condyle screw placement including at least one patient in every age group.CONCLUSIONSOccipital condyle screw fixation is feasible in pediatric patients younger than 10 years. More importantly, all pediatric patients should undergo critical evaluation of the occipital condyle in the axial, sagittal, and coronal planes preoperatively to determine individual suitability for occipital condyle screw placement.

Active Viscoelasticity of Sarcomeres.

The perturbation response of muscle is important for the versatile, stable and agile control capabilities of animals. Muscle resists being stretched by developing forces in the passive tissues and in the active crossbridges. This review focuses on the active perturbation response of the sarcomere. The active response exhibits typical stress relaxation, and thus approximated by a Maxwell material that has a spring and dashpot arranged in series. The ratio of damping to stiffness in this approximation defines the relaxation timescale for dissipating stresses that are developed in the crossbridges due to external perturbations. Current understanding of sarcomeres suggests that stiffness varies nearly linearly with neural excitation, but not much is known about damping. But if both stiffness and damping have the same functional (linear or not) dependence on neural excitation, then the stress relaxation timescale cannot be varied depending on the demands of the task. This implies an unavoidable and biologically unrealistic trade-off between how freely the crossbridges can yield and dissipate stresses when stretched (injury avoidance in agile motions) vs. how long they can maintain perturbation-induced stresses and behave like a solid material (stiffness maintenance for stability). We hypothesize that muscle circumvents this trade-off by varying damping in a nonlinear manner with neural excitation, unlike stiffness that varies linearly. Testing this hypothesis requires new experimental and mathematical characterization of muscle mechanics, and also identifies new design goals for robotic actuators.

The intercostal nerve as a target for diagnostic biopsy.

OBJECTIVE Peripheral nerve biopsy is a useful tool in diagnosing peripheral neuropathies. Sural and gracilis nerves have become the most common targets for nerve biopsy. However, the yield of sural nerve biopsy is limited in patients who have motor neuropathies, and gracilis nerve biopsy presents technical challenges and increased complications. The authors propose the intercostal nerve as an alternative motor nerve target for biopsy. METHODS A total of 4 patients with suspected peripheral neuropathies underwent intercostal nerve biopsy at the authors' institution. A rib interspace that is inferior to the pectoralis muscle and anterior to the anterior axillary line is selected for the procedure. Generally the lower intercostal nerves (i.e., T7-11) are targeted. An incision is made over the inferior aspect of the superior rib at the chosen interspace. Blunt dissection is carried down to the neurovascular bundle and the nerve is isolated, ligated, and cut to send for pathological examination. RESULTS The average operative time for all cases was 73 minutes, with average blood loss of 8 ml. Biopsy results from 1 patient exhibited axonopathy, and the other 3 patients demonstrated axonopathy with demyelination. There were no short- or long-term postoperative complications. None of the patients reported sensory or motor deficits related to the biopsy at 6 weeks postoperatively. CONCLUSIONS The intercostal nerve can be an alternative target for biopsy, especially in patients with predominantly motor neuropathies, due to its mixed sensory and motor fibers, straightforward anatomy, minimal risk of serious sensory deficits, and no risk of motor impairment.

Bilateral transverse sinus stenosis causing intracranial hypertension.

Idiopathic intracranial hypertension (IIH) has been associated with transverse sinus stenosis in a number of cases. Some authors advocate for stent placement when transverse sinus stenosis is responsible for pseudotumor symptoms. A 19-year-old man with IIH, bilateral transverse sinus stenosis was apparent on a CT venography, with reconstitution of the lateral sinus. MRI was then performed, and transverse sinus stenosis was confirmed. An impressive network of dilated collateral veins became apparent on VENBOLD sequences. Treatment options in this case include cerebrospinal fluid (CSF) shunting, optic nerve fenestrations and transverse sinus stenting. A ventriculoperitoneal shunt was placed in this patient, with prompt resolution of pseudotumor symptoms.