Trends in template/fragment-free protein structure prediction

Predicting the structure of a protein from its amino acid sequence is a long-standing unsolved problem in computational biology. Its solution would be of both fundamental and practical importance as the gap between the number of known sequences and the number of experimentally solved structures widens rapidly. Currently, the most successful approaches are based on fragment/template reassembly. Lacking progress in template-free structure prediction calls for novel ideas and approaches. This article reviews trends in the development of physical and specific knowledge-based energy functions as well as sampling techniques for fragment-free structure prediction. Recent physical- and knowledge-based studies demonstrated that it is possible to sample and predict highly accurate protein structures without borrowing native fragments from known protein structures. These emerging approaches with fully flexible sampling have the potential to move the field forward

Chronic ischemic stroke model in cynomolgus monkeys: Behavioral, neuroimaging and anatomical study

Previous nonhuman primate stroke models have employed temporary occlusion of arteries, had limited behavioral testing and imaging, and focused on the short-term outcome. Our goals were 1. to develop a stable model of chronic stroke in the nonhuman primate, 2. to study in vivo the long-term biochemical changes in the area adjacent to the infarct, using proton magnetic resonance spectroscopy ( 1 H MRS), and 3. evaluate these changes in relation to the histopathological effects of stroke. Four adult cynomologous monkeys had an occlusion of the M1 segment of the right MCA. Behavioral tests included a clinical rating scale, motor planning task, fine motor task, and activity monitoring. Eight months afterwards, MRI and 1 H MRS were performed. Following the imaging studies the monkeys were perfused transcardially, their brains extracted and processed. Nissl staining and immunohistochemistry for neuronal markers (NeuN) were performed and used to measure the lesion volume and neuronal optical density (OD). All animals developed a left hemiparesis and were unable to perform a fine motor task with the left hand. There was a significant (31%) decline in the motor planning ability with the nonparetic extremity. Monkeys displayed a stooped posture, episodes of rotation to the side of the lesion, partial left hemianopsia, and transient changes in activity. The clinical signs improved over the first 6-8 weeks but the deficits remained stable for the remaining six months of follow up. MRI demonstrated a subcortical and cortical infarction in the right MCA distribution. 1 H MRS data detected a significant decrease in the N-acetyl-aspartate (NAA)/creatine (Cr) ratio in the area adjacent to the infarction (VOI-St) compared to a mirror area in the contralateral hemisphere (VOI-Co). Histopathological measurements revealed a significant decline in neuronal crosssectional area and neuronal optical density in the region of the VOI-St. We established a stable and reproducible model of chronic stroke in the MCA distribution, in the macaque monkey. Our data indicate that NAA detected by 1 H MRS can be used to measure neuronal loss in vivo and help target this area for intervention. Our model may be particularly suitable for studies testing the effects of therapeutic strategies involving neural or stem cell transplantation, trophic factors or gene therapy

Analysis of magnetic resonance imaging–based blood and cerebrospinal fluid flow measurements in patients with Chiari I malformation: a system approach

Object A pilot study was performed to assess noninvasively the change in intracranial compliance (ICC) and intracranial pressure (ICP) in patients with Chiari I malformation who undergo foramen magnum decompression. The working hypothesis was that the main effect of the decompressive surgery is a change in ICP. Noninvasive cine phase-contrast magnetic resonance (MR) imaging is a motion-sensitive dynamic MR imaging technique that allows for visualization and quantitation of tissue motion and flow. The authors' group has used dynamic phase-contrast MR imaging to visualize and quantify pulsatile blood and cerebrospinal fluid (CSF) flow in the craniospinal system. Methods A system approach has been used to characterize the hemodynamic–hydrodynamic coupling in the craniospinal system and to derive measures for ICC and ICP. Magnetic resonance imaging–based ICC and ICP values are derived from the ratio of the volume and pressure changes that occur naturally during each cardiac cycle. The authors conducted a prospective study of four patients, three of whom were studied before and after decompressive surgery; significant change in MR imaging–derived ICC and ICP values was documented in only one of the three surgically treated patients. A significant change in the dynamics of the intracranial volume change (ICVC) during the cardiac cycle, however, was observed in all three patients. In healthy individuals the ICVC waveform usually consists of the following sequence: monotonic increase in intracranial volume (ICV) during the systolic phase due to increased blood inflow, monotonic decrease in ICV caused by the onset of CSF outflow into the spinal canal, and increase in the venous outflow. A nonmonotonic decline in the ICVC waveform has been observed in all patients with headaches, and a relatively normal waveform was found in those without headaches or whose headaches were resolved or alleviated by the surgery. A “partial-valve” mechanism is proposed as an explanation for the abnormal ICVC dynamics. The monotonic decline in ICVC is interrupted by a “premature” reduction in the CSF outflow. This may be caused by a displacement of the hindbrain into the cervical spinal canal during the systolic phase. This obstructs the CSF flow at the later part of the systolic phase such that the ICV does not continue its gradual decline. Postsurgery, the ICVC waveforms presented a more normal-appearing ICVC dynamics profile. Conclusions Magnetic resonance imaging measurement of transcranial CSF and blood flow may lead to a better understanding of the pathophysiology of Chiari malformations and may prove to be an important diagnostic tool for guiding for the treatment of patients with Chiari I malformation

Posterior Surgical Techniques for Cervical Spondylotic Myelopathy: WFNS Spine Committee Recommendations

Faris, Muhammad/0000-0002-8377-6773WOS: 000488270600006PubMed: 31607074Objective: This study was conducted to determine and recommend the most up-to-date information on the indications, complications, and outcomes of posterior surgical treatments for cervical spondylotic myelopathy (CSM) on the basis of a literature review. Methods: A comprehensive literature search was performed, using the MEDLINE (PubMed), the Cochrane Register of Controlled 'Fria's, and Web of Science databases, for peer-reviewed articles published in English during the last 10 years. Results: Posterior techniques, which include laminectomy alone, laminectomy with fusion, and laminoplasty, are often used in patients with involvement of 3 or more levels. Posterior decompression for CSM is effective for improving patients' neurological function. Complications resulting from posterior cervical spine surgery include injury to the spinal cord and nerve roots, complications related to posterior screw fixation or instrumentation, C5 palsy, spring-back closure of lamina, and postlaminectomy kyphosis. Conclusion: It is necessary to consider multiple factors when deciding on the appropriate operation for a particular patient. Surgeons need to tailor preoperative discussions to ensure that patients are aware of these facts. Further research is needed on the cost-to-benefit analysis of various surgical approaches, the comparative efficacy of surgical approaches using various techniques, and long-term outcomes, as current knowledge is deficient in this regard

Learning Retention of Thoracic Pedicle Screw Placement Using a High-Resolution Augmented Reality Simulator With Haptic Feedback

Background. In this study we evaluated the use of a part-task simulator with 3D and haptic feedback as a training tool for a common neurosurgical procedure – placement of thoracic pedicle screws. Objective. The purpose of this study was to evaluate the learning retention of thoracic pedicle screw placement on a high-performance augmented reality and haptic technology workstation. Methods. Fifty one fellows and residents performed thoracic pedicle screw placement on the simulator. The virtual screws were drilled into a virtual patient’s thoracic spine derived from a computed tomography data set of a real patient. Results: With a 12.5% failure rate, a two-proportion z-test yielded P= 0.08. For performance accuracy, an aggregate Euclidean distance deviation from entry landmark on the pedicle and a similar deviation from the target landmark in the vertebral body yielded P=0.04 from a two sample t-test in which the rejected null hypothesis assumes no improvement in performance accuracy from the practice to the test sessions, and the alternative hypothesis assumes an improvement. Conclusions. The performance accuracy on the simulator was comparable to the accuracy reported in literature on recent retrospective evaluation of such placements. The failure rates indicated a minor drop from practice to test sessions, and also indicated a trend (P=0.08) towards learning retention resulting in improvement from practice to test sessions. The performance accuracy showed a 15% mean score improvement and over 50% reduction in standard deviation from practice to test. It showed evidence (P=0.04) of performance accuracy improvement from practice to test session