Intraoperative Neurophysiological Monitoring During Spinal Cord Stimulation Surgery: A Systematic Review.

Objectives: This study aims to describe the state of literature regarding the use of intraoperative neurophysiological monitoring (IONM) during spinal cord stimulator surgery.

Materials And Methods: A systematic review of the use of IONM during spinal cord stimulation (SCS) surgery was performed using the following three data bases: PubMed, Ovid MEDLINE, and Embase. Research techniques included systematic research following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol by Cochrane, and backward searching.

Deep Brain Stimulation: When to Test Directional?

Background: Directional deep brain stimulation (DBS) allows for steering of the stimulation field, but extensive and time-consuming testing of all segmented contacts is necessary to identify the possible benefit of steering. It is therefore important to determine under which circumstances directional current steering is advantageous.

Methods: Fifty two Parkinson's disease patients implanted in the STN with a directional DBS system underwent a standardized monopolar programming session 5 to 9 months after implantation.

Intraoperative Motor Evoked Responses to Double-Train Paradigm Stimulation for Guiding Lead Placement and Postoperative Programming in Spinal Cord Stimulation for Pain.

Objective: We aimed to demonstrate the feasibility of using motor evoked responses to intraoperative double-train stimulation to guide lead placement and matching of intraoperative contacts with postoperative electrode programming in spinal cord stimulation for pain performed under general anesthesia.

Materials And Methods: The study included a series of 20 consecutive patients with refractory pain operated on under general anesthesia. Either percutaneous or paddle leads were implanted and positioned according to the intraoperative mapping results.

Electrical Stimulation for Cerebral Vasospasm After Subarachnoid Hemorrhage: A Systematic Review.

Objectives: Cerebral vasospasm is a severe and potentially lethal complication in patients with subarachnoid hemorrhage (SAH). Its pathogenesis is still not completely understood. The efficacy of current treatments, such as triple-H therapy or calcium channel blockers, is unsatisfactory, and a new therapy model would therefore be valuable.

Probabilistic Subthalamic Nucleus Stimulation Sweet Spot Integration Into a Commercial Deep Brain Stimulation Programming Software Can Predict Effective Stimulation Parameters.

Objectives: Subthalamic nucleus (STN) deep brain stimulation (DBS) programming in patients with Parkinson disease (PD) may be challenging, especially when using segmented leads. In this study, we integrated a previously validated probabilistic STN sweet spot into a commercially available software to evaluate its predictive value for clinically effective DBS programming.

Materials And Methods: A total of 14 patients with PD undergoing bilateral STN DBS with segmented leads were included.

Subthalamic and pallidal deep brain stimulation for Parkinson's disease-meta-analysis of outcomes.

Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the subthalamic nucleus (STN) has become an established treatment for Parkinson's disease (PD), a recent meta-analysis of outcomes is lacking. To address this gap, we performed a meta-analysis of bilateral STN- and GPi-DBS studies published from 1990-08/2019. Studies with ≥10 subjects reporting Unified Parkinson's Disease Rating Scale (UPDRS) III motor scores at baseline and 6-12 months follow-up were included.

Stereotactic posterior midline approach under direct microscopic view for biopsy of medulla oblongata tumors: technical considerations.

Background: Open and stereotactic transfrontal or transcerebellar approaches have been used to biopsy brainstem lesions.

Method: In this report, a stereotactic posterior and midline approach to the distal medulla oblongata under microscopic view is described. The potential advantages and limitations are discussed, especially bilateral damage of the X nerve nuclei.

Targeting the posterior subthalamic area for essential tremor: proposal for MRI-based anatomical landmarks.

Objective: Deep brain stimulation (DBS) of the posterior subthalamic area (PSA) is an alternative to thalamic DBS for the treatment of essential tremor (ET). The dentato-rubro-thalamic tract (DRTT) has recently been proposed as the anatomical substrate underlying effective stimulation. For clinical purposes, depiction of the DRTT mainly depends on diffusion tensor imaging (DTI)-based tractography, which has some drawbacks.

Exploring host-pathogen interactions through genome wide protein microarray analysis.

During bacterial pathogenesis extensive contacts between the human and the bacterial extracellular proteomes take place. The identification of novel host-pathogen interactions by standard methods using a case-by-case approach is laborious and time consuming. To overcome this limitation, we took advantage of large libraries of human and bacterial recombinant proteins.

Automated harvesting and 2-step purification of unclarified mammalian cell-culture broths containing antibodies.

Therapeutic monoclonal antibodies represent one of the fastest growing segments in the pharmaceutical market. The growth of the segment has necessitated development of new efficient and cost saving platforms for the preparation and analysis of early candidates for faster and better antibody selection and characterization. We report on a new integrated platform for automated harvesting of whole unclarified cell-culture broths, followed by in-line tandem affinity-capture, pH neutralization and size-exclusion chromatography of recombinant antibodies expressed transiently in mammalian human embryonic kidney 293T-cells at the 1-L scale.

Early developability screen of therapeutic antibody candidates using Taylor dispersion analysis and UV area imaging detection.

Therapeutic antibodies represent one of the fastest growing segments in the pharmaceutical market. They are used in a broad range of disease fields, such as autoimmune diseases, cancer, inflammation and infectious diseases. The growth of the segment has necessitated development of new analytical platforms for faster and better antibody selection and characterization.

Catalytic inhibition of topoisomerase II by a novel rationally designed ATP-competitive purine analogue.

Background: Topoisomerase II poisons are in clinical use as anti-cancer therapy for decades and work by stabilizing the enzyme-induced DNA breaks. In contrast, catalytic inhibitors block the enzyme before DNA scission. Although several catalytic inhibitors of topoisomerase II have been described, preclinical concepts for exploiting their anti-proliferative activity based on molecular characteristics of the tumor cell have only recently started to emerge.

The guinea-pig tracheal potential difference as an in vivo model for the study of epithelial sodium channel function in the airways.

Background And Purpose: The epithelial sodium channel (ENaC) is a key regulator of airway mucosal hydration and mucus clearance. Negative regulation of airway ENaC function is predicted to be of clinical benefit in the cystic fibrosis lung. The aim of this study was to develop a small animal model to enable the direct assessment of airway ENaC function in vivo.

Improved expression of kinases in Baculovirus-infected insect cells upon addition of specific kinase inhibitors to the culture helpful for structural studies.

As exemplified by three cases, we show that the addition of a small molecular weight inhibitor to the culture of Baculovirus-infected insect cells can dramatically improve the expression of a recombinant kinase. The expression of the tyrosine kinase KDR was sevenfold higher and mainly in a soluble form, when the KDR inhibitor PTK/ZK was added to the culture at the time of Baculovirus infection. The expression of the catalytic domain of the serine/threonine kinase PKCtheta, which is otherwise not possible with the Baculovirus expression system, was expressed mainly soluble at 120mg/L by the addition of the PKC inhibitor BIM XI to the culture of Baculovirus-infected insect cells.

Biochemical characterization of USP7 reveals post-translational modification sites and structural requirements for substrate processing and subcellular localization.

Ubiquitin specific protease 7 (USP7) belongs to the family of deubiquitinating enzymes. Among other functions, USP7 is involved in the regulation of stress response pathways, epigenetic silencing and the progress of infections by DNA viruses. USP7 is a 130-kDa protein with a cysteine peptidase core, N- and C-terminal domains required for protein-protein interactions.

Crystal structure of human estrogen-related receptor alpha in complex with a synthetic inverse agonist reveals its novel molecular mechanism.

Inverse agonists of the constitutively active human estrogen-related receptor alpha (ERRalpha, NR3B1) are of potential interest for several disease indications (e.g. breast cancer, metabolic diseases, or osteoporosis).

A semi-automated large-scale process for the production of recombinant tagged proteins in the Baculovirus expression system.

The efficient preparation of recombinant proteins at the lab-scale level is essential for drug discovery, in particular for structural biology, protein interaction studies and drug screening. The Baculovirus insect-cell expression system is one of the most widely applied and highly successful systems for production of recombinant functional proteins. However, the use of eukaryotic cells as host organisms and the multi-step protocol required for the generation of sufficient virus and protein has limited its adaptation to industrialized high-throughput operation.

Evidence for ligand-independent transcriptional activation of the human estrogen-related receptor alpha (ERRalpha): crystal structure of ERRalpha ligand binding domain in complex with peroxisome proliferator-activated receptor coactivator-1alpha.

The crystal structure of the ligand binding domain (LBD) of the estrogen-related receptor alpha (ERRalpha, NR3B1) complexed with a coactivator peptide from peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) reveals a transcriptionally active conformation in the absence of a ligand. This is the first x-ray structure of ERRalpha LBD, solved to a resolution of 2.5 A, and the first structure of a PGC-1alpha complex.

Crystal structure of the human RORalpha Ligand binding domain in complex with cholesterol sulfate at 2.2 A.

The retinoic acid-related orphan receptor alpha (RORalpha) is an orphan member of the subfamily 1 of nuclear hormone receptors. Our recent structural and functional studies have led to the hypothesis that cholesterol or a cholesterol derivative is the natural ligand of RORalpha. We have now solved the x-ray crystal structure of the ligand binding domain of RORalpha in complex with cholesterol-3-O-sulfate following a ligand exchange experiment.

Identification of natural ligands of retinoic acid receptor-related orphan receptor alpha ligand-binding domain expressed in Sf9 cells--a mass spectrometry approach.

The ligand-binding domain (LBD) of the human retinoic acid receptor-related orphan receptor (RORalpha-LBD), expressed in Sf9 cells, was purified and analyzed by electrospray ionization-mass spectrometry (ESI-MS). ESI-MS operated under native conditions showed the presence of a fortuitous ligand with molecular weight 386. Further analysis by gas chromatography-mass spectrometry (GC-MS) allowed the identification of the ligands bound to the LBD.

Estrogen receptor modulators: identification and structure-activity relationships of potent ERalpha-selective tetrahydroisoquinoline ligands.

As part of a program aimed at the development of selective estrogen receptor modulators (SERMs), tetrahydroisoquinoline derivative 27 was discovered by high throughput screening. Successive replacements of the p-F substituent of 27 by an aminoethoxy side chain and of the 1-H of the tetrahydroisoquinoline core by a 1-Me group provided analogues 19 and 20. These compounds showed potencies in a cell-based reporter gene assay (ERE assay) varying between 0.

X-ray structure of the hRORalpha LBD at 1.63 A: structural and functional data that cholesterol or a cholesterol derivative is the natural ligand of RORalpha.

The retinoic acid-related orphan receptor alpha (RORalpha) is an orphan member of the subfamily 1 of nuclear hormone receptors. No X-ray structure of RORalpha has been described so far, and no ligand has been identified. We describe the first crystal structure of the ligand binding domain (LBD) of RORalpha, at 1.

Therapies directed at vascular endothelial growth factor.

The inhibition of angiogenesis through vascular endothelial growth factor (VEGF) receptor targeting is a strategy that is relatively tumour selective. The high selectivity achieved with neutralising antibodies, soluble receptors and ribozymes reduces the risk of adverse reactions not related to VEGF inhibition itself. Small-molecule, orally-active protein kinase inhibitors provide an attractive alternative for chronic therapy, although specifically targeting a small subset of protein kinases from the approximately 550 expressed in mammalian cells is a challenge.

Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis.

Inhibitors of epidermal growth factor receptor (EGFR) signaling are among the novel drugs showing great promise for cancer treatment in the clinic. However, the possibility of acquired resistance to such drugs because of tumor cell genetic instabilities has not yet been explored. Here we report the experimental derivation and properties of such cell variants obtained from recurrent tumor xenografts of the human A431 squamous cell carcinoma, after two consecutive cycles of therapy with one of three different anti-EGFR monoclonal antibodies: mR3, hR3, or C225.