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The spontaneous l-isoaspartate protein modification has been observed to negatively affect protein function. However, this modification can be reversed in many proteins in reactions initiated by the protein-l-isoaspartyl (d-aspartyl) O-methyltransferase (PCMT1). It has been hypothesized that an additional mechanism exists in which l-isoaspartate-damaged proteins are recognized and proteolytically degraded. Herein, we describe the protein-l-isoaspartate O-methyltransferase domain-containing protein 1 (PCMTD1) as a putative E3 ubiquitin ligase substrate adaptor protein. The N-terminal domain of PCMTD1 contains l-isoaspartate and S-adenosylmethionine (AdoMet) binding motifs similar to those in PCMT1. This protein also has a C-terminal domain containing suppressor of cytokine signaling (SOCS) box ubiquitin ligase recruitment motifs found in substrate receptor proteins of the Cullin-RING E3 ubiquitin ligases. We demonstrate specific PCMTD1 binding to the canonical methyltransferase cofactor S-adenosylmethionine (AdoMet). Strikingly, while PCMTD1 is able to bind AdoMet, it does not demonstrate any l-isoaspartyl methyltransferase activity under the conditions tested here. However, this protein is able to associate with the Cullin-RING proteins Elongins B and C and Cul5 in vitro and in human cells. The previously uncharacterized PCMTD1 protein may therefore provide an alternate maintenance pathway for modified proteins in mammalian cells by acting as an E3 ubiquitin ligase adaptor protein.Three novel furo-naphthoquinones, enceleamycins A-C (1-3), and a new N-hydroxypyrazinone acid (4) were identified from the strain Amycolatopsis sp. MCC 0218, isolated from a soil sample collected from the Western Ghats of India. Their chemical structure and absolute and relative configurations were established by 1D and 2D NMR spectroscopy, single-crystal X-ray crystallography, and high-resolution mass spectrometry. Compounds 1 and 3 were active against methicillin-susceptible and -resistant Staphylococcus aureus with MIC values of 2-16 μg/mL.

Microvascular decompression (MVD) is the only potential cure for hemifacial spasm (HFS). However, traditional techniques such as the interposition method may have limited effect in some cases. Alternative techniques have been proposed; however, they can be more complex or difficult to perform than the standard approach.

To describe a safe decompression technique-the "shelter method"-which involves creating a shelter-like space around the facial nerve root exit zone and present associated outcomes.

Medical records and intraoperative findings of 92 patients with HFS who underwent MVD using the shelter method between April 1997 and March 2017 were retrospectively reviewed. As a historical control group, we included 53 patients who had undergone MVD by the traditional interposition method before March 1989. The patients were divided into 3 subgroups according to the arteries involved and degree or direction of arterial compression to the seventh nerve. Patient outcomes were assessed as excellent, good, fair, and poor according to the MVD scoring system of the Japan Society for MVD Surgery.

In the shelter method group, complete disappearance of HFS was achieved in 87 patients (94.6%). The curative rate of the shelter method group was significantly higher than that of the interposition method group. The overall complication rates were significantly lower in the shelter method group than in the interposition method group.

Our findings indicate high curative and low complication rates of the shelter method, suggesting that it helps treat HFS caused by various types of arterial compression.

Our findings indicate high curative and low complication rates of the shelter method, suggesting that it helps treat HFS caused by various types of arterial compression.

Increasingly there is an impetus on the part of surgeons to find more minimally invasive approaches to treat spinal pathologies. NSC 23766 supplier Retroperitoneal prepsoas and transpsoas approaches to the lumbar spine are one such example gaining increased attention. Endoscope-assisted approaches may help further reduce soft tissue dissection.

To describe an endoscope-assisted lateral retroperitoneal prepsoas approach for lumbar diskectomy.

Two fresh-frozen thoracolumbar cadaveric specimens were obtained and placed in the right lateral decubitus position. Using a left-sided, retroperitoneal prepsoas approach to the lumbar spine and under endoscopic visualization, diskectomies were performed at the L2/3, L3/4, L4/5, and L5/S1 intervertebral spaces. Qualitative assessment of the extent of central and contralateral foraminal decompression was performed.

The endoscope was found to provide effective visualization at all disk spaces and combined with the anterior retroperitoneal prepsoas approach allowed for effective decompression of all explored disk spaces. Both operators noted difficulty obtaining visualization of the ipsilateral foramen, but adequate central and contralateral foraminal decompression was achievable for central, paracentral, and contralateral far lateral disk protrusions.

Endoscope assistance may improve visualization of the lumbar intervertebral disk spaces during retroperitoneal prepsoas approaches and thereby help to expand the surgical indication for anterior and oblique lumbar interbody fusion.

Endoscope assistance may improve visualization of the lumbar intervertebral disk spaces during retroperitoneal prepsoas approaches and thereby help to expand the surgical indication for anterior and oblique lumbar interbody fusion.

The success of deep brain stimulation (DBS) surgery depends on the accuracy of electrode placement. Several factors can affect this such as brain shift, the quality of preoperative planning, and technical factors. It is crucial to determine whether techniques yield accurate lead placement and effective symptom relief. Many of the studies establishing the accuracy of frameless techniques used intraoperative imaging to further refine lead placement.

To determine whether awake lead placement without intraoperative imaging can achieve similar minimal targeting error while preserving clinical results.

Eighty-two trajectories in 47 patients who underwent awake, frameless DBS lead placement with the Fred Haer Corporation STarFix system for essential tremor or Parkinson's disease were analyzed. Neurological testing during lead placement was used to determine appropriate lead locations, and no intraoperative imaging was performed. Accuracy data were compared with previously performed studies.

The Euclidean error for the patient cohort was 1.79 ± 1.02 mm, and the Pythagorean error was 1.40 ± 0.95 mm. The percentage symptom improvement evaluated by the Unified Parkinson's Disease Rating Scale for Parkinson's disease or the Fahn-Tolosa-Marin scale for essential tremor was similar to reported values at 58% ± 17.2% and 67.4% ± 24.7%, respectively. The operative time was 95.0 ± 30.3 minutes for all study patients.

Awake, frameless DBS surgery with the Fred Haer Corporation STarFix system does not require intraoperative imaging for stereotactic accuracy or clinical effectiveness.

Awake, frameless DBS surgery with the Fred Haer Corporation STarFix system does not require intraoperative imaging for stereotactic accuracy or clinical effectiveness.

To ensure that epilepsy surgery is effective, accurate presurgical localization of the epileptogenic zone is essential. Our previous reports demonstrated that interictal high gamma oscillation (30-70 Hz) regularity (GOR) on intracranial electroencephalograms is related to epileptogenicity.

To examine whether preoperative GOR analysis with interictal high-density electroencephalography (HD-EEG) improves the accuracy of epileptogenic focus localization and enhances postoperative seizure control.

We calculated GOR from 20 seconds of HD-EEG data for 21 patients with refractory focal epilepsy (4 with nonlesional temporal lobe epilepsy) scheduled for epilepsy surgery. Low-resolution brain electromagnetic tomography was used to analyze the high GOR source. To validate our findings, we made comparisons with other conventional localization methods and postoperative seizure outcomes.

In all patients, the areas of interictal high GOR were identified and resected. All patients were seizure-free after the operation. The concordance between the results of interictal high GOR on HD-EEG and those of source estimation of interictal discharge was fully overlapping in 10 cases, partially overlapping in 8 cases, and discordant in 3 cases. The concordance between the results of interictal high GOR on HD-EEG and those of interictal 123 I-iomazenil single-photon emission computed tomography was fully overlapping in 8 cases, partially overlapping in 11 cases, and discordant in 2 cases. In 4 patients with nonlesional temporal lobe epilepsy, the interictal high GOR on HD-EEG was useful in confirming the epileptogenic zone.

The interictal high GOR on HD-EEG is an excellent marker for presurgical epileptogenic zone localization.

The interictal high GOR on HD-EEG is an excellent marker for presurgical epileptogenic zone localization.

There is a paucity of data in the literature describing quantitative exposure of the ventral craniocervical junction through the endonasal corridor in a safe manner mindful of locoregional anatomy.

To quantify ventromedial exposure of O-C1 and C1-2 articular structures after turning an inverted U-shaped nasopharyngeal flap (IUNF) and to obtain measurements assessing the distance of flap margins to adjacent neurovascular structures.

In 8 cadaveric specimens, an IUNF was fashioned using a superior incision below the level of the pharyngeal tubercule of the clivus and lateral incisions in the approximate region of Rosenmuller fossae bilaterally. Measurements with calipers and/or neuronavigation software included flap dimensions, exposure of O-C1 and C1-2 articular structures, inferior reach of IUNF, and proximity of the internal carotid artery (ICA) and hypoglossal nerve to IUNF margins.

The IUNF facilitated exposure of an average of 9 mm of the medial surfaces of the right/left O-C1 joints without transgression of the carotid arteries or hypoglossal nerves. The C1-2 articulation could not be routinely accessed. The margins of the IUNF were not in close (<5 mm) proximity to the ICA in any of the 8 specimens. In 6 of 8 specimens, the dimensions of the IUNF were in close (<5 mm) horizontal or vertical proximity to the hypoglossal foramina.

The IUNF provided safe and reliable access to the medial O-C1 articulation. Given the close proximity of the exocranial hypoglossal foramen, neuronavigation assistance and neuromonitoring with attention to the superolateral IUNF margin are recommended.

The IUNF provided safe and reliable access to the medial O-C1 articulation. Given the close proximity of the exocranial hypoglossal foramen, neuronavigation assistance and neuromonitoring with attention to the superolateral IUNF margin are recommended.The dynamics describing the vicious cycle characteristic of cystic fibrosis (CF) lung disease, initiated by stagnant mucus and perpetuated by infection and inflammation, remain unclear. Here we determine the effect of the CF airway milieu, with persistent mucoobstruction, resident pathogens, and inflammation, on the mucin quantity and quality that govern lung disease pathogenesis and progression. The concentrations of MUC5AC and MUC5B were measured and characterized in sputum samples from subjects with CF (N = 44) and healthy subjects (N = 29) with respect to their macromolecular properties, degree of proteolysis, and glycomics diversity. These parameters were related to quantitative microbiome and clinical data. MUC5AC and MUC5B concentrations were elevated, 30- and 8-fold, respectively, in CF as compared with control sputum. Mucin parameters did not correlate with hypertonic saline, inhaled corticosteroids, or antibiotics use. No differences in mucin parameters were detected at baseline versus during exacerbations.

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