Mechanistic insight into biotransformation of novel triazine-based flame retardant 1,3,5-tris(2,3-dibromopropyl)-1,3,5-triazinane-2,4,6-trione by human cytochrome P450s.

The escalating focus on the environmental occurrence and toxicology of emerging pollutants underscores the imperative need for a profound exploration of their metabolic transformations mediated by human CYP450 enzymes. Such investigations have the potential to unravel the intricate metabolite profiles, substantially altering the toxicological outcomes. In this study, we integrated the computational simulations with in vitro metabolism experiments to investigate the metabolic activity and mechanism of an emerging pollutant, 1,3,5-tris(2,3-dibromopropyl)-1,3,5-triazinane-2,4,6-trione (TDBP-TAZTO), catalyzed by human CYP450s.

Anemia and Optimal Transfusion Thresholds in Brain-Injured Patients: A Narrative Review of the Literature.

Anemia is a highly prevalent condition that may compromise oxygen delivery to vital organs, especially among the critically ill. Although current evidence supports the adoption of a restrictive transfusion strategy and threshold among the nonbleeding critically ill patient, it remains unclear whether this practice should apply to the brain-injured patient, given the predisposition to cerebral ischemia in this patient population, in which even nonprofound anemia may exert a detrimental effect on clinical outcomes. The purpose of this review is to provide an overview of the pathophysiological changes related to impaired cerebral oxygenation in the brain-injured patient and to present the available evidence on the effect of anemia and varying transfusion thresholds on the clinical outcomes of patients with acute brain injury.

Enantioselective metabolism of novel chiral insecticide Paichongding by human cytochrome P450 3A4: A computational insight.

As a novel chiral neonicotinoid insecticide, Paichongding (IPP) has been widely applied in agriculture due to its excellent insecticidal activity. However, the enantioselective metabolism of IPP stereoisomers (5R7R-IPP, 5S7S-IPP, 5R7S-IPP, and 5S7R-IPP) mediated by enzymes in non-target organisms, especially the cytochrome P450s (CYPs), remains unknown. To address this knowledge gap, we developed an integrated computational framework to elucidate the binding interactions and enantioselective metabolism of IPP stereoisomers in human CYP3A4.

Accurate identification and measurement of the precipitate area by two-stage deep neural networks in novel chromium-based alloys.

The performance of advanced materials for extreme environments is underpinned by their microstructure, such as the size and distribution of nano- to micro-sized reinforcing phase(s). Chromium-based superalloys are a recently proposed alternative to conventional face-centred-cubic superalloys for high-temperature applications, , Concentrated Solar Power. Their development requires the determination of precipitate volume fraction and size distribution using Electron Microscopy (EM), as these properties are crucial for the thermal stability and mechanical properties of chromium superalloys.

Compact A15 Frank-Kasper nano-phases at the origin of dislocation loops in face-centred cubic metals.

It is generally considered that the elementary building blocks of defects in face-centred cubic (fcc) metals, e.g., interstitial dumbbells, coalesce directly into ever larger 2D dislocation loops, implying a continuous coarsening process.

Regional Anesthesia Techniques in Modern Neuroanesthesia Practice: A Narrative Review of the Clinical Evidence.

Neurosurgical procedures are often associated with significant postoperative pain that is both underrecognized and undertreated. Given the potentially undesirable side effects associated with general anesthesia and with various pharmacological analgesic regimens, regional anesthetic techniques have gained in popularity as alternatives for providing both anesthesia and analgesia for the neurosurgical patient. The aim of this narrative review is to present an overview of the regional techniques that have been incorporated and continue to be incorporated into modern neuroanesthesia practice, presenting in a comprehensive way the evidence, where available, in support of such practice for the neurosurgical patient.

Multimodal Analgesia and Intraoperative Neuromonitoring.

Intraoperative neuromonitoring has been a valuable tool for ensuring the functional integrity of vital neural structures by providing real-time feedback to the operative team during procedures where neurological structures are at risk. Commonly used intravenous and inhaled anesthetic drugs are known to affect waveform parameters measured with various intraoperative neuromonitoring modalities. While the concept of opioid-sparing multimodal analgesia has gained popularity in recent years, the impact of such a strategy on intraoperative neuromonitoring remains poorly characterized, in contrast to the more well-established concepts and literature regarding the effects of other hypnotic agents on neuromonitoring quality.

Electroencephalographic Burst-Suppression, Perioperative Neuroprotection, Postoperative Cognitive Function, and Mortality: A Focused Narrative Review of the Literature.

Burst-suppression is an electroencephalographic pattern that results from a diverse array of pathophysiological causes and/or metabolic neuronal suppression secondary to the administration of anesthetic medications. The purpose of this review is to provide an overview of the physiological mechanisms that underlie the burst-suppression pattern and to present in a comprehensive way the available evidence both supporting and in opposition to the clinical use of this electroencephalographic pattern as a therapeutic measure in various perioperative settings.

Optimal Hemodynamic Parameters for Brain-injured Patients in the Clinical Setting: A Narrative Review of the Evidence.

Defining optimal hemodynamic targets for brain-injured patients is a challenging undertaking. The physiological interference observed in various intracranial pathologies can have varying effects on cerebral physiology at different time points. This narrative review provides an overview of cerebral autoregulatory physiology and common misconceptions, and examines the physiological considerations and clinical evidence for determining optimal hemodynamic parameters in acutely brain-injured patients with relevance to modern neuroanesthesia and neurocritical care practice.

Correlation Between Processed Electroencephalogram and Clinical Findings During Wake-Up Test in Prone Position for Scheduled Posterior Cervical Spine Surgery: A Case Report.

A 65-year-old man undergoing posterior cervical decompression and fusion demonstrated absent lower extremity evoked potential (EP) after prone positioning and before incision. Localized EP change pointed to either a technical or positional culprit. After excluding technical causes, we performed a wake-up test to rule out positioning as the culprit.

Awake Craniotomy in a Patient With History of Post-Traumatic Stress Disorder-A Clinical Dilemma: A Case Report.

A 32-year-old man undergoing awake craniotomy for tumor resection was previously diagnosed with post-traumatic stress disorder (PTSD)-typically a relative contraindication for awake craniotomy. Preoperative neurocognitive assessment and counseling by a neuroanesthesiologist and neuropsychologist were undertaken to characterize his PTSD, identify triggers, and prepare him for the intraoperative events. Dexmedetomidine and remifentanil were used as intraoperative anxiolytics and analgesics.

Effect of bilateral scalp nerve blocks on postoperative pain and discharge times in patients undergoing supratentorial craniotomy and general anesthesia: a randomized-controlled trial.

Purpose: Post-craniotomy pain is a common clinical issue and its optimal management remains incompletely studied. Utilization of a regional scalp block has the potential advantage of reducing perioperative pain and opioid consumption, thereby facilitating optimal postoperative neurologic assessment. The purpose of this study was to assess the efficacy of regional scalp block on post-craniotomy pain and opioid consumption.

Extensive and modular intrinsically disordered segments in C. elegans TTN-1 and implications in filament binding, elasticity and oblique striation.

TTN-1, a titin like protein in Caenorhabditis elegans, is encoded by a single gene and consists of multiple Ig and fibronectin 3 domains, a protein kinase domain and several regions containing tandem short repeat sequences. We have characterized TTN-1's sarcomere distribution, protein interaction with key myofibrillar proteins as well as the conformation malleability of representative motifs of five classes of short repeats. We report that two antibodies developed to portions of TTN-1 detect an approximately 2-MDa polypeptide on Western blots.

Titin as a giant scaffold for integrating stress and Src homology domain 3-mediated signaling pathways: the clustering of novel overlap ligand motifs in the elastic PEVK segment.

The richness of proline sequences in titins qualifies these giant proteins as the largest source of intrinsically disordered structures in nature. An extensive search and analysis for Src homology domain 3 (SH3) ligand motifs revealed a myriad of broadly distributed SH3 ligand motifs, with the highest density in the PEVK segments of human titin. Besides the canonical class I and II motifs with opposite orientations, novel overlapping motifs consisting of one or more of each canonical motif are abundant.

Titin PEVK segment: charge-driven elasticity of the open and flexible polyampholyte.

The giant protein titin spans half of the sarcomere length and anchors the myosin thick filament to the Z-line of skeletal and cardiac muscles. The passive elasticity of muscle at a physiological range of stretch arises primarily from the extension of the PEVK segment, which is a polyampholyte with dense and alternating-charged clusters. Force spectroscopy studies of a 51 kDa fragment of the human fetal titin PEVK domain (TP1) revealed that when charge interactions were reduced by raising the ionic strength from 35 to 560 mM, its mean persistence length increased from 0.

Binding of copper(II) ions to the polyproline II helices of PEVK modules of the giant elastic protein titin as revealed by ESI-MS, CD, and NMR.

Titin, a family of giant elastic proteins, constitutes an elastic sarcomere matrix in striated muscle. In the I-band region of the sarcomere, the titin PEVK segment acts as a molecular spring to generate elasticity as well as sites of adhesion with parallel thin filaments. Previously, we reported that PEVK consists of tandem repeats of 28 residue modules and that the "polyproline II-coil" motif is the fundamental conformational motif of the PEVK module.

Malleable conformation of the elastic PEVK segment of titin: non-co-operative interconversion of polyproline II helix, beta-turn and unordered structures.

To understand the structural basis of molecular elasticity and protein interaction of the elastic PEVK (Pro-Glu-Val-Lys) segment of the giant muscle protein titin, we carried out a detailed analysis of a representative PEVK module and a 16-module PEVK protein under various environmental conditions. Three conformational states, polyproline II (PPII) helix, beta-turn and unordered coil were identified by CD and NMR. These motifs interconvert without long-range co-operativity.

Interaction of nebulin SH3 domain with titin PEVK and myopalladin: implications for the signaling and assembly role of titin and nebulin.

Skeletal muscle nebulin is thought to determine thin filament length and regulate actomyosin interaction in a calcium/calmodulin or S100 sensitive manner. We have investigated the binding of nebulin SH3 with proline-rich peptides derived from the 28-mer PEVK modules of titin and the Z-line protein myopalladin, using fluorescence, circular dichroism and nuclear magnetic resonance techniques. Of the six peptides studied, PR2 of titin (VPEKKAPVAPPK) and myopalladin MyoP2 (646VKEPPPVLAKPK657) bind to nebulin SH3 with micromolar affinity (approximately 31 and 3.

Intramolecular quenching of tryptophan fluorescence by the peptide bond in cyclic hexapeptides.

Intramolecular quenching of tryptophan fluorescence by protein functional groups was studied in a series of rigid cyclic hexapeptides containing a single tryptophan. The solution structure of the canonical peptide c[D-PpYTFWF] (pY, phosphotyrosine) was determined in aqueous solution by 1D- and 2D-(1)H NMR techniques. The peptide backbone has a single predominant conformation.

An improved method of bronchial stump closure for prevention of bronchopleural fistula in pulmonary resection.

We performed 880 pulmonary resections from January 1982 to June 1988 using Sweet's procedure for closure of the bronchial stump, in which 39 patients (4.4%) developed bronchial fistulas. Bronchoscopic studies showed that bronchopleural fistulas were located mainly at the corner of the stump.