Euchromatin histone-lysine N-methyltransferase 2 regulates the expression of potassium-sodium-activated channel subfamily T member 1 in primary sensory neurons and contributes to remifentanil-induced pain sensitivity.

Intraoperative remifentanil administration has been linked to increased postoperative pain sensitivity. Recent studies have identified the involvement of euchromatic histone-lysine N-methyltransferase 2 (Ehmt2/G9a) in neuropathic pain associated with the transcriptional silencing of many potassium ion channel genes. This study investigates whether G9a regulates the potassium sodium-activated channel subfamily T member 1 (Slo2.2) in remifentanil-induced post-incisional hyperalgesia (RIH) in rodents. We performed remifentanil infusion (1 µg·kg-1·min-1 for 60 min) followed by plantar incision to induce RIH in rodents. Our results showed that RIH was accompanied by increased G9a and H3K9me2 production and decreased Slo2.2 expression 48 h postoperatively. Deletion of G9a rescued Slo2.2 expression in DRG and reduced RIH intensity. Slo2.2 overexpression also reversed this hyperalgesia phenotype. G9a overexpression decreased Slo2.2-mediated leak current and increased excitability in the small-diameter DRG neurons and laminal II small-diameter neurons in the spinal dorsal horn, which was implicated in peripheral and central sensitization. These results suggest that G9a contributes to the development of RIH by epigenetically silencing Slo2.2 in DRG neurons, leading to decreased central sensitization in the spinal cord. The findings may have implications for the development of novel therapeutic targets for the treatment of postoperative pain.

Effects of essential amino acids supplementation in a low-protein diet on growth performance, intestinal health and microbiota of juvenile blotched snakehead (Channa maculata).

Developing a low-protein feed is important for the sustainable advancement of aquaculture. The aim of this study was to investigate the effects of essential amino acid (EAA) supplementation in a low-protein diet on the growth, intestinal health, and microbiota of the juvenile blotched snakehead, Channa maculata in an 8-week trial conducted in a recirculating aquaculture system. Three isoenergetic diets were formulated to include a control group (48.66 % crude protein (CP), HP), a low protein group (42.54 % CP, LP), and a low protein supplementation EAA group (44.44 % CP, LP-AA). The results showed that significantly lower weight gain (WG), specific growth rate (SGR), protein efficiency ratio (PER), and feed efficiency ratio (FER) were observed in fish that were fed LP than in the HP and LP-AA groups (P < 0.05). The HP and LP-AA groups exhibited a significant increase in intestinal villus length, villus width, and muscular thickness compared to the LP group (P < 0.05). Additionally, the HP and LP-AA groups demonstrated significantly higher levels of intestinal total antioxidant capacity (T-AOC), catalase (CAT), and superoxide dismutase (SOD) and lower levels of malondialdehyde (MDA) compared to the LP group (P < 0.05). The apoptosis rate of intestinal cells in the LP group was significantly higher than those in the LP and HP groups (P < 0.05). The mRNA expression levels of superoxide dismutase (sod), nuclear factor kappa B p65 subunit (nfκb-p65), heat shock protein 70 (hsp70), and inhibitor of NF-κBα (iκba) in the intestine were significantly higher in the LP group than those in the HP and LP-AA groups (P < 0.05). The 16s RNA analysis indicated that EAA supplementation significantly increased the growth of Desulfovibrio and altered the intestinal microflora. The relative abundances of Firmicutes and Cyanobacteria were positively correlated with antioxidant parameters (CAT and T-AOC), whereas Desulfobacterota was negatively correlated with sod and T-AOC. The genera Bacillus, Bacteroides, and Rothia were associated with the favorable maintenance of gut health. In conclusion, dietary supplementation with EAAs to achieve a balanced amino acid profile could potentially reduce the dietary protein levels from 48.66 % to 44.44 % without adversely affecting the growth and intestinal health of juvenile blotched snakeheads.

Improved visualization of median, ulnar nerves, and small branches in the wrist and palm using contrast-enhanced magnetic resonance neurography.

Background: Magnetic resonance imaging of peripheral nerves in the wrist and palm is challenging due to the small size, tortuous course, complex surrounding tissues, and accompanying blood vessels. The occurrence of carpal palmar lesions leads to edema, swelling, and mass effect, which may further interfere with the display and identification of nerves. Objective: To evaluate whether contrast-enhanced magnetic resonance neurography (ceMRN) improves the visualization of the morphology and pathology of the median, ulnar nerves, and their small branches in the wrist and palm. Design: An observational study. Methods: In total 57 subjects, including 36 volunteers and 21 patients with carpal palmar lesions, were enrolled and underwent ceMRN and non-contrast MRN (ncMRN) examination at 3.0 Tesla. The degree of vascular suppression, nerve visualization, diagnostic confidence, and lesion conspicuity was qualitatively assessed by two radiologists. Kappa statistics were obtained for inter-reader agreement. The signal-to-noise ratio, contrast ratio (CR), and contrast-to-noise ratio (CNR) of the median nerve were measured. The subjective ratings and quantitative measurements were compared between ncMRN and ceMRN. Results: The inter-reader agreement was excellent (k > 0.8) for all qualitative assessments and visualization assessment of each nerve segment. Compared with ncMRN, ceMRN significantly improved vascular suppression in volunteers and patients (both p < 0.001). The ceMRN significantly enhanced nerve visualization of each segment (all p < 0.05) and diagnostic confidence in volunteers and patients (both p < 0.05). The ceMRN improved lesion conspicuity (p = 0.003) in patients. Quantitatively, ceMRN had significantly higher CRs of nerve versus subcutaneous fat, bone marrow, and vessels and CNR of nerve versus vessel than ncMRN (all p < 0.05). Conclusion: The ceMRN significantly improves the visualization of peripheral nerves and pathology in the wrist and palm by robustly suppressing the signals of fat, bone marrow, and especially vessels in volunteers and patients.

Study on the improvement of magnetic resonance imaging and lesion display of small nerves in the wrist and palm using contrast agents Why was the study done? Because the nerves and branches in the wrist and palm are numerous, small, tortuous, and surrounded by muscles, fat, bones, blood vessels and other tissues, it is difficult to show their complete shape with conventional magnetic resonance imaging. Hand lesions often lead to swelling, edema and masses, which interfere with the display of nerves. Therefore, it is difficult to directly diagnose the relationship between the lesions and nerves in clinical practice. What did the researchers do? The research team used contrast agent plus three-dimensional high-resolution magnetic resonance sequence to display the nerves of volunteers and patients with hand lesions, and used subjective and objective evaluation methods to compare the display effect of the sequence on the nerves before and after the use of contrast agent. What did the researchers find? The imaging method of contrast agent plus three-dimensional high-resolution magnetic resonance sequence can reduce the interference of fat, blood vessels, etc. on nerve display, improve the display effect of each nerve segment of the wrist and palm, increase readers' confidence in identifying nerves, and improve the detection of lesions. What do the findings mean? This study verified the feasibility and advantages of using contrast agents for magnetic resonance imaging of nerves in the wrist and palm. It provides a new method for clinical and imaging diagnosis of hand lesions, which can simultaneously display the morphological characteristics of nerves and lesions, reducing the difficulty of clinical diagnosis and improving the efficiency of imaging diagnosis.

Development and applications of the Anaesthetists' Non-Technical Skills behavioural marker system: a systematic review.

OBJECTIVES: To comprehensively synthesise evidence regarding the validity and reliability of the Anaesthetists' Non-Technical Skills (ANTS) behavioural marker system and its application as a tool for the training and assessment of non-technical skills to improve patient safety. DESIGN: Systematic review. DATA SOURCES: We employed a citation search strategy. The Scopus and Web of Science databases were searched for articles published from 2002 to May 2022. ELIGIBILITY CRITERIA: English-language publications that applied the ANTS system in a meaningful way, including its use to guide data collection, analysis and reporting. DATA EXTRACTION AND SYNTHESIS: Study screening, data extraction and quality assessment were performed by two independent reviewers. We appraised the quality of included studies using the Joanna Briggs Institute Critical Appraisal Checklists. A framework analysis approach was used to summarise and synthesise the included articles. RESULTS: 54 studies were identified. The ANTS system was applied across a wide variety of study objectives, settings and units of analysis. The methods used in these studies varied and included quantitative (n=42), mixed (n=8) and qualitative (n=4) approaches. Most studies (n=47) used the ANTS system to guide data collection. The most commonly reported reliability statistic was inter-rater reliability (n=35). Validity evidence was reported in 51 (94%) studies. The qualitative application outcomes of the ANTS system provided a reference for the analysis and generation of new theories across disciplines. CONCLUSION: Our results suggest that the ANTS system has been used in a wide range of studies. It is an effective tool for assessing non-technical skills. Investigating the methods by which the ANTS system can be evaluated and implemented for training within clinical environments is anticipated to significantly enhance ongoing enhancements in staff performance and patient safety. PROSPERO REGISTRATION NUMBER: CRD42022297773.

Deep gray matters iron deposition is positively associated with white matter hyperintensity in hypertension.

The association and underlying mechanisms between iron deposition and white matter hyperintensity (WMH) remain unclear. In this study, quantitative susceptibility mapping (QSM) was used to quantify deep gray matters iron deposition and to explore the association from both global and regional perspectives. A total of 84 patients with hypertension and 26 healthy controls underwent a strategically acquired gradient echo (STAGE) protocol, and the multi-echo data were used to reconstruct QSM images. The susceptibilities were used to describe iron content. Global region (RI) susceptibilities were measured in regions of interest, and age-related thresholds were used to determine high-iron content region (RII) susceptibilities. Compared with healthy controls, hypertension had higher total WMH scores and regional scores (all p = .001) and higher susceptibilities using the RI or RII analysis (all p < .05). In healthy controls, there was no significant association between susceptibilities and WMH scores. In hypertension, the susceptibilities of deep gray matters were positively correlated with WMH scores (RI analysis: right putamen; RII analysis: bilateral caudate nucleus head, putamen, red nucleus, substantia nigra, and dentate nucleus; age and education corrected p < .05). These findings suggest that iron deposition in deep gray matters was positively associated with WMH in hypertension, especially using the RII analysis.

Effects of qCON and qNOX-guided general anaesthesia management on patient opioid use and prognosis: a study protocol.

INTRODUCTION: The adverse effects of general anaesthetic drugs (especially opioids) cannot be ignored. However, current nociceptive-monitoring techniques still lack consistency in guiding the use of opioids. This trial will study the demand for opioid use and patient prognosis in qCON and qNOX-guided general anaesthesia management. METHODS AND ANALYSIS: This prospective, randomised, controlled trial will randomly recruit 124 patients undergoing general anaesthesia for non-cardiac surgery in equal numbers to either the qCON or BIS group. The qCON group will adjust intraoperative propofol and remifentanil dosage according to qCON and qNOX values, while the BIS group will adjust according to BIS values and haemodynamic fluctuations. The differences between the two groups will be observed in remifentanil dosing and prognosis. The primary outcome will be intraoperative remifentanil use. Secondary outcomes will include propofol consumption; the predictive ability of BIS, qCON and qNOX on conscious responses, noxious stimulus and body movements; and changes in cognitive function at 90 days postoperatively. ETHICS AND DISSEMINATION: This study involves human participants and was approved by the Ethics Committee of the Tianjin Medical University General Hospital (IRB2022-YX-075-01). Participants gave informed consent to participate in the study before taking part. The study results will be published in peer-reviewed journals and presented at relevant academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200059877.

Comparison of the Short-Term Clinical Effectiveness of 5% Dextrose Water, Platelet-rich Plasma and Corticosteroid Injections for Carpal Tunnel Syndrome: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To compare the short-term effectiveness of corticosteroids, 5% dextrose (D5W), and platelet-rich plasma (PRP) injections for treating carpal tunnel syndrome (CTS). DATA SOURCES: Four databases (MEDLINE [PubMed], Embase, the Cochrane Controlled Trials Register, and Web of Science [WOS]) were researched from inception to the first of April 2022. STUDY SELECTION: Two authors independently screened the literature to identify the RCTs meeting the included criteria, which involved comparing corticosteroid, 5% dextrose water (D5W), and PRP injection with each other or placebo-controlled for treating CTS. DATA EXTRACTION: The 2 reviewers independently conducted information extraction, the utcomes included were the changes in Symptom Severity Scale, Functional Status Scale, and Visual Analog Scale at short-term follow-up after drug injection treatment and any adverse events reported. DATA SYNTHESIS: Twelve randomized controlled trials with 749 patients (817 hands) were included. The results of this study suggested that PRP injection was the most likely to relieve symptoms, improve functions, and alleviate pain, with the surface under the cumulative ranking curve being 91.5%, 92.7%, and 80.8%, respectively, after D5W injection (74.4%, 72.2%, 72.1%), and corticosteroid injection (33.7%, 31.9%, 46.2%). The injection of 3 drugs was significantly better than that of a placebo. CONCLUSIONS: From the results of the network meta-analysis, PRP injection is the most recommended treatment among the injection of corticosteroid, D5W, and PRP.

Development and applications of the anaesthetists' non-technical skills behavioural marker system: protocol for a systematic review.

INTRODUCTION: The high incidence of unsafe anaesthetic care leads to adverse events and increases the burden on patient safety. An important reason for unsafe anaesthesia care is the lack of non-technical skills (NTS), which are defined as personal cognitive, social or interpersonal skills, among anaesthetists. The anaesthetists' NTS (ANTS) behavioural marker system has been widely used to evaluate and improve anaesthetists' behavioural performance to ensure patient safety. This protocol describes a planned systematic review aiming to determine the validity and reliability of the ANTS behavioural marker system and its application as a tool for the training and assessment of ANTS and for improving patient safety. METHODS AND ANALYSIS: This systematic review follows the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol. Studies that applied the ANTS behavioural marker system in a meaningful way, including using the ANTS behavioural marker system to guide data collection, analysis, coding, measurement, and/or reporting, which have been published in peer-reviewed journals, will be eligible. A citation search strategy will be employed. We will search Scopus and Web of Science for publications from 2002 to May 2022, which cite the three original ANTS behavioural marker system publications by Fletcher et al. We will also search the references of the relevant reviews for additional eligible studies. For each study, two authors will independently screen papers to determine eligibility and will extract the data. The quality of the included studies will be assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklists. A framework analysis approach that consists of five steps-familiarisation, identifying a thematic data extraction framework, indexing, charting, mapping and interpretation-will be used to synthesise and report the data. ETHICS AND DISSEMINATION: Ethics approval is not required for this study. The findings will be disseminated primarily through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022297773.

Artesunate Alleviates Paclitaxel-Induced Neuropathic Pain in Mice by Decreasing Metabotropic Glutamate Receptor 5 Activity and Neuroinflammation in Primary Sensory Neurons.

Experimental studies on the pathogenetic process of paclitaxel-induced neuropathic pain (PINP) have been initially carried out, but PINP still has no effective therapy. Recently reported studies have highlighted the involvement of glutamate receptors and neuroinflammation in peripheral and central nociceptive transmission in PINP. Artesunate is a first-line antimalarial drug with established efficacy in alleviating pain in a variety of pathologies. The current work assessed whether artesunate inhibits PINP by modulating metabotropic glutamate receptor 5 (mGluR5) and neuroinflammation in mice. The anti-hyperalgesic effect of artesunate was verified by assessing mechanical frequency and thermal latency in the paw withdrawal test as well as spontaneous pain. The expression levels of mGluR5, pain-related receptors and neuroinflammatory markers in dorsal root ganglion (DRG) were examined. In addition, treatment with CHPG and 2-methyl-6-(phenyl ethynyl) pyridine (MPEP) (mGluR5 agonist and antagonist, respectively) was performed to determine mGluR5's role in the anti-hyperalgesic properties of artesunate. We demonstrated artesunate prevented PINP in a dose-dependent manner, while exerting a clear anti-hyperalgesic effect on already existing PINP. Artesunate normalized paclitaxel-related expression changes in DRG mGluR5, NR1, and GluA2, as well as six paclitaxel related neuroinflammation markers. Intrathecal application of MPEP treated PINP by reversing NR1 and GluA2 expression changes but had no effects on chemokines and inflammatory factors. Furthermore, artesunate treatment reversed acute pain following CHPG application. In conclusion, this study revealed that artesunate alleviates paclitaxel-induced hyperalgesia and spontaneous pain by decreasing DRG mGluR5 expression and neuroinflammation in the mouse model of PINP.

Quantitative Susceptibility Mapping of Brain Iron Relating to Cognitive Impairment in Hypertension.

BACKGROUND: Hypertension (HTN) might impair cognition. Brain iron deposition correlates with cognitive impairment. The relationship between brain iron and cognition in HTN patients is less clear. PURPOSE: To measure brain susceptibility in HTN patients using quantitative susceptibility mapping (QSM) and to explore the relationship between brain iron and cognition. STUDY TYPE: Retrospective cross-sectional study. SUBJECTS: Sixty HTN patients (35 with mild cognitive impairment [MCI] and 25 without MCI) and 24 age, gender, and education matched controls. FIELD STRENGTH/SEQUENCE: 3 T; strategically acquired gradient echo (STAGE) imaging protocol for QSM analysis. ASSESSMENT: All subjects underwent Montreal Cognitive Assessment (MoCA) scoring of visuospatial/executive, naming, attention, abstraction, language, delayed memory, and orientation functions. HTN patients were divided into two groups (with and without MCI) depending on the MoCA score. Regions of interest (ROIs) were manually demarcated on the STAGE images by three independent radiologists and susceptibility were determined for bilateral frontal white matter, parietal white matter, occipital white matter, caudate nucleus (CN), putamen (PU), globus pallidus (GP), thalamus (TH), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN). STATISTICAL TESTS: Analysis of variance with post-hoc least significant difference (LSD) tests and Pearson correlation coefficients (r). A P-value <0.05 was considered to be statistically significant. RESULTS: The susceptibility was significantly different in CN, PU, and DN among the three groups. The susceptibility of right CN and left PU were correlated with MoCA scores (r = -0.429 and r = -0.389, respectively). The susceptibility of left PU was also correlated with delayed memory scores (r = -0.664). The susceptibility of left and right GP were correlated with naming scores (r = -0.494 and r = -0.446, respectively) and the susceptibility of left DN were correlated with visuospatial/executive scores (r = 0.479). DATA CONCLUSION: QSM measured brain iron was significantly higher in CN, PU, and DN in HTN patients. Cognitive impairment was correlated with regional brain iron deposition. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

The mTORC1/eIF4E/HIF-1α Pathway Mediates Glycolysis to Support Brain Hypoxia Resistance in the Gansu Zokor, Eospalax cansus.

The Gansu zokor (Eospalax cansus) is a subterranean rodent species that is unique to China. These creatures inhabit underground burrows with a hypoxia environment. Metabolic energy patterns in subterranean rodents have become a recent focus of research; however, little is known about brain energy metabolism under conditions of hypoxia in this species. The mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) coordinates eukaryotic cell growth and metabolism, and its downstream targets regulate hypoxia inducible factor-1α (HIF-1α) under conditions of hypoxia to induce glycolysis. In this study, we compared the metabolic characteristics of hypoxia-tolerant subterranean Gansu zokors under hypoxic conditions with those of hypoxia-intolerant Sprague-Dawley rats with a similar-sized surface area. We exposed Gansu zokors and rats to hypoxia I (44 h at 10.5% O2) or hypoxia II (6 h at 6.5% O2) and then measured the transcriptional levels of mTORC1 downstream targets, the transcriptional and translational levels of glycolysis-related genes, glucose and fructose levels in plasma and brain, and the activity of key glycolysis-associated enzymes. Under hypoxia, we found that hif-1α transcription was upregulated via the mTORC1/eIF4E pathway to drive glycolysis. Furthermore, Gansu zokor brain exhibited enhanced fructose-driven glycolysis under hypoxia through increased expression of the GLUT5 fructose transporter and ketohexokinase (KHK), in addition to increased KHK enzymatic activity, and utilization of fructose; these changes did not occur in rat. However, glucose-driven glycolysis was enhanced in both Gansu zokor and rat under hypoxia II of 6.5% O2 for 6 h. Overall, our results indicate that on the basis of glucose as the main metabolic substrate, fructose is used to accelerate the supply of energy in Gansu zokor, which mirrors the metabolic responses to hypoxia in this species.