Observation of the validity of the upper lip bite test in predicting difficult intubation.

The upper lip bite test (ULBT) is considered an effective method for predicting difficult airways, but data on the ULBT for predicting difficult tracheal intubation are lacking. This study aimed to examine the clinical utility of the ULBT in predicting difficult endotracheal intubation. We conducted an observational case-cohort study of adult patients undergoing elective surgery and requiring endotracheal intubation for general anesthesia. Difficult airway assessment was performed on the recruited patients before the operation, including the ULBT, mouth opening, thyromental distance, modified Mallampati test, and body mass index. The primary outcome was the incidence of difficult tracheal intubation. The receiver operating characteristic curve analysis was used to compare the performance of variables in predicting difficult tracheal intubation. We successfully recruited 2522 patients for analysis and observed 64 patients with difficult tracheal intubation. When predicting difficult tracheal intubation, grade 2 ULBT had a sensitivity of 0.75 and a specificity of 0.54, and grade 3 had a sensitivity of 0.28 and a specificity of 0.75. Compared with mouth opening, the area under the receiver operating characteristic curve of the ULBT was lower in predicting difficult tracheal intubation (0.69 [95% confidence interval: 0.67-0.71] vs. 0.84 [95% confidence interval: 0.82-0.87], P < 0.05).Clinical Trials Registry: ChiCTR-ROC-16009050, principal investigator: Weidong Yao.

Development and validation of a screening method for difficult tracheal intubation based on geometric simulation and computer technology.

BACKGROUND: The anatomical characteristics of difficult airways can be analysed geometrically. This study aims to develop and validate a geometry-assisted difficult airway screening method (GADAS method) for difficult tracheal intubation. METHODS: In the GADAS method, a geometric simulated model was established based on computer graphics. According to the law of deformation of the upper airway on laryngoscopy, the expected visibility of the glottis was calculated to simulate the real visibility on laryngoscopy. Validation of the new method: Approved by the Ethics Committee of Yijishan Hospital of Wannan Medical College. Adult patients who needed tracheal intubation under general anaesthesia for elective surgery were enrolled. The data of patients were input into the computer software to calculate the expected visibility of the glottis. The results of tracheal intubation were recorded by anaesthesiologists. The primary observation outcome was the screening performance of the expected visibility of the glottis for difficult tracheal intubation. RESULTS: The geometric model and software of the GADAS method were successfully developed and are available for use. We successfully observed 2068 patients, of whom 56 patients had difficult intubation. The area under the receiver operating characteristic curve of low expected glottis visibility for predicting difficult laryngoscopy was 0.96 (95% confidence interval [CI]: 0.95-0.96). The sensitivity and specificity were 89.3% (95% CI: 78.1-96.0%) and 94.3% (95% CI: 93.2%-95.3), respectively. CONCLUSIONS: It is feasible to screen difficult-airway patients by applying computer techniques to simulate geometric changes in the upper airway.

USP48/USP31 Is a Nuclear Deubiquitinase that Potently Regulates Synapse Remodeling.

Deubiquitinases present locally at synapses regulate synaptic development, function, and plasticity. It remains largely unknown, however, whether deubiquitinases localized outside of the synapse control synapse remodeling. Here we identify ubiquitin specific protease 48 (USP48; formerly USP31) as a nuclear deubiquitinase mediating robust synapse removal. USP48 is expressed primarily during the first postnatal week in the rodent brain and is virtually restricted to nuclei, mediated by a conserved, 13-amino acid nuclear localization signal. When exogenously expressed, USP48, in a deubiquitinase and nuclear localization-dependent manner, induces striking filopodia elaboration, marked spine loss, and significantly reduced synaptic protein clustering in vitro, and erases ~70% of functional synapses in vivo. USP48 interacts with the transcription factor NF-κB, deubiquitinates NF-κB subunit p65 and promotes its stability and activation, and up-regulates NF-κB target genes known to inhibit synaptogenesis. Depleting NF-κB prevents USP48-dependent spine pruning. These findings identify a novel nucleus-enriched deubiquitinase that plays critical roles in synapse remodeling.

Enantiocontrolled Total Synthesis of (-)-Retigeranic Acid A.

The asymmetric total synthesis of (-)-retigeranic acid A has been realized. The key features of the current synthesis include (1) a Pt-catalyzed Conia-ene 5-exo-dig cyclization of enolyne to establish the key quaternary stereochemical center of C-10 (D/E ring), (2) an intramolecular diastereoselective Prins cyclization to construct the trans-hydrindane backbone (A/B ring), and (3) a late-stage intramolecular Fe-mediated hydrogen atom transfer (HAT) Baldwin-disfavored 5-endo-trig radical cyclization to rapidly assemble vicinal quaternary centers and the core structure of (-)-retigeranic acid A (C ring).

Euphohelides A-C, ent-Abietane-Type Norditerpene Lactones from Euphorbia helioscopia and Their Anti-Inflammatory Activities.

Three unreported ent-abietane-type norditerpene lactones, euphohelides A-C (1-3), and 11 known analogs (4-14) were isolated from the whole plants of Euphorbia helioscopia L. Euphohelide A (1) is an unprecedented 2-nor-ent-abietane lactone bearing a unique 5/6/6/5 tetracyclic system. Euphohelides B (2) and C (3) possess 2-nor-6/6/6/5 and 2,3-dinor-5/6/6/5 dilactone tetracyclic moieties, respectively. Their structures were established by spectroscopic methods, computational ECD, and X-ray crystallographic analyses. A biomimetic synthesis of 1 was achieved from precursor 4 based on the speculative biogenetic pathway. Compounds 1 and 5 significantly alleviated the release of LPS-induced NO with IC50 values of 32.98 ± 1.13 and 33.82 ± 3.25 µM, which might be related to the regulation of the NF-κB signaling pathway.

Dorsomedial prefrontal hypoexcitability underlies lost empathy in frontotemporal dementia.

Empathic function is essential for the well-being of social species. Empathy loss is associated with various brain disorders and represents arguably the most distressing feature of frontotemporal dementia (FTD), a leading form of presenile dementia. The neural mechanisms are unknown. We established an FTD mouse model deficient in empathy and observed that aged somatic transgenic mice expressing GGGGCC repeat expansions in C9orf72, a common genetic cause of FTD, exhibited blunted affect sharing and failed to console distressed conspecifics by affiliative contact. Distress-induced consoling behavior activated the dorsomedial prefrontal cortex (dmPFC), which developed profound pyramidal neuron hypoexcitability in aged mutant mice. Optogenetic dmPFC inhibition attenuated affect sharing and other-directed consolation in wild-type mice, whereas chemogenetically enhancing dmPFC excitability rescued empathy deficits in mutant mice, even at advanced ages when substantial cortical atrophy had occurred. These results establish cortical hypoexcitability as a pathophysiological basis of empathy loss in FTD and suggest a therapeutic strategy.

The value of multiparameter combinations for predicting difficult airways by ultrasound.

BACKGROUND: Based on the upper airway anatomy and joint function parameters examined by ultrasound, a multiparameter ultrasound model for difficult airway assessment (ultrasound model) was established, and we evaluated its ability to predict difficult airways. METHODS: A prospective case-cohort study of difficult airway prediction in adult patients undergoing elective surgery with endotracheal intubation under general anesthesia, and ultrasound phantom examination for difficult airway assessment before anesthesia, including hyomental distance, tongue thickness, mandibular condylar mobility, mouth opening, thyromental distance, and modified Mallampati tests, was performed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of the ultrasound model and conventional airway assessment methods in predicting difficult airways. RESULTS: We successfully enrolled 1000 patients, including 51 with difficult laryngoscopy (DL) and 26 with difficult tracheal intubation (DTI). The area under the ROC curve (AUC) for the ultrasound model to predict DL was 0.84 (95% confidence interval [CI]: 0.82-0.87), and the sensitivity and specificity were 0.75 (95% CI: 0.60-0.86) and 0.82 (95% CI: 0.79-0.84), respectively. The AUC for predicting DTI was 0.89 (95% CI: 0.87-0.91), and the sensitivity and specificity were 0.85 (95% CI: 0.65-0.96) and 0.81 (95% CI: 0.78-0.83), respectively. Compared with mouth opening, thyromental distance, and modified Mallampati tests, the ultrasound model predicted a greater AUC for DL (P < 0.05). Compared with mouth opening and modified Mallampati tests, the ultrasound model predicted a greater AUC for DTI (P < 0.05). CONCLUSIONS: The ultrasound model has good predictive performance for difficult airways. TRIAL REGISTRATION: This study is registered on chictr.org.cn (ChiCTR-ROC-17013258); principal investigator: Jianling Xu; registration date: 06/11/2017).

Effect of individualized treatment strategy on postoperative nausea and vomiting in gynaecological laparoscopic surgery: a double-blind, randomized, controlled trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) have always been a concern of clinicians and may increase medical costs for patients. Consensus guidelines recommend using multiple antiemetics with different mechanisms as prophylaxis in patients at high risk of PONV. Individualized risk scores for nausea and vomiting and individualized treatment strategies are feasible. This study evaluated the effect of individualized treatment strategies on postoperative nausea and vomiting after laparoscopic gynaecological operations. METHODS: This was a double-blind, randomized, controlled trial. A total of 119 adult patients who underwent gynaecological laparoscopic surgery under general anaesthesia were randomly divided into an individualized treatment group or a control group, with the individualized treatment group receiving individualized prevention according to a preoperative risk score of nausea and vomiting and the control group receiving no individualized prevention. Vomiting, retching, nausea, and use of rescue medication were all recorded for 24 h after the operation. The primary outcome variable was complete response, defined as no emesis or the use of rescue medication 24 h postoperatively. RESULTS: The complete response rate was higher in the individualized treatment group (56.7%) than in the control group (23.7%) (95% CI, 0.01-0.27; P < 0.001). The incidences of emesis (18.3% vs. 44.1%, P = 0.002) were significantly lower in the individualized treatment group than in the control group. There were no differences in any nausea (26.7% vs. 33.9%, P = 0.391) or rescue medication use (6.7% vs. 8.5%, P = 0.743). Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently in the individualized treatment group than in the control group. CONCLUSION: In conclusion, this single-centre, double-blind, randomized study suggests that an individualized PONV prophylactic treatment strategy based on the number of PONV risk factors could be a safe and effective regimen to reduce the incidence of PONV in adult patients undergoing laparoscopic gynaecological surgery.

Predicting difficult intubation: the hyomental distance ultrasound evaluation is superior to the thyromental distance.

BACKGROUND: Hyomental distance (HMD), an anatomical feature of the upper airway, can be measured precisely by ultrasonography. But the sensitivity and specificity of HMD compared to thyromental distance (TMD) to predict difficult airways is still unknown. METHODS: A case-cohort study was conducted. The written informed consent was obtained. Elective surgery adult patients undergoing general anaesthesia and tracheal intubation were recruited. The other inclusion criteria were: no maxillofacial deformity, trauma, airway stenosis, known difficult airway. The exclusion criteria were: tracheal intubations or operations were canceled, or patients' data were missing. HMD ultrasound measurements of patients in a sniffing position and other usual airway evaluations were performed before general anaesthesia induction. The primary outcome was the intubation difficulty level. Predictive values were calculated. RESULTS: We successfully enrolled 2357 patients (62 difficult intubation patients) in the cohort study for analysis. The area under the receiver operating characteristic curve (AUC) of the HMD and TMD for predicting difficult intubation was 0.86 (95% CI, 0.84-0.87) and 0.77 (95% CI, 0.75-0.78) respectively (comparison: P < 0.001). With an optimal cut-off value of HMD ≤ 4.9 cm, we observed a sensitivity and specificity of 0.90 (95% CI, 0.80-0.96) and 0.73 (95% CI, 0.71-0.75). Meanwhile, with TMD ≤ 7.0 cm, the sensitivity and specificity were 0.77 (95% CI, 0.65-0.87) and 0.65 (95% CI, 0.63-0.67) respectively. CONCLUSION: In comparison to TMD, HMD measured by ultrasound was more sensitive in predicting difficult intubation.

The epigenetic reader PHF21B modulates murine social memory and synaptic plasticity-related genes.

Synaptic dysfunction is a manifestation of several neurobehavioral and neurological disorders. A major therapeutic challenge lies in uncovering the upstream regulatory factors controlling synaptic processes. Plant homeodomain (PHD) finger proteins are epigenetic readers whose dysfunctions are implicated in neurological disorders. However, the molecular mechanisms linking PHD protein deficits to disease remain unclear. Here, we generated a PHD finger protein 21B-depleted (Phf21b-depleted) mutant CRISPR mouse model (hereafter called Phf21bΔ4/Δ4) to examine Phf21b's roles in the brain. Phf21bΔ4/Δ4 animals exhibited impaired social memory. In addition, reduced expression of synaptic proteins and impaired long-term potentiation were observed in the Phf21bΔ4/Δ4 hippocampi. Transcriptome profiling revealed differential expression of genes involved in synaptic plasticity processes. Furthermore, we characterized a potentially novel interaction of PHF21B with histone H3 trimethylated lysine 36 (H3K36me3), a histone modification associated with transcriptional activation, and the transcriptional factor CREB. These results establish PHF21B as an important upstream regulator of synaptic plasticity-related genes and a candidate therapeutic target for neurobehavioral dysfunction in mice, with potential applications in human neurological and psychiatric disorders.

VALUE OF CORRECTED FLOW TIME IN COMMON CAROTID ARTERY IN PREDICTING VOLUME RESPONSIVENESS UNDER MECHANICAL VENTILATION.

ABSTRACT: Objective: The present study aimed to investigate whether corrected flow time (FTc) in common carotid artery could predict volume responsiveness under mechanical ventilation and to further explore whether the sensitivity and specificity would be influenced by positive end-expiratory pressure (PEEP). Methods: The first stage of this study included 80 patients from the general surgery department undergoing laparotomy. After induction of general anesthesia, FTc in the common carotid artery was measured when hemodynamic indicators, such as blood pressure, heart rate, and cardiac output (CO), were stabilized. Then, 7 mg/kg (ideal body weight) of hydroxyethyl starch 130/0.4 sodium chloride was rapidly infused from the peripheral venous system. The infusion was completed within 15 minutes, and hemodynamic indicators were measured again immediately to evaluate volume responsiveness. The patients with change rate of CO (ΔCO ≥15%) were categorized into the responsive (R) group, whereas those with ΔCO <15% were categorized into the nonresponsive group (NR) group. In the second stage, 29 patients undergoing laparotomy were included. After induction of general anesthesia, PEEP of 0, 5, and 10 cmH 2 O was applied sequentially. Corrected flow time and hemodynamic indicators were recorded. Then, 7 mg/g of hydroxyethyl starch 130/0.4 sodium chloride was rapidly infused for 15 minutes, after which PEEP of 0, 5, and 10 cmH 2 O was applied sequentially, and the indicators were measured again. The patients with FTc equal to or less than the threshold in the first stage were categorized into the R group, otherwise into the NR group. Results: In the first stage of the study, CO and FTc differed significantly between the 2 groups, before and after volume load ( P < 0.05). Mean arterial pressure in the R group was significantly different, whereas heart rate did not differ before and after fluid infusion. Also, heart rate and mean arterial pressure were not significantly different before and after fluid infusion in the NR group. The area under the receiver operating characteristic curve was 0.786 ± 0.056 (95% confidence interval, 0.676-0.896; P = 0.00) for FTc before infusing volume load for predicting volume responsiveness. In the second stage of the study, PEEP did not have significant effects on FTc ( F2, 56 = 1.930, P = 0.155), whereas volume load had statistically significant effects on FTc ( F1, 28 ) = 9.381, P < 0.05). Moreover, FTc differed significantly different before and after fluid infusion ( P < 0.05). The area under the receiver operating characteristic curve for FTc in predicting volume responsiveness was 0.921, 0.805, and 0.719 when PEEP was 0, 5, and 10 cmH 2 O ( P < 0.05), respectively, and the cutoff value of FTc for diagnosing volume responsiveness was 323.42 milliseconds, 326.69 milliseconds, and 312.03 milliseconds, respectively. Conclusion: Corrected flow time in the common carotid artery can predict volume responsiveness under mechanical ventilation, and the predictive performance is not influenced by PEEP. Clinical Trial Registration Clinical register number: ChicTR2000029519.

TLR4-SIRT3 Mechanism Modulates Mitochondrial and Redox Homeostasis and Promotes EPCs Recruitment and Survival.

The low survival rate of endothelial progenitor cells (EPCs) in vivo which are susceptible to adverse microenvironments including inflammation and oxidative stress has become one primary challenge of EPCs transplantation for regenerative therapy. Recent studies reported functional expression of toll-like receptor (TLR) 4 on EPCs and dose-dependent effects of lipopolysaccharide (LPS) on cellular oxidative stress and angiogenic properties. However, the involved mechanism has not yet been elucidated well, and the influence of TLR4 signaling on EPCs survival and function in vivo is unknown. In the present study, we observed the effects of LPS and TLR4/SIRT3 on EPCs mitochondrial permeability and intracellular mitochondrial superoxide. We employed the monocrotaline-induced pulmonary arteriolar injury model to observe the effects of TLR4/SIRT3 on the recruitment and survival of transplanted EPCs. We found the destructive effects of 10 µg/mL LPS on mitochondrial homeostasis, and cellular viability was mediated by TLR4/SIRT3 signals at least partially, and the TLR4 mediates the early-stage recruitment of transplanted EPCs in pulmonary arteriolar inflammation injury; however, SIRT3 has more contribution to the survival of incorporated EPCs and ameliorated arteriolar remodeling in lung vascular tissue. The study provides insights for the critical role of TLR4/SIRT3 in LPS-induced oxidative stress and mitochondrial disorder in EPCs in vitro and in vivo. The TLR4/SIRT3 signaling is important for EPCs resistance against inflammation and oxidative stress and may represent a new manipulating target for developing efficient cell therapy strategy.

4.8% sevoflurane induces activation of autophagy in human neuroblastoma SH-SY5Y cells by the AMPK/mTOR signaling pathway.

Prolonged sevoflurane exposure leads to neurotoxicity. Autophagy plays an important role in promoting cell survival in different conditions. However, the role and mechanism of autophagy in sevoflurane-induced neurotoxicity were not fully elucidated. We attempted to indicate whether sevoflurane could activate the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)-mediated autophagy to attenuate anesthetics-induced neuronal injury in this study. Sevoflurane treatment significantly decreased the cell viability and induced apoptosis of SH-SY5Y cells. The expression level of Bcl-2 decreased, while that of Bax remarkably increased. Meanwhile, autophagy was activated by sevoflurane exposure as evidenced by increased expression levels of autophagy-related proteins (LC3-II and Atg5), decreased expression level of autophagic substrate P62, and increased autophagosomes and autolysosomes. Further autophagosomes and fewer autolysosomes were observed in the presence of Bafilomycin A1, an autolysosomes degradation inhibitor, suggesting that sevoflurane induced autophagic flux rather than inhibiting degradation of autophagy. Activation of autophagy by rapamycin partly reversed the sevoflurane-decreased cell viability. In contrast, inhibition of autophagy by 3-Methyladenine (3-MA) or Atg5-targeted small interfering RNA (siRNA) aggravated the sevoflurane-induced neurotoxicity. Further examination revealed that sevoflurane-induced autophagy was mediated by the AMPK/mTOR signaling pathway, with increased p-AMPK expression and decreased p-mTOR expression. Collectively, these results indicated that sevoflurane activates autophagy by regulating the AMPK/mTOR signaling pathway, which is protective against sevoflurane-induced damage in SH-SY5Y cells. Our results may assist clinicians to develop further promising therapeutic strategies for the neurotoxicity induced by inhaled anesthetics.

Cylindromatosis drives synapse pruning and weakening by promoting macroautophagy through Akt-mTOR signaling.

The lysine-63 deubiquitinase cylindromatosis (CYLD) is long recognized as a tumor suppressor in immunity and inflammation, and its loss-of-function mutations lead to familial cylindromatosis. However, recent studies reveal that CYLD is enriched in mammalian brain postsynaptic densities, and a gain-of-function mutation causes frontotemporal dementia (FTD), suggesting critical roles at excitatory synapses. Here we report that CYLD drives synapse elimination and weakening by acting on the Akt-mTOR-autophagy axis. Mice lacking CYLD display abnormal sociability, anxiety- and depression-like behaviors, and cognitive inflexibility. These behavioral impairments are accompanied by excessive synapse numbers, increased postsynaptic efficacy, augmented synaptic summation, and impaired NMDA receptor-dependent hippocampal long-term depression (LTD). Exogenous expression of CYLD results in removal of established dendritic spines from mature neurons in a deubiquitinase activity-dependent manner. In search of underlying molecular mechanisms, we find that CYLD knockout mice display marked overactivation of Akt and mTOR and reduced autophagic flux, and conversely, CYLD overexpression potently suppresses Akt and mTOR activity and promotes autophagy. Consequently, abrogating the Akt-mTOR-autophagy signaling pathway abolishes CYLD-induced spine loss, whereas enhancing autophagy in vivo by the mTOR inhibitor rapamycin rescues the synaptic pruning and LTD deficits in mutant mice. Our findings establish CYLD, via Akt-mTOR signaling, as a synaptic autophagy activator that exerts critical modulations on synapse maintenance, function, and plasticity.

Lipopolysaccharide increases exosomes secretion from endothelial progenitor cells by toll-like receptor 4 dependent mechanism.

BACKGROUND INFORMATION: Endothelial progenitor cells (EPCs) can exert angiogenic effects by a paracrine mechanism, where exosomes work as an important mediator. Recent studies reported functional expression of toll-like receptor (TLR) 4 on human EPCs and dose-dependent effects of lipopolysaccharide (LPS) on EPC angiogenic properties. To study the effects of TLR4/LPS signaling on EPC-derived exosomes (Exo) and clarify the mechanism, we investigated the role of LPS on exosomes secretion from human EPCs and tested their anti-oxidation/senescence functions. We employed the inhibitors of the plasma membrane Ca2+ -ATPase (PMCA), endoplasmic reticulum Ca2+ -ATPase (ERCA), PLC-IP3 pathway and store-operated calcium entry to assess the effects of LPS on EPC intracellular calcium signalings which critical for exosome secretion. RESULTS: LPS induced the release of Exo in a TLR4-dependent manner in vitro, which effect can be partly abrogated by an membrane-permeable IP 3 R antagonist, 2-aminoethyl diphenylborinate (2-APB), but not PLC inhibitor, U-73122. The LPS can significantly delay the fallback of [Ca2+ ]i after isolating the cellular PMCA activity, and disturb PMCA 1/4 expression. The distribution of elevated intracellular calcium seemed coincident with the development of the multivesicular bodies (MVBs). furthermore, the anti-oxidation/senescence properties of LPS-induced Exo were validated by the senescence-associated ß-galactosidase activity assay and reactive oxygen species (ROS) related H2 DCF-DA assay. CONCLUSIONS: The mechanism of PMCA downregulation and IP3 R-dependent ER Ca2+ release may contribute to the pro-exosomal effects of LPS on EPCs. SIGNIFICANCE: This study provides new insights into the potential role of LPS/TLR4 pathway in regulating EPC-derived exosomes, which may help to develop some feasible approach to manipulate the Exo secretion and promote the clinical application of EPCs therapy in future.

Nomograms for predicting difficult airway based on ultrasound assessment.

BACKGROUND: Accurate prediction of the difficult airway (DA) could help to prevent catastrophic consequences in emergency resuscitation, intensive care, and general anesthesia. Until now, there is no nomogram prediction model for DA based on ultrasound assessment. In this study, we aimed to develop a predictive model for difficult tracheal intubation (DTI) and difficult laryngoscopy (DL) using nomogram based on ultrasound measurement. We hypothesized that nomogram could utilize multivariate data to predict DTI and DL. METHODS: A prospective observational DA study was designed. This study included 2254 patients underwent tracheal intubation. Common and airway ultrasound indicators were used for the prediction, including thyromental distance (TMD), modified Mallampati test (MMT) score, upper lip bite test (ULBT) score temporomandibular joint (TMJ) mobility and tongue thickness (TT). Univariate and the Akaike information criterion (AIC) stepwise logistic regression were used to identify independent predictors of DTI and DL. Nomograms were constructed to predict DL and DTL based on the AIC stepwise analysis results. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of the nomograms. RESULTS: Among the 2254 patients enrolled in this study, 142 (6.30%) patients had DL and 51 (2.26%) patients had DTI. After AIC stepwise analysis, ULBT, MMT, sex, TMJ, age, BMI, TMD, IID, and TT were integrated for DL nomogram; ULBT, TMJ, age, IID, TT were integrated for DTI nomogram. The areas under the ROC curves were 0.933 [95% confidence interval (CI), 0.912-0.954] and 0.974 (95% CI, 0.954-0.995) for DL and DTI, respectively. CONCLUSION: Nomograms based on airway ultrasonography could be a reliable tool in predicting DA. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR-RCS-14004539 ), registered on 13th April 2014.

An optimal tracheal tube preshaping strategy for endotracheal intubation using video laryngoscopy: a randomized controlled trial.

Although video laryngoscopy solves the problem of glottis exposure, it is difficult to deliver the tube to the glottic opening when the tracheal tube is unevenly shaped. This study aimed to compare the effects of different tube shapes on the first-pass success (FPS) rate in patients undergoing video laryngoscopy-assisted tracheal intubation. Three hundred patients above 18 years of age who underwent general anaesthesia and required endotracheal intubation were included in the study. The participants were randomly allocated to three groups with 100 participants in each group as follows: Group A, video laryngoscopes with a self-equipped stylet are used for tube preshaping; Group B: curvature of the video laryngoscope blade is modelled for tube preshaping; Group C: tube preshaping angle is consistent with the video laryngoscope blade, and the bending point is set 1 cm above the tracheal tube cuff. The primary outcome was FPS rates. The secondary outcomes included time to tracheal intubation, haemodynamic responses and adverse events. No significant differences in patient characteristics or airway assessments were noted (P > 0.05). Compared with Groups A, Group B and Group C exhibited a higher FPS rate (68% vs. 86% vs. 92%; P < 0.001). However, there is no significant difference in FPS rate between Group B and Group C (P > 0.05). And the time to tracheal intubation in Group C was significantly less than that in Group A and Group B (22.21 ± 4.01 vs. 19.92 ± 4.11 vs. 17.71 ± 3.47; P < 0.001). The straight-to-cuff stylet preshape angulation of curvature of the blade could provide a higher FPS rate and shorter time to tracheal intubation during video laryngoscopy-assisted endotracheal intubation. Trial registration: Chinese Clinical Trial Registry, ChiCTR1900026019.

Loss of mGluR1-LTD following cocaine exposure accumulates Ca2+-permeable AMPA receptors and facilitates synaptic potentiation in the prefrontal cortex.

Addiction results from drug-elicited alterations of synaptic plasticity mechanisms in dopaminergic reward circuits. Impaired metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) and accumulation of synaptic Ca2+-permeable AMPA receptors (CP-AMPARs) following drug exposure have emerged as important mechanisms underlying drug craving and relapse. Here we show that repeated cocaine exposure in vivo causes transient but complete loss of mGluR1- and mTOR (mammalian target of rapamycin)-dependent LTD in layer 5 pyramidal neurons of mouse prefrontal cortex (PFC), a major dopaminergic target in the reward circuitry. This mGluR1-LTD impairment was prevented by in vivo administration of an mGluR1 positive allosteric modulator (PAM) and rescued by inhibition of dopamine D1 receptors, suggesting that impaired mGluR1 tone and excessive D1 signaling underlie this LTD deficit. Concurrently, CP-AMPARs were generated, indicated by increased sensitivity to the CP-AMPAR inhibitor Naspm and rectification of synaptic AMPAR currents, which were reversed by PAM in cocaine-exposed mice. Finally, these CP-AMPARs mediate an abnormal spike-timing-dependent long-term potentiation enabled by cocaine exposure. Our findings reveal a mechanism by which cocaine impairs LTD and remodels synaptic AMPARs to influence Hebbian plasticity in the PFC. Failure to undergo LTD may prevent the reversal of drug-potentiated brain circuits to their baseline states, perpetuating addictive behaviors.HIGHLIGHTSA mGluR1- and mTOR-dependent LTD is present in the mouse medial prefrontal cortex.Repeated cocaine exposure in vivo temporally but completely abolishes prefrontal mGluR1-LTD.Impaired mGluR1 function and excessive D1 DA signaling likely underlie cocaine impairment of mGluR1-LTD.Ca2+-permeable AMPA receptors are generated by cocaine exposure, likely resulting from mGluR1-LTD impairment, and contribute to a cocaine-induced extended spike timing LTP.

Extraction of alumina from aluminum dross by a non-hazardous alkaline sintering process: Dissolution kinetics of alumina and silica from calcined materials.

The aluminum dross (AD), which causes numerous problems of its management and disposal to environment is a useful resource to extract alumina. This study explains a novel process to extract highly pure alumina (Al2O3) from AD at a high extraction rate without producing the residues and exhaust gases. An experimental set up was designed to perform the grinding of AD for the decomposition of aluminum nitride (AlN) and the removal of salts. Thereby, the desalted dross was used to detect the optimum alkaline (NaOH) calcination parameters and leaching conditions, as well as the dissolution kinetics of alumina and silica. The leaching residues were used to produce Ettringite mineral with calcium-based compounds (including CaO and CaSO4) to avoid the problems of solid waste disposal from the leaching process. Moreover, to purify the alumina, slightly soluble CaSO4 was added in leaching solution to precipitate silicate and the optimum additive/solution ratio (g/mL) was determined. The aluminum hydroxide (Al(OH)3), precipitated after the carbonization was calcinated at 900.0 °C for 2 h to produce γ-alumina. The morphological and mineralogical characterizations of AD, γ-Al2O3 and the synthesized Ettringite mineral were studied by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and X-ray fluorescence (XRF). It was observed that activation temperature of 1000.0 °C, Na2O/Al2O3 molar ratio of 1.4, leaching temperature of 60.0 °C, leaching time of 40.0 min, and the leaching liquid/solid ratio (mL/g) of 25/1 were the optimal parameter conditions to extract alumina with the extraction rate at 86.7% and purity of more than 98%. The results of leaching kinetics' study showed that the dissolution of alumina and silica were both controlled by layer diffusion process with the apparent activation energy of 11.4010 kJ·mol-1 and 2.0556 kJ·mol-1, respectively.