Dunaliella salina Alga Protects against Myocardial Ischemia/Reperfusion Injury by Attenuating TLR4 Signaling.

Myocardial ischemia/reperfusion (I/R) injury is marked by rapid increase in inflammation and not only results in myocardial apoptosis but also compromises the myocardial function. Dunaliella salina (D. salina), a halophilic unicellular microalga, has been used as a provitamin A carotenoid supplement and color additive. Several studies have reported that D. salina extract could attenuate lipopolysaccharides-induced inflammatory effects and regulate the virus-induced inflammatory response in macrophages. However, the effects of D. salina on myocardial I/R injury remain unknown. Therefore, we aimed to investigate the cardioprotection of D. salina extract in rats subjected to myocardial I/R injury that was induced by occlusion of the left anterior descending coronary artery for 1 h followed by 3 h of reperfusion. Compared with the vehicle group, the myocardial infarct size significantly decreased in rats that were pre-treated with D. salina. D. salina significantly attenuated the expressions of TLR4, COX-2 and the activity of STAT1, JAK2, IκB, NF-κB. Furthermore, D. salina significantly inhibited the activation of caspase-3 and the levels of Beclin-1, p62, LC3-I/II. This study is the first to report that the cardioprotective effects of D. salina may mediate anti-inflammatory and anti-apoptotic activities and decrease autophagy through the TLR4-mediated signaling pathway to antagonize myocardial I/R injury.

Postoperative Sore Throat Helps Predict Swallowing Disturbance on Postoperative Day 30 of Anterior Cervical Spine Surgery: A Secondary Exploratory Analysis of a Randomized Clinical Trial of Tracheal Intubation Modes.

Nasotracheal intubation benefits dysphonia recovery after anterior cervical spine surgery (ACSS). The aim of the present study was to investigate the effect of tracheal intubation modes on post-ACSS swallowing function and identify factors associated with deglutition on postoperative day 30 (POD 30). Adult patients were randomized to receive either nasotracheal or orotracheal intubation during surgery. A numerical rating scale (NRS) was used to assess postoperative sore throat, and the Bazaz grading system was used to assess the severity of swallowing disturbance. The primary endpoints were the effect of tracheal intubation modes on postoperative sore throat and deglutition. Thereafter, we further elucidated the predictors of swallowing disturbance on POD 30. Postoperative sore throat and swallowing disturbance did not differ between the nasotracheal and orotracheal intubation groups. A secondary dataset analysis revealed that among 108 patients with complete follow-up until POD 30, 71 (65.7%) presented complete recovery without swallowing disturbance, whereas 37 (34.3%) presented varying degrees of swallowing disturbance. Receiver operating characteristic curve analysis indicated that the NRS score for sore throat predicted a swallowing disturbance-free status on POD 30. The optimal cutoff values were ≤ 4 and ≤ 2 on PODs 1 and 2, respectively. The adjusted odds ratio (OR) for independent predictors was a sore throat NRS score of ≤ 4 on POD 1 (OR 3.2; 95% CI 1.29-7.89; P = 0.012) and score of ≤ 2 on POD 2 (OR 6.67; 95% CI 2.41-18.47; P < 0.001). Therefore, tracheal intubation mode did not affect the incidence of post-ACSS swallowing disturbance, and the severity of sore throat on PODs 1 and 2 could predict a swallowing disturbance-free status on POD 30.The trial was registered at clinicaltrials.gov (Trial No. NCT03240042, date of registration 10/17/2017).

Practice and outcomes of airway management in patients with cervical orthoses.

BACKGROUND/PURPOSE: Increasing evidence indicates an association of video laryngoscopy with the success rate of airway management in patients with neck immobilization. Nevertheless, clinical practice protocols for tracheal intubation in patients immobilized using various types of cervical orthoses and the outcomes remain unclear. METHODS: We retrospectively assessed the tracheal intubation techniques selected for patients immobilized using cervical orthoses from 2015 to 2018. The endpoints were the intubation outcomes of the different techniques and the factors associated with the selection of the technique. RESULTS: We included 218 patients, 118 of whom wore halo vest braces (halo vest group) and 100 wore cervical collars (collar group). GlideScope video laryngoscopy (GVL) and fiberoptic bronchoscopy (FOB) were the initial intubation methods in 98 and 120 patients, respectively. GVL had a higher first-attempt success rate than did FOB in the collar group (p = 0.002) but not in the halo vest group (p = 0.522). GVL was associated with a lower risk of episodes of SaO2< 90% (adjusted relative risk [aRR], 0.11; 95% CI, 0.02-0.67; p = 0.016) and shorter intubation time (aRR, -3.52; 95% CI, -4.79∼-2.25; p < 0.001) in the collar group. However, in the halo vest group, more frequent requirement of a rescue technique (p = 0.002) and necessity of patient awakening (p = 0.001) was noted when GVL was used. Use of the halo vest brace and noting of severe cord compression were independent predictors of the initial selection of FOB. CONCLUSION: Caution should be exercised when using GVL for tracheal intubation in patients immobilized using halo vest braces.

Changes in Sleep Architecture under Sustained Pain in Adult Male Rats Subjected to Neonatal Short-Lasting Local Inflammatory Insult.

Neonatal, short-lasting, local, nociceptive insult by carrageenan can cause long-term alterations in somatosensory and neurohumoral systems. We previously revealed hyporesponsiveness of the autonomic nervous system (ANS) after painful stimulation of adult rats in a neonatal carrageenan-induced pain model. Sleep disturbance has been highly correlated with pain and ANS activity. In the present study, adult rats that had received an intraplantar injection of carrageenan on postnatal day 1 were investigated to determine if there were alterations in their sleep architecture upon the stimulation of pain. Polysomnographic and heart rate variability recordings were carried out, with a wireless transmission of data, for 24 h under baseline conditions and after an intraplantar injection of complete Freund's adjuvant to induce sustained nociception. Increased active awake (AW) and decreased quiet sleep (QS) and paradoxical sleep (PS) times were noted in the control animals. In the carrageenan-treated rats, the AW time increased but with decreased alertness, as revealed by decreases in beta and increases in theta power. The QS time did not decrease. The PS time decreased during the first 12 h, then increased during the following 12 h, suggesting an early rebound of formerly deprived PS time. Sympathetic activation under sustained pain was not apparent in any stage of sleep in carrageenan-treated rats and was even suppressed in AW time. An impaired sympathetic reaction to pain may have contributed to the atypical changes in sleep architecture in these rats. In conclusion, pain in early life has a long-term effect on the cardiovascular-autonomic-electroencephalographic responses to pain later in life. The physiological relevance of these results remains undetermined.

Bibliometric analysis of the top 100 most-cited articles on video laryngoscope from 2011 to 2022.

BACKGROUND: The popularity of video laryngoscope (VL) has increased rapidly since its introduction in the late 1990s. However, a comprehensive overview of VLs evolution and impact is lacking, which merits further investigation. METHODS: We conducted a bibliometric analysis of the top 100 most-cited articles on VL (Top100VL) published between 2011 and 2022 and retrieved from the PubMed and Web of Science databases. Using social network analysis, we identified the subject terms and subject categories of the Top100VL and compared their citation counts across individual subject terms and categories via one-way analysis of variance (ANOVA). Then, we employed the Medical Query Expert software to assess the practical applications of VL. RESULTS: The Top100VL included 65 subjects across nine subject categories, with "anesthesiology" being the most frequently represented category and "coronavirus infections" with the highest impact factor. The citation counts inferred by subject categories significantly correlated with the actual citation counts (Pearson's R = 0.4; p < 0.01). For enhanced visualization, we employed network visualization and Sankey diagrams to display the article characteristics. We highlighted the clinical advantages of VL, including its usefulness in difficult intubations, wider angle of view, and management of pediatric emergencies, as well as its teaching benefits, such as facilitating training programs and a lower learning curve. CONCLUSION: By using bibliometric analysis and natural language processing methods, we effectively summarized the applications of VL in both clinical and teaching settings, particularly in reducing the risk of cross-infection during the Coronavirus Disease 2019 pandemic.

Functional Peptide-Loaded Gelatin Nanoparticles as Eyedrops for Cornea Neovascularization Treatment.

Background: Corneal neovascularization (NV) is a process of abnormal vessel growth into the transparent cornea from the limbus and can disturb the light passing through the cornea, resulting in vision loss or even blindness. The use of nanomedicine as an effective therapeutic formulation in ophthalmology has led to higher drug bioavailability and a slow drug release rate. In this research, we designed and explored the feasibility of a new nanomedicine, gp91 ds-tat (gp91) peptide-encapsulated gelatin nanoparticles (GNP-gp91), for inhibiting corneal angiogenesis. Methods: GNP-gp91 were prepared by a two-step desolvation method. The characterization and cytocompatibility of GNP-gp91 were analyzed. The inhibition effect of GNP-gp91 on HUVEC cell migration and tube formation was observed by an inverted microscope. The drug retention test in mouse cornea was observed by in vivo imaging system, fluorescence microscope, and DAPI/TAMRA staining. Finally, the therapeutic efficacy and evaluation of neovascularization-related factors were conducted through the in vivo corneal NV mice model via topical delivery. Results: The prepared GNP-gp91 had a nano-scale diameter (550.6 nm) with positive charge (21.7 mV) slow-release behavior (25%, 240hr). In vitro test revealed that GNP-gp91 enhanced the inhibition of cell migration and tube formation capacity via higher internalization of HUVEC. Topical administration (eyedrops) of the GNP-gp91 significantly prolongs the retention time (46%, 20 min) in the mouse cornea. In chemically burned corneal neovascularization models, corneal vessel area with a significant reduction in GNP-gp91 group (7.89%) was revealed when compared with PBS (33.99%) and gp91 (19.67%) treated groups via every two days dosing. Moreover, GNP-gp91 significantly reduced the concentration of Nox2, VEGF and MMP9 in NV's cornea. Conclusion: The nanomedicine, GNP-gp91, was successfully synthesized for ophthalmological application. These data suggest that GNP-gp91 contained eyedrops that not only have a longer retention time on the cornea but also can treat mice corneal NV effectively delivered in a low dosing frequency, GNP-gp91 eyedrops provides an alternative strategy for clinical ocular disease treatment in the culture.

Use of higher thromboelastogram transfusion values is not associated with greater blood loss in liver transplant surgery.

Plasma-containing products are given during the pre-anhepatic stage of liver transplant surgery to correct abnormal thromboelastogram (TEG) values and prevent blood loss due to coagulation defects. However, evidence suggests that abnormal TEG results do not always predict bleeding. We questioned what effect using higher TEG values to initiate treatment would have on blood loss. A single transfusion protocol was used for all patients who underwent liver transplantation between 2007 and 2010. Thirty-eight patients received coagulation products when standard TEG cutoff values were exceeded, whereas another 39 patients received coagulation products when the TEG values were 35% greater than normal. The results of postoperative coagulation tests for total blood loss and the use of blood products were compared for the 2 groups. When the critical TEG values for transfusion were higher, significantly fewer units of fresh frozen plasma (5.58 ± 6.49 versus 11.53 ± 6.66 U) and pheresis platelets (1.84 ± 1.33 versus 3.55 ± 1.43 U) were used. There were no differences in blood loss or postoperative blood product use. In conclusion, the use of higher critical TEG values to initiate the transfusion of plasma-containing products is not associated with increased blood loss. Further testing is necessary to identify what TEG value predicts bleeding due to a deficit in coagulation factors.

Intraoperative hypotension in non-emergency decompression surgery for cervical spondylosis: The role of chronic arterial hypertension.

Background: Cervical spondylotic myelopathy and chronic hypertension show a cause-effect relationship. Hypertension increases cardiovascular risk and is associated with intraoperative hypotension. We aimed to evaluate intraoperative hypotension in patients undergoing non-emergency decompression surgery for cervical spondylosis and its association with clinical myelopathy and chronic arterial hypertension. Methods: This retrospective cohort study used healthcare data of adult patients undergoing cervical spine surgeries at Taipei Veterans General Hospital from 2015 to 2019. The primary outcomes were the incidence of intraoperative hypotension and predictive factors, and the secondary outcomes were the association of intraoperative hypotension and postoperative adverse outcomes in the surgical population. Results: Among the 1833 patients analyzed, 795 (43.4%) required vasopressor treatment and 342 (18.7%) showed persistent hypotension. Factors independent associated with hypotension after anesthetic induction were age [odds ratio (OR), 1.15; 95% confidence interval (CI), 1.07-1.23 per 5 years, P < 0.001], male sex (OR, 1.63; 95% CI, 1.21-2.19, P < 0.001), chronic hypertension (OR, 1.77; 95% CI, 1.32-2.38, P < 0.001), upper cervical spine level C0-2 treated (OR, 3.04; 95% CI, 1.92-4.84, P < 0.001 vs. C3-T1), and increased number of spine segments treated (OR, 1.43; 95% CI 1.26-1.63, P < 0.001). Patients who developed intraoperative hypotension experienced more acute postoperative kidney injury (OR, 7.90; 95% CI, 2.34-26.63, P < 0.001), greater need for intensive care (OR, 1.80; 95% CI, 1.24-2.60, P = 0.002), and longer admission after surgery (1.09 days longer, 95% CI 0.06-2.12, P = 0.038). Conclusion: Intraoperative hypotension is common even in non-emergency cervical spine surgery. A history of hypertension independently predicted intraoperative hypotension. Prompt assessments for identifiable features can help ameliorate intraoperative hypotension.

Cervical spine immobilization does not interfere with nasotracheal intubation performed using GlideScope videolaryngoscopy: a randomized equivalence trial.

GlideScope-assisted nasotracheal intubation (NTI) has been proposed as an alternative to difficult orotracheal intubation for critical patients or those under cervical immobilization. We evaluated the difficulty of performing NTI using GlideScope under cervical orthosis. A total of 170 patients scheduled for elective cervical spinal surgery that required NTI were randomized to receive cervical immobilization using a cervical collar (collar group) or no cervical immobilization at all (control group) before anesthetic induction (group assignment at 1:1 ratio). All NTI during anesthetic induction were performed using the GlideScope. The primary outcome was time to intubation. The secondary outcomes were ease of intubation, including the necessity of auxiliary manipulations to assist intubation, and the nasotracheal intubation difficulty scale (nasoIDS). An exploratory analysis identified morphometric parameters as predictors of time to intubation, the necessity of auxiliary manipulations, and a nasoIDS score ≥ 4. For time to intubation, the mean difference (collar group-control) was - 4.19 s, with a 95% confidence interval (CI) of - 13.9 to 5.52 that lay within our defined equivalence margin of 16 s. Multivariate regressions precluded the association of cervical immobilization with a necessity for auxiliary manipulations (adjusted odds ratio [aOR] 0.53, 95% CI [0.26-1.09], P = 0.083) and a nasoIDS ≥ 4 (aOR 0.94 [0.84-1.05], P = 0.280). Among all morphometric parameters, the upper lip bite test class was predictive of a longer time to intubation (all analyses relative to class 1, 14 s longer for class 2, P = 0.032; 24 s longer for class 3, P = 0.070), increased necessity for auxiliary manipulation (aOR 2.29 [1.06-4.94], P = 0.036 for class 2; aOR 6.12 [1.04-39.94], P = 0.045 for class 3), and nasoIDS ≥ 4 (aOR 1.46 [1.14-1.89], P = 0.003 for class 3).The present study demonstrated that GlideScope achieved NTI in patients with or without cervical immobilization equivalently with respect to intubation time and ease.

A Tapered Cuff Tracheal Tube Decreases the Need for Cuff Pressure Adjustment After Surgical Retraction During Anterior Cervical Spine Surgery: A Randomized Controlled, Double-Blind Trial.

Background: Surgical retraction to expose the vertebrae during anterior cervical spine surgery increases tracheal tube cuff pressure and may worsen postoperative sore throat and dysphonia. This randomized double-blind study investigated the effect of cuff shape on intraoperative cuff pressure and postoperative sore throat and dysphonia. Methods: Eighty patients were randomized to tracheal intubation with a tapered cuff or a conventional cylindrical high-volume low-pressure cuff (control) during anesthesia. Intraoperative cuff pressures were compared. The primary outcome was the incidence of pressure adjustment needed when the cuff pressure increased to > 25 mm Hg after surgical retraction. The secondary outcome was the incidence of postoperative sore throat and dysphonia. Results: The incidence of pressure adjustment after surgical retraction was significantly lower in the tapered group than in the control group (13% vs. 48%; P = 0.001; relative risk reduction, 74%). The median [interquartile range (IQR)] cuff pressure (mm Hg) was significantly lower for the tapered cuff than for the control cuff before surgical retraction [9 (7-12) vs. 12 (10-15); P < 0.001] and after retraction [18 (15-23) vs. 25 (18-31); P = 0.007]. The median (IQR) postoperative dysphonia score assessed by a single speech-language pathologist was lower in the tapered group than in the control group [4 (3-6) vs. 5.5 (5-7); P = 0.008]. Conclusion: A tapered cuff tracheal tube decreased the need for the adjustment of cuff pressure after surgical retraction during anterior cervical spine surgery, thereby avoiding intraoperative pressure increase. It also has a better outcome in terms of dysphonia. Clinical Trial Registration: [www.clinicaltrials.gov], identifier [NCT04591769].

Lack of beneficial effect for preemptive analgesia in postoperative pain control: verifying the efficacy of preemptive analgesia with N-methyl-D-aspartate receptor antagonists in a modified animal model of postoperative pain.

BACKGROUND: In previous animal studies, preemptive treatments with N-methyl-d-aspartate (NMDA) antagonists were ineffective at preventing incision-induced allodynia. It is very likely that the model was not clinically relevant for testing treatment effects on postoperative pain. The beneficial effects of preemptive treatment can be verified only by treatments with a pharmacologically proven effect in a specific pain type or animal model. We previously showed that NMDA receptor antagonists effectively alleviate enhanced mechanical hyperalgesia after plantar incision in adult rats that had been given an intraplantar injection of carrageenan as neonates. Here, using this modified model, we tested the efficacy of preemptive treatment with the NMDA antagonist MK-801. METHODS: We injected rat pups subcutaneously with 0.25% carrageenan or saline in the plantar surface of one hindpaw on postnatal day 1. On postnatal day 50, rats were killed and the ipsilateral side of the lumbar spinal cords were harvested for biochemical analysis of the expression of NR2A and NR2B at baseline, 2 hours, 4 hours, 8 hours, and 24 hours after plantar incision (n = 5 per group for each time point). For pharmacological study, rats were allocated into one of the following groups: 1 intrathecal injection of 40 nmol MK-801 15 minutes before plantar incision, 1 intrathecal injection 30 minutes after plantar incision, or 2 injections of 20 nmol or 40 nmol given at 15 minutes and 60 minutes after plantar incision (n = 10 per group for neonatally saline-treated and 12 for carrageenan-treated rats). Paw withdrawal thresholds were measured with von Frey filaments, and weight-bearing percentages were measured hourly after plantar incision. RESULTS: Expressions of NMDA receptor subunits NR2A and NR2B were increased maximally 4 hours postoperatively and were significantly greater in carrageenan-treated rats than in saline-treated rats. Tests of pain sensitivity showed that MK-801 significantly alleviated the incision-induced mechanical hyperalgesia and increased weight-bearing percentage on the injured paw in carrageenan-treated rats. However, preincisional treatment was not superior to postincisional treatment as assessed during the 6-hour postoperative observation period. Groups with 2 successive postoperative injections exhibited prolonged analgesic effects. Only the group that received 2 postoperative injections and increased total dosage had improved analgesic indices. CONCLUSIONS: Under conditions of proven analgesic action of an NMDA antagonist, we demonstrated that preincisional treatment is not more beneficial than postincisional treatment for postoperative pain relief in the modified animal model. Increasing the duration of administration and/or total dosage had an incremental analgesic effect in comparison with a single injection.

Minocycline exhibits synergism with conditioned medium of bone marrow mesenchymal stem cells against ischemic stroke.

Several lines of evidence show that a conditioned medium of bone marrow mesenchymal stem cells (BM-MSCcm) improve functional recovery after ischemic stroke but do not reduce ischemic lesions. It is important to develop a treatment strategy that can exhibit a synergistic effect with BM-MSCcm against ischemic stroke. In this study, the effect of BM-MSCcm and/or minocycline was examined in culture and in a middle cerebral artery occlusion (MCAo) animal model. In neuron-glial cultures, BM-MSCcm and combined treatment, but not minocycline, effectively increased neuronal connection and oligodendroglial survival. In contrast, minocycline and combined treatment, but not BM-MSCcm, reduced toxin-induced free radical production in cultures. Either minocycline or BM-MSCcm, or in combination, conferred protective effects against oxygen glucose deprivation-induced cell damage. In an in vivo study, BM-MSCcm and minocycline were administered to rats 2 h after MCAo. Monotherapy with BM-MSCcm or minocycline after ischemic stroke resulted in 9.4% or 17.5% reduction in infarction volume, respectively, but there was no significant difference. Interestingly, there was a 33.9% significant reduction in infarction volume by combined treatment with BM-MSCcm and minocycline in an in vivo study. The combined therapy also significantly improved grasping power, which was not altered by monotherapy. Furthermore, combined therapy increased the expression of neuronal nuclei in the peri-infarct area and hippocampus, and concurrently decreased the expression of ED1 in rat brain and the peri-infarct zone. Our data suggest that minocycline exhibits a synergistic effect with BM-MSCcm against ischemic stroke not only to improve neurological functional outcome but also to reduce cerebral infarction.

Inhibitory concentration of propofol in combination with dexmedetomidine during microelectrode recording for deep brain stimulator insertion surgeries under general anesthesia.

BACKGROUND: Microelectrode recording (MER) for target refinement is widely used in deep brain stimulator insertion for Parkinson disease. Signals may be influenced by anesthetics when patients receive general anesthesia (GA). This study determined the inhibitory concentration (IC) of propofol on MER signals when it was coadministered with dexmedetomidine. METHODS: Patients were anesthetized with dexmedetomidine (0.5 µg·kg loading, followed by infusion at 0.4 µg·kgh) and propofol through target-controlled infusion for GA with tracheal intubation. The surgeon conducted the online scoring of the background signals, spiking frequency, amplitude, and pattern of single-unit activities by using a 0-10 verbal numerical rating scale (NRS; 0, maximal suppression; 10, minimal suppression), and responses were grouped into suppression (NRS ≤ 6) and nonsuppression (NRS > 6). The median inhibitory concentration (IC50) of propofol (as target effect-site concentrations: Ceprop) was determined using modified Dixon's up-and-down method. Probit regression analysis was further used to obtain the dose-response relationship, and IC05 and IC95 were calculated. RESULTS: Twenty-three adult patients participated in this study. Under the concomitant infusion of dexmedetomidine, the predicted IC50 value (95% CI) of Ceprop for neuronal suppression during MER was 1.29 (1.24-1.34) µg·mL as calculated using modified Dixon's up-and-down method. Using probit analysis, the estimated IC05, IC50, and IC95 values (95% CIs) were 1.17 (0.87-1.23), 1.28 (1.21-1.34), and 1.40 (1.33-1.85) µg·mL, respectively. CONCLUSION: Our data provided reference values of propofol for dosage adjustment to avoid interference on MER under GA when anesthetics have to be continuously infused during recording.

Paeonol Protects Against Myocardial Ischemia/Reperfusion-Induced Injury by Mediating Apoptosis and Autophagy Crosstalk.

Many studies have shown that crosstalk exists between apoptosis and autophagy, despite differences in mechanisms between these processes. Paeonol, a major phenolic compound isolated from Moutan Cortex Radicis, the root bark of Paeonia × suffruticosa Andrews (Paeoniaceae), is widely used in traditional Chinese medicine as an antipyretic, analgesic and anti-inflammatory agent. In this study, we investigated the detailed molecular mechanisms of the crosstalk between apoptosis and autophagy underlying the cardioprotective effects of paeonol in rats subjected to myocardial ischemia/reperfusion (I/R) injury. Myocardial I/R injury was induced by occlusion of the left anterior descending coronary artery (LAD) for 1 h followed by 3 h of reperfusion. Paeonol was intravenously administered 15 min before LAD ligation. We found that paeonol significantly improved cardiac function after myocardial I/R injury and significantly decreased myocardial I/R-induced arrhythmia and mortality. Paeonol also significantly decreased myocardial infarction and plasma LDH activity and Troponin-I levels in carotid blood after I/R. Compared with vehicle treatment, paeonol significantly upregulated Bcl-2 protein expression and significantly downregulated the cleaved forms of caspase-8, caspase-9, caspase-3 and PARP protein expression in the I/R injured myocardium. Myocardial I/R-induced autophagy, including the increase of Beclin-1, p62, LC3-I, and LC3-II protein expression in the myocardium was significantly reversed by paeonol treatment. Paeonol also significantly increased the Bcl-2/Bax and Bcl-2/Beclin-1 ratios in the myocardium after I/R injury. The cardioprotective role of paeonol during I/R injury may be due to its mediation of crosstalk between apoptotic and autophagic signaling pathways, which inhibits apoptosis and autophagic cell death.

Effect of Tracheal Intubation Mode on Cuff Pressure During Retractor Splay and Dysphonia Recovery After Anterior Cervical Spine Surgery: A Randomized Clinical Trial.

MINI: This randomized clinical trial showed different intubation mode in anesthesia did not affect the increase of endotracheal cuff pressure caused by the retractor splay in anterior cervical spine surgery. However, nasotracheal intubation improved postoperative dysphonia recovery after anterior cervical spine surgery. STUDY DESIGN: Prospective, randomized, double-blinded trial. OBJECTIVE: The aim of this study was to investigate whether the mode of tracheal intubation affects intraoperative endotracheal tube cuff pressure on retractor splay and post-anterior cervical spine surgery (ACSS) voice outcome. SUMMARY OF BACKGROUND DATA: The combination of endotracheal tube (ETT) and cervical retractors has been implicated in recurrent laryngeal nerve compression and neuropraxia after ACSS. The asymmetric position of the oroETT within the larynx, as being fixed distally by the cuff and proximally by taping on one side of the mouth, may contribute to unilateral vocal palsy. METHODS: Adult patients undergoing ACSS were randomized to receive either nasotracheal or orotracheal intubation under anesthesia. The primary endpoint was the maximal endotracheal tube cuff pressure (ETCP) when the retractors were set up. After the maximal ETCPs were recorded, then ETCPs were controlled to less than 25 mmHg. Secondary endpoints were self-assessed hoarseness, pitch, and loudness of voice on postoperative days (PODs) 1, 2, 7, and 30. RESULTS: We equally allocated 110 patients to nasotracheal and orotracheal intubation. The maximal ETCP during retractor splay did not differ for both the means and distributions of pressure range. After the surgery, more patients in the nasotracheal intubation group reported none or mild change of voice than did the orotracheal intubation group on PODs 1 and 2, in terms of hoarseness, pitch, and loudness (P = 0.001, 0.001, and 0.005, respectively, on POD 1; P = 0.002, 0.003, and 0.011, respectively, on POD 2). Mixed model analysis demonstrated that patients with nasotracheal intubation had significantly lower dysphonia scores after surgery (estimate treatment effect: -1.62, P < 0.0001). Statistics was adjusted to exclude interaction with ETT sizes. CONCLUSION: The tracheal intubation modes did not affect ETCP during retractor splay. However, nasotracheal intubation had a beneficial effect on dysphonia recovery after ACSS. LEVEL OF EVIDENCE: 2.

Prospective, randomized, double-blinded trial. The aim of this study was to investigate whether the mode of tracheal intubation affects intraoperative endotracheal tube cuff pressure on retractor splay and post-anterior cervical spine surgery (ACSS) voice outcome. The combination of endotracheal tube (ETT) and cervical retractors has been implicated in recurrent laryngeal nerve compression and neuropraxia after ACSS. The asymmetric position of the oroETT within the larynx, as being fixed distally by the cuff and proximally by taping on one side of the mouth, may contribute to unilateral vocal palsy. Adult patients undergoing ACSS were randomized to receive either nasotracheal or orotracheal intubation under anesthesia. The primary endpoint was the maximal endotracheal tube cuff pressure (ETCP) when the retractors were set up. After the maximal ETCPs were recorded, then ETCPs were controlled to less than 25 mmHg. Secondary endpoints were self-assessed hoarseness, pitch, and loudness of voice on postoperative days (PODs) 1, 2, 7, and 30. We equally allocated 110 patients to nasotracheal and orotracheal intubation. The maximal ETCP during retractor splay did not differ for both the means and distributions of pressure range. After the surgery, more patients in the nasotracheal intubation group reported none or mild change of voice than did the orotracheal intubation group on PODs 1 and 2, in terms of hoarseness, pitch, and loudness (P = 0.001, 0.001, and 0.005, respectively, on POD 1; P = 0.002, 0.003, and 0.011, respectively, on POD 2). Mixed model analysis demonstrated that patients with nasotracheal intubation had significantly lower dysphonia scores after surgery (estimate treatment effect: −1.62, P < 0.0001). Statistics was adjusted to exclude interaction with ETT sizes. The tracheal intubation modes did not affect ETCP during retractor splay. However, nasotracheal intubation had a beneficial effect on dysphonia recovery after ACSS. Level of Evidence: 2.

Phellinus linteus Mycelium Alleviates Myocardial Ischemia-Reperfusion Injury through Autophagic Regulation.

The incidence of myocardial ischemia-reperfusion (IR) injury is rapidly increasing around the world and this disease is a major contributor to global morbidity and mortality. It is known that regulation of programmed cell death including apoptosis and autophagy reduces the impact of myocardial IR injury. In this study, the cardioprotective effects and underlying mechanisms of Phellinus linteus (Berk. and Curt.) Teng, Hymenochaetaceae (PL), a type of medicinal mushroom, were examined in rats subjected to myocardial IR injury. The left main coronary artery of rats was ligated for 1 h and reperfused for 3 h. The arrhythmia levels were monitored during the entire process and the infarct size was evaluated after myocardial IR injury. Furthermore, the expression levels of proteins in apoptotic and autophagic pathways were observed. Pretreatment with PL mycelium (PLM) significantly reduced ventricular arrhythmia and mortality due to myocardial IR injury. PLM also significantly decreased myocardial infarct size and plasma lactate dehydrogenase level after myocardial IR injury. Moreover, PLM administration resulted in decreased caspase 3 and caspase 9 activation and increased Bcl-2/Bax ratio. Phosphorylation level of AMPK was elevated while mTOR level was reduced. Becline-1 and p62 levels decreased. These findings suggest that PLM is effective in protecting the myocardium against IR injury. The mechanism involves mediation through suppressed pro-apoptotic signaling and regulation of autophagic signaling, including stimulation of AMPK-dependent pathway and inhibition of beclin-1-dependent pathway, resulting in enhancement of protective autophagy and inhibition of excessive autophagy.

Intraoperative administration of tramadol for postoperative nurse-controlled analgesia resulted in earlier awakening and less sedation than morphine in children after cardiac surgery.

In adults, intraoperative administration of tramadol could result in earlier recovery and less sedation than morphine. In this controlled, randomized, double-blind study, we investigated whether an intraoperative initial dose of tramadol could cause more rapid awakening from general anesthesia, less sedation, and earlier tracheal extubation than morphine in children during the immediate postoperative period. Forty children aged 1-6 yr, scheduled for atrial or ventricular septal defect repair and tracheal extubation in the pediatric intensive care unit, were randomly allocated to receive morphine, initial dose 0.2 mg/kg, or tramadol 2 mg/kg given at the end of sternal closure, followed by nurse-controlled analgesia (bolus 0.02 mg/kg of morphine and 0.2 mg/kg of tramadol) with background infusions (0.015 mg x kg(-1) x h(-1) for morphine and 0.15 mg x kg(-1) x h(-1) for tramadol). Postoperatively, children receiving tramadol had earlier awakening from general anesthesia (P = 0.02) and were less sedated at 1 and 2 h postoperatively (P = 0.03 and P = 0.01, respectively). Tracheal extubation was earlier in the tramadol group (P = 0.01). Lengths of pediatric intensive care unit stay did not differ between groups. Times to first trigger of nurse-controlled analgesia bolus and objective pain scores during the 48 h observation period were comparable between groups. The incidence of desaturation and emesis were similar between groups. The patients ate well and did not differ on Day 1 or Day 2.

Effect of genetic knockout or pharmacologic inhibition of neuronal nitric oxide synthase on complete Freund's adjuvant-induced persistent pain.

Nitric oxide (NO) acts as a neurotransmitter or neuromodulator involving in the modulation of thermal and/or inflammatory hyperalgesia. The neuronal nitric oxide synthase (nNOS) is a key enzyme for NO production in normal neuronal tissues, but its functional role in chronic pain remains unclear. The present study combined a genetic strategy with a pharmacologic approach to address the role of nNOS in the central mechanism of complete Freund's adjuvant (CFA)-induced chronic inflammatory pain. Targeted disruption of the nNOS gene significantly reduced CFA-induced mechanical pain hypersensitivity during the maintenance (but not the development) of inflammatory pain, while it failed to attenuate either development or maintenance of CFA-induced thermal pain hypersensitivity. Intraperitoneal administration of L-N(G)-nitro-arginine methyl ester (L-NAME), a non-specific NOS inhibitor, blocked CFA-evoked thermal and mechanical pain hypersensitivity at both development (2h) and maintenance (24h) phase in wild type mice, but had no effect in the knockout mice. Furthermore, intrathecal injection of either L-NAME or 7-nitroindazole, a selective nNOS inhibitor, markedly attenuated mechanical pain hypersensitivity at both 2 and 24h after CFA injection. Finally, spinal cord nNOS (but not endothelial NOS or inducible NOS) expression was up-regulated at 24h after CFA injection, occurring mainly in the ipsilateral superficial dorsal horn. Together, these data indicate that spinal cord nNOS may be essential for the maintenance of mechanical pain hypersensitivity and that it may also be sufficient for the development of mechanical pain hypersensitivity and for the development and maintenance of thermal pain hypersensitivity after chronic inflammation. Our findings suggest that spinal cord nNOS might play a critical role in central mechanisms of the development and/or maintenance of chronic inflammatory pain.