Kinetic Analysis of the Reaction of Micrometer-Sized Al-Mg Alloy Particles in a Water Vapor Atmosphere.

This study investigated the reaction mechanism of aluminum-magnesium (Al-Mg) alloy particles with water (Al-Mg/H2O) through thermogravimetric analysis-differential scanning calorimetry experiments and kinetic analysis using isoconversional methods and the master plot technique to determine the reaction mechanism function, with the aim of providing insights to support metal powder/water ramjet engine design and combustion characteristics. The results showed that the Al-Mg/H2O reaction occurred in two distinct stages, with stage 1 primarily involving the reaction of Mg elements in the L(Al-Mg) alloy with water while Al played a leading role in stage 2. Notably, the reaction temperatures of Al-Mg particles were significantly lower than those for either Al or Mg particles alone in a water vapor environment. Additionally, the activation energy of stage 1 was lower than that for the individual Al and Mg particles and decreased with increasing Mg content in stage 2. Furthermore, the concentration of Mg in the alloy was found to have a major influence on the reaction mechanism, which followed a random nucleation and growth model. Overall, this work elucidated an alternating endothermic and exothermic staged reaction process for Al-Mg/H2O dominated first by Mg and then Al with kinetic insights providing theoretical support for optimizing Al-Mg alloy compositions for improved ignition and combustion performance in metal powder/water ramjet engines.

Comparison of surgical field visibility during propofol or desflurane anesthesia for middle ear microsurgery.

BACKGROUND: To compare surgical field visibility between patients given propofol/remifentanil (PR) or desflurane/remifentanil (DR) anesthesia. METHODS: A total of 80 adult patients undergoing middle ear microsurgery due to cholesteatoma otitis media with American Society of Anesthesiologists physical status I and II were randomly assigned to the PR or DR groups. The depth of anesthesia was titrated to maintain a Bispectral index (BIS) between 40 and 50. Remifentanil was titrated to maintain the mean blood pressure within ±30% change of the pre-induction value. Surgical field visibility was rated at several timepoints by the surgeons using the Boezaart scores. RESULTS: Average Boezaart scores for surgical field visibility at different time points were < 2 in both PR and DR groups. Surgical field visibility score was lower in the PR group than in the DR group. Requirement for remifentanil was higher in the PR group (850 (488/1330) µg) than in the DR group (258 (143/399) µg, P < 0.0001). The site effect concentration of remifentanil was higher in the PR group (3.6(2.8/5.0)ng/ml) than in the DR group (1.7 (1.0/1.6) ng/ml, P < 0.0001). Hemodynamic profile (i.e., heart rate and mean blood pressure) was similar between groups (P > 0.05). Extubation time (PR group, 21 min vs. DR group, 19 min; P = 0.199) and post-anesthesia care unit time (PR group, 37 min vs. DR group, 34 min; P = 0.324) were comparable between groups. CONCLUSION: Although PR anesthesia resulted in lower surgical field visibility scores than DR anesthesia, both groups had scores < 2, meaning no clinical differences between the two groups. DR provided acceptable operative conditions as well, albeit more remifentanil consumption was noted in the DR group. TRIAL REGISTRATION: China Clinical Research Information Service, ChiCTR-1,800,015,537 . Registered 5 April 2018. Date of enrolment of the first participant to the trial: 2 May 2018.

Dexmedetomidine for tracheal extubation in deeply anesthetized adult patients after otologic surgery: a comparison with remifentanil.

BACKGROUND: Remifentanil and dexmedetomidine are well known to suppress airway reflexes during airway procedures. Smooth tracheal extubation is important after otologic surgery. The purpose of this study is to compare the effectiveness of dexmedetomidine or remifentanil infusion for producing smooth tracheal extubation in deeply anesthetized patients after otologic surgery. METHODS: Seventy-four ASA I-II adult patients (18-60 years old) scheduled for elective otologic surgery were randomly assigned to one of three groups: sevoflurane-remifentanil (Group SR, n = 25), sevoflurane-dexmedetomidine (0.5 µg/kg) (Group SD5, n = 24), or sevoflurane-dexmedetomidine (0.7 µg/kg) (Group SD7, n = 25). Remifentanil or dexmedetomidine were administered for 10 min at the end of surgery. The primary outcome was the rate of smooth extubation. Respiratory pattern, airway obstruction, hemodynamic and respiratory profiles, time to awake, rescue analgesics in the post-anesthesia care unit (PACU), and postoperative nausea and vomiting (PONV) were also recorded. RESULTS: The rate of smooth tracheal extubation as defined 1 min post-extubation was the same for Groups SR and SD7 (P > 0.05), but the rate of smooth extubation was lower for Group SD5 than for the other two groups (p < 0.05). During extubation, the respiratory rate was lower in Group SR than in both dexmedetomidine groups (p < 0.05). The hemodynamic profiles at extubation were similar between groups (p > 0.05), but the mean arterial pressure and heart rate were higher in Group SR at 10 and 15 min after extubation (p < 0.05). The incidence of airway obstruction and time to awake were comparable for all groups (p > 0.05). The need for rescue analgesic in the PACU was more common in Group SR than in both dexmedetomidine groups (P < 0.01). Compared to Group SR, both dexmedetomidine groups had less PONV on postoperative day 1 (p < 0.05). CONCLUSION: Combined with 1 MAC sevoflurane, dexmedetomidine 0.7 ug/kg and remifentanil provided similar rates for smooth tracheal extubation in spontaneously breathing, anesthetized adults. Dexmedetomidine exhibited opioid-sparing effects postoperatively and was associated with less PONV than remifentanil.

DL-3-n-butylphthalide alleviates motor disturbance by suppressing ferroptosis in a rat model of Parkinson's disease.

DL-3-n-butylphthalide (NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke. NBP has shown recent potential as a treatment for Parkinson's disease. However, the underlying mechanism of action of NBP remains poorly understood. In this study, we established a rat model of Parkinson's disease by intraperitoneal injection of rotenone for 28 successive days, followed by intragastric injection of NBP for 14-28 days. We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson's disease, inhibited loss of dopaminergic neurons and aggregation of α-synuclein, and reduced iron deposition in the substantia nigra and iron content in serum. These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor, ferritin light chain, and transferrin 1. NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson's disease. Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition, oxidative stress, and ferroptosis in the substantia nigra.

Tracheal extubation of deeply anesthetized pediatric patients: a comparison of sevoflurane and sevoflurane in combination with low-dose remifentanil.

PURPOSE: We aimed to observe the emergence characteristics of children tracheally extubated in deep anesthesia with sevoflurane or sevoflurane in combination with low-dose remifentanil. METHODS: We randomly allocated 50 pediatric patients undergoing elective electronic cochlear implantation to groups either receiving sevoflurane (Group S, n = 25), or sevoflurane plus low-dose remifentanil (Group SR, n = 25), during extubation from anesthesia. In Group S, subjects were tracheally extubated while breathing 1.3 times the minimal effective concentration of sevoflurane. In Group SR, subjects were tracheally extubated while breathing 1.0 times the minimal effective concentration of sevoflurane with 0.02-0.05 µg · kg(-1) per min remifentanil. Recovery characteristics and airway complications were noted. RESULTS: There was no significant difference in age, weight, sex, and duration of anesthesia. The average remifentanil rate was 0.036 µg · kg(-1) per min, and compared with Group S, patients in Group SR had a lower respiratory rate (17.3 vs 20.2 per minute, P < 0.05) and a higher ETCO(2) (52.3 vs 49.4 mmHg, P < 0.05). Oral airway usage was also less frequent in Group SR (44% vs 16%, P < 0.01). Additionally, the time from extubation to spontaneous eye opening was shorter in Group SR (10.9 min vs 19.6 min, P < 0.01). Finally, six patients in Group S and five patients in Group SR had a pediatric anesthesia emergence delirium score >10. CONCLUSIONS: Low-dose remifentanil in combination with sevoflurane provided rapid recovery and was safe for deep tracheal extubation in deep anesthesia in pediatric patients.

Propofol-remifentanil intravenous anesthesia and spontaneous ventilation for airway foreign body removal in children with preoperative respiratory impairment.

PURPOSE: To investigate the efficacy and safety of propofol-remifentanil total intravenous anesthesia (TIVA) and spontaneous ventilation for foreign body (FB) removal in pediatric patients with preoperative respiratory impairment. METHODS: We carried out a prospective observational clinical study of FB removal using a rigid bronchoscope under propofol-remifentanil TIVA and spontaneous ventilation in 65 pediatric patients who presented with preoperative respiratory impairment. Heart rate, blood pressure, pulse oxygen saturation (SpO(2)), respiratory rate, endtidal CO(2) (ETCO(2))(ETCO2), induction time, and remifentanil rate were recorded. Adverse events, the intervention for these events, and the duration of postoperative care were also of interest. RESULTS: Sixty children completed the study. The mean induction time was 12.3 min. During the procedure, the maximum remifentanil rate was 0.14 µg · kg(-1) · min(-1). Light breath holding occurred in 16 (26.7%) patients. No severe breath holding or body movements were observed. An SpO(2) below 90% occurred in 10 (16.7%) cases. No progressive desaturation was observed. The mean ETCO(2) at the end of the procedures was 7.91 KPa and returned to normal 5 min after the procedure. In the postanesthesia care unit (PACU), no hypoxemia was observed and the mean recovery time was 23.4 min. No laryngospasm, pneumothorax, or arrhythmias were observed. CONCLUSION: Propofol-remifentanil TIVA and spontaneous ventilation are effective and safe techniques to manage anesthesia during airway FB removal in children with preoperative respiratory impairment.

Paracrine Hedgehog signaling in stomach and intestine: new roles for hedgehog in gastrointestinal patterning.

BACKGROUND & AIMS: Hedgehog signaling is critical in gastrointestinal patterning. Mice deficient in Hedgehog signaling exhibit abnormalities that mirror deformities seen in the human VACTERL (vertebral, anal, cardiac, tracheal, esophageal, renal, limb) association. However, the direction of Hedgehog signal flow is controversial and the cellular targets of Hedgehog signaling change with time during development. We profiled cellular Hedgehog response patterns from embryonic day 10.5 (E10.5) to adult in murine antrum, pyloric region, small intestine, and colon. METHODS: Hedgehog signaling was profiled using Hedgehog pathway reporter mice and in situ hybridization. Cellular targets were identified by immunostaining. Ihh-overexpressing transgenic animals were generated and analyzed. RESULTS: Hedgehog signaling is strictly paracrine from antrum to colon throughout embryonic and adult life. Novel findings include the following: mesothelial cells of the serosa transduce Hedgehog signals in fetal life; the hindgut epithelium expresses Ptch but not Gli1 at E10.5; the 2 layers of the muscularis externa respond differently to Hedgehog signals; organogenesis of the pyloric sphincter is associated with robust Hedgehog signaling; dramatically different Hedgehog responses characterize stomach and intestine at E16; and after birth, the muscularis mucosa and villus smooth muscle consist primarily of Hedgehog-responsive cells and Hh levels actively modulate villus core smooth muscle. CONCLUSIONS: These studies reveal a previously unrecognized association of paracrine Hedgehog signaling with several gastrointestinal patterning events involving the serosa, pylorus, and villus smooth muscle. The results may have implications for several human anomalies and could potentially expand the spectrum of the human VACTERL association.

Dynamic patterning at the pylorus: formation of an epithelial intestine-stomach boundary in late fetal life.

In the adult mouse, distinct morphological and transcriptional differences separate stomach from intestinal epithelium. Remarkably, the epithelial boundary between these two organs is literally one cell thick. This discrete junction is established suddenly and precisely at embryonic day (E) 16.5, by sharpening a previously diffuse intermediate zone. In the present study, we define the dynamic transcriptome of stomach, pylorus, and intestinal tissues between E14.5 and E16.5. We show that establishment of this boundary is concomitant with the induction of over a thousand genes in intestinal epithelium, and these gene products provide intestinal character. Hence, we call this process intestinalization. We identify specific transcription factors (Hnf4 gamma, Creb3l3, and Tcfec) and examine signaling pathways (Hedgehog and Wnt) that may play a role in this process. Finally, we define a unique expression domain at the pylorus itself and detect novel pylorus-specific patterns for the transcription factor Gata3 and the secreted protein nephrocan.

Pyrin and ASC co-localize to cellular sites that are rich in polymerizing actin.

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in the MEFV locus, which encodes the protein pyrin. While it is known that pyrin is expressed in myeloid cells and several fibroblastic cell types, the exact function of pyrin in these cells and the mechanism underlying the pathological effect of pyrin mutations have yet to be revealed. Here, we document that in migrating human monocytes, pyrin protein is dramatically polarized at the leading edge, where it co-localizes with polymerizing actin. ASC (Apoptosis-associated Speck protein with CARD domain), a known pyrin-interacting protein and a critical component of the inflamma-some, is also located at the leading edge in migrating monocytes. Similarly, both pyrin and ASC concentrate in dynamically polymerizing actin-rich tails generated by Listeria monocytogenes. Pyrin's B-box and coiled-coil region is required for its association with Listeria tails. Pyrin also binds, with low affinity and via the same domains, to actin, VASP, and Arp3. Though disease-causing mutations in pyrin do not appear to alter its localization to the leading edge or to Listeria rocket tails, they could potentially have important functional consequences in the context of processes such as migration and cell synapse formation. The co-localization of pyrin and ASC together at such sites may provide an important link between cytoskeletal signaling and inflammasome function.

Electromyographic Response of Facial Nerve Stimulation Under Partial Neuromuscular Blockade During Resection of Vestibular Schwannoma.

OBJECTIVE: To evaluate whether use of partial nondepolarizing neuromuscular blocking agents, at a train-of-four level 1, compromise facial nerve monitoring during vestibular schwannoma (VS) resection. METHODS: Sixty consecutive patients undergoing VS resection were enrolled into a partial peripheral neuromuscular blockade group or free of neuromuscular blockade group. Stimulation threshold to elicit an electromyographic response amplitude of at least 100 µV was recorded at the proximal and distal facial nerve after VS removal. The proximal-to-distal ratio of amplitude of the orbicularis oculi and oris muscles was calculated. RESULTS: All patients successfully passed the electromyography monitoring test. Mean electrical stimulation thresholds were higher in the peripheral neuromuscular blockade group than in the free of neuromuscular blockade group (0.12 mA vs. 0.06 mA at proximal site, P = 0.001; 0.08 mA vs. 0.03 mA at distal site, P = 0.0002). The differences in median proximal-to-distal amplitude ratios were not statistically significant in both groups. There was a trend toward more patients needing phenylephrine. Recovery profiles were comparable in the 2 groups. CONCLUSIONS: Although mean stimulation threshold to elicit a response amplitude was higher in the peripheral neuromuscular blockade group than in the free of neuromuscular blockade group at the proximal site, the stimulation thresholds in both groups were sufficient for facial nerve monitoring in VS surgery, indicating no clinical difference in both groups.

Pyrin, product of the MEFV locus, interacts with the proapoptotic protein, Siva.

Mutations in pyrin cause the autoinflammatory disorder familial Mediterranean fever (FMF), a syndrome characterized by sporadic and unpredictable attacks of fever and localized severe pain. Currently, it is not clear how attacks are triggered, nor why they spontaneously resolve after 2 or 3 days. In fact, the cellular function of the pyrin protein and the molecular underpinnings of its malfunction in FMF have so far eluded clear definition. The identification of pyrin-interacting proteins has the potential to increase our understanding of the cellular networks in which pyrin functions. Previous reports have established that pyrin interacts with the apoptotic protein ASC, the cytoskeletal adaptor protein PSTPIP1, the inflammatory caspase, Caspase-1 and certain forms of the cytosolic anchoring protein 14-3-3. Here, we report that pyrin also interacts with Siva, a pro-apoptotic protein first identified for its interaction with the cytosolic tail of CD27, a TNF family receptor. The interaction between pyrin and Siva involves the C-terminal B30.2/rfp/SRPY domain of pyrin and exon 1 of Siva. We show that Siva and pyrin are indeed co-expressed in human neutrophils, monocytes, and synovial cells. Furthermore, using a novel protein/protein interaction assay, we demonstrate that pyrin can recruit Siva to ASC specks, establishing a potential platform for intersection of ASC and Siva function. Finally, we show that pyrin modulates the apoptotic response to oxidative stress mediated by Siva. Thus, the Siva-pyrin interaction may be a potential target for future therapeutic strategies.

A second expressed kininogen gene in mice.

We isolated PCR, RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE-PCR)-, and RT-PCR-generated clones from mouse kininogen family transcripts. DNA sequencing indicated that the clones were from two distinct genes. One set (K1) is from the previously reported mouse kininogen gene. The second set (K2) has an open reading frame, is 93% identical to K1 in the overlapping nucleotide sequence, and, unlike T-kininogens in the rat, encodes a bradykinin motif identical to K1. We discovered that K2 exists with two different 5' ends. We used RT-PCR to determine the distribution and relative abundance of K1 and K2 mRNA in mouse tissues. K2 is transcribed and K1 and K2 are generally both expressed in the same tissues; however, they differ in their regulation of the alternative splicing event that yields either low-molecular-weight kininogen (LMWK) or high-molecular-weight kininogen (HMWK). For example, in the liver K1 is expressed as both HMWK and LMWK, whereas K2 is only expressed as LMWK. Conversely, in the kidney K2 is strongly expressed as both HMWK and LMWK, whereas K1 is not expressed as HMWK and expressed only very weakly as LMWK.

Sevoflurane in combination with remifentanil for tracheal extubation after otologic surgery.

PURPOSE: The effects of i.v. remifentanil in combination with an inhaled anesthetic to facilitate tracheal extubation of deeply anesthetized adults after otologic surgery are investigated. METHODS: Fifty patients undergoing middleear surgery were recruited for the study. All patients were administered deep anesthesia (i.v. fentanil, propofol, and mivacurium) and intubated, with subsequent administration of inhaled sevoflurane for anesthesia maintenance. Prior to endotracheal tube removal, the patients received i.v. dexamethasone, ondansetron hydrochloride, and parecoxib and were randomly allocated to two groups. In group S (n = 25), anesthesia was maintained with sevoflurane alone (1.3 times the minimum effective alveolar concentration [MAC]), while patients in group SR (n = 25) received low-dose i.v. remifentanil and a reduced dose of sevoflurane (1.0 MAC). RESULTS: The mean remifentanil dosage was 0.028 µg/kg per minute. Relative to patients in group S, patients in group SR had a significantly lower mean respiratory rate (6.4 breaths per minute versus 15.8 breaths per minute, p < 0.01) and end-tidal carbon dioxide pressure (48.1 mm Hg versus 52.1 mm Hg, p < 0.05) after extubation. Postextubation airway obstructions requiring nasal airway placement were less frequent in group SR (14 cases versus 2 cases in group S, p < 0.05); patients in group SR also had a shorter mean time to awakening (19.5 minutes versus 15.8 minutes, p < 0.05) and a shorter mean time to orientation (31.4 minutes versus 26.1 minutes, p < 0.05). CONCLUSION: Sevoflurane combined with remifentanil provided rapid recovery and appeared to be safe for deep-anesthesia tracheal extubation in adult patients after otologic surgery.

Lipopolysaccharide-induced expression of multiple alternatively spliced MEFV transcripts in human synovial fibroblasts: a prominent splice isoform lacks the C-terminal domain that is highly mutated in familial Mediterranean fever.

OBJECTIVE: To investigate the expression of the familial Mediterranean fever (FMF) gene (MEFV) in human synovial fibroblasts. METHODS: MEFV messenger RNA in synovial fibroblasts, chondrocytes, and peripheral blood leukocytes (PBLs) was analyzed by semiquantitative and real-time polymerase chain reaction and ribonuclease protection assay. The subcellular localization of pyrin, the MEFV product, was determined in transfected synovial fibroblasts and HeLa cells with plasmids encoding pyrin isoforms. Native pyrin was detected with an antipyrin antibody. RESULTS: MEFV was expressed in synovial fibroblasts, but not in chondrocytes. Four alternatively spliced transcripts were identified: an extension of exon 8 (exon 8ext) resulting in a frameshift that predicts a truncated protein lacking exons 9 and 10, the addition of an exon (exon 4a) predicting a truncated protein at exon 5, the in-frame substitution of exon 2a for exon 2, and the previously described removal of exon 2 (exon 2Delta). Exon 8ext transcripts represented 27% of the total message population in synovial fibroblasts. All other alternatively spliced transcripts were rare. Consensus and alternatively spliced transcripts were induced by lipopolysaccharide in synovial fibroblasts and PBLs. In transfected cells, the proteins encoded by all highly expressed splice forms were cytoplasmic. In contrast, native pyrin was predominantly nuclear in synovial fibroblasts, neutrophils, and dendritic cells, but was cytoplasmic in monocytes. CONCLUSION: Several MEFV transcripts are expressed and inducible in synovial fibroblasts. A prominent isoform lacks the C-terminal domain that contains the majority of mutations found in patients with FMF. While recombinant forms of all major pyrin isoforms are cytoplasmic, native pyrin is nuclear in several cell types. Thus, mechanisms in addition to splicing patterns must control pyrin's subcellular distribution.