Prolonged Induction Time Research Articles

Comparative analysis of the therapeutic efficacy of remimazolam tosylate and propofol in older adults undergoing painless endoscopic retrograde cholangiopancreatography.

The aim of this study is to conduct a comparative analysis of the therapeutic outcomes associated with the administration of remimazolam and propofol during painless endoscopic retrograde cholangiopancreatography (ERCP) procedures in older adults. A total of 140 older adults who underwent elective painless ERCP were randomly assigned to two groups using the random number table method: the remimazolam group and the propofol group, each consisting of 70 patients. In the remimazolam group, anesthesia was administered using a combination of remimazolam and opioids, while in the propofol group, a combination of propofol and opioids was used. Comparative assessments between the two groups included anesthesia induction time, first induction success rate, intraoperative hemodynamics, awakening duration, stress response index, and the incidence of adverse reactions. The remimazolam group exhibited a prolonged anesthesia induction time compared to the propofol group and a lower success rate of first induction (P < 0.05). At the point of endoscope entry (T2) and 10min post-operation (T3), patients in the remimazolam group demonstrated higher mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) values compared to those in the propofol group (P < 0.05). Furthermore, the remimazolam group had shorter durations for eye-opening, consciousness recovery, and residence in the recovery room compared to the propofol group (P < 0.05). Post-surgery levels of epinephrine (E), norepinephrine (NE), and cortisol (Cor) at 24h were lower in the remimazolam group than in the propofol group (P < 0.05). The incidence of adverse reactions was significantly lower in the remimazolam group (18.57%) compared to the propofol group (31.43%) (P < 0.05). Remimazolam exhibits a longer induction time compared to propofol in the painless diagnosis and treatment of ERCP in older adults. However, it provides a more stable circulatory state post-induction and throughout the operation, reduces stress response, enables rapid recovery, and has a lower incidence of serious adverse reactions. These attributes suggest that remimazolam has potential for widespread clinical application and adoption. clinicaltrials.gov, identifier ChiCTR2400080926.

ω-Carboxyl Terminated Cellulose Esters are Effective Crystallization Inhibitors for Challenging Drugs

Polymeric additives are widely used to delay drug crystallization from supersaturated solutions, which is critical for enhancing oral bioavailability by amorphous solid dispersion (ASD). The efficacy of these polymers relies on their capacity to inhibit nucleation and subsequent crystal growth. Drug nucleation is pivotal to crystallization; therefore, effective polymers are essential for suppressing nucleation from supersaturated solutions. We studied the performance of cellulose ω-carboxyalkanoates designed as crystallization inhibitors by measuring their influence on nucleation induction times of poorly soluble drugs celecoxib, posaconazole, and enzalutamide, from supersaturated solutions. In the absence of polymers, crystallization occurred within 5 to 15 minutes for all three drugs. Polymer hydrophobicity strongly influenced effectiveness in crystallization inhibition. Hydrophobic polymers prolonged induction times for up to 8 hours, while hydrophilic polymers were less effective, except for cellulose acetate glutarate (CA1.18-GA1.21; degrees of substitution acetate 1.18, glutarate 1.21). The cellulose ω-carboxyalkanoates had glass transition temperatures well above 100 °C, outstanding for ASD stability requirements. We investigated the impact of these designed polymers on surface tension and found that it only weakly influenced crystallization inhibition. Among the nine crafted cellulose derivatives, water-soluble CA1.18-GA1.21 emerged as a highly promising ASD polymer, preventing crystallization for 2-8 hours for all fast-crystallizing model compounds.

Substantia Innominata Glutamatergic Neurons Modulate Sevoflurane Anesthesia in Male Mice.

Accumulated evidence suggests that brain regions that promote wakefulness also facilitate emergence from general anesthesia (GA). Glutamatergic neurons in the substantia innominata (SI) regulate motivation-related aversive, depressive, and aggressive behaviors relying on heightened arousal. Here, we hypothesize that glutamatergic neurons in the SI are also involved in the regulation of the effects of sevoflurane anesthesia. With a combination of fiber photometry, chemogenetic and optogenetic tools, behavioral tests, and cortical electroencephalogram recordings, we investigated whether and how SI glutamatergic neurons and their projections to the lateral hypothalamus (LH) regulate sevoflurane anesthesia in adult male mice. Population activity of glutamatergic neurons in the SI gradually decreased upon sevoflurane-induced loss of consciousness (LOC) and slowly returned as soon as inhalation of sevoflurane discontinued before recovery of consciousness (ROC). Chemogenetic activation of SI glutamatergic neurons dampened the animals' sensitivity to sevoflurane exposure, prolonged induction time (mean ± standard deviation [SD]; 389 ± 67 seconds vs 458 ± 53 seconds; P = .047), and shortened emergence time (305 seconds, 95% confidence interval [CI], 242-369 seconds vs 207 seconds, 95% CI, 135-279 seconds; P = .004), whereas chemogenetic inhibition of these neurons facilitated sevoflurane anesthesia. Furthermore, optogenetic activation of SI glutamatergic neurons and their terminals in LH induced cortical activation and behavioral emergence from different depths of sevoflurane anesthesia. Our study shows that SI glutamatergic neuronal activity facilitates emergence from sevoflurane anesthesia and provides evidence for the involvement of the SI-LH glutamatergic pathway in the regulation of consciousness during GA.

Preparation of EPDM/silicon nanofibers-graphene nanocomposites with enhanced interfacial structure: Highly reinforcing and stabilizing effect

Aiming at designing enhanced interfacial structure, TA@SiNF/PGNs hybrids with hydrogen bonding and π-π conjugation were constructed through wrapping of polyrhodanine on graphene nanosheets (GNs) and self-polymerization of tannic acid (TA) onto SiNF surface. EPDM/TA@SiNF/PGNs nanocomposites were further prepared and the enhanced interfacial interactions were achieved, which promoted good dispersion of the hybrid nanofillers. Compared with EPDM, addition of TA@SiNF/PGNs resulted in a significant increase in mechanical strength and fracture toughness, and the mechanical strength of EPDM/TA@SiNF/PGNs was much better than EPDM/TA@SiNF or EPDM/PGNs due to the increased crosslinking density, indicating remarkably reinforcing and toughening effect of TA@SiNF/PGNs. In addition, the lower compression set and higher contact stress relaxation coefficient were achieved, revealing an improvement of compressive resilience. Moreover, TA@SiNF/PGNs effectively slowed down the deterioration of mechanical properties after thermo-oxidative aging, and the higher retention of crosslinking density and prolonged oxidation induction time confirmed the excellent stabilization effect of TA@SiNF/PGNs.

Glutamatergic neurons in the paraventricular hypothalamic nucleus regulate isoflurane anesthesia in mice.

The glutamatergic-mediated excitatory system in the brain is vital for the regulation of sleep-wake and general anesthesia. Specifically, the paraventricular hypothalamic nucleus (PVH), which contains mainly glutamatergic neurons, has been shown to play a critical role in sleep-wake. Here, we sought to explore whether the PVH glutamatergic neurons have an important effect on the process of general anesthesia. We used c-fos staining and in vivo calcium signal recording to observe the activity changes of the PVH glutamatergic neurons during isoflurane anesthesia and found that both c-fos expression in the PVH and the calcium activity of PVH glutamatergic neurons decreased in isoflurane anesthesia and significantly increased during the recovery process. Chemogenetic activation of PVH glutamatergic neurons prolonged induction time and shortened emergence time from anesthesia by decreasing the depth of anesthesia. Using chemogenetic inhibition of PVH glutamatergic neurons under isoflurane anesthesia, we found that inhibition of PVH glutamatergic neurons facilitated the induction process and delayed the emergence accompanied by deepening the depth of anesthesia. Together, these results identify a crucial role for PVH glutamatergic neurons in modulating isoflurane anesthesia.

Efficacy and safety of Ciprofol for procedural sedation and anesthesia in non-operating room settings

Study objectiveCiprofol, a novel intravenous anesthetic, provides rapid recovery in patients undergoing colonoscopy. We aimed to examine the efficacy and safety of ciprofol in comparison with propofol for sedation or anesthesia in non-operating room settings including endoscopic submucosal dissection, endoscopic retrograde cholangiopancreatography, and flexible bronchoscopy (FB). DesignProspective, randomized, double-blind, parallel-group clinical trial. SettingUniversity-affiliated teaching hospital. PatientsWe recruited 207 patients scheduled for an endoscopic procedure from October 2021 to December 2021. InterventionsPatients were randomized into three groups according to the dose during induction (n = 69 each): 1) ciprofol 6 mg/kg/h, 2) ciprofol 8 mg/kg/h, or 3) propofol 40 mg/kg/h. Ciprofol or propofol was administered throughout the procedure. MeasurementsThe primary outcome was the success rate of sedation or anesthesia for the procedures. Secondary outcomes included induction time, endoscope insertion time, recovery time, discharge time, incidence of drug-related adverse events (AEs), neurological and inflammatory outcomes. Main resultsThe procedure success rates in the three groups were 100%. The induction time in the 6 (3.3 ± 1.0 min) and 8 mg/kg/h (2.9 ± 0.6 min) ciprofol groups was longer than that in the propofol group (2.5 ± 0.6 min) only in patients undergoing FB (p = 0.004). The time for patients to be fully alert and discharged from the post-anesthesia care unit was comparable across the three groups (p > 0.05). The incidence of drug-related AEs in the propofol and 6 and 8 mg/kg/h ciprofol groups was 84.1%, 76.8%, and 79.7%. No pain on injection was reported by ciprofol groups. Neurological outcomes and inflammatory responses were comparable among the three groups. ConclusionsCiprofol induced a level of sedation or anesthesia equivalent to that induced by propofol in non-operating room settings except for a prolonged induction time in patients undergoing FB. Ciprofol had a safety profile similar to that of propofol. No pain on injection was reported by ciprofol.

Development and validation of a prediction model for preoperative anxiety in children aged 2-12 years old.

Children with preoperative anxiety are at risk of perioperative adverse events, such as reflux aspiration, prolonged induction time, wake agitation, and delirium. Identifying children at high risk of severe preoperative anxiety may help anesthesiologists intervene and manage them in advance. The authors hypothesized that the risk of developing serious preoperative anxiety in children is predictable by variables related to basic information about the parent and child. We developed a clinical prediction model to identify patients vulnerable to severe preoperative anxiety among children aged 2-12 years. We enrolled patients aged 2-12 years who underwent elective surgery under general anesthesia and divided them into derivation (n=340, 70.8%) and validation (n=140, 29.2%) groups. Preoperative anxiety was assessed using the modified Yale Preoperative Anxiety Scale, and a high level of preoperative anxiety was defined as a score of >30. The following predictors were collected preoperatively: gender, age, weight, children's education level, only child, history of surgery, waiting time in the anesthesia waiting area, parental education level, parental anxiety, whether venous access had been established in the ward, and whether they had received anti-anxiety interventions. A prediction model was built using binary logistic regression analysis; bootstrap was applied for internal validation, and external validation was performed using the validation datasets. The prediction model had good discrimination, with an area under the receiver operator characteristic curve (AUC) of 0.961 (95% CI=0.943-0.979) and 0.896 (95% CI=0.842-0.950) in the derivation and validation cohorts, respectively. The predictive variables included in the final clinical model were pharmacological intervention (OR=0.008, 95% CI=0.002-0.025), nonpharmacological intervention (OR=0.342, 95% CI=0.104-1.127), parental education level (OR=0.211, 95% CI=0.108-0.411), parental anxiety (OR=6.15, 95% CI=2.396-15.786), only child (OR=2.417, 95% CI=1.065-5.488), history of surgery (OR=3.513, 95% CI=1.137-10.860), and age (OR=0.692, 95% CI=0.500-0.957). In this study, a clinical prediction model was developed and validated for the first time. The proposed clinical prediction model can help doctors identify children most likely to develop a high level of preoperative anxiety. ChiCTR2100054409 (https://www.chictr.org.cn/index.aspx).

Novel multifunctional antioxidants for polymers using eugenol as biogenic building block

Novel molecular and polymeric antioxidants (AO) were successfully synthesized using eugenol (4-allyl-2-methoxyphenol) as biogenic starting material. The structure of the novel stabilizers was confirmed by 1H-, 13C NMR spectra and Fourier Transform Infrared Spectrometry (FTIR). Furthermore, the polymeric stabilizers are characterized by Size-Exclusion Chromatography (SEC). Thermal gravimetric analysis (TGA) showed high temperature stability above 250 °C proving potential suitability as stabilizers for polyolefins. The impact of the molecular and polymeric antioxidants on the processing behavior and degradation of polypropylene (PP) was examined by prolonged extrusion experiments and oxidation induction time (OIT) measurements. Moreover, the long-term oxidative stability of the PP compounds during accelerated aging was investigated. The novel antioxidants provide excellent processing stability of PP.

The Impact of Cannabidiol on the Induction of Isoflurane Anesthesia and Recovery in Wistar Rats.

Background: Beside others, neuroinhibitory and sedative effects of CBD were documented. Aim and Methods: The aim of the study was to assess the dose-related effects of CBD premedication on the course of isoflurane anesthesia. Wistar rats were pretreated with different doses of CBD 1 h before isoflurane anesthesia. In the pretreatment, animals were given CBD at doses of 100, 20, 10, or 2 mg kg-1. Before the fifth (control) anesthesia, the animals were given only mid-chain triglyceride oil, which served as a solvent in the CBD formulation. The induction time was determined, and on awakening, the time to appearance of the flexion reflex and the recovery from anesthesia were determined. Results: Statistical analysis showed a significantly shorter induction time if animals were pretreated with 20 mg kg-1 CBD. In addition, pretreatment with 100 mg kg-1 CBD resulted in a prolonged induction time, while on awakening, delayed appearance of reflexes and prolonged recovery from anesthesia compared to pretreatment with 20 mg kg-1 CBD were observed. Conclusions: The results indicate that the influence of CBD on the course of isoflurane anesthesia depends on the dose and can reduce the induction time. Although this study was performed in laboratory rats, in clinical practice, these data should be considered when CBD-treated patients undergo isoflurane anesthesia.

Mild therapeutic hypothermia after out-of-hospital cardiac arrest: What does really matter?

Mild therapeutic hypothermia (MTH) is a recommended treatment of comatose patients after out-of-hospital cardiac arrest (OHCA). The aim of the study was to examine determinants of clinical outcome in OHCA survivors treated with MTH and variables associated with MTH induction time. Presented herein is an analysis of combined results from a retrospective and a prospective observational study which included 90 OHCA survivors treated with MTH from January 2010 to March 2018. Multivariate regression analysis was performed to determine variables associated with poor neurologic outcome (Cerebral Performance Category 3-5), mortality, and prolonged induction time. At hospital discharge, 59 (65.6%) patients were alive, of whom 36 (61%) had a good neurologic outcome. Older patients (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.03-1.12) with lower Glasgow Coma Scale (GCS) (OR 0.49, 95% CI 0.30-0.80) were at higher risk of poor neurological outcome. The predictors of in-hospital death included: older age (OR 1.08, 95% CI 1.02-1.13), lower GCS score (OR 0.47, 95% CI 0.25-0.85), presence of cardiogenic shock (OR 3.43, 95% CI 1.11-10.53), and higher doses of adrenaline (OR 1.27, 95% CI 1.04-1.56). Longer induction was associated with shorter cardio-pulmonary resuscitation (CPR) (unstandardized coefficient -3.95, 95% CI -7.09 to -0.81) and lower lactate level (unstandardized coefficient -18.55, 95% CI -36.10 to -1.01). Unfavorable neurologic outcome in OHCA patients treated with MTH is associated with age and lower GCS score. Risk factors for in-hospital mortality include age, high-dose adrenaline administration, lower GCS score and presence of cardiogenic shock. CPR duration and lactate level were predictive of prolonged MTH induction time.

Bioinspired Hybrid Micro/Nanostructure Composited Membrane with Intensified Mass Transfer and Antifouling for High Saline Water Membrane Distillation.

Membrane distillation (MD) holds great promise for high-saline solution treatment, but it is typically impeded by the trade-off between the high mass transfer and antifouling properties of the membrane. Herein, a new MD utilized membrane with bioinspired micro/nanostructure (lotus leaf and fish gill) was constructed on commercial PP membrane, which can simultaneously enhance the permeation flux and antifouling in the hypersaline MD operation. On the basis of the classic nucleation theory and hydrodynamics simulation, the nanoscale structure can intensify the interfacial nanoscale turbulent flow and hinder the crystal deposition, which works like the fish gill. In addition, the optimized nanoscale feature size renders the membrane with the heterogeneous nucleation barrier very similar to the homogeneous system, which works like the lotus leaf and hinders the induced nucleation effectively. The microscale structure as the supporting platform of nanostructure can additionally enlarge the effective evaporative surface with superior hydrophobicity and then promote the permeation transfer through the membrane. The hybrid micro/nanostructures render the fabricated membrane with excellent high-permeation flux and significantly prolonged fouling induction time, which sheds light on a new approach for the development of ideal MD utilized membrane.

Continuous infusion versus intermittent bolus injection of propofol during endoscopic retrograde cholangiopancreatography.

Background/AimsIt is unclear whether continuous infusion or intermittent bolus injection of propofol is better for achieving adequate sedation in endoscopic retrograde cholangiopancreatography (ERCP). We aimed to compare the efficacy and safety of continuous infusion and intermittent bolus injection of propofol during therapeutic ERCP.MethodsIn this prospective study, we randomly assigned 232 patients undergoing therapeutic ERCP to either continuous infusion (CI group, n = 113) or intermittent bolus injection (BI group, n = 119) of propofol. The primary outcome was the quality of sedation as assessed by the endoscopist. Other sedation-related parameters included sedation induction time, total dose of propofol, recovery time, involuntary patient movement, and adverse events.ResultsOverall satisfaction with sedation by the endoscopist and monitoring nurse were significantly higher in the CI group than the BI group (mean satisfaction score, 9.66 vs. 8.0 and 9.47 vs. 7.96, respectively, p < 0.01 for both). However, patients in the CI group had a significantly longer sedation induction time (5.28 minutes vs. 4.34 minutes, p < 0.01) and received a higher dose of propofol than patients in the BI group (4.22 mg/kg vs. 2.08 mg/kg, p < 0.01). There was no significant difference in adverse events between the two groups.ConclusionsContinuous infusion of propofol during therapeutic ERCP had the advantage over intermittent bolus injection of maintaining a constant level of sedation without increasing adverse events. However, it was associated with an increased total dose of propofol and prolonged sedation induction time.

Direct insights into the pore-scale mechanism of low-salinity waterflooding in carbonates using a novel calcite microfluidic chip

One of the key open questions in the area of low or controlled salinity water flooding (LSWF or CSWF) is how the observed oil recovery at macro-scale (e.g. Darcy or core-scale) can the explained and what underlying microscopic mechanisms drive it. Thus far, the micromodel investigation of LSWF has been limited to sandstones, remaining challenging to apply to carbonates. In this paper we aim to i) extend the capability to fabricate a novel calcite micromodel using Iceland spar calcite crystal, ii) investigate the pore-scale mechanisms leading to oil recovery from carbonates.A target crude oil-brine-rock (COBR) system was first selected. To screen potential brines which can produce low-salinity-effect (LSE) and to guide the design of the micromodel experiments, contact angle measurements were carried out using two methods: i) contact angle under fixed, and ii) under dynamic salinity condition. The micromodel displacement experiments were then performed by flooding an oil saturated model with high salinity water followed by low salinity water injection to displace the high salinity water and observe any potential changes to the configuration and saturation of the residual oil. Additionally, the effect of connate water presence on the efficiency of LSE was investigated. To account for the time effects of the low salinity process, the experiments were monitored for an extended time period in order of several days to a month.For the COBR system studied in the micromodel, the results clearly show that when brine salinity is lowered the microscopic sweep efficiency is improved; providing a direct in-situ evidence for wettability alteration to a more water-wetting state. The presence of connate water enhanced the efficiency of LSWF both in terms of speed (time-scale) and quantity of oil recovery. It is postulated that in the presence of connate water an initial water-film around the calcite surface is present which facilitates the diffusive transport of brine ions when low salinity is injected. Thus it is favorable to have an initial water film present; a case for mixed-wettability. We observed that the oil production was non-instantaneous characterized by a prolonged induction time and a slow “layer-by-layer” recovery either from the pore body or throat wall; a process we refer to as “peel-off”. Before the oil can be removed from the calcite surface, de-wetting (or de-pinning) patterns were formed which grew and coalesced toward formation of a clearly visible larger pattern. Ultimately, the remaining oil under low salinity was comparatively much less compared to the end of high salinity step.The observed mechanism of the oil recovery and the slow associated time have direct implications for the pore-scale simulation of the process and upscaling to Darcy-scale, and the design of laboratory experiments to avoid false negative results. They would also likely imply lack of a clear oil-bank observation at core scale.

Facile construction of enhanced multiple interfacial interactions in EPDM/zinc dimethacrylate (ZDMA) rubber composites: Highly reinforcing effect and improvement mechanism of sealing resilience

Based on Zn2+-carboxyl coordination strategy, EPDM-g-Glu/ZDMA composite was prepared by grafting of maleic anhydride (MAH)/glutamic acid (Glu) onto EPDM chains via reactive melting process and in situ formation of zinc dimethacrylate (ZDMA) through convenient two-roll milling/hot-pressing process. Zn2+-carboxyl coordination was proved to be formed, and ZDMA uniformly dispersed in matrix and rapidly polymerized to form single rod-shaped PZDMA containing Zn2+-based ionic multiplet during vulcanization, which was tightly embedded in matrix with strong interfacial interaction. Compared with EPDM/ZDMA composite, higher polymerization degree of ZDMA and thicker immobilized EPDM layer were achieved with reducing size of PZDMA clusters for EPDM-g-Glu/ZDMA composite. In addition, multiple interactions with higher covalent (Ve1) and ionic crosslinking density formed. Moreover, higher retention of Ve1 after ageing was obtained, while thermo-oxidative ageing process was retarded with prolonged oxidation induction time. Thus simultaneously remarkable enhancement of energy dissipation, mechanical and durable sealing resilience performance were achieved for EPDM rubber.

Anaesthetic efficacy of Aqui-S, Benzoak, and MS-222 on lumpfish (Cyclopterus lumpus) fries. Impact from temperature, salinity, and fasting

Large numbers of lumpfish are produced for the Norwegian salmon industry and are used to combat sea lice infestations. Periodically high mortality of farmed lumpfish demonstrates the need to improve farming conditions and animal welfare. As part of such efforts, the present work tested the efficacy of three anaesthetic chemicals on lumpfish fries (average weight of 0.97 g). The anaesthetic impact from salinity (15 ppt–18 ppt), temperature (12°C versus 7 and 18°C), and fasting conditions (three days) was also examined. Surgical anaesthesia was induced within 3 to 5 min (preferred time) at concentrations of 18 mg/L (Aqui-S), 37.5 mg/L (Benzoak), and 60 mg/L (buffered MS-222). Safety margins were regarded as low when using Aqui-S; therefore, this chemical was not considered suitable for prolonged exposures. The lumpfish made a rapid recovery from both Benzoak and MS-222 even after 20 min of exposure. A 6°C increase in exposure temperature (reaching 18°C) was found to delay or inhibit recovery. The effect of a 5°C decrease (down to 7°C) significantly reduced induction time for MS-222 and was insignificant for Aqui-S, while it prolonged Benzoak induction time significantly and gave a longer recovery period. Fasting resulted in 70% recovery after 20 min of Aqui-S exposure compared to 0% in fed fish but had only minor effects on Benzoak and MS-222. Use of brackish water (15 ppt–18 ppt) gave 20% recovery from Aqui-S and significantly shorter recovery time from MS-222 exposure, while the effects on Benzoak were insignificant.

Activation of Parabrachial Nucleus Glutamatergic Neurons Accelerates Reanimation from Sevoflurane Anesthesia in Mice.

The parabrachial nucleus (PBN), which is a brainstem region containing glutamatergic neurons, is a key arousal nucleus. Injuries to the area often prevent patient reanimation. Some studies suggest that brain regions that control arousal and reanimation are a key part of the anesthesia recovery. Therefore, we hypothesize that the PBN may be involved in regulating emergence from anesthesia. We investigated the effects of specific activation or inhibition of PBN glutamatergic neurons on sevoflurane general anesthesia using the chemogenetic "designer receptors exclusively activated by designer drugs" approach. Optogenetic methods combined with polysomnographic recordings were used to explore the effects of transient activation of PBN glutamatergic neuron on sevoflurane anesthesia. Immunohistochemical techniques are employed to reveal the mechanism by which PBN regulated sevoflurane anesthesia. Chemogenetic activation of PBN glutamatergic neurons by intraperitoneal injections of clozapine-N-oxide decreased emergence time (mean ± SD, control vs. clozapine-N-oxide, 55 ± 24 vs. 15 ± 9 s, P = 0.0002) caused by sevoflurane inhalation and prolonged induction time (70 ± 15 vs. 109 ± 38 s, n = 9, P = 0.012) as well as the ED50 of sevoflurane (1.48 vs. 1.60%, P = 0.0002), which was characterized by a rightward shift of the loss of righting reflex cumulative curve. In contrast, chemogenetic inhibition of PBN glutamatergic neurons slightly increased emergence time (56 ± 26 vs. 87 ± 26 s, n = 8, P = 0.034). Moreover, instantaneous activation of PBN glutamatergic neurons expressing channelrhodopsin-2 during steady-state general anesthesia with sevoflurane produced electroencephalogram evidence of cortical arousal. Immunohistochemical experiments showed that activation of PBN induced excitation of cortical and subcortical arousal nuclei during sevoflurane anesthesia. Activation of PBN glutamatergic neurons is helpful to accelerate the transition from general anesthesia to an arousal state, which may provide a new strategy in shortening the recovery time after sevoflurane anesthesia.

Maternal age and body mass index at term: Risk factors for requiring an induced labour for a late-term pregnancy

IntroductionWe investigated the role of body mass index (BMI) and maternal age on the risk of late-term induction, prolonged induction time and caesarean section (CS) after induction. Material and MethodsThis is a retrospective, observational study. All women without any fetal or maternal pathological condition, uterine scars or any other indication for an elective caesarean birth and had a singleton foetus in the cephalic position at term were included. ResultsA total of 4006 women had a spontaneous onset of labour and 612 were induced for a late-term pregnancy. Labour induction was significantly more common in overweight (Adj Odds Ratio (OR) 1.48 95%CI 1.22–1.78) and obese (Adj OR 1.63 95%CI 1.24–2.14) women. Among induced women, a BMI ≥ 30 was a risk factor for a prolonged induction time in both nulliparous (AdjOR 2.4, 95%CI 1.02–5.67) and multiparous women (AdjOR 4.24, 95%CI 1.02–17.6). A BMI > 25–29.9 was significantly associated with a prolonged induction time only in nulliparous women (AdjOR 1.86 95%CI 1.05–3.30). A CS was more frequent in overweight (AdjOR 1.74, 95% CI 1.052.89) and obese women (AdjOR 2.72, 95%CI 1.42–5.25). Nulliparous women ageed 30–34 years had an induction time longer than women <30 years (OR 2.04 95%CI 1.07–3.91). ConclusionsThe results of this study suggest that a BMI > 25 kg/m2 at term of pregnancy is a risk factor for the induction of labour during a late-term pregnancy, a prolonged induction time and higher caesarean section rate.

Ubiquitin Carboxyl Terminal Hydrolase L1 Attenuates TNF-α-Mediated Vascular Smooth Muscle Cell Migration Through Suppression of NF-κB Activation.

Ubiquitin carboxyl terminal hydrolase L1 (UCH-L1) is one of the deubiquitinating enzymes in the ubiquitin-proteasome system. It has been shown that UCH-L1 could markedly decrease neointima formation through suppressing vascular smooth muscle cell (VSMC) proliferation in the balloon-injured rat carotid. However, whether UCH-L1 plays roles in VSMC migration remains to be determined. In this study, the primary VSMCs were isolated from aortic media of rats and TNF-α to was used to induce VSMC migration. Using a modified Boyden chamber and wound healing assay, it was found that TNF-α can dose and time-dependently induce VSMC migration with a maximal effect at 10 ng/mL. Moreover, UCH-L1 expression increased gradually with the prolonged induction time at 10 ng/mL of TNF-α. UCH-L1 content in VSMC was then modulated by recombinant adenoviruses expressing UCH-L1 or RNA interference to evaluate its roles in cell migration. The results showed that over-expression of UCH-L1 attenuated VSMC migration, while knockdown of it enhanced cell migration significantly no matter whether TNF-α treatment or not. Finally, the effect of UCH-L1 on NF-κB activation was demonstrated by NF-κB nuclear translocation and DNA binding activity, and the levels of IL-6 and IL-8 in cell culture media were examined by ELISA. It was showed that UCH-L1 over-expression inhibited NF-κB activation and decrease IL-6 and IL-8 levels, while knockdown of it enhanced NF-κB activation and increase IL-6 and IL-8 levels during TNF-α treatment. These data suggest that UCH-L1 can inhibit TNF-α-induced VSMCs migration, and this kind of effect may partially due to its suppression role in NF-κB activation.

Enhanced oxidation stability of highly cross-linked ultrahigh molecular weight polyethylene by tea polyphenols for total joint implants

Despite being currently state-of-the-art to prevent the oxidation of irradiated ultrahigh molecular weight polyethylene (UHMWPE) bearings, vitamin E (VE) poses concerns in the loss of cross-linking efficiency and is limited to be used at very low concentrations. It thus emphasizes the urgent demand for more efficient stabilizers. In this study, oxidation stability of highly cross-linked UHMWPE was demonstrated to be enhanced by tea polyphenols, such as lipid-soluble tea polyphenols (lsPPT), epigallocatechin gallate (EGCG), and lipid-soluble epigallocatechin gallate (lsEGCG). These antioxidants were blended with UHMWPE granules and consolidated by compression molding prior to E-beam irradiation. The presence of tea polyphenols substantially prolonged oxidation induction time of the irradiated UHMWPE before and after accelerated aging. Especially, lsEGCG was significantly superior to VE in terms of stabilizing capacity. Explained by the hydrogen donation mechanism, tea polyphenols with multiple phenolic hydroxyls could scavenge more radiation-induced free radicals than VE with only one phenolic hydroxyl, which was verified by the electron spin resonance spectra. Intriguingly, tea polyphenols showed less inhibitive effect on the cross-link density of irradiated UHMWPE than VE. Besides, there is no significant difference in crystallinity, mechanical performance as well as in vitro biocompatibility between the irradiated UHMWPE stabilized by tea polyphenols and VE. These findings highlight tea polyphenols, especially lsEGCG, are promising alternatives to extend the life span of UHMWPE implants.

Amphiphilic Copolymers Containing POSS and SBMA with N-Vinylcaprolactam and N-Vinylpyrrolidone for THF Hydrate Inhibition.

Icelike gas hydrates deposited in the pipelines under low temperatures and high pressures could remarkably reduce the transport efficiency, and a low dosage of water-soluble polymers could act as kinetic hydrate inhibitors (KHIs) to prevent gas hydrate formation. It was believed that the hydrophobic moiety in the water-soluble polymers played a vital role in enhancing the KHI performance. In this work, amphiphilic copolymers containing hydrophobic polyhedral oligomeric silsesquioxane (POSS) and superhydrophilic sulfobetaine methacrylate (SBMA) as well as N-vinylcaprolactam (VCap) and N-vinylpyrrolidone (VP) were prepared, and an efficient effect of the obtained amphiphilic copolymers on tetrahydrofuran (THF) hydrate inhibition was found. When a certain amount of the amphiphilic copolymers was introduced, the THF hydrate as an analogue of structure II gas hydrates presented a prolonged induction time and gave rise to a looser state rather than a crystalline solid. Analyses of low-field nuclear magnetic resonance and differential scanning calorimetry verified that there were strong interactions between the copolymer and water molecules by incorporation of SBMA units, which could enhance the KHI properties of the prepared amphiphilic copolymers. Additionally, the hydrophobic POSS in the amphiphilic copolymers could possibly modulate the hydrophilic/hydrophobic balance, contributing to the synergistical ability of the copolymers for THF hydrate inhibition. It was suggested that the amphiphilic copolymers containing POSS and zwitterionic units with VCap or VP could have potential for the inhibition and antiaggregation of gas hydrates in the transportation pipelines.