AIM:To determine whether topical lidocaine benefits esophagogastroduoduenoscopy(EGD) by decreasing propofol dose necessary for sedation or procedurerelated complications.METHODS:The study was designed as a prospective...AIM:To determine whether topical lidocaine benefits esophagogastroduoduenoscopy(EGD) by decreasing propofol dose necessary for sedation or procedurerelated complications.METHODS:The study was designed as a prospective,single centre,double blind,randomised clinical trial and was conducted in 2012 between January and May(NCT01489891).Consecutive patients undergoing EGD were randomly assigned to receive supplemental topical lidocaine(L;50 mg in an excipient solution which was applied as a spray to the oropharynx) or placebo(P;taste excipients solution without active substance,similarly delivered) prior to the standard propofol sedation procedure.The propofol was administered as a bolus intravenous(iv) dose,with patients in the L and P groups receiving initial doses based on the patient’s American Society of Anaesthesiologists(ASA) classification(ASAⅠ-Ⅱ:0.50-0.60 mg/kg;ASA Ⅲ-Ⅳ:0.25-0.35 mg/kg),followed by 10-20 mg iv dose every 30-60 s at the anaesthetist’s discretion.Vital signs,anthropometric measurements,amount of propofol administered,sedation level reached,examination time,and the subjective assessments of the endoscopist’s and anaesthetist’s satisfaction(based upon a four point Likert scale) were recorded.All statistical tests were performed by the Stata statistical software suite(Release 11,2009;StataCorp,LP,College Station,TX,United States).RESULTS:No significant differences were found between the groups treated with lidocaine or placebo in terms of total propofol dose(310.7 ± 139.2 mg/kg per minute vs 280.1 ± 87.7 mg/kg per minute,P = 0.15) or intraprocedural propofol dose(135.3 ± 151.7 mg/kg per minute vs 122.7 ± 96.5 mg/kg per minute,P = 0.58).Only when the L and P groups were analysed with the particular subgroups of female,【 65-year-old,and lower anaesthetic risk level(ASA Ⅰ-Ⅱ) was a statistically significant difference found(L:336.5 ± 141.2 mg/kg per minute vs P:284.6 ± 91.2 mg/kg per minute,P = 0.03) for greater total propofol requirements).The total incidence of complications was also similar between the two groups,with the L group showing a complication rate of 32.2%(95%CI:21.6-45.0) and the P group showing a complication rate of 26.7%(95%CI:17.0-39.0).In addition,the use of lidocaine had no effect on the anaesthetist’s or endoscopist’s satisfaction with the procedure.Thus,the endoscopist’s satisfaction Likert assessments were equally distributed among the L and P groups:unsatisfactory,[L:6.8%(95%CI:2.2-15.5) vs P:0%(95%CI:0-4.8);neutral,L:10.1%(95%CI:4.2-19.9) vs P:15%(95%CI:7.6-25.7)];satisfactory,[L:25.4%(95%CI:10-29.6) vs P:18.3%(95%CI:15.5-37.6);and very satisfactory,L:57.6%(95%CI:54-77.7) vs P:66.6%(95%CI:44.8-69.7)].Likewise,the anaesthetist’s satisfaction Likert assessments regarding the ease of maintaining a patient at an optimum sedation level without agitation or modification of the projected sedation protocol were not affected by the application of lidocaine,as evidenced by the lack of significant differences between the scores for the placebo group:unsatisfactory,L:5.8%(95%CI:1.3-13.2) vs P:0%(95%CI:0-4.8);neutral,L:16.9%(95%CI:8.9-28.4) vs P:16.7%(95%CI:8.8-27.7);satisfactory,L:15.2%(95%CI:7.7-26.1) vs P:20.3%(95%CI:11.3-31.6);and very satisfactory,L:62.7%(95%CI:49.9-74.3) vs P:63.3%(95%CI:50.6-74.7).CONCLUSION:Topical pharyngeal anaesthesia is safe in EGD but does not reduce the necessary dose of propofol or improve the anaesthetist’s or endoscopist’s satisfaction with the procedure.展开更多
A complex network of cellular receptors,RNA targeting pathways,and small-molecule signaling provides robust plant immunity and tolerance to viruses.To maximize their fitness,viruses must evolve control mechanisms to b...A complex network of cellular receptors,RNA targeting pathways,and small-molecule signaling provides robust plant immunity and tolerance to viruses.To maximize their fitness,viruses must evolve control mechanisms to balance host immune evasion and plant-damaging effects.The genus Potyvirus comprises plant viruses characterized by RNA genomes that encode large polyproteins led by the P1 protease.A P1 autoinhibitory domain controls polyprotein processing,the release of a downstream functional RNAsilencing suppressor,and viral replication.Here,we show that P1Pro,a plum pox virus clone that lacks the P1 autoinhibitory domain,triggers complex reprogramming of the host transcriptome and high levels of abscisic acid(ABA)accumulation.A meta-analysis highlighted ABA connections with host pathways known to control RNA stability,turnover,maturation,and translation.Transcriptomic changes triggered by P1Pro infection or ABA showed similarities in host RNA abundance and diversity.Genetic and hormone treatment assays showed that ABA promotes plant resistance to potyviral infection.Finally,quantitative mathematical modeling of viral replication in the presence of defense pathways supported self-control of polyprotein processing kinetics as a viral mechanism that attenuates the magnitude of the host antiviral response.Overall,our findings indicate that ABA is an active player in plant antiviral immunity,which is nonetheless evaded by a self-controlled RNA virus.展开更多
基金Supported by Empresa Pública Hospital del Sur,Parla(Madrid) Spain
文摘AIM:To determine whether topical lidocaine benefits esophagogastroduoduenoscopy(EGD) by decreasing propofol dose necessary for sedation or procedurerelated complications.METHODS:The study was designed as a prospective,single centre,double blind,randomised clinical trial and was conducted in 2012 between January and May(NCT01489891).Consecutive patients undergoing EGD were randomly assigned to receive supplemental topical lidocaine(L;50 mg in an excipient solution which was applied as a spray to the oropharynx) or placebo(P;taste excipients solution without active substance,similarly delivered) prior to the standard propofol sedation procedure.The propofol was administered as a bolus intravenous(iv) dose,with patients in the L and P groups receiving initial doses based on the patient’s American Society of Anaesthesiologists(ASA) classification(ASAⅠ-Ⅱ:0.50-0.60 mg/kg;ASA Ⅲ-Ⅳ:0.25-0.35 mg/kg),followed by 10-20 mg iv dose every 30-60 s at the anaesthetist’s discretion.Vital signs,anthropometric measurements,amount of propofol administered,sedation level reached,examination time,and the subjective assessments of the endoscopist’s and anaesthetist’s satisfaction(based upon a four point Likert scale) were recorded.All statistical tests were performed by the Stata statistical software suite(Release 11,2009;StataCorp,LP,College Station,TX,United States).RESULTS:No significant differences were found between the groups treated with lidocaine or placebo in terms of total propofol dose(310.7 ± 139.2 mg/kg per minute vs 280.1 ± 87.7 mg/kg per minute,P = 0.15) or intraprocedural propofol dose(135.3 ± 151.7 mg/kg per minute vs 122.7 ± 96.5 mg/kg per minute,P = 0.58).Only when the L and P groups were analysed with the particular subgroups of female,【 65-year-old,and lower anaesthetic risk level(ASA Ⅰ-Ⅱ) was a statistically significant difference found(L:336.5 ± 141.2 mg/kg per minute vs P:284.6 ± 91.2 mg/kg per minute,P = 0.03) for greater total propofol requirements).The total incidence of complications was also similar between the two groups,with the L group showing a complication rate of 32.2%(95%CI:21.6-45.0) and the P group showing a complication rate of 26.7%(95%CI:17.0-39.0).In addition,the use of lidocaine had no effect on the anaesthetist’s or endoscopist’s satisfaction with the procedure.Thus,the endoscopist’s satisfaction Likert assessments were equally distributed among the L and P groups:unsatisfactory,[L:6.8%(95%CI:2.2-15.5) vs P:0%(95%CI:0-4.8);neutral,L:10.1%(95%CI:4.2-19.9) vs P:15%(95%CI:7.6-25.7)];satisfactory,[L:25.4%(95%CI:10-29.6) vs P:18.3%(95%CI:15.5-37.6);and very satisfactory,L:57.6%(95%CI:54-77.7) vs P:66.6%(95%CI:44.8-69.7)].Likewise,the anaesthetist’s satisfaction Likert assessments regarding the ease of maintaining a patient at an optimum sedation level without agitation or modification of the projected sedation protocol were not affected by the application of lidocaine,as evidenced by the lack of significant differences between the scores for the placebo group:unsatisfactory,L:5.8%(95%CI:1.3-13.2) vs P:0%(95%CI:0-4.8);neutral,L:16.9%(95%CI:8.9-28.4) vs P:16.7%(95%CI:8.8-27.7);satisfactory,L:15.2%(95%CI:7.7-26.1) vs P:20.3%(95%CI:11.3-31.6);and very satisfactory,L:62.7%(95%CI:49.9-74.3) vs P:63.3%(95%CI:50.6-74.7).CONCLUSION:Topical pharyngeal anaesthesia is safe in EGD but does not reduce the necessary dose of propofol or improve the anaesthetist’s or endoscopist’s satisfaction with the procedure.
基金supported by funds to J.A.G.from the Ministerio de Ciencia e Innovaciòn(Spain),grants BIO2016-80572-R and PID2019-109380RBI00/AEI/10.13039/501100011033(AEI-FEDER)funded by grant K124705 from the National Research Development and Innovation Office(Hungary)+2 种基金S.M.-B.by grant 2017 SGR 980 from the Generalitat de Catalunya(Spain)supported by NIH grant HG006620the recipient of a post-doctoral fellowship from Academia Sinica(Taiwan).
文摘A complex network of cellular receptors,RNA targeting pathways,and small-molecule signaling provides robust plant immunity and tolerance to viruses.To maximize their fitness,viruses must evolve control mechanisms to balance host immune evasion and plant-damaging effects.The genus Potyvirus comprises plant viruses characterized by RNA genomes that encode large polyproteins led by the P1 protease.A P1 autoinhibitory domain controls polyprotein processing,the release of a downstream functional RNAsilencing suppressor,and viral replication.Here,we show that P1Pro,a plum pox virus clone that lacks the P1 autoinhibitory domain,triggers complex reprogramming of the host transcriptome and high levels of abscisic acid(ABA)accumulation.A meta-analysis highlighted ABA connections with host pathways known to control RNA stability,turnover,maturation,and translation.Transcriptomic changes triggered by P1Pro infection or ABA showed similarities in host RNA abundance and diversity.Genetic and hormone treatment assays showed that ABA promotes plant resistance to potyviral infection.Finally,quantitative mathematical modeling of viral replication in the presence of defense pathways supported self-control of polyprotein processing kinetics as a viral mechanism that attenuates the magnitude of the host antiviral response.Overall,our findings indicate that ABA is an active player in plant antiviral immunity,which is nonetheless evaded by a self-controlled RNA virus.