Gluconic acid aqueous solution: A bio-based catalytic medium for organic synthesis

Gluconic acid is non-toxic, non-volatile, non-corrosive, and easily biodegradable chemical, which can be produced from biomass using several methods: oxidation by molecular oxygen using heterogeneous catalysis, enzymatic oxidation, and microbial fermentation. Being highly soluble in water, gluconic acid can form concentrated aqueous solutions, and its 50% aqueous solution has found application as a catalytic medium for organic synthesis. For some reactions, gluconic acid aqueous solutions (GAAS) outperform conventional and green solvents when used as media for organic synthesis. GAAS was found to be particularly efficient in the Knoevenagel condensation, the Michael addition, and multicomponent reactions based on them. These and other chemical transformations utilizing GAAS as a medium are discussed in this review. We also compare the effectiveness of GAAS as a new green catalytic medium and the performance of other solvents and catalysts.     

Association between Haemagglutination inhibiting antibodies and protection against clade 6B viruses in 2013 and 2015

BackgroundThe epidemiology of the pandemic A(H1N1) virus has been changing as population immunity continues to co-evolve with the virus. The impact of genetic changes in the virus on human’s susceptibility is an outstanding important question in vaccine design. In a community-based study, we aim to (1) determine the genetic characteristics of 2009–2015 pandemic H1N1 viruses, (2) assess antibody response following natural infections and (3) assess the correlation of A/California/07/09 antibody titers to protection in the 2013 and 2015 epidemics.MethodsIn a household transmission study, serum specimens from 253 individuals in Managua, Nicaragua were analyzed. Combined nose and throat swabs were collected to detect RT-PCR confirmed influenza infection and virus sequencing. Hemagglutination inhibition assays were performed and the protective titer for circulating H1N1pdm was determined.ResultsClade 6B pandemic H1N1 viruses predominated in Nicaragua during the 2013 and 2015 seasons. Our household transmission study detected a household secondary attack rate of 17% in 2013 and 33% in 2015. Infected individuals, including vaccinees, showed an apparent antibody response to A/California/07/09. Baseline titers of A/California/07/09 antibodies were found to associate with protection in both seasons. A titer of ≥1:40 correlated to a 44% protection in children, a 29% protection in adults 15–49 years old and a 51% protection in adults 50–85 years old.ConclusionIn 2013 and 2015, antibody titers to A/California/07/09 associated with an infection risk reduction amongst exposed household contacts. This is consistent with a detectable vaccine effectiveness reported in a number of studies. Genetic changes in clade 6B viruses might have led to a reduced immunity in some whereas others might have been less affected. The use of human serologic data is important in virus characterization and if performed in a timely manner, could assist in vaccine strain selection.     

Cell attenuated porcine epidemic diarrhea virus strain Zhejiang08 provides effective immune protection attributed to dendritic cell stimulation

Since 2010, the porcine epidemic diarrhea coronavirus (PEDV) has caused significant damage to the global pork industry. However, classical PEDV vaccine strains only provide limited protection against emerging strains. In this study, we successfully isolated and attenuated the PEDV epidemic strain Zhejiang08, which was characterized by good cell adaptation and high-titer production 48 h post infection in Vero E6 cells. The attenuated virus induced a high level of virus-specific neutralizing antibodies until 120 days after immunization in piglets and provided complete protection when challenged with an emerging virus strain on day 14 post immunization. Moreover, the capability to activate dendritic cells (DCs) of this isolate was identified. Higher expression levels of IL-12 and IFN-γ were recorded in DCs after treatment with Zhejiang08 for 24 h. Furthermore, genome sequencing and phylogenetic analysis revealed high homology between the main antigen epitopes of Zhejiang08 and PEDV pandemic isolates following 2011. Combining the glycosylation site prediction results and their distribution within the spatial structure of the S protein, led to the conclusion that the observed more effective host immune response of Zhejiang08 compared to CV777 was possibly associated with a lack of the potential glycosylation site in the 296 amino acids of the S protein. In summary, we illustrated that the attenuated virus represents a promising vaccine candidate.     

Allergic reaction to abciximab with atypical manifestations

Abciximab (ReoPro, Eli Lilly and Company, Indianapolis, Indiana) is an intravenous agent that had been approved for treatment of acute coronary syndrome undergoing coronary interventions. It is a chimeric monoclonal antibody fragment that binds to the glycoprotein IIb/IIIa receptor with a potential for the development of an immune response to variable portions within the antigen binding site following its administration.We describe a 58-year-old man who developed sudden headache, short of breath, choking and restlessness after receiving Abciximab for coronary intervention. Discontinuation of abciximab and administration of intravenous fluids, steroid and antihistamines led to improvement of his symptoms gradually.     

右美托咪啶对幕上病灶切除术后患者镇静作用的临床效果观察

目的观察右美托咪啶应用于幕上病灶切除术后镇静作用的临床效果。方法选择幕上病灶切除术后患者40例(均在麻醉恢复室),年龄18～60岁,随机分为两组,每组20例。试验组:10min静脉泵注右美托咪啶0.8μg/kg后,以0.6μg.kg-1.h-1维持40min;对照组:10min静脉泵注生理盐水10ml后,20ml生理盐水静脉泵注40min。记录患者血压、心率、呼吸等变化,观察给药后患者镇静作用以及不良反应的发生情况。结果试验组给入右美托咪啶后HR、MAP均低于基础值,对比对照组差异具有统计学意义(P<0.05);RR各个时间点则无明显变化;试验组均达到Ramsay镇静分级Ⅳ级状态。结论右美托咪啶(负荷量0.8μg/kg,维持0.6μg.kg-1.h-1)应用于幕上病灶切除术后患者取得了满意的镇静效果。     

Design,synthesis and biological evaluation of novel quinoline [4,3-b]chromene derivatives as AChE inhibitors through an efficient one-pot,four-component microwave-mediated reaction

An efficient synthesis of chromeno[4,3-b]quinoline derivatives via one-pot, four-component reaction of 4-hydroxycoumarin, formaldehyde, cyclohexanedione, ammonium ceric nitrate under microwave irradiation was accomplished. The structures of these compounds were unambiguously confirmed by single crystal X-ray diffraction. Furthermore, the anti-AChE activities of these compounds in vitro were investigated at concentrations of 20 μM and 50 μM by using a standard Ellman’s method. The relationship of inhibitory activities and structures of these chromeno [4,3-b]quinolines was also systematically studied. Of all the compounds investigated, 4ag emerged as the most potent AChE inhibitor with IC₅₀ values of 5.63 µM, and it might be used as potent lead for the development anti-AChE agents. Moreover, molecular modelling was conducted to understand the optimal interaction of AChE with these types of compounds.     

Post-infectious irritable bowel syndrome:Mechanistic insights into chronic disturbances following enteric infection

Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery.The appearance of new IBS symptoms following an infectious event is defined as post-infectiousIBS.Indeed,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare burden.Additionally,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in IBS.Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful infections.Consequently,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and duration.This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.     

美沙拉嗪对溃疡性结肠炎患者肠道黏膜屏障功能和免疫功能的系统评价

目的探讨美沙拉嗪应用于溃疡性结肠炎对患者肠道黏膜屏障功能与免疫功能的影响。方法选取2016年3月~2017年2月在我院接受治疗的溃疡性结肠炎患者93例,按照用药不同,分成美沙拉嗪组(n=47)和柳氮磺吡啶组(n=46),于用药前和用药1疗程、2疗程后,比较两组免疫功能、肠道黏膜屏障功能变化及肠黏膜恢复情况。结果用药前,两组Ig A、Ig G、Ig M、Fas/Fas L及CD4+、CD8+和CD4+/CD8+差异均不显著(P0.05),用药1疗程、2疗程后,两组各项指标均显著变化,且用药1疗程后的各项指标与2疗程后均有显著差异(P0.05),美沙拉嗪组用药1疗程、2疗程后Ig A、Ig G、Ig M、CD4+、CD4+/CD8+显著高于柳氮磺吡啶组,Fas/Fas L、CD8+显著低于柳氮磺吡啶组(P0.05);用药前,两组肠道黏膜屏障功能指标差异均不显著(P0.05),用药1疗程、2疗程后,两组各项肠道黏膜屏障功能表达水平均显著降低,且用药1疗程与用药2疗程各项指标间有显著差异(P0.05),实验组用药1疗程、2疗程后DAO、LAC、PCT、LPS、D-LA均显著低于柳氮磺吡啶组(P0.05);用药前,两组肠黏膜临床症状总积分无显著差异(P0.05),用药1疗程、2疗程后,两组临床症状总积分均显著下降,美沙拉嗪组显著低于柳氮磺吡啶组(P0.05)。结论对于溃疡性结肠炎患者,可采取美沙拉嗪进行治疗,能够有效促进肠黏膜恢复,其作用机制可能和改善肠道黏膜屏障功能与调节免疫功能有关。     

Time-integrated propulsive and braking impulses do not depend on walking speed

BackgroundEnhancing propulsion during walking is often a focus in physical therapy for those with impaired gait. However, there is no consensus in the literature for assessing braking and propulsion. Both are typically measured from the anterior-posterior ground reaction force (AP-GRF). While normalization of AP-GRF force by bodyweight is commonly done in the analysis, different methods for AP-GRF time axis normalization are used.Research questionDoes walking speed affect propulsion and/or braking, and how do different methods for calculating propulsion and braking impact the conclusion, in both healthy adults and those with lower limb impairment?MethodsWe investigated three different analysis methods for assessing propulsion. 1. BW-TimeIntegration: Bodyweight (BW) normalized time integration of AP-GRF (units of BWs). 2. BW-%StanceIntegration: BW normalized AP-GRF is resampled to percent stance phase prior to integration (units of BW%Stance). 3. BW-Peak: BW normalized peak force (units of BW). We applied these methods to two data sets. One data set included AP-GRFs from trials of slow, self-selected, and fast walking speeds for 203 healthy controls (HCs); a second data set included subjects with lower limb orthopedic injuries.ResultsUsing the BW-TimeIntegration method, we found no effect of walking speed on propulsion for HCs. Time integration over the longer stance phase of slower walking balanced the lower magnitude AP-GRFs of slower walking, resulting in a time-integrated impulse that was the same regardless of walking speed. In contrast, the other two methods that are not time integration methods found that propulsion increased with walking speed. Similarly, in the gait pathology data set, differences in results were found depending on the analysis method used.SignificanceFor many gait studies concerning propulsion and/or braking, the impulse measure used should be related to the body’s change of momentum, necessitating an analysis method with a time integration of the AP-GRF.