Feature tracking computed tomography-derived left ventricular global longitudinal strain in patients with aortic stenosis: a comparative analysis with echocardiographic measurements

BackgroundLeft ventricular (LV) systolic function is a prognostic factor in patients with severe aortic stenosis (AS). Multi-detector row computed tomography (MDCT) data are key in the evaluation of patients undergoing transcatheter aortic valve implantation (TAVI) and when acquired retrospectively, LV systolic function can be assessed. Novel software permits assessment of LV global longitudinal strain (GLS) from MDCT data.ObjectivesThe present study investigated the feasibility of feature tracking MDCT-derived LV GLS and its agreement with echocardiographic LV GLS in patients treated with TAVI.MethodsLV GLS was measured on transthoracic echocardiography using speckle tracking analysis and on dynamic MDCT using feature tracking technology. Agreement between the measurements of two different modalities was assessed using Bland-Altman analysis.ResultsA total of 214 patients (51% male, mean age: 80 ± 7 years) were analysed. Mean LV GLS on echocardiography was −13.91 ± 4.32%, whereas mean feature tracking MDCT-derived GLS was −12.46 ± 3.97%. Correlation of measurements between feature tracking MDCT-derived LV GLS and echocardiographic LV GLS demonstrated a large effect size (r = 0.791, p < 0.001). On Bland-Altman analysis, feature tracking MDCT-derived strain analysis underestimated LV GLS compared to echocardiography with a mean difference of 1.44% (95% limits of agreement −3.85% - 6.73%).ConclusionsAssessment of LV GLS on dynamic feature tracking MDCT data is feasible in TAVI patients. Compared to speckle tracking echocardiography, feature tracking MDCT underestimates the value of LV GLS.     

Engineering of Escherichia coli strains for plasmid biopharmaceutical production: Scale-up challenges

Plasmid-based vaccines and therapeutics have been making their way into the clinic in the last years. The existence of cost-effective manufacturing processes capable of delivering high amounts of high-quality plasmid DNA (pDNA) is essential to generate enough material for trials and support future commercialization. However, the development of pDNA manufacturing processes is often hampered by difficulties in predicting process scale performance of Escherichia coli cultivation on the basis of results obtained at lab scale. This paper reports on the differences observed in pDNA production when using shake flask and bench-scale bioreactor cultivation of E. coli strains MG1655ΔendAΔrecA and DH5α in complex media with 20 g/L of glucose. MG1655ΔendAΔrecA produced 5-fold more pDNA (9.8 mg/g DCW) in bioreactor than in shake flask (1.9 mg/g DCW) and DH5α produced 4-fold more pDNA (8 mg/g DCW) in bioreactor than in shake flask (2 mg/g DCW). Accumulation of acetate was also significant in shake flasks but not in bioreactors, a fact that was attributed to a lack of control of pH.     

Booster immune response in children 6–7 years of age,randomly assigned to four groups with two MMR vaccines applied by aerosol or by injection

Importance

Aerosol immunization may be a useful tool to reach and sustain the elimination of measles, rubella, and congenital rubella syndrome. We compared booster seroresponses to aerosolized or injected MMR vaccines containing different strains of measles (Attenuvax or Edmonston–Zagreb) and mumps (Jeryl–Lynn or Leningrad–Zagreb).

Objective

To assess the safety and immunogenicity of two MMR: Vaccines administered by aerosol.

Methods

A randomized and controlled clinical trial was conducted to evaluate the safety and booster responses to the MMR SII (Serum Institute of India) and MMR II (Merck Sharp & Dhome) vaccines, both of which were administered by aerosol (ae) or injection (inj) to Mexican children aged 6–7 years in elementary schools. The seroresponses were evaluated by PRN (measles) and ELISA (rubella and mumps). Adverse events were followed-up for 28 days after the immunization.

Results

Two hundred and fifty-three of 260 children completed the one-month follow-up. All participants reached protective seropositivity for measles and rubella after immunization, and 98.3 to 100% reached protective seropositivity for mumps (p = 0.552). The proportions of the seroresponses (a 2-fold rise from the baseline antibody titers) to measles were 38.3% for MMR SII (ae), 31.3% for MMR II (ae), 37.5% for MMR SII (inj), and 44.6% for MMR II (inj) (p = 0.483). The seroresponses for rubella were 26.7% for MMR SII (ae), 31.3% for MMR II (ae), 46.9% for MMR SII (inj), and 40.0% for MMR II (inj) (p = 0.086). The seroresponse to mumps were 31.7% for MMR SII (ae), 25.0% for MMR II (ae), 48.4% for MMR SII (inj), and 53.9% for MMR II (inj) (p = 0.002). The difference in the seroresponse of a 4-fold rise from the baseline antibody titers was not statistically significant. Only mild adverse events were noted.

Conclusion

Aerosolized vaccines were as safe and as immunogenic as injected vaccines.

Protocol registration

CMN 2010-005 (National Regulatory Authority).     

Lateral boundary mechanosensing by adherent cells in a collagen gel system

Cell adhesion responses to in-depth physical properties such as substrate roughness and topography are well described but little is known about the influence of lateral physical cues such as tissue boundaries on the function of adherent cells. Accordingly, we developed a model system to examine remote cell sensing of lateral boundaries. The model employs floating thin collagen gels supported by rigid grids of varying widths. The dynamics, lengths, and numbers of cell extensions were regulated by grid opening size, which in turn determined the distance of cells from rigid physical boundaries. In smaller grids (200 μm and 500 μm wide), cell-induced deformation fields extended to, and were resisted by, the grid boundaries. However, in larger grids (1700 μm wide), the deformation field did not extend to the grid boundaries, which strongly affected the mean length and number of cell extensions (∼60% reduction). The generation of cell extensions in collagen gels required expression of the β1 integrin, focal adhesion kinase and actomyosin activity. We conclude that the presence of physical boundaries interrupts the process of cell-mediated collagen compaction and fiber alignment in the collagen matrix and enhances the formation of cell extensions. This new cell culture platform provides a geometry that more closely approximates the native basement membrane and will help to elucidate the roles of cell extensions and lateral mechanosensing on extracellular matrix remodeling by invasion and degradation.     

心肌梗死患者左心室局域舒张功能的应变成像

目的探索冠心病患者左心室舒张各期局部心肌应变成像特点及其在评价左心室局域舒张功能的可能性。方法对54例前壁心肌梗死患者(MI组)和78名正常对照组(NOR组)左室心肌进行组织多普勒成像检查。记录心尖二腔动态图像,应用应变成像描记技术获取左心室各阶段心肌同步应变成像,测量等容舒张期(IR)、快速充盈期(RF)、缓慢充盈期(SF)、心房收缩期(AC)局部心肌应变值变化幅度,对两组结果进行对比分析。结果在NOR组舒张各期,66/78(85%)例的应变值(S)按前壁心尖、心底、中部的顺序,呈负值增大的梯度变化;MI组符合这一规律仅占9/54(17%)例。IR期:NOR组564/624(90.4%)节段为向上波段且走行较一致;MI组向上波段有123/432(28.5%)节段,且各节段波走行不一致,两组相比,P<0.05。RF期:NOR组为快速向上波段(576/624节段,92.3%);MI组向上波段少(102/432节段,23.6%),两组相比P<0.01。SF期:与NOR组多为水平节段相比,MI组在缺血节段多为向上波段,P<0.05。结论局部心肌缺血梗死导致主动舒张期的局部心肌应变成像显著异常。应变成像能敏感、直观、无创地定量评价局域舒张功能。     

大鼠和兔胃的张力和应力依赖于部位和方向

目的确定大鼠和兔胃组织条的单轴压力-应变特性,研究胃的零应力状态。方法纵向组织条(平行于小弯)和环形组织条(垂直于小弯)取自胃底(腺性部分)和前胃(非腺性部分)。根据零应力和无载荷状态长度的变化计算残余应变,应用张力拉伸仪进行应力-应变实验。从数字图像测量每个组织条的厚度和宽度,从组织条得到的数据与从体外完整胃得到的数据进行比较。结果胃腺性部分的残余应力和残余应变比非腺性部分大,大鼠胃的残余应力和残余应变比兔大。就应力-应变而言,腺性部分比非腺性部分硬,纵向腺性部分比环向腺性部分硬,大鼠胃组织条比兔胃组织条硬。从组织条得到的数据与从体外完整胃得到的数据有可比性,从而表明所获得的实验数据在生理范围内。结论大鼠和兔胃的张力和应力依赖于部位、方向和种属。由于胃的几何形状复杂,应用影像技术和机械数据进行三维图像重建所获得的数据对于全面评估胃的功能非常重要。     

应变率成像评价冠心病患者冠状动脉支架置入术前后左室舒张功能

目的:探讨应变率成像(SRI)技术定量评价冠心病患者冠状动脉支架置入术前后左室舒张功能的临床价值。方法:25例冠心病患者于支架置入术前后行超声心动图检查,采用脉冲多普勒获取二尖瓣口血流流速曲线并测量二尖瓣口E峰(VE)、A峰(VA)及E峰下降时间(DT),采用应变率成像获取左室狭窄冠脉供血节段(狭窄节段)和非狭窄冠脉供血节段(非狭窄节段)的收缩期峰值应变率(SRS)及舒张早期峰值应变率(SRE),计算术后VE的增长率(△VE%)及SRE的增长率(△SRE%),比较分析术前术后各项观测指标。结果:支架置入术前狭窄节段与非狭窄节段的SRS无显著差异(P>0.05),而狭窄节段的SRE明显低于非狭窄节段(P<0.01)。术后各节段的SRS及非狭窄节段的SRE无显著变化(P>0.05),而狭窄节段的SRE显著增加(P<0.01),其增长率△SRE%显著高于非狭窄节段(P<0.01),并且发现25例患者狭窄节段的△SRE与二尖瓣口的△VE成明显正相关(r=0.54,P<0.01)。结论:应变率成像技术可定量检测心肌运动变化情况,监测支架置入术前后左室局部心肌功能,评价支架置入术的疗效。     

Differential sensitivities of mouse strains to morphine and [Dmt1]DALDA analgesia

[Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH(2)), is a highly potent and selective mu-opioid agonist. Nevertheless, systemic [Dmt(1)]DALDA retained its analgesic actions in MOR-1 knockout animals and CXBK mice despite the inactivity of morphine in these mice. [Dmt(1)]DALDA was 6-fold less potent in C57BL/6J mice than in CD-1 mice, whereas morphine potency did not differ between the two strains. Thus, [Dmt(1)]DALDA is a highly selective mu-opioid analgesic with significant pharmacological differences with the prototypic mu-opioid morphine.     

Characteristics of electroacupuncture-induced analgesia in mice: variation with strain,frequency, intensity and opioid involvement

The present study was conducted to evaluate the characteristics of electroacupuncture (EA)-induced analgesia in mice. Three inbred strains of mice (DBA/2, C57BL/6J, BALB/c) and three outbred strains (ICR, LACA, NIH) were used in the experiment. Two pairs of metallic needles were inserted into acupoints ST 36 and SP 6 connected to an electric pulse generator. EA parameters were set as constant current output with alteration of a positive and negative square wave, 0.6 ms in pulse width for 2 Hz and 0.3 ms for 100 Hz. Tail-flick latencies evoked by radiant heat were measured before, during and after EA stimulation. We found that (1) DBA/2 mice showed a significantly more potent analgesic effect than the other five strains in response to both 100 and 2 Hz EA. In this case, the intensities were 1.0-2.0-2.0 mA, 10 min for each intensity totally 30 min. (2) EA analgesia increased as the intensity of stimulation increased from 0.5 to 2.0 mA, but it remained at this plateau when the intensity further increased from 2.0 to 3.0 mA. (3) 10.0 mg x kg(-1) naloxone was needed to block the analgesic effect induced by 2 Hz EA of 2.0 mA, but to block that by 100 Hz, 25.0 mg x kg(-1) was necessary. (4) A positive correlation was observed between analgesia induced by morphine at the dose of 5.0 mg x kg(-1) and by 100 Hz EA in two tested strains DBA/2 and C57BL/6J. In conclusion, EA induces reliable, strain-dependent analgesia in mice. The naloxone-reversibility of EA, a measure of whether it is opioid or non-opioid mediated, is dependent upon intensity and frequency.