Cell shape and cell-wall organization in Gram-negative bacteria

In bacterial cells, the peptidoglycan cell wall is the stress-bearing structure that dictates cell shape. Although many molecular details of the composition and assembly of cell-wall components are known, how the network of peptidoglycan subunits is organized to give the cell shape during normal growth and how it is reorganized in response to damage or environmental forces have been relatively unexplored. In this work, we introduce a quantitative physical model of the bacterial cell wall that predicts the mechanical response of cell shape to peptidoglycan damage and perturbation in the rod-shaped Gram-negative bacterium Escherichia coli. To test these predictions, we use time-lapse imaging experiments to show that damage often manifests as a bulge on the sidewall, coupled to large-scale bending of the cylindrical cell wall around the bulge. Our physical model also suggests a surprising robustness of cell shape to peptidoglycan defects, helping explain the observed porosity of the cell wall and the ability of cells to grow and maintain their shape even under conditions that limit peptide crosslinking. Finally, we show that many common bacterial cell shapes can be realized within the same model via simple spatial patterning of peptidoglycan defects, suggesting that minor patterning changes could underlie the great diversity of shapes observed in the bacterial kingdom.     

Arterial wall compliance in diabetes.

A non-invasive Doppler ultrasound technique, based on the measurement of pulse wave velocity along the aorta, has been used to deduce aortic compliance in 25 Type 1 and 25 Type 2 diabetic patients. Thirteen of the Type 1 diabetic group had their compliance measured within 1 year of diabetes first being clinically diagnosed. All compliance values were normalized for age and sex variations using data previously obtained from over 600 normal, non-diabetic subjects (mean normalized compliance +/- SD; 100 +/- 15%). The results show that Type 1 diabetic patients have significantly more distensible aortas (132 +/- 26%) than their age- and sex-matched non-diabetic counterparts (100 +/- 12%) (p less than 0.01), while Type 2 diabetic patients have significantly stiffer aortas (74 +/- 21%) than their age- and sex-matched non-diabetic counterparts (100 +/- 18%) (p less than 0.01). The young Type 1 diabetic patients measured within 1 year of diagnosis have aortas ranging up to 78% more distensible (151 +/- 15%) than their age- and sex-matched non-diabetic controls (100 +/- 11%) (p less than 0.001). These results support findings by other groups that adult diabetic patients have less distensible arteries than normal, but contradict reports in the literature dating back over 20 years that diabetic children have stiffer arteries than normal children.     

Design and Mechanical Compatibility of Nylon Bionic Cancellous Bone Fabricated by Selective Laser Sintering

In order to avoid the stress shielding phenomenon in orthopedic bionic bone implantation, it is necessary to consider the design of mechanical compatible implants imitating the host bone. In this study, we developed a novel cancellous bone structure design method aimed at ensuring the mechanical compatibility between the bionic bone and human bone by means of computer-aided design (CAD) and finite element analysis technology (specifically, finite element modeling (FEM)). An orthogonal lattice model with volume porosity between 59% and 96% was developed by means of CAD. The effective equivalent elastic modulus of a honeycomb structure with square holes was studied by FEM simulation. With the purpose of verifying the validity of the cancellous bone structure design method, the honeycomb structure was fabricated by selective laser sintering (SLS) and the actual equivalent elastic modulus of the honeycomb structure was measured with a uniaxial compression test. The experimental results were compared with the FEM values and the predicted values. The results showed that the stiffness values of the designed structures were within the acceptable range of human cancellous bone of 50–500 MPa, which was similar to the stiffness values of human vertebrae L1 and L5. From the point of view of mechanical strength, the established cellular model can effectively match the elastic modulus of human vertebrae cancellous bone. The functional relationship between the volume porosity of the nylon square-pore honeycomb structure ranging from 59% to 96% and the effective elastic modulus was established. The effect of structural changes related to the manufacture of honeycomb structures on the equivalent elastic modulus of honeycomb structures was studied quantitatively by finite element modeling.     

各种降压药对原发性高血压患者动脉弹性功能的影响

目的评价不同类型降压药对原发性高血压患者大小动脉弹性功能的影响。方法 105例1～2级原发性高血压患者,随机分为5组:氢氯噻嗪组(12.5 mg 1次/d,n=18)、比索洛尔组(5 mg 1次/d,n=20)、氨氯地平组(5 mg 1次/d,n=24)、苯那普利组(10 mg 1次/d,n=22)、缬沙坦组(80 mg 1次/d,n=21)。治疗4周后,如血压仍>140/90 mmHg,剂量加倍,疗程共12周。治疗前后观察大、小动脉弹性指数(C_1,C_2)及肱踝脉搏波传导速度(baPWV)。结果1)治疗12周后各组血压均有显著的降低,但各组间的血压变化无显著差别。比索洛尔组治疗后心率明显减慢[治疗后(66±4)比治疗前(74±7)次/mm,P<0.05]。2)调整血压降低幅度及 C_1、C_2、baPWV 基础值后,氨氯地平、苯那普利、缬沙坦对 C_1、C_2、baPWV 仍有显著性改善作用,比索洛尔及氢氯噻嗪对 C_1、C_2、baPWV则无显著性改善作用。3)baPWV 变化百分比与 DBP 下降幅度呈正相关(r=0.314,P<0.05),与 SBP 下降幅度无关(r=0.108,P>0.05)。结...     

PAYMENTS,PROMOTION, AND THE PURPLE PILL

Understanding competition in the US drug market requires knowing how sensitive demand is to prices. The relevant prices for insured consumers are copayments. There are many studies of copayment elasticity in the health literature, but they are of limited applicability for studies of competition. Because of a paucity of data, such studies typically control for neither competitor copayment nor advertising. Whereas previous studies examined copayment sensitivity when copayments for branded drugs move in unison, this study examines copayment sensitivity when copayments diverge. This study uses unique panel data of insurance copayments and utilization for 77 insurance groups, as well as data on advertising. The results indicate that demand can be much more sensitive to copayment than previously recognized. Manufacturers selling drugs with higher copayments than branded competitors can lose substantial market share. Manufacturers can offset the loss of demand by increasing advertising to physicians, but it is costly. Copyright © 2013 John Wiley & Sons, Ltd.     

Machines that Go ‘Ping’: Medical Technology and Health Expenditures in OECD Countries

Technology is believed to be a major determinant of increasing health spending. The main difficulty to quantify its effect is to find suitable proxies to measure medical technological innovation. This paper's main contribution is the use of data on approved medical devices and drugs to proxy for medical technology. The effects of these variables on total real per capita health spending are estimated using a panel model for 18 Organisation for Economic Co‐operation and Development (OECD) countries covering the period 1981–2012. The results confirm the substantial cost‐increasing effect of medical technology, which accounts for almost 50% of the explained historical growth of spending. Despite the overall net positive effect of technology, the effect of two subgroups of approvals on expenditure is significantly negative. These subgroups can be thought of as representing ‘incremental medical innovation’, whereas the positive effects are related to radically innovative pharmaceutical products and devices. A separate time series model was estimated for the USA because the FDA approval data in fact only apply to the USA, while they serve as proxies for the other OECD countries. Our empirical model includes an indicator of obesity, and estimations confirm the substantial contribution of this lifestyle variable to health spending growth in the countries studied. Copyright © 2014 John Wiley & Sons, Ltd.     

What Happens to Patterns of Food Consumption when Food Prices Change? Evidence from A Systematic Review and Meta‐Analysis of Food Price Elasticities Globally

Recent years have seen considerable interest in examining the impact of food prices on food consumption and subsequent health consequences. Fiscal policies targeting the relative price of unhealthy foods are frequently put forward as ways to address the obesity epidemic. Conversely, various food subsidy interventions are used in attempts to reduce levels of under‐nutrition. Information on price elasticities is essential for understanding how such changes in food prices affect food consumption. It is crucial to know not only own‐price elasticities but also cross‐price elasticities, as food substitution patterns may have significant implications for policy recommendations. While own‐price elasticities are common in analyses of the impact of food price changes on health, cross‐price effects, even though generally acknowledged, are much less frequently included in analyses, especially in the public health literature. This article systematically reviews the global evidence on cross‐price elasticities and provides combined estimates for seven food groups in low‐income, middle‐income and high‐income countries alongside previously estimated own‐price elasticities. Changes in food prices had the largest own‐price effects in low‐income countries. Cross‐price effects were more varied and depending on country income level were found to be reinforcing, undermining or alleviating own‐price effects. Copyright © 2014 John Wiley & Sons, Ltd.     

血管回声跟踪技术对冠心病患者动脉弹性与血管内皮舒张功能关系的研究

目的 探讨冠心病患者动脉弹性与血管内皮舒张功能的关系.方法 应用E-Tracking技术测量30例冠心病患者与34例正常对照组颈动脉硬化参数,包括压力应变弹性系数(Ep)、硬化度(β)和顺应性(AC),同时采用高分辨率血管超声法检测受试者肱动脉血流介导的内皮依赖性血管舒张功能(FMD),并进行相关分析.结果 冠心病组血流介导的肱动脉舒张反应明显低于对照组[(10.10±3.98)%与(16.32±2.42)%,P＜0.05];冠心病组Ep、β与正常对照组相比明显增高[(135.27±21.10)%与(111.67±29.53)%,P＜0.01]、[(10.18±1.26)%与(9.07±1.95)%,P＜0.01];但冠心病组的AC明显低于正常对照组[(0.56士0.14)%与(0.73士0.18)%,P＜0.05];内皮依赖性血管扩张(EDD%)与Ep、β负相关(r＝-0.634,P＜0.01;r＝-0.505,P＜0.01),与AC呈正相关(r＝0.668,P＜0.01).结论 冠心病患者肱动脉内皮依赖性血管舒张功能受损和动脉弹性降低,且两者之间有相关性,提示 E-Tracking 技术和FMD一样能够判断动脉功能异常,具有简便、快速、无创性、测量结果精确的优点.     

肝淀粉样变影像学表现

目的 观察肝淀粉样变的影像学表现。方法 回顾性分析11例病理确诊的肝淀粉样变患者的临床、影像及病理学资料，观察肝淀粉样变的特征性影像学表现。结果 7例患者接受CT扫描，平扫CT表现为肝脏体积弥漫性增大、肝实质密度不均匀减低；其中5例接受增强CT扫描，动脉期肝实质见斑片状强化或未见异常强化，脾脏轻度均匀强化，门脉期及延迟期见肝实质内大片状"窗凌花"样强化减低区，脾脏强化程度稍减低；2例动脉期示双肾皮质强化程度减低，皮髓质分界不清。8例接受MR扫描，肝脏体积明显增大，边缘光滑，肝实质T1WI信号均匀、T2WI稍均匀增高，肝纹理明显减少；脾脏体积正常或稍大，信号正常或均匀减低；其中3例接受增强扫描，门脉期及延迟期见肝实质内弥漫斑片状"窗凌花"样强化减低区；2例门脉期及延迟期脾脏强化程度稍减低；1例动脉期见双肾皮质强化程度减低。5例接受肝脏瞬时弹性超声成像，所测肝实质硬度值均≥75 kPa。结论 肝淀粉样变影像学表现具有一定特征性，有助于早期诊断、监测病情及评估疗效。     

Effects of matrix elasticity and cell density on human mesenchymal stem cells differentiation

Human mesenchymal stem cells (hMSCs) can differentiate into various cell types, including osteogenic and chondrogenic cells. The matrix elasticity and cell seeding density are important factors in hMSCs differentiation. We cultured hMSCs at different seeding densities on polyacrylamide hydrogels with different stiffness corresponding to Young's moduli of 1.6 ± 0.3 and 40 ± 3.6 kPa. The promotion of osteogenic marker expression by hard gel is overridden by a high seeding density. Cell seeding density, however, did not influence the chondrogenic marker expressions induced by soft gel. These findings suggest that interplays between cell–matrix and cell–cell interactions contribute to hMSCs differentiation. The promotion of osteogenic differentiation on hard matrix was shown to be mediated through the Ras pathway. Inhibition of Ras (RasN17) significantly decreased ERK, Smad1/5/8 and AKT activation, and osteogenic markers expression. However, constitutively active Ras (RasV12) had little effect on osteogenic marker expression, suggesting that the Ras pathways are necessary but not sufficient for osteogenesis. Taken together, our results indicate that matrix elasticity and cell density are important microenvironmental cues driving hMSCs proliferation and differentiation. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1360–1365, 2013