The Relative Importance of Topography and RGD Ligand Density for Endothelial Cell Adhesion

The morphology and function of endothelial cells depends on the physical and chemical characteristics of the extracellular environment. Here, we designed silicon surfaces on which topographical features and surface densities of the integrin binding peptide arginine-glycine-aspartic acid (RGD) could be independently controlled. We used these surfaces to investigate the relative importance of the surface chemistry of ligand presentation versus surface topography in endothelial cell adhesion. We compared cell adhesion, spreading and migration on surfaces with nano- to micro-scaled pyramids and average densities of 6×102–6×1011 RGD/mm2. We found that fewer cells adhered onto rough than flat surfaces and that the optimal average RGD density for cell adhesion was 6×105 RGD/mm2 on flat surfaces and substrata with nano-scaled roughness. Only on surfaces with micro-scaled pyramids did the topography hinder cell migration and a lower average RGD density was optimal for adhesion. In contrast, cell spreading was greatest on surfaces with 6×108 RGD/mm2 irrespectively of presence of feature and their size. In summary, our data suggest that the size of pyramids predominately control the number of endothelial cells that adhere to the substratum but the average RGD density governs the degree of cell spreading and length of focal adhesion within adherent cells. The data points towards a two-step model of cell adhesion: the initial contact of cells with a substratum may be guided by the topography while the engagement of cell surface receptors is predominately controlled by the surface chemistry

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Permian plants from the Chutani Formation (Titicaca Group, Northern Altiplano of Bolivia): II. The morphogenus Glossopteris

Fossil plants belonging to the morphogenera Glossopteris, Pecopteris and Asterotheca were collected from the upper part of the Chutani Formation (Titicaca Group), near the town of San Pablo de Tiquina, on the southeastern shore of Lake Titicaca (northern Altiplano, Bolivia). This paper presents the first description of specimens of the morphogenus Glossopteris from Bolivia. The Bolivian specimens of Glossopteris consist of poorly-preserved impressions, although they present the diagnostic features of this morphogenus. They are fragments of leaves with secondary veins of taeniopterid-type, typical of glossopterids from Late Permian deposits of Gondwana. The only species of Pecopteris confirmed in the first part of this study, i.e. P. dolianitii Rösler and Rohn (see Vieira et al. 2004), was previously reported from the Late Permian beds of the Rio do Rasto and Estrada Nova formations in the Paraná Basin (southern Brazil). Therefore, a Late Permian age is proposed for the fossil plant-bearing beds of the Chutani Formation based on the analyzed assemblage. The phytogeographic implications of this new find are briefly analyzed.<br>Plantas fósseis, pertencentes aos morfo-gêneros Glossopteris, Pecopteris e Asterotheca, foram coletadas na porção superior da seção aflorante da Formação Chutani, próxima ao povoado de San Pablo de Tiquina, sudeste do lago Titicaca (Altiplano norte, Bolívia). Este trabalho apresenta a primeira descrição de espécimes do morfo-gênero Glossopteris provenientes da Bolívia. Os espécimes estudados de Glossopteris consistem em impressões foliares pobremente preservadas nas quais feições diagnósticas estão presentes. Os fragmentos foliares apresentam venação secundária do tipo teniopteróide, uma característica típica de glossopterídeas encontradas em depósitos do Permiano Superior do Gondwana. Por sua vez, a única espécie de Pecopteris confirmada para estes níveis da Formação Chutani, i.e. P. dolianitii Rohn and Rösler (ver Vieira et al. 2004), foi previamente assinalada para estratos do Permiano Superior da Bacia do Paraná (formações Estrada Nova e Rio do Rasto). Portanto, uma idade neopermiana é tentativamente proposta para os níveis da Formação Chutani que contém a associação estudada. As implicações fitogeográficas deste novo achado são brevemente analisadas

Multimodal Pain Management after Total Hip and Knee Arthroplasty at the Ranawat Orthopaedic Center

Improvements in pain management techniques in the last decade have had a major impact on the practice of total hip and knee arthroplasty (THA and TKA). Although there are a number of treatment options for postoperative pain, a gold standard has not been established. However, there appears to be a shift towards multimodal approaches using regional anesthesia to minimize narcotic consumption and to avoid narcotic-related side effects. Over the last 10 years, we have used intravenous patient-controlled analgesia (PCA), femoral nerve block (FNB), and continuous epidural infusions for 24 and 48 hours with and without FNB. Unfortunately, all of these techniques had shortcomings, not the least of which was suboptimal pain control and unwanted side effects. Our practice has currently evolved to using a multimodal protocol that emphasizes local periarticular injections while minimizing the use of parenteral narcotics. Multimodal protocols after THA and TKA have been a substantial advance; they provide better pain control and patient satisfaction, lower overall narcotic consumption, reduce hospital stay, and improve function while minimizing complications. Although no pain protocol is ideal, it is clear that patients should have optimum pain control after TKA and THA for enhanced satisfaction and function

High resolution skin-like sensor capable of sensing and visualizing various sensations and three dimensional shape

Human skin contains multiple receptors, and is able to sense various stimuli such as temperature, pressure, force, corrosion etc, and to feel pains and the shape of objects. The development of skin-like sensors capable of sensing these stimuli is of great importance for various applications such as robots, touch detection, temperature monitoring, strain gauges etc. Great efforts have been made to develop high performance skin-like sensors, but they are far from perfect and much inferior to human skin as most of them can only sense one stimulus with focus on pressure (strain) or temperature, and are unable to visualize sensations and shape of objects. Here we report a skin-like sensor which imitates real skin with multiple receptors, and a new concept of pain sensation. The sensor with very high resolution not only has multiple sensations for touch, pressure, temperature, but also is able to sense various pains and reproduce the three dimensional shape of an object in contact