Editorial: Review and Perspective on the Soft Matter Modeling of Cellular Mechanobiology

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Wettability influences cell behavior on superhydrophobic surfaces with different topographies

Surface wettability and topography are recognized as critical factors influencing cell behavior on biomaterials. So far only few works have reported cell responses on surfaces exhibiting extreme wettability in combination with surface topography. The goal of this work is to study whether cell behavior on superhydrophobic surfaces is influenced by surface topography and polymer type. Biomimetic superhydrophobic rough surfaces of polystyrene and poly(l-lactic acid) with different micro/nanotopographies were obtained from smooth surfaces using a simple phase-separation based method. Total protein was quantified and showed a less adsorption of bovine serum albumin onto rough surfaces as compared to smooth surfaces of the same material. The mouse osteoblastic MC3T3-E1 cell line and primary bovine articular chondrocytes were used to study cell attachment and proliferation. Cells attached and proliferate better in the smooth surfaces. The superhydrophobic surfaces allowed cells to adhere but inhibited their proliferation. This study indicates that surface wettability, rather than polymer type or the topography of the superhydrophobic surfaces, is a critical factor in determining cell behavior

Role of large-scale advection and small-scale turbulence on vertical migration of gyrotactic swimmers

In this work, we use direct-numerical-simulation-based Eulerian-Lagrangian simulations to investigate the dynamics of small gyrotactic swimmers in free-surface turbulence. We consider open-channel flow turbulence in which bottom-heavy swimmers are dispersed. Swimmers are characterized by different vertical stability, so that some realign to swim upward with a characteristic time smaller than the Kolmogorov timescale, while others possess a reorientation time longer than the Kolmogorov timescale. We cover one order of magnitude in the flow Reynolds number and two orders of magnitude in the stability number, which is a measure of bottom heaviness. We observe that large-scale advection dominates vertical motion when the stability number, scaled on the local Kolmogorov timescale of the flow, is larger than unity: This condition is associated to enhanced migration toward the surface, particularly at low Reynolds number, when swimmers can rise through surface renewal motions that originate directly from the bottom boundary turbulent bursts. Conversely, small-scale effects become more important when the Kolmogorov-based stability number is below unity: Under this condition, migration toward the surface is hindered, particularly at high Reynolds, when bottom-boundary bursts are less effective in bringing bulk fluid to the surface. In an effort to provide scaling arguments to improve predictions of models for motile microorganisms in turbulent water bodies, we demonstrate that a Kolmogorov-based stability number around unity represents a threshold beyond which swimmer capability to reach the free surface and form clusters saturates

Awareness, treatment, and control of hypertension in the elderly in a general practice experience

In 3858 ambulatory elderly people (age greater than or equal to 65 years) prevalence of hypertension was 67.8%. The hypertensive status was unknown to both the doctor and the patient in 21.4% of cases. More than 90% of known hypertensives were treated, but hypertension could be considered as controlled in less than 30% of them

Phase I/II study of single-agent bortezomib for the treatment of patients with myelofibrosis. Clinical and biological effects of proteasome inhibition.

A phase I/II trial was undertaken to determine maximum tolerated dose (MTD), toxicity, clinical efficacy and biological activity of bortezomib in patients with advanced stage primary or post-polycythemia vera/post-essential thrombocythemia myelofibrosis (MF). Bortezomib (0.8, 1.0, or 1.3 mg/m(2)) was administered on days 1, 4, 8, and 11 by intravenous push to patients previously resistant to at least one line of therapy, or with an intermediate/high risk IWG’s score [1]. Therapy was repeated every 28 days for 6 cycles. At 1.3 mg/m(2) dose, one of six patients experienced a dose limiting toxicity, and this was determined to be the MTD. Neither remissions or clinical improvements were recorded in 16 patients treated at this dose level, fulfilling the early stopping rule in the Simon two-stage study design. Major toxicity was on thrombocytopenia. In 9 out of 15 patients bortezomib proved able to reduce bone marrow vessel density. However, the agent was associated with worsening of markers of disease activity, like enhancement of hematopoietic CD34-positive progenitor cell mobilization, WT-1 gene expression in mononuclear cells, and down-regulation of CXCR4 expression on CD34-positive cells. Occurrence of both beneficial and detrimental biological effects claims further investigation on the mechanisms of the drug in MF

Numerical simulations of aggregate breakup in bounded and unbounded turbulent flows

Breakup of small aggregates in fully developed turbulence is studied by means of direct numerical simulations in a series of typical bounded and unbounded flow configurations, such as a turbulent channel flow, a developing boundary layer, and homogeneous isotropic turbulence. Aggregate breakup occurs when the local hydrodynamic stress $\sigma\sim \varepsilon^{1/2}$, where $\varepsilon$ is the energy dissipation at the position of the aggregate, overcomes a given threshold $\sigma_\mathrm{cr}$, characteristic for a given type of aggregates. Results show that the breakup rate decreases with increasing threshold. For small thresholds, it develops a universal scaling among the different flows. For high thresholds, the breakup rates show strong differences among the different flow configurations, highlighting the importance of non-universal mean-flow properties. To further assess the effects of flow inhomogeneity and turbulent fluctuations, results are compared with those obtained in a smooth stochastic flow. Furthermore, we discuss limitations and applicability of a set of independent proxies

The treatment of polycythaemia vera: an update in the JAK2 era

The clinical course of polycythaemia vera is marked by a high incidence of thrombotic complications, which represent the main cause of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of transformation into acute leukaemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients should be treated with phlebotomy and low-dose aspirin. Cytotoxic therapy is indicated in high-risk patients, with the drug of choice being hydroxyurea because its leukaemogenicity is low. The recent discovery of JAK2 V617F mutation in the vast majority of polycythaemia vera patients opens new avenues for the treatment of this disease. Novel therapeutic options theoretically devoid of leukaemic risk, such as alpha-interferon and imatinib, affect JAK2 expression in some patients. Nevertheless, these drugs require further clinical experience and, for the time being, should be reserved for selected cases

Plasma Phospholipid Omega‐3 Fatty Acids and Incidence of Postoperative Atrial Fibrillation in the OPERA Trial

Background: Long‐chain polyunsaturated omega‐3 fatty acids (n‐3 PUFA) demonstrated antiarrhythmic potential in experimental studies. In a large multinational randomized trial (OPERA), perioperative fish oil supplementation did not reduce the risk of postoperative atrial fibrillation (PoAF) in cardiac surgery patients. However, whether presupplementation habitual plasma phospholipid n‐3 PUFA, or achieved or change in n‐3 PUFA level postsupplementation are associated with lower risk of PoAF is unknown. Methods and Results: In 564 subjects undergoing cardiac surgery between August 2010 and June 2012 in 28 centers across 3 countries, plasma phospholipid levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were measured at enrollment and again on the morning of cardiac surgery following fish oil or placebo supplementation (10 g over 3 to 5 days, or 8 g over 2 days). The primary endpoint was incident PoAF lasting ≥30 seconds, centrally adjudicated, and confirmed by rhythm strip or ECG. Secondary endpoints included sustained (≥1 hour), symptomatic, or treated PoAF; the time to first PoAF; and the number of PoAF episodes per patient. PoAF outcomes were assessed until hospital discharge or postoperative day 10, whichever occurred first. Relative to the baseline, fish oil supplementation increased phospholipid concentrations of EPA (+142%), DPA (+13%), and DHA (+22%) (P<0.001 each). Substantial interindividual variability was observed for change in total n‐3 PUFA (range=−0.7% to 7.5% after 5 days of supplementation). Neither individual nor total circulating n‐3 PUFA levels at enrollment, morning of surgery, or change between these time points were associated with risk of PoAF. The multivariable‐adjusted OR (95% CI) across increasing quartiles of total n‐3 PUFA at enrollment were 1.0, 1.06 (0.60 to 1.90), 1.35 (0.76 to 2.38), and 1.19 (0.64 to 2.20); and for changes in n‐3 PUFA between enrollment and the morning of surgery were 1.0, 0.78 (0.44 to 1.39), 0.89 (0.51 to 1.55), and 1.01 (0.58 to 1.75). In stratified analysis, demographic, medication, and cardiac parameters did not significantly modify these associations. Findings were similar for secondary PoAF endpoints. Conclusions: Among patients undergoing cardiac surgery, neither higher habitual circulating n‐3 PUFA levels, nor achieved levels or changes following short‐term fish oil supplementation are associated with risk of PoAF. Clinical Trial Registration URL: Clinicaltrials.gov Unique identifier: NCT0097048