Three-Dimensional Quantification of Cellular Traction Forces and Mechanosensing of Thin Substrata by Fourier Traction Force Microscopy

We introduce a novel three-dimensional (3D) traction force microscopy (TFM) method motivated by the recent discovery that cells adhering on plane surfaces exert both in-plane and out-of-plane traction stresses. We measure the 3D deformation of the substratum on a thin layer near its surface, and input this information into an exact analytical solution of the elastic equilibrium equation. These operations are performed in the Fourier domain with high computational efficiency, allowing to obtain the 3D traction stresses from raw microscopy images virtually in real time. We also characterize the error of previous two-dimensional (2D) TFM methods that neglect the out-of-plane component of the traction stresses. This analysis reveals that, under certain combinations of experimental parameters (\ie cell size, substratums' thickness and Poisson's ratio), the accuracy of 2D TFM methods is minimally affected by neglecting the out-of-plane component of the traction stresses. Finally, we consider the cell's mechanosensing of substratum thickness by 3D traction stresses, finding that, when cells adhere on thin substrata, their out-of-plane traction stresses can reach four times deeper into the substratum than their in-plane traction stresses. It is also found that the substratum stiffness sensed by applying out-of-plane traction stresses may be up to 10 times larger than the stiffness sensed by applying in-plane traction stresses

Thrombocytopenia Is Associated with Acute Respiratory Distress Syndrome Mortality: An International Study

Background: Early detection of the Acute Respiratory Distress Syndrome (ARDS) has the potential to improvethe prognosis of critically ill patients admitted to the intensive care unit (ICU). However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions. Objectives: This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies. Methods: We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA. Results: Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70–18.3), pulmonary injury (OR: 3.22; 95% CI: 1.60–6.47), and thrombocytopenia, defined as platelet count <80×103/µL, (OR: 2.67; 95% CI: 1.27–5.62)were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07–1.57) but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96–1.62). The presence of both thrombocytopenia and ARDS substantially increased 60-daymortality. Sensitivity analyses showed that a platelet count of <100×103/µLin combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients. Conclusions: This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality

Adsorptive potential of Zn–Al and Mg–Fe layered double hydroxides for the removal of 2–nitrophenol from aqueous solutions

Two layered double hydroxides (LDH) of the type Zn–Al and Mg–Fe were synthesized, characterized and used as adsorbents to uptake 2–nitrophenol (2–NP) from aqueous solutions. XRD, FTIR, SEM, EDS, AFM and N2 adsorption/desorption curves were used to characterize the Zn–Al–LDH and Mg–Fe–LDH. The potential of both layered double hydroxides to adsorb 2–NP was investigated by adsorption kinetics, equilibrium, thermodynamics and consecutive adsorption/desorption cycles. The characterization indicated a high crystallinity degree and a well–organized and lamellar structure, confirming the efficiency of the synthesis. Elovich was the better kinetic model to describe the 2–NP adsorption onto Zn–Al–LDH, while Pseudo–second order was the best for Mg–Fe–LDH. For both LDHs, the adsorption equilibrium followed the Freundlich model. The process was endothermic, being the maximum adsorption capacities of 290 and 165 mg g–1 for Zn–Al–LDH and Mg–Fe–LDH, respectively. LDHs can be applied for five adsorption/desorption cycles with excellent adsorption capacities. It can be concluded that Zn–Al–LDH and Mg–Fe–LDH are promising materials to treat waters and wastewaters containing 2–nitropheno

A qualitative study of enablers and barriers influencing the incorporation of social accountability values into organisational culture: a perspective from two medical schools

Background: Definitions of social accountability describe the obligation of medical schools to direct education, research and service activities towards addressing the priority health concerns of the population they serve. While such statements give some direction as to how the goal might be reached, it does not identify what factors might facilitate or hinder its achievement. This study set out to identify and explore enablers and barriers influencing the incorporation of social accountability values into medical schools. Methods: Semi structured interviews of fourteen senior staff in Bar Ilan and Leeds medical schools were undertaken following a literature review. Participants were recruited by purposive sampling in order to identify factors perceived to play a part in the workings of each institution. Results: Academic prestige was seen as a key barrier that was dependent on research priorities and student selection. The role of champions was considered to be vital to tackle staff perceptions and facilitate progress. Including practical community experience for students was felt to be a relevant way in which the curriculum could be designed through engagement with local partners. Conclusions: Successful adoption of social accountability values requires addressing concerns around potential negative impacts on academic prestige and standards. Identifying and supporting credible social accountability champions to disseminate the values throughout research and education departments in medical and other faculties is also necessary, including mapping onto existing work streams and research agendas. Demonstrating the contribution the institution can make to local health improvement and regional development by a consideration of its economic footprint may also be valuable

How do undergraduate medical students perceive social accountability?

Aim: The concept of social accountability within undergraduate training is embedded within the remit of medical schools. Little is known of how medical students perceive social accountability, recognize aspects of their training contributing to the development of this concept and cultivate the underpinning values. Methods: Students nearing graduation were recruited to participate in focus groups designed to explore their perceptions of social accountability, which curricular aspects had contributed to their understanding, and to investigate the implications of individual variations in training. Results: Students expressed limited appreciation of the concept of social accountability and acknowledged little explicit teaching around underpinning core concepts such as awareness of local health needs, advocacy and nurturing of altruism. However, participants recognized numerous aspects of the course and learning initiatives as impacting on their attitudes towards this concept implicitly. Conclusion: This study highlights areas of their undergraduate training that students recognize as having the greatest impact on their development into socially accountable professionals. It poses some significant challenges for health care educators in addressing unintended consequences, including an outcome-driven educational approach, in reducing students’ capacity or willingness to engage in curricular challenges often designed to embed this concept

A multiscale hybrid model for pro-angiogenic calcium signals in a vascular endothelial cell

Cytosolic calcium machinery is one of the principal signaling mechanisms by which endothelial cells (ECs) respond to external stimuli during several biological processes, including vascular progression in both physiological and pathological conditions. Low concentrations of angiogenic factors (such as VEGF) activate in fact complex pathways involving, among others, second messengers arachidonic acid (AA) and nitric oxide (NO), which in turn control the activity of plasma membrane calcium channels. The subsequent increase in the intracellular level of the ion regulates fundamental biophysical properties of ECs (such as elasticity, intrinsic motility, and chemical strength), enhancing their migratory capacity. Previously, a number of continuous models have represented cytosolic calcium dynamics, while EC migration in angiogenesis has been separately approached with discrete, lattice-based techniques. These two components are here integrated and interfaced to provide a multiscale and hybrid Cellular Potts Model (CPM), where the phenomenology of a motile EC is realistically mediated by its calcium-dependent subcellular events. The model, based on a realistic 3-D cell morphology with a nuclear and a cytosolic region, is set with known biochemical and electrophysiological data. In particular, the resulting simulations are able to reproduce and describe the polarization process, typical of stimulated vascular cells, in various experimental conditions.Moreover, by analyzing the mutual interactions between multilevel biochemical and biomechanical aspects, our study investigates ways to inhibit cell migration: such strategies have in fact the potential to result in pharmacological interventions useful to disrupt malignant vascular progressio