A novel ischemia reperfusion injury hereditary tissue model for pressure ulcers progression.

Ischemia reperfusion injury (IRI) involvement in pressure ulcers (PU) progression via a surge of oxidative stress and inflammatory responses is well documented. IRI strongly depends on the mechanical loading history. We present a generalized IRI model considering external loading, dynamic tissue healing capacity, accumulating mechanical and reperfusion-mediated damages and competing repair processes of saturating nature. Reperfusion depends on strain and strain rate to enhance loading history sensitivity. Tissue-specific ulceration susceptibility is assumed dependent on variable accumulated damage. We study damage evolution under cyclic loading having several strain expulsion profiles and demonstrate load relief history has critical impact on PU progression. Abrupt load removal generally follows existing models representing extreme repair/damage. We show (first time in silico) that under certain conditions (previously experimentally identified), IRI becomes repairing rather than damaging. In particular, we recapitulate the preconditioning and postconditioning IRI hallmarks. Finally, it is customary among physicians and nurses to promptly alleviate mechanical load applied to patients lying in bed for extended periods and in risk of developing PUs. We demonstrate this practice can be harmful. If load removal is performed early while reperfusion is still beneficial, then this conduct is suitable. However, if critical tissue damage has been crossed, then abrupt expulsion can constitute the worst-case scenario for patient outcome. If no preliminary patient documentation is available, we recommend gradual load removal since risks of accelerated damage eventually leading to ulceration supersede the improved repair potential benefit.

The Humboldt Penguin (Spheniscus humboldti) Rete Tibiotarsale - A supreme biological heat exchanger.

Humans are unable to survive low temperature environments without custom designed clothing and support systems. In contrast, certain penguin species inhabit extremely cold climates without losing substantial energy to self-heating (emperor penguins ambient temperature plummets to as low as -45°C). Penguins accomplish this task by relying on distinct anatomical, physiological and behavioral adaptations. One such adaptation is a blood vessel heat exchanger called the 'Rete Tibiotarsale' - an intermingled network of arteries and veins found in penguins' legs. The Rete existence results in blood occupying the foot expressing a lower average temperature and thus the penguin loosing less heat to the ground. This study examines the Rete significance for the species thermal endurance. The penguin anatomy (leg and main blood vessels) is reconstructed using data chiefly based on the Humboldt species. The resulting model is thermally analyzed using finite element (COMSOL) with the species environment used as boundary conditions. A human-like blood vessel configuration, scaled to the penguin's dimensions, is used as a control for the study. Results indicate that the Rete existence facilitates upkeep of 25-65% of the species total metabolic energy production as compared with the human-like configuration; thus making the Rete probably crucial for penguin thermal endurance. Here, we quantitatively link for the first time the function and structure of this remarkable physiological phenotype.

Human embryonic stem cells exhibit increased propensity to differentiate during the G1 phase prior to phosphorylation of retinoblastoma protein.

While experimentally induced arrest of human embryonic stem cells (hESCs) in G1 has been shown to stimulate differentiation, it remains unclear whether the unperturbed G1 phase in hESCs is causally related to differentiation. Here, we use centrifugal elutriation to isolate and investigate differentiation propensities of hESCs in different phases of their cell cycle. We found that isolated G1 cells exhibit higher differentiation propensity compared with S and G2 cells, and they differentiate at low cell densities even under self-renewing conditions. This differentiation of G1 cells was partially prevented in dense cultures of these cells and completely abrogated in coculture with S and G2 cells. However, coculturing without cell-to-cell contact did not rescue the differentiation of G1 cells. Finally, we show that the subset of G1 hESCs with reduced phosphorylation of retinoblastoma has the highest propensity to differentiate and that the differentiation is preceded by cell cycle arrest. These results provide direct evidence for increased propensity of hESCs to differentiate in G1 and suggest a role for neighboring cells in preventing differentiation of hESCs as they pass through a differentiation sensitive, G1 phase.

Floating electrode dielectrophoresis.

In practice, dielectrophoresis (DEP) devices are based on micropatterned electrodes. When subjected to applied voltages, the electrodes generate nonuniform electric fields that are necessary for the DEP manipulation of particles. In this study, electrically floating electrodes are used in DEP devices. It is demonstrated that effective DEP forces can be achieved by using floating electrodes. Additionally, DEP forces generated by floating electrodes are different from DEP forces generated by excited electrodes. The floating electrodes' capabilities are explained theoretically by calculating the electric field gradients and demonstrated experimentally by using test-devices. The test-devices show that floating electrodes can be used to collect erythrocytes (red blood cells). DEP devices which contain many floating electrodes ought to have fewer connections to external signal sources. Therefore, the use of floating electrodes may considerably facilitate the fabrication and operation of DEP devices. It can also reduce device dimensions. However, the key point is that DEP devices can integrate excited electrodes fabricated by microtechnology processes and floating electrodes fabricated by nanotechnology processes. Such integration is expected to promote the use of DEP devices in the manipulation of nanoparticles.