Optical coherence tomography measurements of biological fluid flows with picolitre spatial localization

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Interest in studying the human and animal microcirculation has burgeoned in recent years. In part this has been driven by recent advances in volumetric microscopy modalities, which allow the study of the 3-D morphology of the microcirculation without the limitations of 2-D intra-vital microscopy. In this paper we highlight the power of optical coherence tomography (OCT) to image the normal and pathological microcirculation with picolitre voxel sizes. Both Doppler and speckle-variance methods are employed to characterize complex rheological flows both in-vitro and in-vivo. GPU accelerated image registration methods are demonstrated in order to mitigate problems of bulk tissue motion in methods based on speckle decorrelation. In-vivo images of the human nailfold microcirculation are shown

Effects of the Santa Barbara, Calif., Oil Spill on the Apparent Abundance of Pelagic Fishery Resources

Many studies have been made of the effects of oil on marine invertebrates, plants (marine algae and phytoplankton), and vertebrates such as seabirds and marine mammals. An excellent review of these findings, which includes some references to fish and pathological effects of aromatic hydrocarbons, has been published by the Royal Society, London (Clark, 1982). That review dealt with the environmental effects of such major oil spills or releases such as those by the tankers Torry Canyon (119,000 t) on the south coast of England, Metula (50-56,000 t) in the Straits of Magellan, Argo Merchant (26,000 t) off Cape Cod, and the super tanker Amoco Cadiz (223,000 t) on the coast of northern Brittany. Those spills were studied to determine their effect on living resources. In contrast there are few references on the impact of oil spills on pelagic fishery resources

A miR-335/COX-2/PTEN axis regulates the secretory phenotype of senescent cancer-associated fibroblasts

AGING applies the Creative Commons Attribution License (CCAL) to all works we publishWe acknowledge the financial support of the University of Sheffield, The Pathological Society London, The University of Otago-Dunedin and the Development and Promotion of Science and Technology Talents Project, The Royal Thai Government. ICP is supported by a University of Malaya-MOHE High Impact Research grant (UM.C/625/1/HIR/MOHE/DENT/22)

Microconfined flow behavior of red blood cells by image analysis techniques

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Red blood cells (RBCs) perform essential functions in human body, such as gas exchange between blood and tissues, thanks to their ability to deform and flow in the microvascular network. The high RBC deformability is mainly due to the viscoelastic properties of the cell membrane. Since an impaired RBC deformability could be found in some diseases, such as malaria, sickle cell anemia, diabetes and hereditary disorders, there is the need to provide further insight into measurement of RBC deformability in a physiologically-relevant flow field. Here, we report on an imaging-based in vitro systematic microfluidic investigation of RBCs flowing either in microcapillaries or in a microcirculation-mimicking device containing a network of microchannels of diameter comparable to cell size. RBC membrane shear elastic modulus and surface viscosity have been investigated by using diverging channels, while RBC time recovery constant have been measured in start-up experiments. Moreover, RBC volume and surface area have been measured in microcapillary flow. The comprehension of the single cell behavior led to the analysis of the RBC flow-induced clustering. Overall, our results provide a novel technique to estimate RBC deformability, that can be used for the analysis of pathological RBCs, for which reliable quantitative methods are still lacking

A model of oxygen dynamics in the cerebral microvasculature and the effects of morphology on flow and metabolism

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.The cerebral microvasculature plays a vital role in adequately supplying blood to the brain. Determining the health of the cerebral microvasculature is important during pathological conditions, such as stroke and dementia. Recent studies have shown the complex behaviour of cerebral metabolic rate with transit time distribution. In this paper, we extend a recently developed technique to solve for residue function and transit time distribution in an existing physiologically accurate model of the cerebral microvasculature to calculate cerebral metabolism. We present the mathematical theory based on solving the mass transport equation followed by results of the simulations. It is found that oxygen extraction fraction and cerebral metabolic rate are dependent on both mean and heterogeneity of the transit time distribution. For changes in cerebral blood flow, a positive correlation can be observed between mean transit time and oxygen extraction fraction, and a negative correlation between mean transit time and metabolic rate of oxygen. The metabolic rate is thus affected more significantly by cerebral blood flow than oxygen extraction fraction. A negative correlation can also be observed between transit time heterogeneity and the metabolic rate of oxygen for a constant cerebral blood flow. The heterogeneity of the transit time distribution also has an effect on the response of oxygen extraction fraction and cerebral metabolic rate to sudden changes. These results provide information on the role of the cerebral microvasculature and its effects on flow and metabolism. They thus open up the possibility of obtaining additional valuable clinical information for diagnosing and treating cerebrovascular diseases

Mind the gap? The persistence of pathological discourses in urban regeneration policy

Urban regeneration policy has historically framed policy problems using a discourse that pathologises areas and spatial communities. Since 2001 in England, and 2002 in Scotland a structural change in policy has occurred where citywide partnerships are now meant overcome structural spatial inequalities, countering pathological explanations. This paper uses historical and discourse analysis to evaluate one of the major community regeneration strategies developed by the Scottish Executive in 2002: Better Communities in Scotland: Closing the Gap. It seeks to ask whether structural change in policy was paralleled by discursive change; what discursive path dependence is evidenced? The text is placed in the historic context of UK urban renewal policies dating back to the launch of the Urban Programme in 1968 and particularly the policy discourse created by the influential Conservative government policy of 1988 New Life for Urban Scotland and the wider discourses of poverty and neighbourhood renewal policy created by Labour governments since 1997. The close textual analysis of the text shows that Better Communities in Scotland continues to pathologise spatial communities. Although this suggests a degree of historical path dependency, the historic breadth of the analysis also problematises simple historical determinism

Interleukin-17 regulates matrix metalloproteinase activity in human pulmonary tuberculosis.

Tuberculosis (TB) is characterized by extensive pulmonary matrix breakdown. Interleukin-17 (IL-17) is key in host defence in TB but its role in TB-driven tissue damage is unknown. We investigated the hypothesis that respiratory stromal cell matrix metalloproteinase (MMP) production in TB is regulated by T-helper 17 (TH -17) cytokines. Biopsies of patients with pulmonary TB were analysed by immunohistochemistry (IHC), and patient bronchoalveolar lavage fluid (BALF) MMP and cytokine concentrations were measured by Luminex assays. Primary human airway epithelial cells were stimulated with conditioned medium from human monocytes infected with Mycobacterium tuberculosis (Mtb) and TH -17 cytokines. MMP secretion, activity, and gene expression were determined by ELISA, Luminex assay, zymography, RT-qPCR, and dual luciferase reporter assays. Signalling pathways were examined using phospho-western analysis and siRNA. IL-17 is expressed in TB patient granulomas and MMP-3 is expressed in adjacent pulmonary epithelial cells. IL-17 had a divergent, concentration-dependent effect on MMP secretion, increasing epithelial secretion of MMP-3 (p < 0.001) over 72 h, whilst decreasing that of MMP-9 (p < 0.0001); mRNA levels were similarly affected. Both IL-17 and IL-22 increased fibroblast Mtb-dependent MMP-3 secretion but IL-22 did not modulate epithelial MMP-3 expression. Both IL-17 and IL-22, but not IL-23, were significantly up-regulated in BALF from TB patients. IL-17-driven MMP-3 was dependent on p38 MAP kinase and the PI3K p110α subunit. In summary, IL-17 drives airway stromal cell-derived MMP-3, a mediator of tissue destruction in TB, alone and with monocyte-dependent networks in TB. This is regulated by p38 MAP kinase and PI3K pathways. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

Impaired decidual natural killer cell regulation of vascular remodelling in early human pregnancies with high uterine artery resistance

During human pregnancy, natural killer (NK) cells accumulate in the maternal decidua, but their specific roles remain to be determined. Decidual NK (dNK) cells are present during trophoblast invasion and uterine spiral artery remodelling. These events are crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Remodelling of spiral arteries is impaired in the dangerous pregnancy complication pre-eclampsia. We studied dNK cells isolated from pregnancies at 9-14 weeks' gestation, screened by uterine artery Doppler ultrasound to determine resistance indices which relate to the extent of spiral artery remodelling. dNK cells were able to promote the invasive behaviour of fetal trophoblast cells, partly through HGF. Cells isolated from pregnancies with higher resistance indices were less able to do this and secreted fewer pro-invasive factors. dNK cells from pregnancies with normal resistance indices could induce apoptotic changes in vascular smooth muscle and endothelial cells in vitro, events of importance in vessel remodelling, partly through Fas signalling. dNK cells isolated from high resistance index pregnancies failed to induce vascular apoptosis and secreted fewer pro-apoptotic factors. We have modelled the cellular interactions at the maternal-fetal interface and provide the first demonstration of a functional role for dNK cells in influencing vascular cells. A potential mechanism contributing to impaired vessel remodelling in pregnancies with a higher uterine artery resistance is presented. These findings may be informative in determining the cellular interactions contributing to the pathology of pregnancy disorders where remodelling is impaired, such as pre-eclampsia. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd