Rapid turnover of the recirculating lymphocyte pool in vivo

Lymphocytes are unique among blood cells in their capacity to continually recirculate between blood and the tissues via the lymph. Previous estimates of lymphocyte lifespan in vivo and the turnover of the recirculating lymphocyte pool have been deduced from indirect labeling techniques. Using the fluorescent dye PKH-26, individual labeled cells have been tracked in sheep for periods >2 months. By direct measurement their lifespan was calculated. This label was found to be stable in vivo, allowing long-term analysis of the characteristics of the recirculating lymphocyte pool. It Is possible to calculate the rate of turnover of cells of the recirculating pool based on the rate at which labeled cells disappear from the lymphatic circulation. The recirculating lymphocyte pool was found to repopulate itself every 16.5 ± 3.0 days. Using this label, it was estimated that recirculating lymphocytes divide on average once every 29.8 ± 6.8 days. Labeled erythrocytes were also examined and found to have an average lifespan of 153 days, demonstrating no dye loss over the 2 month period of observation. These data suggest that the recirculating lymphocyte pool is a highly dynamic compartment, with a high rate of turnover and peripheral cell division in vivo. This is the first report of the direct measurement of the in vivo turnover of recirculating lymphocyte pools, and this method may now be used to further analyze the lifespan of individual lymphocyte subsets and the in vivo lifespan of other cell types in viv

A survey of patient preferences for a placebo orodispersible tablet

This abstract looks at a survey of patient preferences for a placebo orodispersible table

Research Exchange - April 6, 2021 Anatomy of a Good Paper - Choosing Research Topics

Robert Davison and Alan Dennis discuss considerations in selecting a good and relevant research topics. Moderated by Amber Young, Davison and Dennis will focus on positioning and motivation to improve the overall contribution to IS research. Additionally, discussions focus on the limitations of gap-spotting and the position that research should be meaningful in its academic and practical implications

Group V Phospholipase A2 Induces Leukotriene Biosynthesis in Human Neutrophils through the Activation of Group IVA Phospholipase A2

We reported previously that exogenously added human group V phospholipase A2 (hVPLA2) could elicit leukotriene B4 (LTB4) biosynthesis in human neutrophils (Han, S. K., Kim, K. P., Koduri, R., Bittova, L., Munoz, N. M., Leff, A. R., Wilton, D. C., Gelb, M. H., and Cho, W. (1999) J. Biol. Chem. 274, 11881-11888). To determine the mechanism of the hVPLA2-induced LTB4 biosynthesis in neutrophils, we thoroughly examined the effects of hVPLA2 and their lipid products on the activity of group IVA cytosolic PLA2 (cPLA2) and LTB4 biosynthesis under different conditions. As low as 1 nM exogenous hVPLA2 was able to induce the release of arachidonic acid (AA) and LTB4. Typically, AA and LTB4 were released in two phases, which were synchronized with a rise in intracellular calcium concentration ([Ca2+]i) near the perinuclear region and cPLA2 phosphorylation. A cellular PLA2 assay showed that hVPLA2 acted primarily on the outer plasma membrane, liberating fatty acids and lysophosphatidylcholine (lyso-PC), whereas cPLA2 acted on the perinuclear membrane. Lyso-PC and polyunsaturated fatty acids including AA activated cPLA2 and 5-lipoxygenase by increasing [Ca2+]i and inducing cPLA2 phosphorylation, which then led to LTB4 biosynthesis. The delayed phase was triggered by the binding of secreted LTB4 to the cell surface LTB4 receptor, which resulted in a rise in [Ca2+]i and cPLA2 phosphorylation through the activation of mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2. These results indicate that a main role of exogenous hVPLA2 in neutrophil activation and LTB4 biosynthesis is to activate cPLA2 and 5-lipoxygenase primarily by liberating from the outer plasma membrane lyso-PC that induces [Ca2+]i increase and cPLA2 phosphorylation and that hVPLA2-induced LTB4 production is augmented by the positive feedback activation of cPLA2 by LTB4

Severity and management of psoriasis within primary care

Background: Scottish Intercollegiate Guidelines Network and National Institute of Health and Care Excellence guidelines stress the importance of assessing patients with psoriasis for psoriatic arthritis, comorbidities associated with severe disease and quality of life (QoL). The purpose of the study was to evaluate the primary care management of psoriasis in relation to disease severity and QoL from apatient's perspective. Methods: A cross-sectional survey of adults (≥18 years) with psoriasis managed in primary care was conducted in Scotland over 1-year (2012-2013). Patients with psoriasis were identified and invited to participate in the online/telephone survey. The questionnaires included; Dermatology Life Quality Index (DLQI), Self-Administered Psoriasis Area and Severity Index (SAPASI), Psoriasis Epidemiology Screening Tool (PEST). The primary outcome measure was DLQI. Secondary outcomes included; demographics; comorbidities; involvement of different body sites; SAPASI and PEST scores. Relationships between measures were analysed using univariate analysis. Results: The mean age of patients (n = 905) was 54.5 years (SD = 16.1), 436 (48.2 %) were men, and median DLQI and SAPASI scores were 4.0 and 6.0, respectively. Current psoriasis treatments were topical only (587, 64.9 %), oral medications or phototherapy (122, 13.5%), biologics (26, 3 %) and none (156, 17.2 %). Despite SIGN recommendations,256 of 391 patients (65.5 %) with a DLQI >5 (at least a moderate effect on QoL) had not seen a specialist during the past year. According to PEST scores, 259 patients (28.6 %) had symptoms suggestive of psoriatic arthritis requiring rheumatology referral. Conclusion: National recommendations are not being fully implemented in primary care in patients with psoriasis or psoriatic arthritis

An advanced numerical model of friction stir welding of DH36 steel

A numerical model of Friction Stir Welding (FSW) of DH36 steel plate (6mm thickness) has been developed using a CFD technique. Two welding speed conditions were used, a low welding speed of 200 RPM - 100mm/min, and a high welding speed of 550RPM- 400 mm/min. The heat generation, material flow and strain rate were calculated based on plastic deformation and frictional contact between the tool and workpiece. A CFD-based model has been produced to represent the asymmetry in temperature distribution between the advancing and retreating side, the material flow and the strain rate. The geometry of the model includes the tool plunged into the plate. The cooling system was also included in the simulation by calculating the heat flux lost for each part of the tool. The heat generated by viscous dissipation away from the tool was also taken into account. The total heat generated was divided into the individual tool parts (shoulder, probe side and probe end) and was found to be in good agreement with the experimental results for the areas affected by these parts. The maximum temperature obtained for the slow welding speed was 1012oC and for the high welding speed was 1250oC. Experimental metallographic examination has also been carried out on DH36 FSW steel plates to validate the CFD model. SEM analysis showed the formation of a fine microstructure of bainite, acicular ferrite and ferrite/cementite aggregate in the welded zone as compared to the ferrite/pearlite morphology in the base metal. It is found from the CFD and experimental results that the high speed welding conditions can produce defects such as wormholes and cracks in the welds associated with the probe side and probe end due to the lack of material flow especially on the advancing side. Tensile and fatigue testing were carried out for both slow and high welding speed samples, which broke outside the welded region in the tensile test, however, slow welding speed samples show more resistance to fatigue test and survived 644128 cycles, the high speed welding samples failed after 111,736 cycles under the same load

Modelling of friction stir welding of 304 stainless steel

A 3-D Eulerian steady-state CFD model has been developed to simulate the Friction Stir Welding (FSW) of 6mm plate 304 stainless steel (304SS). The Polycrystalline BoroNitride- Tungsten Rhenium (PCBN-WRe) hybrid tool was modelled with the workpiece in a fully sticking condition. The viscosity of stainless steel was calculated from the flow stress equation taken from a previous study of hot working carried out in a range of temperatures between 800oC-1200 oC and strain rates 0.001 s-1 to 5 s-1. The model predicted the temperature distribution in the Stirred Zone (SZ) for three welding cases including low, intermediate and high rotational speed/traverse speeds. The model also predicts that localised melting may occur if the tool rotational speed exceeds 400RPM. Finally, the model suggested a larger probe (12mm diameter at the shoulder base and 5.8mm length) with a stationary shoulder would prevent the localised melting and allow an increase in welding speeds without the associated introduction of stagnant zone related weld defects

Economic Impact of Beef Cattle Best Management Practices in South Texas: Stocking Strategies during Drought

In a drought situation, forage is normally reduced due to lack of adequate moisture. Moreover, the availability of hay may become limited, and hay prices often escalate. Cow-calf producers are faced with the integral decision to maintain their herds and supplemental feed or reduce the herd to minimize feeding requirements and costs. The management decision to maintain versus destock can significantly impact producer profits and financial position. This paper illustrates the financial implications of alternative management stocking strategies in a drought situation optimizing profitability of ranching operations