OX40 Ligand and Programmed Cell Death 1 Ligand 2 Expression on Inflammatory Dendritic Cells Regulates CD4 T Cell Cytokine Production in the Lung during Viral Disease

CD4-T-helper-cell (Th) differentiation is influenced by costimulatory molecules expressed on conventional dendritic cells (DCs) in regional lymph nodes and results in specific patterns of cytokine production. However, the function of costimulatory molecules on ‘inflammatory’ (CD11b+) DCs in the lung during recall responses is not fully understood, but important for development of novel interventions to limit immunopathological responses to infection. Using a mouse model in which vaccination with vaccinia virus vectors expressing the respiratory syncytial virus (RSV) fusion protein (rVVF) or attachment protein (rVVG) leads to type 1- or type 2-biased cytokine responses respectively upon RSV-challenge, we found expression of CD40 and OX40L on lung inflammatory DCs was higher in rVVF- than in rVVG-primed mice early after RSV-challenge, while the reverse was observed later in the response. Conversely, PD-L2 was higher in rVVG-primed mice throughout. Inflammatory DCs isolated at the resolution of inflammation revealed OX40L on type 1-biased DCs promoted IL-5, while on type 2-biased DCs enhanced IFNγ production by antigen-reactive Th cells. In contrast, PD-L2 promoted IFNγ production irrespective of conditions, suppressing IL-5 only if expressed on type 1-biased DCs. Thus, OX40L and PD-L2 expressed on DCs differentially regulate cytokine production during recall responses in the lung. Manipulation of these costimulatory pathways may provide a novel approach to controlling pulmonary inflammatory responses

Review article: the role of the microcirculation in liver cirrhosis

BACKGROUND: Intrahepatic microvascular derangements and microcirculatory dysfunction are key in the development of liver cirrhosis and its associated complications. While much has been documented relating to cirrhosis and the dysfunction of the microcirculation in the liver parenchyma, far less is known about the state of the extrahepatic microcirculation and the role this may have in the pathogenesis of multiple organ failure in end stage liver cirrhosis. AIM: To provide an update on the role of the microcirculation in the pathophysiology of cirrhosis and its associated complications and briefly discuss some of the imaging techniques which may be used to directly investigate the microcirculation. METHODS: A Medline literature search was conducted using the following search terms: ‘cirrhosis’, ‘microcirculation’, ‘circulation’, ‘systemic’, ‘inflammation’, ‘peripheral’, ‘hepatorenal’ and ‘hepatopulmonary’. RESULTS: Significant heterogeneous microvascular alterations exist in patients with cirrhosis. Data suggest that the systemic inflammation, associated with advanced cirrhosis, induces microcirculatory dysregulation and contributes to haemodynamic derangement. The resultant vasoconstriction and hypoperfusion in the systemic extrahepatic microvasculature, is likely to be instrumental in the pathophysiology of organ failure in decompensated cirrhosis, however the mechanistic action of vasoactive agents used to correct the circulatory disturbance of advanced cirrhosis is poorly understood. CONCLUSIONS: Further research into the role of the microcirculation in patients with liver cirrhosis, will improve physicians understanding of the pathophysiology of cirrhosis, and may provide a platform for real time evaluation of an individual's microcirculatory response to vasoactive mediators, thus guiding their therapy

Can primary care data be used to monitor regional smoking prevalence? An analysis of The Health Improvement Network primary care data

<p>Abstract</p> <p>Background</p> <p>Accurate and timely regional data on smoking trends allow tobacco control interventions to be targeted at the areas most in need and facilitate the evaluation of such interventions. Electronic primary care databases have the potential to provide a valuable source of such data due to their size, continuity and the availability of socio-demographic data. UK electronic primary care data on smoking prevalence from The Health Improvement Network (THIN) have previously been validated at the national level, but may be less representative at the regional level due to reduced sample sizes. We investigated whether this database provides valid regional data and whether it can be used to compare smoking prevalence in different UK regions.</p> <p>Methods</p> <p>Annual estimates of smoking prevalence by government office region (GOR) from THIN were compared with estimates of smoking prevalence from the General Lifestyle Survey (GLF) from 2000 to 2008.</p> <p>Results</p> <p>For all regions, THIN prevalence data were generally found to be highly comparable with GLF data from 2006 onwards.</p> <p>Conclusions</p> <p>THIN primary care data could be used to monitor regional smoking prevalence and highlight regional differences in smoking in the UK.</p

Internet of Things for Water Sustainability

The water is a finite resource. The issue of sustainable withdrawal of freshwater is a vital concern being faced by the community. There is a strong connection between the energy, food, and water which is referred to as water-food-energy nexus. The agriculture industry and municipalities are struggling to meet the demand of water supply. This situation is particularly exacerbated in the developing countries. The projected increase in world population requires more fresh water resources. New technologies are being developed to reduce water usage in the field of agriculture (e.g., sensor guided autonomous irrigation management systems). Agricultural water withdrawal is also impacting ground and surface water resources. Although the importance of reduction in water usage cannot be overemphasized, major efforts for sustainable water are directed towards the novel technology development for cleaning and recycling. Moreover, currently, energy technologies require abundant water for energy production. Therefore, energy sustainability is inextricably linked to water sustainability. The water sustainability IoT has a strong potential to solve many challenges in water-food-energy nexus. In this chapter, the architecture of IoT for water sustainability is presented. An in-depth coverage of sensing and communication technologies and water systems is also provided

Physiological responses during ascent to high altitude and the incidence of acute mountain sickness.

Acute mountain sickness (AMS) occurs when there is failure of acclimatisation to high altitude. The aim of this study was to describe the relationship between physiological variables and the incidence of AMS during ascent to 5300 m. A total of 332 lowland-dwelling volunteers followed an identical ascent profile on staggered treks. Self-reported symptoms of AMS were recorded daily using the Lake Louise score (mild 3-4; moderate-severe ≥5), alongside measurements of physiological variables (heart rate, respiratory rate (RR), peripheral oxygen saturation (SpO2 ) and blood pressure) before and after a standardised Xtreme Everest Step-Test (XEST). The overall occurrence of AMS among participants was 73.5% (23.2% mild, 50.3% moderate-severe). There was no difference in gender, age, previous AMS, weight or body mass index between participants who developed AMS and those who did not. Participants who had not previously ascended >5000 m were more likely to get moderate-to-severe AMS. Participants who suffered moderate-to-severe AMS had a lower resting SpO2 at 3500 m (88.5 vs. 89.6%, p = 0.02), while participants who suffered mild or moderate-to-severe AMS had a lower end-exercise SpO2 at 3500 m (82.2 vs. 83.8%, p = 0.027; 81.5 vs. 83.8%, p 5000 m (OR 2.740, p-value 0.003) predicted the development of moderate-to-severe AMS. The Xtreme Everest Step-Test offers a simple, reproducible field test to help predict AMS, albeit with relatively limited predictive precision

Cuff inflation time significantly affects blood flow recorded with venous occlusion plethysmography

© 2019, The Author(s). Purpose: We tested whether the values of limb blood flow calculated with strain-gauge venous occlusion plethysmography (VOP) differ when venous occlusion is achieved by automated, or manual inflation, so providing rapid and slower inflation, respectively. Method: In 9 subjects (20–30 years), we calculated forearm blood flows (FBF) values at rest and following isometric handgrip at 70% maximum voluntary contraction (MVC) when rapid, or slower inflation was used. Result: Rapid and slower cuff inflation took 0.23 ± 0.01 (mean ± SEM) and 0.92 ± 0.02 s, respectively, reflecting the range reported in published studies. At rest, FBF calculated from the 1st cardiac cycle after rapid and slower inflation gave similar values: 10.5 ± 1.4 vs. 9.6 ± 1.3 ml dl − 1  min − 1 , respectively (P > 0.05). However, immediately post-contraction, FBF was ~ 40% lower with slower inflation: 54.6 ± 5.1 vs. 33.8 ± 4.2 ml dl − 1  min − 1 (P < 0.01). The latter value was similar to that calculated over the 3rd cardiac cycle following rapid inflation: 2nd cardiac cycle: 40.5 ± 4.5; 3rd cycle: 32.6 ± 4.5 ml dl − 1  min − 1 . Regression analyses of FBFs recorded at intervals post-contraction showed those calculated over the 1st, 2nd, or 3rd cardiac cycles with rapid inflation correlated well with those from the 1st cardiac cycle with manual inflation (r = 0.79, 0.82, 0.79; P < 0.01). However, only the slope for the 3rd cycle with rapid inflation vs. slower inflation was close to unity (2.07, 1.34, and 0.94, respectively). Conclusion: These findings confirm that the 1st cardiac cycle following venous occlusion should be used when calculating FBF using VOP and, but importantly, indicate that cuff inflation should be almost instantaneous; just ≥ 0.9 s leads to substantial underestimation, especially at high flows

Effects of dietary nitrate supplementation on microvascular physiology at 4559 m altitude – a randomised controlled trial (Xtreme Alps)

Native highlanders (e.g. Sherpa) demonstrate remarkable hypoxic tolerance, possibly secondary to higher levels of circulating nitric oxide (NO) and increased microcirculatory blood flow. As part of the Xtreme Alps study (a randomised placebo-controlled trial of dietary nitrate supplementation under field conditions of hypobaric hypoxia), we investigated whether dietary supplementation with nitrate could improve NO availability and microvascular blood flow in lowlanders. Plasma measurements of nitrate, nitrite and nitroso species were performed together with measurements of sublingual (sidestream dark-field camera) and forearm blood flow (venous occlusion plethysmography) in 28 healthy adult volunteers resident at 4559 m for 1 week; half receiving a beetroot-based high-nitrate supplement and half receiving an identically-tasting low nitrate 'placebo'. Dietary supplementation increased plasma nitrate concentrations 4-fold compared to the placebo group, both at sea level (SL; 19.2 vs 76.9 μM) and at day 5 (D5) of high altitude (22.9 vs 84.3 μM,

Venous identity requires BMP signalling through ALK3

Venous endothelial cells are molecularly and functionally distinct from their arterial counterparts. Although veins are often considered the default endothelial state, genetic manipulations can modulate both acquisition and loss of venous fate, suggesting that venous identity is the result of active transcriptional regulation. However, little is known about this process. Here we show that BMP signalling controls venous identity via the ALK3/BMPR1A receptor and SMAD1/SMAD5. Perturbations to TGF-β and BMP signalling in mice and zebrafish result in aberrant vein formation and loss of expression of the venous-specific gene Ephb4, with no effect on arterial identity. Analysis of a venous endothelium-specific enhancer for Ephb4 shows enriched binding of SMAD1/5 and a requirement for SMAD binding motifs. Further, our results demonstrate that BMP/SMAD-mediated Ephb4 expression requires the venous-enriched BMP type I receptor ALK3/BMPR1A. Together, our analysis demonstrates a requirement for BMP signalling in the establishment of Ephb4 expression and the venous vasculature

tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis

Angiogenesis requires co-ordination of multiple signalling inputs to regulate the behaviour of endothelial cells (ECs) as they form vascular networks. Vascular endothelial growth factor (VEGF) is essential for angiogenesis and induces downstream signalling pathways including increased cytosolic calcium levels. Here we show that transmembrane protein 33 (tmem33), which has no known function in multicellular organisms, is essential to mediate effects of VEGF in both zebrafish and human ECs. We find that tmem33 localises to the endoplasmic reticulum in zebrafish ECs and is required for cytosolic calcium oscillations in response to Vegfa. tmem33-mediated endothelial calcium oscillations are critical for formation of endothelial tip cell filopodia and EC migration. Global or endothelial-cell-specific knockdown of tmem33 impairs multiple downstream effects of VEGF including ERK phosphorylation, Notch signalling and embryonic vascular development. These studies reveal a hitherto unsuspected role for tmem33 and calcium oscillations in the regulation of vascular development

Atmospheric pitting corrosion of aircraft aluminium alloys

Aircraft aluminium alloys tend to be engineered to maximise their mechanical properties and therefore have an increased susceptibility to localised corrosion. The Australian Defense Force (ADF) have witnessed numerous occurrences of localised corrosion on aluminium alloys that have in some cases reduced structural integrity of the aircraft and in most cases lead to costly repair. The initiation and growth of pitting corrosion on aircraft exposed to atmospheric conditions is not fully understood due to the majority of pervious work concentrating on immersed experiments