Endothelial dysfunction: a comprehensive appraisal

The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the vasodilatation produced by drugs that are NO donors, such as nitroglycerine, called "endothelium independent". The vasodilatation is quantified by measuring the arterial diameter with high resolution ultrasonography. Laser-Doppler techniques are now starting to be used that also consider tissue perfusion. There is so much proof about endothelial dysfunction that it is reasonable to believe that there is diagnostic and prognostic value in its evaluation for the late outcome. There is no doubt that endothelial dysfunction contributes to the initiation and progression of atherosclerotic disease and could be considered an independent vascular risk factor. Although prolonged randomized clinical trials are needed for unequivocal evidence, the data already obtained allows the methods of evaluation of endothelial dysfunction to be considered useful in clinical practice and have overcome the experimental step, being non-invasive increases its value making it use full for follow-up of the progression of the disease and the effects of different treatments

Contamination of Mesenchymal Stem-Cells with Fibroblasts Accelerates Neurodegeneration in an Experimental Model of Parkinson’s Disease

Pre-clinical studies have supported the use of mesenchymal stem cells (MSC) to treat highly prevalent neurodegenerative diseases such as Parkinson’s disease (PD) but preliminary trials have reported controversial results. In a rat model of PD induced by MPTP neurotoxin, we first observed a significant bilateral preservation of dopaminergic neurons in the substantia nigra and prevention of motor deficits typically observed in PD such as hypokinesia, catalepsy, and bradykinesia, following intracerebral administration of human umbilical cord-derived MSC (UC-MSC) early after MPTP injury. However, surprisingly, administration of fibroblasts, mesenchymal cells without stem cell properties, as a xenotransplantation control was highly detrimental, causing significant neurodegeneration and motor dysfunction independently of MPTP. This observation prompted us to further investigate the consequences of transplanting a MSC preparation contaminated with fibroblasts, a plausible circumstance in cell therapy since both cell types display similar immunophenotype and can be manipulated in vitro under the same conditions. Here we show for the first time, using the same experimental model and protocol, that transplantation of UC-MSC induced potent neuroprotection in the brain resulting in clinical benefit. However, co-transplantation of UC-MSC with fibroblasts reverted therapeutic efficacy and caused opposite damaging effects, significantly exacerbating neurodegeneration and motor deficits in MPTP-exposed rats. Besides providing a rationale for testing UC-MSC transplantation in early phases of PD aiming at delaying disease progression, our pre-clinical study suggests that fibroblasts may be common cell contaminants affecting purity of MSC preparations and clinical outcome in stem cell therapy protocols, which might also explain discrepant clinical results

Evaluation of RGB-D Multi-Camera Pose Estimation for 3D Reconstruction

Advances in visual sensor devices and computing power are revolutionising the interaction of robots with their environment. Cameras that capture depth information along with a common colour image play a significant role. These devices are cheap, small, and fairly precise. The information provided, particularly point clouds, can be generated in a virtual computing environment, providing complete 3D information for applications. However, off-the-shelf cameras often have a limited field of view, both on the horizontal and vertical axis. In larger environments, it is therefore often necessary to combine information from several cameras or positions. To concatenate multiple point clouds and generate the complete environment information, the pose of each camera must be known in the outer scene, i.e., they must reference a common coordinate system. To achieve this, a coordinate system must be defined, and then every device must be positioned according to this coordinate system. For cameras, a calibration can be performed to find its pose in relation to this coordinate system. Several calibration methods have been proposed to solve this challenge, ranging from structured objects such as chessboards to features in the environment. In this study, we investigate how three different pose estimation methods for multi-camera perspectives perform when reconstructing a scene in 3D. We evaluate the usage of a charuco cube, a double-sided charuco board, and a robot’s tool centre point (TCP) position in a real usage case, where precision is a key point for the system. We define a methodology to identify the points in the 3D space and measure the root-mean-square error (RMSE) based on the Euclidean distance of the actual point to a generated ground-truth point. The reconstruction carried out using the robot’s TCP position produced the best result, followed by the charuco cuboid; the double-sided angled charuco board exhibited the worst performance

Towards a dendrochronologically refined date of the Laacher See Eruption

The precise date of the Laacher See eruption (LSE), central Europe’s largest Late Pleistocene volcanic event that occurred around 12,900 years ago, is still unknown. Here, we outline the potential of combined high-resolution dendrochronological, wood anatomical and radiocarbon (14C) measurements, to refine the age of this major Plinian eruption. Based on excavated trees that were killed during the explosive LSE and buried under its pyroclastic deposits, we describe how a firm date of the eruption might be achieved, and how the resulting temporal precision would further advance our understanding of the environmental and societal impacts of this event. Moreover, we discuss the relevance of an accurate LSE date for improving the synchronization of European terrestrial and lacustrine Late Glacial to Holocene archives, and outline how the proposed, interdisciplinary dating approach can be applied to other large, yet undated, volcanic eruptions

Past millennium hydroclimate variability from Corsican pine tree-ring chronologies

Palaeoclimatic evidence is necessary to place the current warming and drying trends of the Mediterranean region in a long‐term perspective of pre‐industrial variability. Annually resolved and absolutely dated climate proxies that extend back into medieval times are, however, limited to a few sites only. Here we present a network of long ring width chronologies from Pinus nigra tree‐line sites in northern Corsica (France) that cohere exceptionally well over centuries and support the development of a single high‐elevation pine chronology extending back to 974 CE. We apply various detrending methods to these data to retain high‐to‐low frequency ring width variability and scale the resulting chronologies against instrumental precipitation and drought observations to produce hydroclimate reconstructions for the last millennium. Proxy calibration and transfer are challenged by a lack of high‐elevation meteorological data, however, limiting our understanding of precipitation changes in sub‐alpine tree‐line environments. Our new reconstructions extend beyond existing records and provide evidence for low‐frequency precipitation variability in the central‐western Mediterranean from 974–2016 CE. Comparison with a European scale drought reconstruction network shows that regional predictor chronologies are needed to accurately estimate long‐term hydroclimate variability on Corsica

Climate-induced severe water scarcity events as harbinger of global grain price

The severe water scarcity (SWS) concept allows for consistent analysis of the supply and demand for water sourced grain production worldwide. Thus, the primary advantage of using SWS is its ability to simultaneously accommodate the spatial extent and temporal persistence of droughts using climatic data. The SWS concept was extended here to drivers of global grain prices using past SWS events and prices of three dominant grain crops: wheat, rice and maize. A significant relation between the SWS affected area and the prices of wheat was confirmed. The past price–SWS association was then used to project future wheat prices considering likely climate change scenarios until 2050 and expected SWS extent. The projected wheat prices increase with increasing SWS area that is in turn a function of greenhouse gas emissions. The need to act to reduce greenhouse gas emissions is again reinforced assuming the SWS-price relation for wheat is unaltered

Pregnancy Does Not Affect HIV Incidence Test Results Obtained Using the BED Capture Enzyme Immunoassay or an Antibody Avidity Assay

Accurate incidence estimates are needed for surveillance of the HIV epidemic. HIV surveillance occurs at maternal-child health clinics, but it is not known if pregnancy affects HIV incidence testing.We used the BED capture immunoassay (BED) and an antibody avidity assay to test longitudinal samples from 51 HIV-infected Ugandan women infected with subtype A, C, D and intersubtype recombinant HIV who were enrolled in the HIVNET 012 trial (37 baseline samples collected near the time of delivery and 135 follow-up samples collected 3, 4 or 5 years later). Nineteen of 51 women were also pregnant at the time of one or more of the follow-up visits. The BED assay was performed according to the manufacturer's instructions. The avidity assay was performed using a Genetic Systems HIV-1/HIV-2 + O EIA using 0.1M diethylamine as the chaotropic agent.During the HIVNET 012 follow-up study, there was no difference in normalized optical density values (OD-n) obtained with the BED assay or in the avidity test results (%) when women were pregnant (n = 20 results) compared to those obtained when women were not pregnant (n = 115; for BED: p = 0.9, generalized estimating equations model; for avidity: p = 0.7, Wilcoxon rank sum). In addition, BED and avidity results were almost exactly the same in longitudinal samples from the 18 women who were pregnant at only one study visit during the follow-up study (p = 0.6, paired t-test).These results from 51 Ugandan women suggest that any changes in the antibody response to HIV infection that occur during pregnancy are not sufficient to alter results obtained with the BED and avidity assays. Confirmation with larger studies and with other HIV subtypes is needed

Reconstructing 800 years of summer temperatures in Scotland from tree rings

We thank The Carnegie Trust for the Universities of Scotland for providing funding for Miloš Rydval’s PhD. The Scottish pine network expansion has been an ongoing task since 2007 and funding must be acknowledged to the following projects: EU project ‘Millennium’ (017008-2), Leverhulme Trust project ‘RELiC: Reconstructing 8000 years of Environmental and Landscape change in the Cairngorms (F/00 268/BG)’ and the NERC project ‘SCOT2K: Reconstructing 2000 years of Scottish climate from tree rings (NE/K003097/1)’.This study presents a summer temperature reconstruction using Scots pine tree-ring chronologies for Scotland allowing the placement of current regional temperature changes in a longer-term context. ‘Living-tree’ chronologies were extended using ’subfossil’ samples extracted from nearshore lake sediments resulting in a composite chronology > 800 years in length. The North Cairngorms (NCAIRN) reconstruction was developed from a set of composite blue intensity high-pass and ring-width low-pass chronologies with a range of detrending and disturbance correction procedures. Calibration against July-August mean temperature explains 56.4% of the instrumental data variance over 1866-2009 and is well verified. Spatial correlations reveal strong coherence with temperatures over the British Isles, parts of western Europe, southern Scandinavia and northern parts of the Iberian Peninsula. NCAIRN suggests that the recent summer-time warming in Scotland is likely not unique when compared to multi-decadal warm periods observed in the 1300s, 1500s, and 1730s, although trends before the mid-16th century should be interpreted with some caution due to greater uncertainty. Prominent cold periods were identified from the 16th century until the early 1800s – agreeing with the so-called Little Ice Age observed in other tree-ring reconstructions from Europe - with the 1690s identified as the coldest decade in the record. The reconstruction shows a significant cooling response one year following volcanic eruptions although this result is sensitive to the datasets used to identify such events. In fact, the extreme cold (and warm) years observed in NCAIRN appear more related to internal forcing of the summer North Atlantic Oscillation.Publisher PDFPeer reviewe