Low umbilical artery vascular flow resistance and fetal outcome.

Background. An abnormally high [above mean + 2 standard deviations (SD)] umbilical artery (UA) pulsatility index (PI) indicates impaired fetal outcome, whereas the impact of an "abnormally" low (below mean -2 SD) PI is unknown. Methods. Perinatal outcome was compared between cases with a UA PI less than mean -2 SD (group A: high-risk cases selected from a database, n = 330; group B: unselected cases, n = 39) and unselected controls (group C) with a PI within mean ± 2 SD (n = 863) at Doppler velocimetry. Groups B and C were retrieved from a population-based sample. The unpaired t-test, Mann-Whitney U-test, chi2-test and Fisher's exact probability test were used for statistical comparisons with a two-tailed p < 0.05 being significant. Results. No significant differences were found between group A vs. group C and group B vs. group C regarding perinatal mortality, Apgar scores at 1, 5 or 10 min, or arterial or venous cord blood pH. Postterm pregnancy in group A carried no additional risk. For obvious reasons, operative delivery and neonatal intensive care were more common in group A than in group C, but no such differences were found between groups B and C. The mean birthweight was 3.7% higher in group B than in group C (p = 0.049). Conclusions. Deeming a UA PI below the lower reference limit as "abnormally" low is a statistical definition that was not reflected by a biological imperfection. Instead, a low UA PI promoted fetal growth

Epistemonikos and KSR Evidence

This article presents an evaluation of the two databases Epistemonikos and KSR Evidence, in the context of conducting evidence maps at the Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU). &nbsp; Methods: 36 systematic reviews included in published SBU Evidence Maps were used as a gold standard records (GSR). Title searches, as well as subject searches, were performed. Result: Title searches showed that Epistemonikos covers 97% of the GSR, and KSR Evidence covers 94%. Structured subject searches retrieved a part of the references, 58% from KSR Evidence and 48% from Epistemonikos. Conclusion: Epistemonikos and KSR Evidence are valuable resources for identifying systematic reviews, but not sufficient to replace any of the databases usually used for SBUs Evidence Maps. Mesh: Databases, Bibliographic; Information Storage and Retrieval; Review Literature as Topic; Evidence-Based Medicine &nbsp

Combining [(11)C]-AnxA5 PET imaging with serum biomarkers for improved detection in live mice of modest cell death in human solid tumor xenografts

BACKGROUND: In vivo imaging using Annexin A5-based radioligands is a powerful technique for visualizing massive cell death, but has been less successful in monitoring the modest cell death typically seen in solid tumors after chemotherapy. Here we combined dynamic positron emission tomography (PET) imaging using Annexin A5 with a serum-based apoptosis marker, for improved sensitivity and specificity in assessment of chemotherapy-induced cell death in a solid tumor model. METHODOLOGY/PRINCIPAL FINDINGS: Modest cell death was induced by doxorubicin in a mouse xenograft model with human FaDu head and neck cancer cells. PET imaging was based on (11)C-labeled Sel-tagged Annexin A5 ([(11)C]-AnxA5-ST) and a size-matched control. 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]-FDG) was utilized as a tracer of tissue metabolism. Serum biomarkers for cell death were ccK18 and K18 (M30 Apoptosense® and M65). Apoptosis in tissue sections was verified ex vivo for validation. Both PET imaging using [(11)C]-AnxA5-ST and serum ccK18/K18 levels revealed treatment-induced cell death, with ccK18 displaying the highest detection sensitivity. [(18)F]-FDG uptake was not affected by this treatment in this tumor model. [(11)C]-AnxA5-ST gave robust imaging readouts at one hour and its short half-life made it possible to perform paired scans in the same animal in one imaging session. CONCLUSIONS/SIGNIFICANCE: The combined use of dynamic PET with [(11)C]-AnxA5-ST, showing specific increases in tumor binding potential upon therapy, with ccK18/K18 serum measurements, as highly sensitive markers for cell death, enabled effective assessment of modest therapy-induced cell death in this mouse xenograft model of solid human tumors.VetenskapsrådetPublishe

Dimensioning a energy system for the new school in Jumkil : implementing geothermal heat pump, photovoltaic system and battery storage

The purpose of this study is to develop a modern and energy efficient system solution for a school in Jumkil, combining solar power, battery storage and geothermal heat pump system. By using models, simulations and available literature the study examines the dimensions of the included components for optimal coverage of the schools energy demand. The type of solar cells used is monochrystalline silicon solar cells and from an economical point of view, the installed effect should be 55 kWp. For such a solution the optimal battery capacity is 60 kWh and the battery technique used is vanadium redox flow battery. The vanadium redox flow battery technique is safe, have a long lifetime as well as a high depth of discharge. Implementing a smaller photovoltaic plant of 22 kWp reduces the need of battery capacity to 20 kWh. The battery is used for several applications, for example storage of the excess solar production and reducing the power peaks to eliminate expensive charge. An inverter heat pump of 79 kW is installed to cover the heat demand. The study also shows that a geothermal automatically controlled heat pump combined with floor heating is the best combination to reduce electricity costs annually. In interaction with the self-produced power and the vanadium redox flow battery the system allows the school to reduce their electricity consumption and thus the need of buying power from the grid decreases.Syftet med studien är att designa en modern och energieffektiv systemlösning för en skola i Jumkil där systemlösningen består av en solcellsanläggning, ett batterilager och en varvtalsstyrd värmepump. Genom att använda modeller, simuleringar och tillgänglig litteratur undersöker studien vilka dimensioner de olika komponenterna bör ha för att täcka skolans värme- och elbehov. Solcellerna som implementeras är av typen monokristallina kiselsolceller och från ett ekonomiskt perspektiv bör den installerade effekten vara 55 kWp. För en sådan lösning är den optimala batterikapaciteten 60 kWh och är av typen flödesbatteri. Fördelarna med flödesbatterier är att de är säkra, har lång livslängd och stort urladdningsdjup. Om en mindre solcellsanläggning med en installerad effekt på 22 kWp installeras kan batterikapaciteten reduceras till 20 kWh. Batteriet används bland annat för att lagra överskottet av producerad solel och för att kapa effekttoppar vilket minskar kostnaderna för inköpt el. Även en bergvärmepump med en effekt på 79 kW installeras för att täcka värmebehovet. Studien visar att kombinationen av bergvärmepumpen och golvvärme är det bästa sättet att minska årliga elkostnader. Tillsammans med den egenproducerade elen och flödesbatteriet kan skolan minska sin elförbrukning och på så sätt minska behovet av att köpa el från nätet

Toxicity and health effects of ultrafine particles: Towards an understanding of the relative impacts of different transport modes

Exposure to particulate matter (PM) has been associated with a wide range of adverse health effects, but it is still unclear how particles from various transport modes differ in terms of toxicity and associations with different human health outcomes. This literature review aims to summarize toxicological and epidemiological studies of the effect of ultrafine particles (UFPs), also called nanoparticles (NPs, <100 nm), from different transport modes with a focus on vehicle exhaust (particularly comparing diesel and biodiesel) and non-exhaust as well as particles from shipping (harbor), aviation (airport) and rail (mainly subway/underground). The review includes both particles collected in laboratory tests and the field (intense traffic environments or collected close to harbor, airport, and in subway). In addition, epidemiological studies on UFPs are reviewed with special attention to studies aimed at distinguishing the effects of different transport modes. Results from toxicological studies indicate that both fossil and biodiesel NPs show toxic effects. Several in vivo studies show that inhalation of NPs collected in traffic environments not only impacts the lung, but also triggers cardiovascular effects as well as negative impacts on the brain, although few studies compared NPs from different sources. Few studies were found on aviation (airport) NPs, but the available results suggest similar toxic effects as traffic-related particles. There is still little data related to the toxic effects linked to several sources (shipping, road and tire wear, subway NPs), but in vitro results highlighted the role of metals in the toxicity of subway and brake wear particles. Finally, the epidemiological studies emphasized the current limited knowledge of the health impacts of source-specific UFPs related to different transport modes. This review discusses the necessity of future research for a better understanding of the relative potencies of NPs from different transport modes and their use in health risk assessment.This research was supported by the European Commision's Horizon 2020 research and innovation programme: nPETS (grant agreement No 954377, https://www.npets-project. eu/) aimed at studying the sub 100 nm particles emitted from transport.Peer reviewe

Novel standards in the measurement of rat insulin granules combining electron microscopy, high-content image analysis and in silico modelling

Knowledge of number, size and content of insulin secretory granules is pivotal for understanding the physiology of pancreatic beta cells. Here we re-evaluated key structural features of rat beta cells, including insulin granule size, number and distribution as well as cell size

Multivesicular exocytosis in rat pancreatic beta cells

AIMS/HYPOTHESIS: To establish the occurrence, modulation and functional significance of compound exocytosis in insulin-secreting beta cells. METHODS: Exocytosis was monitored in rat beta cells by electrophysiological, biochemical and optical methods. The functional assays were complemented by three-dimensional reconstruction of confocal imaging, transmission and block face scanning electron microscopy to obtain ultrastructural evidence of compound exocytosis. RESULTS: Compound exocytosis contributed marginally (&lt;5% of events) to exocytosis elicited by glucose/membrane depolarisation alone. However, in beta cells stimulated by a combination of glucose and the muscarinic agonist carbachol, 15-20% of the release events were due to multivesicular exocytosis, but the frequency of exocytosis was not affected. The optical measurements suggest that carbachol should stimulate insulin secretion by ∼40%, similar to the observed enhancement of glucose-induced insulin secretion. The effects of carbachol were mimicked by elevating [Ca(2+)](i) from 0.2 to 2 μmol/l Ca(2+). Two-photon sulforhodamine imaging revealed exocytotic events about fivefold larger than single vesicles and that these structures, once formed, could persist for tens of seconds. Cells exposed to carbachol for 30 s contained long (1-2 μm) serpentine-like membrane structures adjacent to the plasma membrane. Three-dimensional electron microscopy confirmed the existence of fused multigranular aggregates within the beta cell, the frequency of which increased about fourfold in response to stimulation with carbachol. CONCLUSIONS/INTERPRETATION: Although contributing marginally to glucose-induced insulin secretion, compound exocytosis becomes quantitatively significant under conditions associated with global elevation of cytoplasmic calcium. These findings suggest that compound exocytosis is a major contributor to the augmentation of glucose-induced insulin secretion by muscarinic receptor activation

The Cell Adhesion Molecule “CAR” and Sialic Acid on Human Erythrocytes Influence Adenovirus In Vivo Biodistribution

Although it has been known for 50 years that adenoviruses (Ads) interact with erythrocytes ex vivo, the molecular and structural basis for this interaction, which has been serendipitously exploited for diagnostic tests, is unknown. In this study, we characterized the interaction between erythrocytes and unrelated Ad serotypes, human 5 (HAd5) and 37 (HAd37), and canine 2 (CAV-2). While these serotypes agglutinate human erythrocytes, they use different receptors, have different tropisms and/or infect different species. Using molecular, biochemical, structural and transgenic animal-based analyses, we found that the primary erythrocyte interaction domain for HAd37 is its sialic acid binding site, while CAV-2 binding depends on at least three factors: electrostatic interactions, sialic acid binding and, unexpectedly, binding to the coxsackievirus and adenovirus receptor (CAR) on human erythrocytes. We show that the presence of CAR on erythrocytes leads to prolonged in vivo blood half-life and significantly reduced liver infection when a CAR-tropic Ad is injected intravenously. This study provides i) a molecular and structural rationale for Ad–erythrocyte interactions, ii) a basis to improve vector-mediated gene transfer and iii) a mechanism that may explain the biodistribution and pathogenic inconsistencies found between human and animal models