Suchergebnisse

Verapamil is a Ca2+ channel blocker and is highly prescribed as an anti-anginal, antiarrhythmic and antihypertensive drug. Ketamine, an antagonist of the Ca2+-permeable N-methyl-D-aspartate-type glutamate receptors, is a pediatric anesthetic. Previously we have shown that acetyl L-carnitine (ALCAR) reverses ketamine-induced attenuation of heart rate and neurotoxicity in zebrafish embryos. Here, we used 48 h post-fertilization zebrafish embryos that were exposed to relevant drugs for 2 or 4 h. Heart beat and overall development were monitored in vivo. In 48 h post-fertilization embryos, 2 mM ketamine reduced heart rate in a 2 or 4 h exposure and 0.5 mM ALCAR neutralized this effect. ALCAR could reverse ketamine's effect, possibly through a compensatory mechanism involving extracellular Ca2+ entry through L-type Ca2+ channels that ALCAR is known to activate. Hence, we used verapamil to block the L-type Ca2+ channels. Verapamil was more potent in attenuating heart rate and inducing morphological defects in the embryos compared to ketamine at specific times of exposure. ALCAR reversed cardiotoxicity and developmental toxicity in the embryos exposed to verapamil or verapamil plus ketamine, even in the presence of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, an inhibitor of intracellular Ca2+ release suggesting that ALCAR acts via effectors downstream of Ca2+. In fact, ALCAR's protective effect was blunted by oligomycin A, an inhibitor of adenosine triphosphate synthase that acts downstream of Ca2+ during adenosine triphosphate generation. We have identified, for the first time, using in vivo studies, a downstream effector of ALCAR that is critical in abrogating ketamine- and verapamil-induced developmental toxicities. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Tuberculosis- (TB) associated stigma is a well-documented phenomenon with various factors, both individual and societal, manifesting its role in shaping health-seeking behavior and contributing to suboptimal TB care in Pakistan. The objective of this study was to assess TB-related knowledge and perceived stigma among community members. This was a cross-sectional survey using a convenience sample of 183 individuals recruited between October and December 2017. A validated stigma measurement tool developed by Van Rie et al. was adapted. Data was analyzed using SPSS version 20.0. A clear majority was aware that TB is curable disease and that it is transmitted by coughing. However, respondents also thought that TB spread through contaminated food, sharing meals, sharing utensils, and by having sexual intercourse with a TB patient. In addition, females, unemployed, and persons having less than six years of education were also more likely to associate stigma with TB. We found an association between the lack of knowledge about TB and perceived stigma. This study highlights the need for improved TB-related education among communities.

The global COVID-19 pandemic has brought unprecedented disruption to lives and livelihoods around the world. These disruptions have brought into sharp focus experiences of vulnerability but also, at times, evidence of resilience as people and institutions gear up to respond to the crisis. Drawing on intensive qualitative enquiry in 16 villages of Himalayan India and Nepal, this paper documents both dark and bright spots from the early days of the pandemic. We find intense experiences of fear and uncertainty, heightened food insecurity, and drastic reductions in livelihood opportunities. However, we also find a wide range of individual and collective responses as well as a patchwork of policy support mechanisms that have provided at least some measure of basic security. Local elected governments have played a critical role in coordinating responses and delivering social support, however the nature of their actions varies as a result of different institutional arrangements and state support systems in the two countries. Our findings highlight the changing nature of vulnerability in the present era, as demographic shifts, growing off-farm employment and dependence on remittances, and increasing market integration have all brought about new kinds of exposure to risk for rural populations in the context of the present disruption and beyond. Most importantly, our research shows the critical importance of strong systems of state support for protecting basic well-being in times of crises. Based on these findings, we argue that there is a need for greater knowledge of how local institutions work in tandem with a broader set of state support mechanisms to generate responses for urgent challenges; such knowledge holds the potential to develop governance systems that are better able to confront diverse shocks that households face, both now and in the future. (C) 2020 The Author(s). Published by Elsevier Ltd.

Recently, the application of renewable energy sources (RESs) for power distribution systems is growing immensely. This advancement brings several advantages, such as energy sustainability and reliability, easier maintenance, cost-effective energy sources, and ecofriendly. The application of RESs in maritime systems such as port microgrids massively improves energy efficiency and reduces the utilization of fossil fuels, which is a serious threat to the environment. Accordingly, ports are receiving several initiatives to improve their energy efficiency by deploying different types of RESs based on the power electronic converters. This paper conducts a systematic review to provide cutting-edge state-of-the-art on the modern electrification and infrastructure of seaports taking into account some challenges such as the environmental aspects, energy efficiency enhancement, renewable energy integration, and legislative and regulatory requirements. Moreover, the technological methods, including electrifications, digitalization, onshore power supply applications, and energy storage systems of ports, are addressed. Furthermore, details of some operational strategies such as energy-aware operations and peak-shaving are delivered. Besides, the infrastructure scheme to enhance the energy efficiency of modern ports, including port microgrids and seaport smart microgrids are delivered. Finally, the applications of nascent technologies in seaports are presented.

The placenta is a transient organ, essential for development and survival of the unborn fetus. It interfaces the body of the pregnant woman with the unborn child and secures transport of endogenous and exogenous substances. Maternal and fetal blood are thereby separated at any time, by the so-called placental barrier. Current in vitro approaches fail to model this multifaceted structure, therefore research in the field of placental biology is particularly challenging. The present study aimed at establishing a novel model, simulating placental transport and its implications on development, in a versatile but reproducible way. The basal membrane was replicated using a gelatin-based material, closely mimicking the composition and properties of the natural extracellular matrix. The microstructure was produced by using a high-resolution 3D printing method – the two-photon polymerization (2PP). In order to structure gelatin by 2PP, its primary amines and carboxylic acids are modified with methacrylamides and methacrylates (GelMOD-AEMA), respectively. High-resolution structures in the range of a few micrometers were produced within the intersection of a customized microfluidic device, separating the x-shaped chamber into two isolated cell culture compartments. Human umbilical-vein endothelial cells (HUVEC) seeded on one side of this membrane simulate the fetal compartment while human choriocarcinoma cells, isolated from placental tissue (BeWo B30) mimic the maternal syncytium. This barrier model in combination with native flow profiles can be used to mimic the microenvironment of the placenta, investigating different pharmaceutical, clinical and biological scenarios. As proof-of-principle, this bioengineered placental barrier was used for the investigation of transcellular transport processes. While high molecular weight substances did not permeate, smaller molecules in the size of glucose were able to diffuse through the barrier in a time-depended manner. We envision to apply this bioengineered placental barrier for pathophysiological research, where altered nutrient transport is associated with health risks for the fetus. ; Austrian Science Funds (FWF) ; European Union's Horizon 2020 ; European Research Council (ERC)