The choice of indicators influences conclusions about the educational gradient of sex-specific alcohol consumption

There has been considerable public interest in reports on harmful alcohol consumption of higher educated females. This study assesses the robustness of this finding with representative German data using ten different indicators of alcohol consumption. This cross-sectional study used data of the Epidemiological Survey on Substance Abuse from 2012. 4,225 females and 3,239 males represent the German population aged 18-64. It presents ten indicators of alcohol consumption by sex and education and provides group specific means and 95 %-confidence intervals. The main results are: (1) Higher educated males and females are drinking alcohol more frequently than lower educated males and females. (2) When drinking, higher educated males and females tend to drink less alcohol than lower educated males and females. (3) Only when using an indicator for hazardous alcohol consumption with different thresholds for males and females, the results indicate a pattern that significantly exposes hazardous alcohol consumption in the group of higher educated females. Concerning the choice of indicators, this study shows that sex-specific threshold-based indicators of alcohol consumption may lead to different conclusions as the majority of other indicators

Developing a Medical Institution Management System through Promoting Social Accountability

The paper regards the implementation of social accountability principles into the system of medical institution management as the target of research. The process of personnel management is viewed as its research subject. The paper aims to develop the system of incentives for medical institution personnel based on the principles of social accountability. The research methods and tools applied in the study are analysis of content and internal enterprise documentation, staff member interviews and statistical methods of data processing. The expected research outcome is the implementation phase of the social accountability management system resulted in the development of the Code of corporate conduct. The article advocates the view, that the Code of Conduct should be based on the diagnosis of the state of corporate culture and motivate employees of the organization. The management team of medical institution can set their own social and reasonable quality management system, which will enable it to promote and involve staff in the process of improvement

Astrocyte mediated modulation of blood-brain barrier permeability does not correlate with a loss of tight junction proteins from the cellular contacts

In the central nervous system (CNS) complex endothelial tight junctions (TJs) form a restrictive paracellular diffusion barrier, the blood-brain barrier (BBB). Pathogenic changes within the CNS are frequently accompanied by the loss of BBB properties, resulting in brain edema. In order to investigate whether BBB leakiness can be monitored by a loss of TJ proteins from cellular borders, we used an in vitro BBB model where brain endothelial cells in co-culture with astrocytes form a tight permeability barrier for 3H-inulin and 14C-sucrose. Removal of astrocytes from the co-culture resulted in an increased permeability to small tracers across the brain endothelial cell monolayer and an opening of the TJs to horseradish peroxidase as detected by electron microscopy. Strikingly, opening of the endothelial TJs was not accompanied by any visible change in the molecular composition of endothelial TJs as junctional localization of the TJ-associated proteins claudin-3, claudin-5, occludin, ZO-1 or ZO-2 or the adherens junction-associated proteins β-catenin or p120cas did not change. Thus, opening of BBB TJs is not readily accompanied by the complete loss of the junctional localization of TJ protein

A potent and selective inhibitor for the modulation of MAGL activity in the neurovasculature.

Chronic inflammation and blood-brain barrier dysfunction are key pathological hallmarks of neurological disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Major drivers of these pathologies include pro-inflammatory stimuli such as prostaglandins, which are produced in the central nervous system by the oxidation of arachidonic acid in a reaction catalyzed by the cyclooxygenases COX1 and COX2. Monoacylglycerol lipase hydrolyzes the endocannabinoid signaling lipid 2-arachidonyl glycerol, enhancing local pools of arachidonic acid in the brain and leading to cyclooxygenase-mediated prostaglandin production and neuroinflammation. Monoacylglycerol lipase inhibitors were recently shown to act as effective anti-inflammatory modulators, increasing 2-arachidonyl glycerol levels while reducing levels of arachidonic acid and prostaglandins, including PGE2 and PGD2. In this study, we characterized a novel, highly selective, potent and reversible monoacylglycerol lipase inhibitor (MAGLi 432) in a mouse model of lipopolysaccharide-induced blood-brain barrier permeability and in both human and mouse cells of the neurovascular unit: brain microvascular endothelial cells, pericytes and astrocytes. We confirmed the expression of monoacylglycerol lipase in specific neurovascular unit cells in vitro, with pericytes showing the highest expression level and activity. However, MAGLi 432 did not ameliorate lipopolysaccharide-induced blood-brain barrier permeability in vivo or reduce the production of pro-inflammatory cytokines in the brain. Our data confirm monoacylglycerol lipase expression in mouse and human cells of the neurovascular unit and provide the basis for further cell-specific analysis of MAGLi 432 in the context of blood-brain barrier dysfunction caused by inflammatory insults

Synthetic α-Helical Peptides as Potential Inhibitors of the ACE2 SARS-CoV-2 Interaction

During viral cell entry, the spike protein of SARS-CoV-2 binds to the α1-helix motif of human angiotensin-converting enzyme 2 (ACE2). Thus, alpha-helical peptides mimicking this motif may serve as inhibitors of viral cell entry. For this purpose, we employed the rigidified diproline-derived module ProM-5 to induce α-helicity in short peptide sequences inspired by the ACE2 α1-helix. Starting with Ac-QAKTFLDKFNHEAEDLFYQ-NH2 as a relevant section of α1, a series of peptides, N-capped with either Ac-βHAsp-[ProM-5] or Ac-βHAsp-PP, were prepared and their α-helicities were investigated. While ProM-5 clearly showed a pronounced effect, an even increased degree of helicity (up to 63 %) was observed in sequences in which non-binding amino acids were replaced by alanine. The binding affinities of the peptides towards the spike protein, as determined by means of microscale thermophoresis (MST), revealed only a subtle influence of the α-helical content and, noteworthy, led to the identification of an Ac-βHAsp-PP-capped peptide displaying a very strong binding affinity (KD=62 nM)

ПРИНЦИПИ ПЛАНУВАННЯ ТА ОРГАНІЗАЦІЇ ІННОВАЦІЙНОЇ ДІЯЛЬНОСТІ НА ВУГІЛЬНИХ ШАХТАХ

Розглянуто особливості галузевого планування та організації виробництва як фактора, що впливає на інноваційну діяльність вугільних підприємств, напрямки планування та оцінки економічної ефективності інновацій у вугільному виробництві, питання формування звітності впровадження іннова-цій та використання результатів його аналізу. The article focuses on the peculiarities of the branch planning and organisation of manufacture as the factor, which influences the innovation activity of coal mining enterprises. The article also deals with planning and evaluation of economic efficiency of the innovations in coal industry. It also covers the issues of reporting on the introduction of innovations and applying the results of its analysis

Brain endothelial tricellular junctions as novel sites for T cell diapedesis across the blood–brain barrier

The migration of activated T cells across the blood-brain barrier (BBB) is a critical step in central nervous system (CNS) immune surveillance and inflammation. Whereas T cell diapedesis across the intact BBB seems to occur preferentially through the BBB cellular junctions, impaired BBB integrity during neuroinflammation is accompanied by increased transcellular T cell diapedesis. The underlying mechanisms directing T cells to paracellular versus transcellular sites of diapedesis across the BBB remain to be explored. By combining in vitro live-cell imaging of T cell migration across primary mouse brain microvascular endothelial cells (pMBMECs) under physiological flow with serial block-face scanning electron microscopy (SBF-SEM), we have identified BBB tricellular junctions as novel sites for T cell diapedesis across the BBB. Downregulated expression of tricellular junctional proteins or protein-based targeting of their interactions in pMBMEC monolayers correlated with enhanced transcellular T cell diapedesis, and abluminal presence of chemokines increased T cell diapedesis through tricellular junctions. Our observations assign an entirely novel role to BBB tricellular junctions in regulating T cell entry into the CNS. This article has an associated First Person interview with the first author of the paper

Detector Systems Engineering for Extremely Large Instruments

The scientific detector systems for the ESO ELT first-light instruments, HARMONI, MICADO, and METIS, together will require 27 science detectors: seventeen 2.5 $\mu$m cutoff H4RG-15 detectors, four 4K x 4K 231-84 CCDs, five 5.3 $\mu$m cutoff H2RG detectors, and one 13.5 $\mu$m cutoff GEOSNAP detector. This challenging program of scientific detector system development covers everything from designing and producing state-of-the-art detector control and readout electronics, to developing new detector characterization techniques in the lab, to performance modeling and final system verification. We report briefly on the current design of these detector systems and developments underway to meet the challenging scientific performance goals of the ELT instruments.Comment: Proceedings of the SPIE Astronomical Telescopes and Instrumentation Conference 202

The effect of cartilage and bone density of mushroom-shaped, photooxidized, osteochondral transplants: an experimental study on graft performance in sheep using transplants originating from different species

BACKGROUND: Differences in overall performance of osteochondral photooxidized grafts were studied in accordance of their species origin and a new, more rigorous cleansing procedure using alcohol during preparation. METHODS: Photooxidized mushroom-shaped grafts of bovine, ovine, human and equine origin were implanted in the femoral condyles of 32 sheep (condyles: n = 64). No viable chondrocytes were present at the time of implantation. Grafts were evaluated at 6 months using plastic embedded sections of non-decalcified bone and cartilage specimens. Graft incorporation, the formation of cyst-like lesions at the base of the cartilage junction as well as cartilage morphology was studied qualitatively, semi-quantitatively using a score system and quantitatively by performing histomorphometrical measurements of percentage of bone and fibrous tissue of the original defects. For statistical analysis a factorial analysis of variance (ANOVA- test) was applied. RESULTS: Differences of graft performance were found according to species origin and cleansing process during graft preparation. According to the score system cartilage surface integrity was best for equine grafts, as well as dislocation or mechanical stability. The equine grafts showed the highest percentage for bone and lowest for fibrous tissue, resp. cystic lesions. The new, more rigorous cleansing process decreased cartilage persistence and overall graft performance. CONCLUSION: Performance of grafts from equine origin was better compared to bovine, ovine and human grafts. The exact reason for this difference was not proven in the current study, but could be related to differences in density of cartilage and subchondral bone between species