Induction of VEGF and VEGF receptor gene expression by hypoxia: Divergent regulation in vivo and in vitro

Induction of VEGF and VEGF receptor gene expression by hypoxia: Divergent regulation in vivo and in vitro. This study examined the expression of EPO,VEGF and VEGF receptor gene under conditions of reduced oxygen supply in primary cultures of rat hepatocytes, and compared it with the expression of these genes in hypoxic rat livers in vivo. To this end we exposed male Sprague-Dawley rats to hypoxia (10% and 8% O2), carbon monoxide (0.1% CO) or injected cobalt chloride (60 mg/kg CoCl2) subcutaneously. For the in vitro experiments we used primary cultures of rat hepatocytes which were kept at high (20% O2) and low (1% O2) oxygen tensions for three hours. The EPO mRNA was up-regulated by hypoxia in vitro and in vivo about 10-fold. The VEGF mRNA was up-regulated fivefold in the hepatocytes only, whereas the in vivo mRNA levels remained unchanged. The mRNA levels of flt-1 were up-regulated threefold by 8% O2 in livers, dependent on the strength of hypoxia (10% caused no changes in flt-1 gene expression) and on the kind of hypoxic stimulus (8% O2 was as effective as 0.1% CO and more effective than cobalt). The mRNA levels of flk-1/KDR and flt-4 remained unchanged in the liver. In vitro there were no changes in the mRNA levels of flt-1, flt-4 and flk-1/KDR. Consequently, the in vivo regulation of VEGF, which might be modulated by induction of flt-1 receptor gene expression, differs from the in vitro cell culture situation and might be different from the EPO regulationin viv

Repetition of attempted suicide among immigrants in Europe

Objectives: To compare frequencies of suicide attempt repetition in immigrants and local European populations, and the timing of repetition in these groups. Method: Data from 7 European countries, comprising 10 574 local and 3032 immigrant subjects, were taken from the World Health Organization European Multicentre Study on Suicidal Behaviour and the ensuing Monitoring Suicidal Behaviour in Europe (commonly referred to as MONSUE) project. The relation between immigrant status and repetition of suicide attempt within 12-months following first registered attempt was analyzed with binary logistic regression, controlling for sex, age, and method of attempt. Timing of repetition was controlled for sex, age, and the recommended type of aftercare. Results: Lower odds of repeating a suicide attempt were found in Eastern European (OR 0.50; 95% CI 0.41 to 0.61, P < 0.001) and non-European immigrants (OR 0.68; 95% CI 0.51 to 0.90, P < 0.05), compared with the locals. Similar patterns were identified in the sex-specific analysis. Eastern European immigrants tended to repeat their attempt much later than locals (OR 0.58; 95% CI 0.35 to 0.93, P < 0.05). In general, 32% of all repetition occurred within 30 days. Repetition tended to decrease with age and was more likely in females using harder methods in their index attempt (OR 1.29; 95% CI 1.08 to 1.54, P < 0.01). Large variations in the general repetition frequency were identified between the collecting centres, thus influencing the results. Conclusions: The lower repetition frequencies in non-Western immigrants, compared with locals, in Europe stands in contrast to their markedly higher tendency to attempt suicide in general, possibly pointing to situational stress factors related to their suicidal crisis that are less persistent over time. Our findings also raise the possibility that suicide attempters and repeaters constitute only partially overlapping populations

Investigation of the joining zone formation of impact extruded hybrid components by varied forming sequence and partial cooling

Hybrid material concepts enable the combination of beneficial properties of different materials to extend the limited potential of monolithic components. When it comes to steel and aluminium, a wear-resistant and a lightweight metal are combined to produce a weight-reduced high-performance component with load-adapted areas. A method to create hybrid gear shafts is a novel approach called Tailored Forming. The process chain consists of joining e. g. by friction welding and subsequent impact extrusion under elevated temperature. Before forming, an axial temperature gradient is set in the serial arranged semi-finished products to adjust the different yield stresses of the dissimilar materials through induction heating of the steel part. The subsequent forming is intended to positively influence the joining zone thermo-mechanically and geometrically. However, prior work indicated a limitation of the influence on the joining zone in forward rod extrusion. Therefore, approaches are being researched that enable a stronger formation of the joining zone geometry to influence the resulting bond qualities through surface enlargement. A forward rod extrusion process of friction welded hybrid semi-finished products made of 20MnCr5 (AISI 5120H) combined with EN AW-6082 (AA6082) was carried out experimentally. Complementary to prior investigations, in which mainly the aluminium section was reduced through the die angle followed by the steel, the forming sequence of the materials was reversed to increase the joining zone surface with variation of the forming path. Additionally, a cooling of the aluminium side was realized through an immersion cooling to adjust maximum temperature gradients and further equalize the different yield stresses. Hardness tests, metallographic and SEM images of cross-sections were taken to evaluate the bond quality with regard to the temperature influence, joining zone formation, occurring defects and the resulting intermetallic compound (IMC). Impact extrusion with initially steel formed followed by aluminium resulted in a spherical formation of the joining zone and consequently in greater surface area, but also lead to partial defects in the IMC. The partial cooling of the aluminium allowed higher temperature gradients to be set, thus reducing defects through improved material flow in the joining zone

Mind the gap: Lücke in der Masern-IgG-Antikörper-Prävalenz bei Kindern unter zwei Jahren in Niedersachsen und Bremen

Säuglinge und Kinder bis zum zweiten Lebensjahr sind eine besonders vulnerable Gruppe für Maserninfektionen. Für sie werden in Deutschland gegenüber anderen Altersgruppen zwei- bis 40-fach höhere Erkrankungsinzidenzen beobachtet und sie sind häufiger von schweren, komplikationsbehafteten Verläufen betroffen. Gegenüber Säuglingen, deren Mütter eine Masernimmunität aufgrund einer Masernwildvirusinfektion erworben haben, ist der Nestschutz bei Säuglingen von ausschließlich durch die Impfung immunisierten Müttern verkürzt. Detaillierte Seroprävalenzdaten für unter Zweijährige lagen in Deutschland jedoch bisher nicht vor. In der vorliegenden Studie wurden Masern-IgG-Antikörperbestimmungen aus den Jahren 2006 bis 2019 von 1.523 Kindern unter zwei Jahren nach Altersgruppen stratifiziert ausgewertet. Es zeigte sich, dass spätestens nach dem 9. Lebensmonat keine maternalen Masern-IgG-Antikörper mehr nachweisbar sind. Die Ergebnisse stützen somit die derzeitige Empfehlung, bei erhöhtem Exposi-tionsrisiko den Zeitpunkt der ersten MMR-Impfung auf neun Monate vorzuverlegen und unterstreichen die Notwendigkeit, Impfquoten insbesondere bei Kleinkindern, aber auch bei jungen Erwachsenen zu steigern.Peer Reviewe

Low-Temperature Phase of the Cd2_2Re2_2O7_7 Superconductor: Ab initio Phonon Calculations and Raman Scattering

Using an {\it ab initio} approach, we report a phonon soft mode in the tetragonal structure described by the space group $I4_{1}22$ of the $1$ K $5d$ superconductor Cd$_2$Re$_2$O$_7$. It induces an orthorhombic distortion to a crystal structure described by the space group $F222$ which hosts the superconducting state. This new phase has a lower total energy than the other known crystal structures of Cd$_2$Re$_2$O$_7$. Comprehensive temperature dependent Raman scattering experiments on isotope enriched samples, $^{116}$Cd$_2$Re$_2{^{18}}$O$_7$, not only confirm the already known structural phase transitions but also allow us to identify a new characteristic temperature regime around $\sim 80$ K, below which the Raman spectra undergo remarkable changes with the development of several sharp modes and mode splitting. Together with the results of the \textit{ab initio} phonon calculations we take these observations as strong evidence for another phase transition to a novel low-temperature crystal structure of Cd$_2$Re$_2$O$_7$.Comment: 7 pages, 8 figure

Gender distribution of suicide attempts among immigrant groups in European countries—an international perspective

Background: Studies report high rates of suicide attempts for female immigrants. This study assesses variations in the distribution of suicide attempts across gender in immigrant and non-immigrant groups in Europe. Method: Data on 64 native and immigrant groups, including 17 662 local and 3755 immigrant person-cases collected, between 1989 and 2003, in 24 million person-years were derived from the WHO/EURO Multicentre Study on Suicidal Behaviour. Female-to-male ratios of suicide attempt rates (SARs) were calculated for all groups. Results: The cases were combined into four major categories: hosts; European and other Western immigrants; non-European immigrants; and Russian immigrants. The non-European immigrants included higher female SARs than the Europeans, both hosts and immigrants. Unlike the other groups, the majority of suicide attempters among the Russian immigrants in Estonia and Estonian hosts were male. This was also true for immigrants from Curaçao, Iran, Libya and Sri Lanka. When the single groups with a male majority were excluded, the correlation between female and male SARs was relatively high among the European immigrants (r = 0.74, P < 0.0005) and lower among the non-European immigrants (r = 0.55, P < 0.03). Generalized estimating equation analysis yielded a highly significant difference (P < 0.0005) in gender ratios of suicide attempts between hosts (ratio 1.52) and both non-European immigrants (ratio 2.32) and Russian immigrants (0.68), but not the European immigrants. Conclusions: The higher suicide attempt rates in non-European immigrant females compared with males may be indicative of difficulties in the acculturation processes in Europe. Further understanding of factors underlying suicidal behaviour in immigrant and minority groups is necessary for planning effective prevention strategie

Immigration and recommended care after a suicide attempt in Europe: equity or bias?

This report describes the investigation of care recommendations in the medical system across European countries to immigrants who attempted suicide. Data from seven European countries with 8865 local and 2921 immigrant person-cases were derived from the WHO/EURO Multicentre Study on Suicidal Behaviour and ensuing MONSUE (Monitoring Suicidal Behaviour in Europe) project. The relationship between immigrant status and type of aftercare recommended was analysed with binary logistic regression, adjusting for gender, age, method of attempt and the Centre collecting the data. Clear disparities were identified in the care recommendation practices toward immigrants, compared with hosts, over and above differing policies by the European Centre

A bipolar taxonomy of adult human brain sulcal morphology related to timing of fetal sulcation and trans-sulcal gene expression gradients

We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (N=34,725; 45-82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented also by the bipolar distribution of sulci on a linear-to-complex dimension. Linear sulci were more heritable and typically located in unimodal cortex; complex sulci were less heritable and typically located in heteromodal cortex. Aligning these results with an independent fetal brain MRI cohort (N=228; 21-36 gestational weeks), we found that linear sulci formed earlier, and the earliest and latest-forming sulci had the least between-adult variation. Using high-resolution maps of cortical gene expression, we found that linear sulcation is mechanistically underpinned by trans-sulcal gene expression gradients enriched for developmental processes.</p

Hydrocortisone therapy for patients with septic shock

Background Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin. Methods In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days; the dose was then tapered during a 6-day period. At 28 days, the primary outcome was death among patients who did not have a response to a corticotropin test. Results Of the 499 patients in the study, 233 (46.7%) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone group and 36.1% in the placebo group, P=0.69) or between those who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P=1.00). At 28 days, 86 of 251 patients in the hydrocortisone group (34.3%) and 78 of 248 patients in the placebo group (31.5%) had died (P=0.51). In the hydrocortisone group, shock was reversed more quickly than in the placebo group. However, there were more episodes of superinfection, including new sepsis and septic shock. Conclusions Hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed. (ClinicalTrials.gov number, NCT00147004 [ClinicalTrials.gov] .)Peer reviewedPublisher PD

Author Correction: Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders

An amendment to this paper has been published and can be accessed via a link at the top of the paper