Methylglyoxal induces platelet hyperaggregation and reduces thrombus stability by activating PKC and inhibiting PI3K/Akt pathway

Diabetes is characterized by a dysregulation of glucose homeostasis and platelets from patients with diabetes are known to be hyper-reactive and contribute to the accelerated development of vascular diseases. Since many of the deleterious effects of glucose have been attributed to its metabolite methylgyloxal (MG) rather than to hyperglycemia itself, the aim of the present study was to characterize the effects of MG on platelet function. Washed human platelets were pre-incubated for 15 min with MG and platelet aggregation, adhesion on matrix-coated slides and signaling (Western blot) were assessed ex vivo. In vivo, the effect of MG on thrombus formation was determined using the FeCl3-induced carotid artery injury model. MG potentiated thrombin-induced platelet aggregation and dense granule release, but inhibited platelet spreading on fibronectin and collagen. In vivo, MG accelerated thrombus formation but decreased thrombus stability. At the molecular level, MG increased intracellular Ca2+ and activated classical PKCs at the same time as inhibiting PI3K/Akt and the β3-integrin outside-in signaling. In conclusion, these findings indicate that the enhanced MG concentration measured in diabetic patients can directly contribute to the platelet dysfunction associated with diabetes characterized by hyperaggregability and reduced thrombus stability

Starburst or AGN Dominance in Submillimetre-Luminous Candidate AGN?

It is widely believed that ultraluminous infrared (IR) galaxies and active galactic nuclei (AGN) activity are triggered by galaxy interactions and merging, with the peak of activity occurring at z~2, where submillimetre galaxies are thousands of times more numerous than local ULIRGs. In this evolutionary picture, submillimetre galaxies (SMGs) would host an AGN, which would eventually grow a black hole (BH) strong enough to blow off all of the gas and dust leaving an optically luminous QSO. To probe this evolutionary sequence we have focussed on the 'missing link' sources, which demonstrate both strong starburst (SB) and AGN signatures, in order to determine if the SB is the main power source even in SMGs when we have evidence that an AGN is present from their IRAC colours. The best way to determine if a dominant AGN is present is to look for their signatures in the mid-infrared with the Spitzer IRS, since often even deep X-ray observations miss identifying the presence of AGN in heavily dust-obscured SMGs. We present the results of our audit of the energy balance between star-formation and AGN within this special sub-population of SMGs -- where the BH has grown appreciably to begin heating the dust emission.Comment: 2 pages, 1 figure. To appear in "Hunting for the Dark: The Hidden Side of Galaxy Formation", Malta, 19-23 Oct. 2009, eds. V.P. Debattista and C.C. Popescu, AIP Conf. Ser., in pres

Real-Time MRI of Continent and Stress Incontinent Male Patients after Orthotopic Ileal Neobladder

Introduction: The aim of this study was to correlate anatomic differences with continence status in male patients after cystoprostatectomy and ileal neobladder using real-time magnetic resonance imaging. Patients and Methods: Anatomic differences of 14 male patients (7 daytime continent and 7 stress incontinent) with ileal neobladder were determined by measuring the orthogonal distance of the bladder neck to the pubococcygeal line (PCL) to correlate anatomic differences with continence status. Results: The median distance of the bladder neck to PCL was +5.4 mm in continent patients before voiding whereas in incontinent patients it was +2 mm (p = 0.012). During the Valsalva maneuver, the median distance in continent patients was +4 and in incontinent patients -3 mm (p = 0.003). At the end of micturition, the median distance was +2.3 mm in continent patients and -12 mm in incontinent patients (p = 0.002). Conclusions: The bladder neck in incontinent patients showed more pronounced mobility in relation to the PCL during micturition and the Valsalva maneuver as compared to continent patients. In addition, the ileal neobladder was positioned significantly lower in the pelvis of incontinent patients. These preliminary results suggest that a stable bladder neck may be an important factor to reach full continence in patients with ileal neobladder. Copyright (C) 2011 S. Karger AG, Base

Physicians' working conditions and job satisfaction : does hospital ownership in Germany make a difference?

Background: A growing number of German hospitals have been privatized with the intention of increasing cost effectiveness and improving the quality of health care. Numerous studies investigated what possible qualitative and economic consequences these changes issues might have on patient care. However, little is known about how this privatization trend relates to physicians' working conditions and job satisfaction. It was anticipated that different working conditions would be associated with different types of hospital ownership. To that end, this study's purpose is to compare how physicians, working for both public and privatized hospitals, rate their respective psychosocial working conditions and job satisfaction. Methods: The study was designed as a cross-sectional comparison using questionnaire data from 203 physicians working at German hospitals of different ownership types (private for-profit, public and private nonprofit). Results: The present study shows that several aspects of physicians' perceived working conditions differ significantly depending on hospital ownership. However, results also indicated that physicians' job satisfaction does not vary between different types of hospital ownership. Finally, it was demonstrated that job demands and resources are associated with job satisfaction, while type of ownership is not. Conclusion: This study represents one of a few studies that investigate the effect of hospital ownership on physicians work situation and demonstrated that the type of ownership is a potential factor accounting for differences in working conditions. The findings provide an informative basis to find solutions improving physicians' work at German hospitals

Scoliosis : density-equalizing mapping and scientometric analysis

Background: Publications related to scoliosis have increased enormously. A differentiation between publications of major and minor importance has become difficult even for experts. Scientometric data on developments and tendencies in scoliosis research has not been available to date. The aim of the current study was to evaluate the scientific efforts of scoliosis research both quantitatively and qualitatively. Methods: Large-scale data analysis, density-equalizing algorithms and scientometric methods were used to evaluate both the quantity and quality of research achievements of scientists studying scoliosis. Density-equalizing algorithms were applied to data retrieved from ISI-Web. Results: From 1904 to 2007, 8,186 items pertaining to scoliosis were published and included in the database. The studies were published in 76 countries: the USA, the U.K. and Canada being the most productive centers. The Washington University (St. Louis, Missouri) was identified as the most prolific institution during that period, and orthopedics represented by far the most productive medical discipline. "BRADFORD, DS" is the most productive author (146 items), and "DANSEREAU, J" is the author with the highest scientific impact (h-index of 27). Conclusion: Our results suggest that currently established measures of research output (i.e. impact factor, h-index) should be evaluated critically because phenomena, such as self-citation and co-authorship, distort the results and limit the value of the conclusions that may be drawn from these measures. Qualitative statements are just tractable by the comparison of the parameters with respect to multiple linkages. In order to obtain more objective evaluation tools, new measurements need to be developed

Short hairpin-loop-structured oligodeoxynucleotides reduce HSV-1 replication

The Herpes simplex virus (HSV) is known as an infectious agent and widespread in the human population. The symptoms of HSV infections can range from mild to life threatening, especially in immune-compromised individuals. HSV infections are commonly treated with the guanosine analogue Aciclovir, but reports of resistance are increasing. Efforts are made to establish single-stranded antisense oligodeoxynucleotides (as) and small interfering ribonucleic acids (siRNAs) for antiviral treatment. Recently, another class of short interfering nucleic acids, partially double-stranded hairpin loop-structured 54 mer oligodeoxynucleotides (ODNs), was shown to allow hydrolysis of HIV RNA by binding to the viral RNA. This leads to a substrate for the viral RNase H. To assess the potential of such ODNs for inhibition of HSV-1 replication, five partially double-stranded ODNs were designed based on the sequences of known siRNAs against HSV-1 with antiviral activity. Three of them are directed against early and two against leaky late genes. Primary human lung fibroblasts, MRC-5, and African green monkey kidney cells, Vero, were transfected with ODNs and subsequently infected. The effect on HSV-1 replication was determined by analyzing the virus titer in cell culture supernatants by quantitative PCR and plaque assays. An inhibitory effect was observed with all five selected ODNs, with two cases showing statistical significance in both cell types. The observed effect was sequence-specific and dose dependent. In one case the ODN was more efficient than a previously described siRNA directed against the same target site in the mRNA of UL5, a component of the helicase/primase complex. HSV-1 virions and ODNs can be applied simultaneously without transfection reagent, but at a 50-fold higher concentration to Vero cells with similar efficiencies. The results underline the potential of partially double-stranded hairpin loop-structured ODNs as antiviral agents

On the Fine Interior of Three-dimensional Canonical Fano Polytopes

The Fine interior $\Delta^{\text{FI}}$ of a $d$-dimensional lattice polytope $\Delta$ is a rational subpolytope of $\Delta$ which is important for constructing minimal birational models of non-degenerate hypersurfaces defined by Laurent polynomials with Newton polytope $\Delta$. This paper presents some computational results on the Fine interior of all $674,\!688$ three-dimensional canonical Fano polytopes.Comment: 27 pages, 7 figure

Das neue Gentechnikgesetz - ein Gentechnikverhinderungsgesetz?

In addition to existing juridical analyses of the new German act for genetic engineering, this article deals with an environmental economic assessment. It is examined what kind of external costs will arise by using/applying genetic engineering and how they will be allocated. Our focus is on the costs that explicitly evolve from the societal postulated coexistence of conventional/ organic farms and users of biotechnology. If the protection of the existing production is accepted, as postulated by politics, the new act internalizes the so called market losses relatively well. In this context, the design of precautionary duties that have to be still established by law is of utmost importance. To avoid the dangers of an excessive liability by the farmer, it is from an economic point of view a good alternative, if the producers of genetically modified crops take the responsibility for any litigation claims to farmers. Furthermore negotiations between neighbouring farms could be an option to keep the costs for damage prevention to a minimum. Erganzend zu den bereits vorliegenden juristischen Analysen des neuen deutschen Gentechnikgesetzes beschaftigt sich der vorliegende Artikel mit einer umweltokonomischen Beurteilung. Untersucht wird, welche externen Kosten bei der Nutzung der "Grunen Gentechnik" entstehen und wie sie auf die Beteiligten verteilt werden. Dabei liegt der Fokus auf den Kosten, die explizit fur die gesellschaftlich geforderte Koexistenz von konventionellen/ okologischen Betrieben und Nutzern der Gentechnik entstehen. Wird der politisch gesetzte estandsschutz fur die bestehenden Produktionssysteme akzeptiert, so zeigt sich, dass eine korrekte Internalisierung der so genannten Vermarktungsschaden relativ gut erreicht werden kann. In diesem Zusammenhang spielt jedoch die Ausgestaltung der Vorsorgepflichten, die noch in einer Rechtsverordnung zur Guten fachlichen Praxis festgeschrieben warden mussen, eine erhebliche Rolle. Um der Gefahr einer Ubermasshaftung durch Landwirte zu begegnen, ist aus okonomischer Sicht die Haftungsubernahme durch die Hersteller der gentechnisch veranderten Pflanzen eine gute Moglichkeit. Auch bieten sich Verhandlungslosungen zwischen benachbarten Landwirten an, um eine kostenminimale Vermeidung von Schaden zu erreichen. Schlusselworter: gentechnikgesetz, haftung, koexistenz, vermarktungsschadenact for genetic engineering, liability, coexistence, market loss, Agricultural and Food Policy, Research and Development/Tech Change/Emerging Technologies, K32, Q55,

Das neue Gentechnikgesetz Рein Gentechnikverhinderungsgesetz? Eine umwelțkonomische Analyse der haftungsrechtlichen Neuerungen im Gentechnikgesetz

In this article, legal consequences of the new German genetic engineering act are analyzed. In addition environmental economic analysis is presented of those parts of the act that introduce new litigation regulation to farmers. The different kinds of external costs arising from genetic engineering of plants and their allocation to different actors are considered. The paper focuses on the costs resulting from the postulated coexistence of conventional/organic farms and users of biotechnology. Excessive liability of farmers can be avoided, if the producers of genetically modified seeds accept any litigation claims against farmers. Furthermore, negotiations between neighbouring farms can be an option to keep the costs of damage prevention at reasonable levels.genetic engineering act, liability, coexistence, market loss, precautionary principle, Agricultural and Food Policy, Environmental Economics and Policy, Research and Development/Tech Change/Emerging Technologies, Risk and Uncertainty,

The ancient heritage of water ice in the solar system

Identifying the source of Earth's water is central to understanding the origins of life-fostering environments and to assessing the prevalence of such environments in space. Water throughout the solar system exhibits deuterium-to-hydrogen enrichments, a fossil relic of low-temperature, ion-derived chemistry within either (i) the parent molecular cloud or (ii) the solar nebula protoplanetary disk. Utilizing a comprehensive treatment of disk ionization, we find that ion-driven deuterium pathways are inefficient, curtailing the disk's deuterated water formation and its viability as the sole source for the solar system's water. This finding implies that if the solar system's formation was typical, abundant interstellar ices are available to all nascent planetary systems.Comment: 33 pages, 7 figures including main text and supplementary materials. Published in Scienc