Circulating proteoglycans and glycosaminoglycans during critical illness

The endothelial glycocalyx is the carbohydrate rich inner layer of the blood vessels. Important components of the glycocalyx are the proteoglycans with their attached glycosaminoglycans. At this location these molecules contribute to the adhesion and transport of leucocytes to inflamed tissue, the anticoagulation as well as the transport of fluid across the vessel wall. All these functions are disturbed during severe sepsis. The present thesis aims at determining if these molecules are increased in concentration of septic patients and/or if the blood levels provide additional information useful in the management of these patients. We found that circulating levels of glycosaminoglycans, and in particular heparan sulphate and hyaluronic acid, main glycosaminoglycans on the vessel wall, were higher in in septic shock patients compared to control patients. Furthermore, the concentration was higher in the patients that did not survive the disease. These results indicate that analysis may be useful and that the increased level is probably due to shedding from the glycocalyx. Severe haemorrhage is accompanied with development of a systemic inflammatory reaction. We found increased plasma levels of heparan sulphate during haemorrhagic shock in the rat, indicating damage to the glycocalyx. Treatment of the blood loss with fresh frozen plasma, albumin or Ringer’s acetate had no significant difference in the release of heparan sulphate. Transcapillary escape rate for albumin was not affected by bleeding, indicating that the induced damage to the glycocalyx was insufficient to affect the permeability. In a mixed cohort of intensive care patients circulating levels of the proteoglycans syndecan-1 was increased compared to controls. No difference was detected between patients with different underlying conditions. This indicates that syndecan-1 release is a general consequence of critical illness that probably has limited value as a marker in clinical practice

Publication of original research in urologic journals - a neglected orphan?

The pathophysiologic mechanisms behind urologic disease are increasingly being elucidated. The object of this investigation was to evaluate the publication policies of urologic journals during a period of progressively better understanding and management of urologic disease. Based on the ISI Web of Knowledge Journal Citation Reports and the PubMed database, the number and percentage of original experimental, original clinical, review or commentarial articles published between 2002–2010 in six leading urologic journals were analyzed. “British Journal of Urology International”, “European Urology”, “Urologic Oncology-Seminars and Original Investigations” (“Urologic Oncology”), “Urology”, “The Journal of Urology”, and “World Journal of Urology” were chosen, because these journals publish articles in all four categories. The publication policies of the six journals were very heterogeneous during the time period from 2002 to 2010. The percentage of original experimental and original clinical articles, related to all categories, remained the same in “British Journal of Urology International”, “Urologic Oncology”, “Urology” and “The Journal of Urology”. The percentage of experimental reports in “World Journal of Urology” between 2002–2010 significantly increased from 10 to 20%. A distinct elevation in the percentage of commentarial articles accompanied by a reduction of clinical articles became evident in “European Urology” which significantly correlated with a large increase in the journal’s impact factor. No clearly superior policy could be identified with regard to a general increase in the impact factors from all the journals. The publication policy of urologic journals does not expressly reflect the increase in scientific knowledge, which has occurred over the period 2002–2010. One way of increasing the exposure of urologists to research and expand the interface between experimental and clinical research, would be to enlarge the percentage of experimental articles published. There is no indication that such policy would be detrimental to a journal’s impact factor

Resistance after chronic application of the HDAC-inhibitor valproic acid is associated with elevated Akt activation in renal cell carcinoma in vivo

Targeted drugs have significantly improved the therapeutic options for advanced renal cell carcinoma (RCC). However, resistance often develops, negating the benefit of these agents. In the present study, the molecular mechanisms of acquired resistance towards the histone deacetylase (HDAC) inhibitor valproic acid (VPA) in a RCC in vivo model were investigated. NMRI:nu/nu mice were transplanted with Caki-1 RCC cells and then treated with VPA (200 mg/kg/day). Controls remained untreated. Based on tumor growth dynamics, the mice were divided into “responders” and “non-responders” to VPA. Histone H3 and H4 acetylation and expression of cell signaling and cell cycle regulating proteins in the RCC mouse tumors were evaluated by Western blotting. Tumor growth of VPA responders was significantly diminished, whereas that of VPA non-responders even exceeded control values. Cdk1, 2 and 4 proteins were strongly enhanced in the non-responders. Importantly, Akt expression and activity were massively up-regulated in the tumors of the VPA non-responders. Chronic application (12 weeks) of VPA to Caki-1 cells in vitro evoked a distinct elevation of Akt activity and cancer cells no longer responded with cell growth reduction, compared to the short 2 week treatment. We assume that chronic use of an HDAC-inhibitor is associated with (re)-activation of Akt, which may be involved in resistance development. Consequently, combined blockade of both HDAC and Akt may delay or prevent drug resistance in RCC

Al-Shabaab i Somalia

Efter Barré regimens fall 1991 kom de södra och centrala delarna av Somalia att regeras av lokala rövarband och klanrebeller. Parallellt bildades den islamska unionen al Ittihad al Islam (AIAI) som politisk motpol till den internationellt sammansatta övergångsregeringen bland annat FN och Afrikanska Unionen understött skapandet av under mitten av 1990talet. Delar av (AIAI) kom att transformeras till en lokalt förankrad islamistisk organisation av domstolar, ICU, vars mål var att upprätta en strikt islamistisk stat grundad i nationalism. Allt eftersom situationen i Somalia fortsatte att försämras ökade den internationella närvaron både i form av militära interventioner och fredsbevarande personal samtidigt som al-Qaida gjorde närmanden för upprättanet av ett sammarbete med ICU. Paradoxen av internationell sekulär närvaro i en stat där en islamistisk organisation (ICU) snabbt ökade sitt inflytande och sin legitimitet lade grunden för en militant islamistisk avknoppning av organisationen kallad al-Shabaab. En avknoppning som snabbt kom att bli betydande i det Somaliska samhället och dess utvekling

Influence of petrographic textures on the shapes of impact experiment fine fragments measuring several tens of microns: Comparison with Itokawa regolith particles

In 2010, fine regolith particles on asteroid Itokawa were recovered by the Hayabusa mission. The three-dimensional microstructure of 48 Itokawa particles smaller than 120 µm was examined in previous studies. The shape distribution of Itokawa particles is distributed around the mean values of the axial ratio 2:√2:1, which is similar to laboratory impact fragments larger than several mm created in catastrophic disruptions. Thus, the Itokawa particles are considered to be impact fragments on the asteroid's surface. However, there have never been any laboratory impact experiments investigating the shapes of fine fragments smaller than 120 µm, and little is known about the relation between the shapes of fine fragments and the petrographic textures within those fragments. In this study, in order to investigate the relation between the petrographic textures and the shapes of fine fragments by impacts, the shapes of 2163 fine fragments smaller than 120 µm are examined by synchrotron radiation-based microtomography at SPring-8. Most samples are fine fragments from basalt targets, obtained in previous laboratory impact experiments by Michikami et al. (2016). Moreover, two impacts into L5 chondrite targets were carried out and the shapes of their fine fragments are examined for comparison. The results show that the shape distributions of fine fragments in basalt targets are similar regardless of impact energy per target mass (in contract to the shape distribution of relatively large fragments, which are affected by impact energy), and are similar to those in L5 chondrite targets and Itokawa regolith particles. The physical process producing these fine fragments would be due to multiple rarefaction waves in the target. Besides, the petrographic textures do not significantly affect the shapes of fine fragments in our experiments. On the other hand, according to Molaro et al. (2015), the shapes of the fragments produced by thermal fatigue by the day-night temperature cycles on the asteroid surface are influenced by the petrographic textures. Therefore, we conclude that the Itokawa particles are not the products of thermal fatigue but impact fragments on the asteroid surface

Satellite galaxies in groups in the CIELO Project I: Gas removal from galaxies and its re-distribution in the intragroup medium

We study the impact of the environment on galaxies as they fall in and orbit in the potential well of a Local Group (LG) analogue, following them with high cadence. The analysis is performed on eight disc satellite galaxies from the CIELO suite of hydrodynamical simulations. All galaxies have stellar masses within the range [10 8.1 -109.56 ] M⊙h-1. We measure tidal torques, ram pressure, and specific star formation rates (sSFRs) as a function of time, and correlate them with the amount of gas lost by satellites along their orbits. Stronger removal episodes occur when the disc plane is oriented perpendicular to the direction of motion. More than one peripassage is required to significantly modify the orientations of the discs with respect to the orbital plane. The gas removed during the interaction with the central galaxies may also be found opposite to the direction of motion, depending on the orbital configuration. Satellites are not totally quenched when the galaxies reach their first peripassage and continue forming about 10 per cent of the final stellar mass after this event. The fraction of removed gas is found to be the product of the joint action of tidal torque and ram pressure, which can also trigger new star formation activity and subsequent supernova feedback.Fil: Rodríguez Moncada, Silvio Ribamar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Garcia Lambas, Diego Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentina. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; ArgentinaFil: Padilla, Nelson David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Tissera, P.. Pontificia Universidad Católica de Chile; ChileFil: Bignone, Lucas Axel. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Dominguez Tenreiro, Rosa. Pontificia Universidad Católica de Chile; ChileFil: Gonzalez, R.. Pontificia Universidad Católica de Chile; ChileFil: Pedrosa, Susana Elizabeth. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; Argentin

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

El grupo Frankliniella tritici en la región de América Central, el Caribe y México (Terebrantia: Thripidae) y descripción de una nueva especie para México, Frankliniella oaxacensis

El género Frankliniella es de gran diversidad en los trópicosy de alta complejidad taxonómica. El grupo tritici se ha definido en este trabajo con base en los caracteres mayormente funcionales para definir el grupo de especies más restringido cercanas a las especies Frankliniella tritici y Frankliniella cubensis. Las variaciones del collar en el segmento antenal III se manifiestan en algunas especies de la serie cephalica y en algunas especies como Frankliniella standleyana y Frankliniella pineticola es evidente una modificación en forma de cono truncado. Este trabajo presenta una breve sinopsis y revisión de los grupos de especies dentro de Frankliniella incluyendo especies de las regiones del Caribe, América Central y México