A comparison of non-HDL and LDL cholesterol goal attainment in a large, multinational patient population: The Lipid Treatment Assessment Project 2

Objective: This study evaluated the success in attaining non-HDL-cholesterol (non-HDL-C) goals in the multinational L-TAP 2 study. Methods: 9955 patients >= 20 years of age with dyslipidemia on stable lipid-lowering therapy were enrolled from nine countries. Results: Success rates for non-HDL-C goals were 86% in low, 70% in moderate, and 52% in high-risk patients (63% overall). In patients with triglycerides of >200 mg/dL success rates for non-HDL-C goals were 35% vs. 69% in those with <= 200 mg/dL (p < 0.0001). Among patients attaining their LDL-C goal, 18% did not attain their non-HDL-C goal. In those with coronary disease and at least two risk factors, only 34% and 30% attained respectively their non-HDL-C and LDL-C goals. Rates of failure in attaining both LDL-C and non-HDL-C goals were highest in Latin America. Conclusions: Non-HDL-C goal attainment lagged behind LDL-C goal attainment; this gap was greatest in higher-risk patients. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

Synthesis and characterization of a diruthenium(II,III)-ketoprofen compound and study of the in vitro effects on CRC cells in comparison to the naproxen and ibuprofen derivatives

A new diruthenium(II,III) complex, of formula [Ru2Cl(ket)(4)], Ruket, containing the non-steroidal anti-inflammatory drug ketoprofen was synthesized and mainly characterized by electrospray ionization mass spectrometry (ESI-MS), UV-Vis-IR electronic spectroscopy and FTIR and Raman vibrational spectroscopies. The four drug-carboxylato bridging ligands stabilize a Ru-2(II,III) mixed valent core in a paddlewheel type structure as confirmed by ESI mass spectra, electronic and vibrational spectroscopies and magnetic measurements. Ruket and the analogous compounds containing ibuprofen, Ruibp, and naproxen, Runpx, were tested for the biological effects in the human colon carcinoma cells HT-29 and Caco-2 expressing high and low levels of COX-2 respectively. All compounds only weakly affected the proliferation of the colorectal cancer cells HT-29 and Caco-2, and similarly only partially inhibited the production/activity of MMP-2 and MMP-9 by HT-29 cells, suggesting that COX-2 inhibition by these drugs can only partially be involved in the pharmacological effects of these derivatives. (c) 2012 Elsevier Ltd. All rights reserved.

Measures of quality of life in children with cochlear implant: systematic review

The use of cochlear implant (CI) in children enables the development of listening and communication skills, allowing the child's progress in school and to be able to obtain, maintain and carry out an occupation. However, the progress after the CI has different results in some children, because many children are able to interact and participate in society, while others develop limited ability to communicate verbally. The need for a better understanding of CI outcomes, besides hearing and language benefits, has spurred the inclusion of quality of life measurements (QOL) to assess the impact of this technology. OBJECTIVE: Identify the key aspects of quality of life assessed in children with cochlear implant. METHOD: Through a systematic literature review, we considered publications from the period of 2000 to 2011. CONCLUSION: We concluded that QOL measurements in children include several concepts and methodologies. When referring to children using CI, results showed the challenges in broadly conceptualizing which quality of life domains are important to the child and how these areas can evolve during development, considering the wide variety of instruments and aspects evaluated.

Comparative analysis of the anterior and posterior length and deflection angle of the cranial base, in individuals with facial pattern I, II and III

Objective: This study evaluated the variations in the anterior cranial base (S-N), posterior cranial base (S-Ba) and deflection of the cranial base (SNBa) among three different facial patterns (Pattern I, II and III). Method: A sample of 60 lateral cephalometric radiographs of Brazilian Caucasian patients, both genders, between 8 and 17 years of age was selected. The sample was divided into 3 groups (Pattern I, II and III) of 20 individuals each. The inclusion criteria for each group were the ANB angle, Wits appraisal and the facial profile angle (G’.Sn.Pg’). To compare the mean values obtained from (SNBa, S-N, S-Ba) each group measures, the ANOVA test and Scheffé’s Post-Hoc test were applied. Results and Conclusions: There was no statistically significant difference for the deflection angle of the cranial base among the different facial patterns (Patterns I, II and III). There was no significant difference for the measures of the anterior and posterior cranial base between the facial Patterns I and II. The mean values for S-Ba were lower in facial Pattern III with statistically significant difference. The mean values of S-N in the facial Pattern III were also reduced, but without showing statistically significant difference. This trend of lower values in the cranial base measurements would explain the maxillary deficiency and/or mandibular prognathism features that characterize the facial Pattern III.

Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen

Human endogenous retroviruses (HERVs) arise from ancient infections of the host germline cells by exogenous retroviruses, constituting 8% of the human genome. Elevated level of envelope transcripts from HERVs-W has been detected in CSF, plasma and brain tissues from patients with Multiple Sclerosis (MS), most of them from Xq22.3, 15q21.3, and 6q21 chromosomes. However, since the locus Xq22.3 (ERVWE2) lack the 5' LTR promoter and the putative protein should be truncated due to a stop codon, we investigated the ERVWE2 genomic loci from 84 individuals, including MS patients with active HERV-W expression detected in PBMC. In addition, an automated search for promoter sequences in 20 kb nearby region of ERVWE2 reference sequence was performed. Several putative binding sites for cellular cofactors and enhancers were found, suggesting that transcription may occur via alternative promoters. However, ERVWE2 DNA sequencing of MS and healthy individuals revealed that all of them harbor a stop codon at site 39, undermining the expression of a full-length protein. Finally, since plaque formation in central nervous system (CNS) of MS patients is attributed to immunological mechanisms triggered by autoimmune attack against myelin, we also investigated the level of similarity between envelope protein and myelin oligodendrocyte glycoprotein (MOG). Comparison of the MOG to the envelope identified five retroviral regions similar to the Ig-like domain of MOG. Interestingly, one of them includes T and B cell epitopes, capable to induce T effector functions and circulating Abs in rats. In sum, although no DNA substitutions that would link ERVWE2 to the MS pathogeny was found, the similarity between the envelope protein to MOG extends the idea that ERVEW2 may be involved on the immunopathogenesis of MS, maybe facilitating the MOG recognizing by the immune system. Although awaiting experimental evidences, the data presented here may expand the scope of the endogenous retroviruses involvement on MS pathogenesis

Is there a link between the type of habitat and the patterns of abundance of holothurians in shallow rocky reefs?

[EN] The presence of a mosaic of habitats, largely determined by sea urchin grazing, across shallow rocky reefs may potentially influence in differences in the distribution patterns of invertebrates. The aim of this paper was to assess, using a correlative approach, whether the type of habitat influences the abundance patterns of holothurians in the eastern Atlantic. We hypothesized that abundances of large (> 10 cm) holothurians varied among four types of habitat (3 vegetated habitats with low abundances of the sea urchin D. antillarum versus ?barrens? with hyperabundances of sea urchins), and that these differences were consistent at a hierarchy of spatial scales, including two islands and several replicated sites within each type of habitat and island. Three species of large holothurians were found, accounting for a total of 300 specimens. We found remarkable differences in abundances of holothurians between the ?barrens? and the three vegetated habitats. This pattern was strongest for the numerically dominant species, Holothuria sanctorii. Total abundances of holothurians were between 5 ? 46 times more abundant in ?barrens? compared with the vegetated habitats. Inter-habitat differences were species-specific with some inconsistent patterns from one island to the other. The total abundances of holothurians tended to increase with the abundance of sea urchins within ?barrens?. Our study suggests that there may be a link, at least for the dominant species Holothuria sanctorii, between the distribution and abundances of large holothurians and the habitat across shallow-waters of the eastern Atlantic.

Study of apoptotic deletion mediated by Bifidobacterium longum with construction of recombinant strains for Serpin encoding gene and phenotypes comparison in a pig cell model

The first part of the research project of the Co-Advisorship Ph.D Thesis was aimed to select the best Bifidobacterium longum strains suitable to set the basis of our study. We were looking for strains with the abilities to colonize the intestinal mucosa and with good adhesion capacities, so that we can test these strains to investigate their ability to induce apoptosis in “damaged” intestinal cells. Adhesion and apoptosis are the two process that we want to study to better understand the role of an adhesion protein that we have previously identified and that have top scores homologies with the recent serpin encoding gene identified in B. longum by Nestlè researchers. Bifidobacterium longum is a probiotic, known for its beneficial effects to the human gut and even for its immunomodulatory and antitumor activities. Recently, many studies have stressed out the intimate relation between probiotic bacteria and the GIT mucosa and their influence on human cellular homeostasis. We focused on the apoptotic deletion of cancer cells induced by B. longum. This has been valued in vitro, performing the incubation of three B.longum strains with enterocyte-like Caco- 2 cells, to evidence DNA fragmentation, a cornerstone of apoptosis. The three strains tested were defined for their adhesion properties using adhesion and autoaggregation assays. These features are considered necessary to select a probiotic strain. The three strains named B12, B18 and B2990 resulted respectively: “strong adherent”, “adherent” and “non adherent”. Then, bacteria were incubated with Caco-2 cells to investigate apoptotic deletion. Cocultures of Caco-2 cells with B. longum resulted positive in DNA fragmentation test, only when adherent strains were used (B12 and B18). These results indicate that the interaction with adherent B. longum can induce apoptotic deletion of Caco-2 cells, suggesting a role in cellular homeostasis of the gastrointestinal tract and in restoring the ecology of damaged colon tissues. These results were used to keep on researching and the strains tested were used as recipient of recombinant techniques aimed to originate new B.longum strains with enhanced capacity of apoptotic induction in “damaged” intestinal cells. To achieve this new goal it was decided to clone the serpin encoding gene of B. longum, so that we can understand its role in adhesion and apoptosis induction. Bifidobacterium longum has immunostimulant activity that in vitro can lead to apoptotic response of Caco-2 cell line. It secretes a hypothetical eukaryotic type serpin protein, which could be involved in this kind of deletion of damaged cells. We had previously characterised a protein that has homologies with the hypothetical serpin of B. longum (DD087853). In order to create Bifidobacterium serpin transformants, a B. longum cosmid library was screened with a PCR protocol using specific primers for serpin gene. After fragment extraction, the insert named S1 was sub-cloned into pRM2, an Escherichia coli - Bifidobacterium shuttle vector, to construct pRM3. Several protocols for B. longum transformation were performed and the best efficiency was obtained using MRS medium and raffinose. Finally bacterial cell supernatants were tested in a dotblot assay to detect antigens presence against anti-antitrypsin polyclonal antibody. The best signal was produced by one starin that has been renamed B. longum BLKS 7. Our research study was aimed to generate transformants able to over express serpin encoding gene, so that we can have the tools for a further study on bacterial apoptotic induction of Caco-2 cell line. After that we have originated new trasformants the next step to do was to test transformants abilities when exposed to an intestinal cell model. In fact, this part of the project was achieved in the Department of Biochemistry of the Medical Faculty of the University of Maribor, guest of the abroad supervisor of the Co-Advisorship Doctoral Thesis: Prof. Avrelija Cencic. In this study we examined the probiotic ability of some bacterial strains using intestinal cells from a 6 years old pig. The use of intestinal mammalian cells is essential to study this symbiosis and a functional cell model mimics a polarised epithelium in which enterocytes are separated by tight junctions. In this list of strains we have included the Bifidobacterium longum BKS7 transformant strain that we have previously originated; in order to compare its abilities. B. longum B12 wild type and B. longum BKS7 transformant and eight Lactobacillus strains of different sources were co-cultured with porcine small intestine epithelial cells (PSI C1) and porcine blood monocytes (PoM2) in Transwell filter inserts. The strains, including Lb. gasseri, Lb. fermentum, Lb. reuterii, Lb. plantarum and unidentified Lactobacillus from kenyan maasai milk and tanzanian coffee, were assayed for activation of cell lines, measuring nitric oxide by Griess reaction, H202 by tetramethylbenzidine reaction and O2 - by cytochrome C reduction. Cytotoxic effect by crystal violet staining and induction on metabolic activity by MTT cell proliferation assay were tested too. Transepithelial electrical resistance (TER) of polarised PSI C1 was measured during 48 hours co-culture. TER, used to observe epithelium permeability, decrease during pathogenesis and tissue becomes permeable to ion passive flow lowering epithelial barrier function. Probiotics can prevent or restore increased permeability. Lastly, dot-blot was achieved against Interleukin-6 of treated cells supernatants. The metabolic activity of PoM2 and PSI C1 increased slightly after co-culture not affecting mitochondrial functions. No strain was cytotoxic over PSI C1 and PoM2 and no cell activation was observed, as measured by the release of NO2, H202 and O2 - by PoM2 and PSI C1. During coculture TER of polarised PSI C1 was two-fold higher comparing with constant TER (~3000 ) of untreated cells. TER raise generated by bacteria maintains a low permeability of the epithelium. During treatment Interleukin-6 was detected in cell supernatants at several time points, confirming immunostimulant activity. All results were obtained using Lactobacillus paracasei Shirota e Carnobacterium divergens as controls. In conclusion we can state that both the list of putative probiotic bacteria and our new transformant strain of B. longum are not harmful when exposed to intestinal cells and could be selected as probiotics, because can strengthen epithelial barrier function and stimulate nonspecific immunity of intestinal cells on a pig cell model. Indeed, we have found out that none of the strains tested that have good adhesion abilities presents citotoxicity to the intestinal cells and that non of the strains tested can induce cell lines to produce high level of ROS, neither NO2. Moreover we have assayed even the capacity of producing certain citokynes that are correlated with immune response. The detection of Interleukin-6 was assayed in all our samples, including B.longum transformant BKS 7 strain, this result indicates that these bacteria can induce a non specific immune response in the intestinal cells. In fact, when we assayed the presence of Interferon-gamma in cells supernatant after bacterial exposure, we have no positive signals, that means that there is no activation of a specific immune response, thus confirming that these bacteria are not recognize as pathogen by the intestinal cells and are certainly not harmful for intestinal cells. The most important result is the measure of Trans Epithelial Electric Resistance that have shown how the intestinal barrier function get strengthen when cells are exposed to bacteria, due to a reduction of the epithelium permeability. We have now a new strain of B. longum that will be used for further studies above the mechanism of apoptotic induction to “damaged cells” and above the process of “restoring ecology”. This strain will be the basis to originate new transformant strains for Serpin encoding gene that must have better performance and shall be used one day even in clinical cases as in “gene therapy” for cancer treatment and prevention.

Outcome of HIV-infected patients with hepatocellular carcinoma: a comparison with HIV negative controls

Background and rationale for the study. This study investigated whether human immunodeficiency virus (HIV) infection adversely affects the prognosis of patients diagnosed with hepatocellular carcinoma (HCC).Thirty-four HIV-positive patients with chronic liver disease, consecutively diagnosed with HCC from 1998 to 2007 were one-to-one matched with 34 HIV negative controls for: sex, liver function (Child-Turcotte-Pugh class [CTP]), cancer stage (BCLC model) and, whenever possible, age, etiology of liver disease and modality of cancer diagnosis. Survival in the two groups and independent prognostic predictors were assessed. Results. Among HIV patients 88% were receiving HAART. HIV-RNA was undetectable in 65% of cases; median lymphocyte CD4+ count was 368.5/mmc. Etiology of liver disease was mostly related to HCV infection. CTP class was: A in 38%, B in 41%, C in 21% of cases. BCLC cancer stage was: early in 50%, intermediate in 23.5%, advanced in 5.9%, end-stage in 20.6% of cases. HCC treatments and death causes did not differ between the two groups. Median survival did not differ, being 16 months (95% CI: 6-26) in HIV positive and 23 months (95% CI: 5-41) in HIV negative patients (P=0.391). BCLC cancer stage and HCC treatment proved to be independent predictors of survival both in the whole population and in HIV patients. Conclusions. Survival of HIV infected patients receiving antiretroviral therapy and diagnosed with HCC is similar to that of HIV negative patients bearing this tumor. Prognosis is determined by the cancer bulk and its treatment.

Changes in tumor stiffness for early prediction of tumor response to sorafenib: a proof-of-concept study with elastosonography in an animal model of Hepatocellular Carcinoma (HCC)

Background and aims: Sorafenib is the reference therapy for advanced Hepatocellular Carcinoma (HCC). No method exists to predict in the very early period subsequent individual response. Starting from the clinical experience in humans that subcutaneous metastases may rapidly change consistency under sorafenib and that elastosonography a new ultrasound based technique allows assessment of tissue stiffness, we investigated the role of elastonography in the very early prediction of tumor response to sorafenib in a HCC animal model. Methods: HCC (Huh7 cells) subcutaneous xenografting in mice was utilized. Mice were randomized to vehicle or treatment with sorafenib when tumor size was 5-10 mm. Elastosonography (Mylab 70XVG, Esaote, Genova, Italy) of the whole tumor mass on a sagittal plane with a 10 MHz linear transducer was performed at different time points from treatment start (day 0, +2, +4, +7 and +14) until mice were sacrified (day +14), with the operator blind to treatment. In order to overcome variability in absolute elasticity measurement when assessing changes over time, values were expressed in arbitrary units as relative stiffness of the tumor tissue in comparison to the stiffness of a standard reference stand-off pad lying on the skin over the tumor. Results: Sor-treated mice showed a smaller tumor size increase at day +14 in comparison to vehicle-treated (tumor volume increase +192.76% vs +747.56%, p=0.06). Among Sor-treated tumors, 6 mice showed a better response to treatment than the other 4 (increase in volume +177% vs +553%, p=0.011). At day +2, median tumor elasticity increased in Sor-treated group (+6.69%, range –30.17-+58.51%), while decreased in the vehicle group (-3.19%, range –53.32-+37.94%) leading to a significant difference in absolute values (p=0.034). From this time point onward, elasticity decreased in both groups, with similar speed over time, not being statistically different anymore. In Sor-treated mice all 6 best responders at day 14 showed an increase in elasticity at day +2 (ranging from +3.30% to +58.51%) in comparison to baseline, whereas 3 of the 4 poorer responders showed a decrease. Interestingly, these 3 tumours showed elasticity values higher than responder tumours at day 0. Conclusions: Elastosonography appears a promising non-invasive new technique for the early prediction of HCC tumor response to sorafenib. Indeed, we proved that responder tumours are characterized by an early increase in elasticity. The possibility to distinguish a priori between responders and non responders based on the higher elasticity of the latter needs to be validated in ad-hoc experiments as well as a confirmation of our results in humans is warranted.

Identification and dissolution behavior of the secondary uranium minerals in the corrosion products of Depleted Uranium (DU) ammunition formed in soils

In der vorliegenden Studie wurden verschiedene Techniken eingesetzt um drei Proben (4, 7, and 8) die aus denrnKorrosionsprodukten von aus dem Kosovo Krieg stammenden Munitionskugeln, bestehend aus abgereichertem Uranrn(Depleted Uranium - DU), zu untersuchen. Als erstes Verfahren wurde die Raman-Spektroskopie eingesetzt. Hierbeirnzeigte sichin den Proben, charakterisiert durch einen Doppelpeak, die Anwesenheit von Schoepitrn(UO2)8O2(OH)12(H2O)12. Der erste und zweite Peakzeigte sich im Spektralbereich von 840,3-842,5 cm-1rnbeziehungsweise 853,6-855,8 cm-1. Diese Werte stimmen mit den Literaturwerten für Raman-Peaks für Schoepitrnüberein. Des Weiteren wurde bei dieser Untersuchungsmethode Becquerelite Ca(UO2)6O4(OH)6(H2O)8 mit einemrnPeak im Bereich zwischen 829 to 836 cm-1 gefunden. Aufgrund des Fehlens des Becquerelitespektrums in derrnSpektralbibliothek wurde eine in der Natur vorkommende Variante analysiert und deren Peak bei 829 cm-1 bestimmt,rnwas mit den Ergebnissen in den Proben korrespondiert. Mittels Röntgenbeugung (X-Ray Diffraction, XRD) zeigtenrnsich in allen Proben ähnliche Spektren. Das lässt darauf schließen, dass das pulverisierte Material in allen Probenrndas gleiche ist. Hierbei zeigte sich eine sehr gute Übereinstimmung mit Schoepit und/oder meta-rnSchoepit(UO2)8O2(OH)12(H2O)10, sowie Becquerelite. Weiterhin war weder Autunit, Sabugalit noch Uranylphosphatrnanwesend, was die Ergebnisse einer anderen Studie, durchgeführt an denselben Proben, wiederlegt. DiernAnwesenheit von P, C oder Ca im Probenmaterial konnte ausgeschlossen werden. Im Falle von Calciumkann diesrnmit der Anwesenheit von Uran erklärt werden, welches aufgrund seines Atomradius bevorzugt in Becquerelite (1:6)rneingebaut wird. Die beiden Hauptpeaks für Uran lagen im Falle von U 4f 7/2 bei 382.0 eV und im Falle von U 4f 5/2rnbei 392 eV. Diese Werte mit den Literaturwerten für Schoepit und meta-Schoepitüberein. Die Ergebnissernelektronenmikroskopischen Untersuchung zeigen U, O, Ca, Ti als dominante Komponenten in allen Messungen.rnElemente wie Si, Al, Fe, S, Na, und C wurden ebenfalls detektiert; allerdings kann nicht ausgeschlossen werden,rndass diese Elemente aus dem Boden in der unmittelbaren Umgebung der Munitionsgeschosse stammen. Gold wurdernebenfalls gemessen, was aber auf die Goldarmierung in den Probenaufbereitungsbehältern zurückgeführt werdenrnkann. Die Elektronenmikroskopie zeigte außerdem einige Stellen in denen elementares Uran und Bodenmineralernsowie sekundäre Uranminerale auftraten. Die Elementübersicht zeigt einen direkten Zusammenhang zwischen U andrnCa und gleichzeitig keine Korrelation zwischen U und Si, oder Mg. Auf der anderen Seite zeigte sich aber einrnZusammenhang zwischen Si und Al da beide Konstituenten von Bodenmineralen darstellen. Eine mit Hilfe derrnElektronenstrahlmikroanalyse durchgeführte quantitative Analyse zeigte den Massenanteil von Uran bei ca. 78 - 80%,rnwas mit den 78,2% and 79,47% für Becquerelite beziehungsweise Schoepit aufgrund ihrer Summenformelrnkorrespondiert. Zusätzlich zeigt sich für Calcium ein Massenanteil von 2% was mit dem Wert in Becquerelite (2.19%)rnrecht gut übereinstimmt. Der Massenanteil von Ti lag in einigen Fällen bei 0,77%, was auf eine noch nicht korrodierternDU-Legierung zurückzuführen ist. Ein Lösungsexperiment wurde weiterhin durchgeführt, wobei eine 0,01 M NaClO4-rnLösung zum Einsatz kam in der die verbliebene Probensubstanz der Korrosionsprodukte gelöst wurde;rnNatriumperchlorate wurde hierbei genutzt um die Ionenstärke bei 0,01 zu halten. Um Verunreinigungen durchrnatmosphärisches CO2 zu vermeiden wurden die im Versuch für die drei Hauptproben genutzten 15 Probenbehälterrnmit Stickstoffgas gespült. Eine Modelkalkulation für den beschriebenen Versuchsaufbau wurde mit Visual MINTEQrnv.3.0 für die mittels vorgenannten Analysemethoden beschriebenen Mineralphasen im pH-Bereich von 6 – 10 imrnFalle von Becquerelite, und Schoepit berechnet. Die modellierten Lösungskurven wurden unter An- und Abwesenheitrnvon atmosphärischem CO2 kalkuliert. Nach dem Ende des Lösungsexperiments (Dauer ca. 6 Monate) zeigten diernKonzentrationen des gelösten Urans, gemessen mittels ICP-OES, gute Übereinstimmung mit den modelliertenrnSchoepit und Becquerelite Kurven. Auf Grund des ähnlichen Löslichkeitverhaltens war es nicht möglich zwichen denrnbeiden Mineralen zu unterscheiden. Schoepit kontrolliert im sauren Bereich die Löslichkeit des Urans, währendrnbecquerelit im basichen am wenigsten gelöst wird. Des Weiteren bleibt festzuhalten, dass ein Anteil an CO2 in diernverschlossenen Probenbehälter eingedrungen ist, was sich mit der Vorhersage der Modeldaten deckt. Die Löslichkeitrnvon Uran in der Lösung als Funktion des pH-Wertes zeigte die niedrigsten Konzentrationen im Falle einer Zunahmerndes pH-Wertes von 5 auf 7 (ungefähr 5,1 x 10-6 mol/l) und einer Zunahme des pH-Wertes auf 8 (ungefähr 1,5 x 10-6rnmol/l bei). Oberhalb dieses Bereichs resultiert jeder weitere Anstieg des pH-Wertes in einer Zunahme gelösten Uransrnin der Lösung. Der ph-Wert der Lösung wie auch deren pCO2-Wert kontrollieren hier die Menge des gelösten Urans.rnAuf der anderen Seite zeigten im Falle von Becquerelite die Ca-Konzentrationen höhere Werte als erwartet, wobeirnwahrscheinlich auf eine Vermischung der Proben mit Bodensubstanz zurückgeführt werden kann. Abschließendrnwurde, unter Berücksichtigung der oben genannten Ergebnisse, eine Fallstudie aus Basrah (Irak) diskutiert, wo inrnzwei militärischen Konflikten Uranmunition in zwei Regionen unter verschiedenen Umweltbedingungen eingesetztrnwurden.

Identification and genetic diversity in phytoplasmas associated with diseases of cassava and other agronomic relevant crops in south-east Asia and Latin America

Identification and genetic diversity of phytoplasmas infecting tropical plant species, selected among those most agronomically relevant in South-east Asia and Latin America were studied. Correlation between evolutionary divergence of relevant phytoplasma strains and their geographic distribution by comparison on homologous genes of phytoplasma strains detected in the same or related plant species in other geographical areas worldwide was achieved. Molecular diversity was studied on genes coding ribosomal proteins, groEL, tuf and amp besides phytoplasma 16S rRNA. Selected samples infected by phytoplasmas belonging to diverse ribosomal groups were also studied by in silico RFLP followed by phylogenetic analyses. Moreover a partial genome annotation of a ‘Ca. P. brasiliense’ strain was done towards future application for epidemiological studies. Phytoplasma presence in cassava showing frog skin (CFSD) and witches’ broom (CWB) diseases in Costa Rica - Paraguay and in Vietnam – Thailand, respectively, was evaluated. In both cases, the diseases were associated with phytoplasmas related to aster yellows, apple proliferation and “stolbur” groups, while only phytoplasma related to X-disease group in CFSD, and to hibiscus witches’ broom, elm yellows and clover proliferation groups in CWB. Variability was found among strains belonging to the same ribosomal group but having different geographic origin and associated with different disease. Additionally, a dodder transmission assay to elucidate the role of phytoplasmas in CWB disease was carried out, and resulted in typical phytoplasma symptoms in periwinkle plants associated with the presence of aster yellows-related strains. Lethal wilt disease, a severe disease of oil palm in Colombia that is spreading throughout South America was also studied. Phytoplasmas were detected in symptomatic oil palm and identified as ‘Ca. P. asteris’, ribosomal subgroup 16SrI-B, and were distinguished from other aster yellows phytoplasmas used as reference strains; in particular, from an aster yellows strain infecting corn in the same country.

Radiolabeling of defined polymer architectures with fluorine-18 and iodine-131 for ex vivo and in vivo evaluation : visualization of structure-property relationships

Nuclear medicine imaging techniques such as PET are of increasing relevance in pharmaceutical research being valuable (pre)clinical tools to non-invasively assess drug performance in vivo. Therapeutic drugs, e.g. chemotherapeutics, often suffer from a poor balance between their efficacy and toxicity. Here, polymer based drug delivery systems can modulate the pharmacokinetics of low Mw therapeutics (prolonging blood circulation time, reducing toxic side effects, increasing target site accumulation) and therefore leading to a more efficient therapy. In this regard, poly-N-(2-hydroxypropyl)-methacrylamide (HPMA) constitutes a promising biocompatible polymer. Towards the further development of these structures, non-invasive PET imaging allows insight into structure-property relationships in vivo. This performant tool can guide design optimization towards more effective drug delivery. Hence, versatile radiolabeling strategies need to be developed and establishing 18F- as well as 131I-labeling of diverse HPMA architectures forms the basis for short- as well as long-term in vivo evaluations. By means of the prosthetic group [18F]FETos, 18F-labeling of distinct HPMA polymer architectures (homopolymers, amphiphilic copolymers as well as block copolymers) was successfully accomplished enabling their systematic evaluation in tumor bearing rats. These investigations revealed pronounced differences depending on individual polymer characteristics (molecular weight, amphiphilicity due to incorporated hydrophobic laurylmethacrylate (LMA) segments, architecture) as well as on the studied tumor model. Polymers showed higher uptake for up to 4 h p.i. into Walker 256 tumors vs. AT1 tumors (correlating to a higher cellular uptake in vitro). Highest tumor concentrations were found for amphiphilic HPMA-ran-LMA copolymers in comparison to homopolymers and block copolymers. Notably, the random LMA copolymer P4* (Mw=55 kDa, 25% LMA) exhibited most promising in vivo behavior such as highest blood retention as well as tumor uptake. Further studies concentrated on the influence of PEGylation (‘stealth effect’) in terms of improving drug delivery properties of defined polymeric micelles. Here, [18F]fluoroethylation of distinct PEGylated block copolymers (0%, 1%, 5%, 7%, 11% of incorporated PEG2kDa) enabled to systematically study the impact of PEG incorporation ratio and respective architecture on the in vivo performance. Most strikingly, higher PEG content caused prolonged blood circulation as well as a linear increase in tumor uptake (Walker 256 carcinoma). Due to the structural diversity of potential polymeric carrier systems, further versatile 18F-labeling strategies are needed. Therefore, a prosthetic 18F-labeling approach based on the Cu(I)-catalyzed click reaction was established for HPMA-based polymers, providing incorporation of fluorine-18 under mild conditions and in high yields. On this basis, a preliminary µPET study of a HPMA-based polymer – radiolabeled via the prosthetic group [18F]F-PEG3-N3 – was successfully accomplished. By revealing early pharmacokinetics, 18F-labeling enables to time-efficiently assess the potential of HPMA polymers for efficient drug delivery. Yet, investigating the long-term fate is essential, especially regarding prolonged circulation properties and passive tumor accumulation (EPR effect). Therefore, radiolabeling of diverse HPMA copolymers with the longer-lived isotope iodine-131 was accomplished enabling in vivo evaluation of copolymer P4* over several days. In this study, tumor retention of 131I-P4* could be demonstrated at least over 48h with concurrent blood clearance thereby confirming promising tumor targeting properties of amphiphilic HPMA copolymer systems based on the EPR effect.

Frequency-dependent response of snow in uniaxial compression and comparison with numerical simulation

La determinazione del modulo di Young è fondamentale nello studio della propagazione di fratture prima del rilascio di una valanga e per lo sviluppo di affidabili modelli di stabilità della neve. Il confronto tra simulazioni numeriche del modulo di Young e i valori sperimentali mostra che questi ultimi sono tre ordini di grandezza inferiori a quelli simulati (Reuter et al. 2013)⁠. Lo scopo di questo lavoro è stimare il modulo di elasticità studiando la dipendenza dalla frequenza della risposta di diversi tipi di neve a bassa densità, 140-280 kg m-3. Ciò è stato fatto applicando una compressione dinamica uniassiale a -15°C nel range 1-250 Hz utilizzando il Young's modulus device (YMD), prototipo di cycling loading device progettato all'Istituto per lo studio della neve e delle valanghe (SLF). Una risposta viscoelastica della neve è stata identificata a tutte le frequenze considerate, la teoria della viscoelasticità è stata applicata assumendo valida l'ipotesi di risposta lineare della neve. Il valore dello storage modulus, E', a 100 Hz è stato identificato come ragionevolmente rappresentativo del modulo di Young di ciascun campione neve. Il comportamento viscoso è stato valutato considerando la loss tangent e la viscosità ricavata dai modelli di Voigt e Maxwell. Il passaggio da un comportamento più viscoso ad uno più elastico è stato trovato a 40 Hz (~1.1•10-2 s-1). Il maggior contributo alla dissipazione è nel range 1-10 Hz. Infine, le simulazioni numeriche del modulo di Young sono state ottenute nello stesso modo di Reuter et al.. La differenza tra le simulazioni ed i valori sperimentali di E' sono, al massimo, di un fattore 5; invece, in Reuter et al.⁠, era di 3 ordini di grandezza. Pertanto, i nostri valori sperimentali e numerici corrispondono meglio, indicando che il metodo qui utilizzato ha portato ad un miglioramento significativo.

Reproducibility and validity of video screen measurements of gait in children with spastic cerebral palsy

PURPOSE: To determine the reproducibility and validity of video screen measurement (VSM) of sagittal plane joint angles during gait. METHODS: 17 children with spastic cerebral palsy walked on a 10m walkway. Videos were recorded and 3d-instrumented gait analysis was performed. Two investigators measured six sagittal joint/segment angles (shank, ankle, knee, hip, pelvis, and trunk) using a custom-made software package. The intra- and interrater reproducibility were expressed by the intraclass correlation coefficient (ICC), standard error of measurements (SEM) and smallest detectable difference (SDD). The agreement between VSM and 3d joint angles was illustrated by Bland-Altman plots and limits of agreement (LoA). RESULTS: Regarding the intrarater reproducibility of VSM, the ICC ranged from 0.99 (shank) to 0.58 (trunk), the SEM from 0.81 degrees (shank) to 5.97 degrees (trunk) and the SDD from 1.80 degrees (shank) to 16.55 degrees (trunk). Regarding the interrater reproducibility, the ICC ranged from 0.99 (shank) to 0.48 (trunk), the SEM from 0.70 degrees (shank) to 6.78 degrees (trunk) and the SDD from 1.95 degrees (shank) to 18.8 degrees (trunk). The LoA between VSM and 3d data ranged from 0.4+/-13.4 degrees (knee extension stance) to 12.0+/-14.6 degrees (ankle dorsiflexion swing). CONCLUSION: When performed by the same observer, VSM mostly allows the detection of relevant changes after an intervention. However, VSM angles differ from 3d-IGA and do not reflect the real sagittal joint position, probably due to the additional movements in the other planes.