Molecular Mechanisms Underlying Hepatocellular Carcinoma

Hepatocarcinogenesis is a complex process that remains still partly understood. That might be explained by the multiplicity of etiologic factors, the genetic/epigenetic heterogeneity of tumors bulks and the ignorance of the liver cell types that give rise to tumorigenic cells that have stem cell-like properties. The DNA stress induced by hepatocyte turnover, inflammation and maybe early oncogenic pathway activation and sometimes viral factors, leads to DNA damage response which activates the key tumor suppressive checkpoints p53/p21Cip1 and p16INK4a/pRb responsible of cell cycle arrest and cellular senescence as reflected by the cirrhosis stage. Still obscure mechanisms, but maybe involving the Wnt signaling and Twist proteins, would allow pre-senescent hepatocytes to bypass senescence, acquire immortality by telomerase reactivation and get the last genetic/epigenetic hits necessary for cancerous transformation. Among some of the oncogenic pathways that might play key driving roles in hepatocarcinogenesis, c-myc and the Wnt/β-catenin signaling seem of particular interest. Finally, antiproliferative and apoptosis deficiencies involving TGF-β, Akt/PTEN, IGF2 pathways for instance are prerequisite for cancerous transformation. Of evidence, not only the transformed liver cell per se but the facilitating microenvironment is of fundamental importance for tumor bulk growth and metastasis

Extreme abundance of ammonoids in mass accumulations from the Late Devonian of the Moroccan Anti-Atlas

The eastern Anti-Atlas is renowned for its highly fossiliferous outcrops of Devonian rocks. Ammonoids occur in rock-forming numbers at many localities in the Tafilalt and Maïder. This study addresses the questions of how many ammonoids are preserved within a standardized area as well as over the whole Tafilalt and Maïder basins, and how these mass occurrences formed. Five samples from the Tafilalt and Maïder were analysed. The ammonoids contained therein were prepared, measured and counted as a base for estimates of the orders of magnitude of the total number of preserved ammonoids and their biomass within the respective Famennian strata in the eastern Anti-Atlas. Two samples were stratigraphically assigned to the lower Famennian, two samples to the middle Famennian and one sample to the upper Famennian. For these samples, estimates for a standardized area of 1 km2 and a layer thickness of 100 mm lie between 19.9×109 and 1.25×1010 ammonoids. The estimated numbers for the whole study area with a retrodeformed size of 15 512.5 km2 and a sediment thickness of 100 mm, ranges from 30.9×1013 to 19.4×1014 ammonoids and a annual accumulation of 15.4×109 to 97.1×109 ammonoid conchs. This corresponds to a annual total palaeo-biomass that ranges from 25 954 t to 47 058 t within the whole study area and from 1.67 t to 3.03 t within an area of 1 km2. Based on these results and size-distribution in the samples, the ecological role of the small and highly abundant, subspherical ammonoids from the early and middle Famennian is discussed and reproductive rates are estimated. With ca. 230 eggs produced by an adult female, cheiloceratids and small maeneceratids from the early Famennian deposits are at the lower end of ammonoid reproductive rates. Key words: Cephalopoda, Ammonoidea, palaeoecology, biomass, fecundity, Famennian, Anti-Atla

Messung und Anwendung von anisotropen NMR Parametern in gestreckten Polymergelen und flüssigkristallinen Phasen und metabolische Studien an chinesischen Heilpflanzen

Diese Arbeit befasst sich mit verschiedenen Themen im Bereich der NMR-Spektroskopie, unter anderem mit der Etablierung von neuen Orientierungsmedien, mit der Strukturaufklärung unter Verwendung anisotroper NMR Parameter bzw. mit der Messung und statistischen Auswertung metabolischer Daten von chinesischen Heilpflanzen

A new Meckel’s cartilage from the Devonian Hangenberg black shale in Morocco and its position in chondrichthyan jaw morphospace

Fossil chondrichthyan remains are mostly known from their teeth, scales or fin spines only, whereas their cartilaginous endoskeletons require exceptional preservational conditions to become fossilized. While most cartilaginous remains of Famennian (Late Devonian) chondrichthyans were found in older layers of the eastern Anti-Atlas, such fossils were unknown from the Hangenberg black shale (HBS) and only a few chondrichthyan teeth had been found therein previously. Here, we describe a Meckel’s cartilage from the Hangenberg black shale in Morocco, which is the first fossil cartilage from these strata. Since no teeth or other skeletal elements have been found in articulation, we used elliptical Fourier (EFA), principal component (PCA), and hierarchical cluster (HCA) analyses to morphologically compare it with 41 chondrichthyan taxa of different size and age and to evaluate its possible systematic affiliation. PCA and HCA position the new specimen closest to some acanthodian and elasmobranch jaws. Accordingly, a holocephalan origin was excluded. The jaw shape as well as the presence of a polygonal pattern, typical for tessellated calcified cartilage, suggest a ctenacanth origin and we assigned the new HBS Meckel’s cartilage to the order Ctenacanthiformes with reservations

Prevention of urinary tract infection in spinal cord-injured patients: safety and efficacy of a weekly oral cyclic antibiotic (WOCA) programme with a 2 year follow-up--an observational prospective study.

POPULATION: Spinal cord injury (SCI) patients with neurogenic bladder have an increased risk for symptomatic urinary tract infection (UTI). Recurrent UTI requires multiple courses of antibiotic therapy, markedly increasing the incidence of multidrug-resistant (MDR) bacteria. METHODS: During an observational prospective study, we determined the safety and efficacy of a weekly oral cyclic antibiotic (WOCA) regimen to prevent UTI in SCI adult patients with neurogenic bladder undergoing clean intermittent catheterization. The WOCA regimen consisted of the alternate administration of an antibiotic once per week over a period of at least 2 years. The antibiotics chosen were efficient for UTI, well tolerated and with low selection pressure. RESULTS: There was a significant decrease in antimicrobial consumption linked to the dramatic decrease in the incidence of UTI. Before intervention, there were 9.4 symptomatic UTIs per patient-year, including 197 episodes of febrile UTI responsible for 45 hospitalizations. Under the WOCA regimen there were 1.8 symptomatic UTIs per patient-year, including 19 episodes of febrile UTI. No severe adverse events and no new cases of colonization with MDR bacteria were reported. CONCLUSIONS: In this prospective, observational pilot study a novel approach to the prevention and treatment of UTI in SCI was investigated. Our study shows the benefit of WOCA in preventing UTI in SCI patients

Coated Blade Spray Ion Mobility Spectrometry

Coated blade spray (CBS) is a microextraction technology with blades that serve as both the extraction device and the electrospray ionization (ESI) emitter. CBS is designed for easy and rapid extraction of analytes in complex matrices as well as ESI directly from the blade. The technology selectively enriches the components of interest on a coated metal blade. The coating consists of a selective polymer. So far, CBS has only been coupled with mass spectrometry but never with ion mobility spectrometry (IMS), where ions are separated and detected based on their ion mobility in a drift gas under the influence of an electric field, while instrumentation is compact and easy to operate so that the advantages of CBS can be particularly well exploited. Therefore, this work focuses on coupling CBS with our previously described ESI-IMS. The ion mobility spectrometer has a drift length of only 75 mm and provides a high resolving power of RP = 100. In this work, preliminary measurements of CBS-IMS are presented. In particular, the detection of benzodiazepines and ketamine in drinks and the pesticide isoproturon in water samples is shown to demonstrate the feasibility of CBS-IMS

Présentation de "La Grammaticalisation - La Terminologie"

Le volume 18 des Travaux du CLAIX traite de deux thèmes : –la grammaticalisation, avec des articles de Sibylle Kriegel, Daniel Jacob, Dominique Batoux, Charles Zaremba, Georgia Katselou, Eva Agnel, Alain Girod & Pierre Larcher, Aïno Niklas-Salminen, Robert Roudet ;–la terminologie, avec des articles de Robert Vion, Jaap J. Spa, Denis Autesserre, Christian Touratier, Kate Howe.La première partie a pour but de cerner et de théoriser la notion de grammaticalisation, en s’appuyant sur le point de vue classique d’Antoine Meillet revu par Christian Lehmann et en essayant de l’élargir. Elle propose ensuite quelques études empiriques portant principalement sur le verbe : l’histoire des deux parfaits du grec moderne, la genèse de l’auxiliaire du futur hongrois, l’apparition des voix passive et causative du créole seychellois, la grammaticalisation d’ordre aspectuel correspondant aux verbes dits supports de l’allemand, et la formation du mode impératif et du temps passé du polonais. Deux phénomènes de grammaticalisation concernant le nom sont aussi abordés : la formation, en finnois contemporain, d’un article défini, et le figement de certains emplois du datif en russe.La seconde partie essaie de faire le point sur des questions de terminologie, notamment autour de la notion de modalité, des notions de prédicat et de thème, et des catégories temporelles du verbe

Enchondromas and atypical cartilaginous tumors at the proximal humerus treated with intralesional resection and bone cement filling with or without osteosynthesis: retrospective analysis of 42 cases with 6 years mean follow-up

Background: Enchondromas and atypical cartilaginous tumors (ACT) are often located at the proximal humerus. Most lesions can be followed conservatively, but surgical resection may alleviate pain, avoid pathological fractures, and prevent transformation into higher grade chondrosarcomas. Rigorous intralesional resection and filling with polymethylmethacrylate bone cement has been proposed for enchondromas but also for ACT, as an alternative for extralesional resection. We intended to analyze radiological, clinical, and functional outcome of this strategy and compare bone cement without osteosynthesis to bone cement compound osteosynthesis, which has not been analyzed so far. Methods: We retrospectively analyzed 42 consecutive patients (mean follow-up 73 months; range 8–224) after curettage and bone cement filling with or without osteosynthesis. Exclusion criteria were Ollier’s disease and cancellous bone filling. Twenty-five patients only received bone cement. Seventeen patients received additional proximal humerus plate for compound osteosynthesis to increase stability after curettage. Demographics and radiological and clinical outcome were analyzed including surgery time, blood loss, hospitalization, recurrences, and complications. An additional telephone interview at the final follow-up assessed postoperative satisfaction, pain, and function in the quick disabilities of the arm, shoulder, and hand (DASH) score and the Musculoskeletal Tumor Society (MSTS) score. Statistics included the Student T tests, Mann-Whitney U tests, and chi-square tests. Results: No osteosynthesis compared to compound osteosynthesis showed smaller tumors (4.2 (± 1.5) cm versus 6.6 (± 3.0) cm; p = 0.005) and smaller bone cement fillings after curettage (5.7 (± 2.1) cm versus 9.6 (± 3.2) cm; p = 0.0001). A score evaluating preoperative scalloping and soft-tissue extension did not significantly differ (1.9 (± 0.9) versus 2.0 (± 1.0); rating scale 0–4; p = 0.7). Both groups showed high satisfaction (9.2 (± 1.5) versus 9.2 (± 0.9); p = 0.5) and low pain (1.0(±1.7) versus 1.9(±1.8); p = 0.1) in a rating scale from 0 to 10. Clinical and functional outcome was excellent for both groups in the DASH score (6.0 (± 11.8) versus 11.0 (± 13.2); rating scale 0–100; p = 0.2) and the MSTS score (29.0 (± 1.7) versus 28.7 (± 1.1); rating scale 0–30; p = 0.3). One enchondroma recurrence was found in the group without osteosynthesis. Complications (one fracture and one intra-articular screw) were only detected after osteosynthesis. Osteosynthesis had longer surgery time (70 (± 21) min versus 127 (± 22) min; p < 0.0001), more blood loss (220 (± 130) ml versus 460 (± 210) ml; p < 0.0001), and longer stay in the hospital (6 (± 2) days versus 8 (± 2) days; p = 0.004). Conclusions: Intralesional tumor resection was oncologically safe and clinically successful with or without osteosynthesis. Osteosynthesis did not reduce the risk for fracture but was more invasive