Natural history of patients with non cirrhotic portal hypertension: Comparison with patients with compensated cirrhosis

Background. The knowledge of natural history of patients with portal hypertension (PH) not due to cirrhosis is less well known than that of cirrhotic patients. Aim. To describe the clinical presentation and the outcomes of 89 patients with non-cirrhotic PH (25 with non-cirrhotic portal hypertension, INCPH, and 64 with chronic portal vein thrombosis, PVT) in comparison with 77 patients with Child A cirrhosis. Methods. The patients were submitted to a standardized clinical, laboratory, ultrasonographic and endoscopic follow-up. Variceal progression, incidence of variceal bleeding, portal vein thrombosis, ascites and survival were recorded. Results. At presentation, the prevalence of varices, variceal bleeding and ascites was similar in the 3 groups. During follow-up, the rate of progression to varices at risk of bleeding (p<0.0001) and the incidence of first variceal bleeding (p=0.02) were significantly higher in non-cirrhotic then in cirrhotic patients. A PVT developed in 32% of INCPH patients and in 18% of cirrhotics (p=0.02). Conclusions. In the patients with non–cirrhotic PH variceal progression is more rapid and bleeding more frequent than in cirrhotics. Patients with INCPH are particularly prompt to develop PVT. This observational study suggests that the management of patients with non-cirrhotic PH should take into consideration the natural history of portal hypertension in these patients and cannot be simply derived by the observation of cirrhotic patients

Effect of in Situ and Laboratory Compaction on the Retention Behaviour of a Clayey Soil

International audience; A clayey soil has been tested in the laboratory in order to investigate the influence of the compaction procedure on the soil retention behaviour. In common engineering practice, data available for modelling are those of the soil compacted in the laboratory and soil behaviour during the earth structures lifecycle is predicted on that basis. This practice, however, seems to overlook the fact that construction procedures in the field might differ significantly from the compaction techniques used in the laboratory and this may induce considerable differences in material texture and therefore in the soil behaviour. The investigation shown in the present work aims to provide further insight into this aspect and to help endorsing or refuting the validity of such practice

High CTLA-4 expression correlates with poor prognosis in thymoma patients

Thymomas, tumors that arise from epithelial cells of the thymus gland, are the most common neoplasms of the anterior mediastinum, with an incidence rate of approximately 2.5 per million/year. Cytotoxic T Lymphocyte Antigen 4 (CTLA-4 or CD152) exerts inhibitory activity on T cells, and since its oncogenic role in the progression of different types of tumors, it has emerged as a potential therapeutic target in cancer patients. In this study, we assessed the expression of CTLA-4 both at mRNA and protein levels in paraffin embedded-tissues from patients with thymomas. Furthermore, we evaluated the relationship between CTLA-4 expression and the clinical-pathologic characteristics and prognosis in patients with thymomas. Sixty-eight patients with median age corresponding to 62 years were included in this analysis. Thymomas were classified accordingly to the WHO and Masaoka-Koga for histochemical analysis and for prognostic significance. A statistical difference was found between CTLA-4 mRNA levels in human normal thymus compared with thymoma specimens. CTLA-4 expression was statistically found to progressively increase in A, B1, B2, AB and it was maximal in B3 thymomas. According to Masaoka-Koga pathological classification, CTLA-4 expression was lower in I, IIA and IIB, and higher in invasive III and IV stages. By confocal microscopy analysis we identified the expression of CTLA-4 both in tumor cells and in CD45+ tumor-infiltrating leukocytes, mainly in B3 and AB thymomas. Finally, CTLA-4 overexpression significantly correlates with reduced overall survival in thymoma patients and in atypical thymoma subgroup, suggesting that it represents a negative prognostic factor

Detection of urinary exosomal HSD11B2 mRNA expression: a useful novel tool for the diagnostic approach of dysfunctional 11β-HSD2-related hypertension

Apparent mineralocorticoid excess (AME) is an autosomal recessive disorder caused by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme deficiency, traditionally assessed by measuring either the urinary cortisol metabolites ratio (tetrahydrocortisol+allotetrahydrocortisol/tetrahydrocortisone, THF+5αTHF/THE) or the urinary cortisol/cortisone (F/E) ratio. Exosomal mRNA is an emerging diagnostic tool due to its stability in body fluids and its biological regulatory function. It is unknown whether urinary exosomal HSD11B2 mRNA is related to steroid ratio or the HSD11B2 662 C&gt;G genotype (corresponding to a 221 A&gt;G substitution) in patients with AME and essential hypertension (EH)

Genome-scale deconvolution of RNA structure ensembles

RNA structure heterogeneity is a major challenge when querying RNA structures with chemical probing. We introduce DRACO, an algorithm for the deconvolution of coexisting RNA conformations from mutational profiling experiments. Analysis of the SARS-CoV-2 genome using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and DRACO, identifies multiple regions that fold into two mutually exclusive conformations, including a conserved structural switch in the 3' untranslated region. This work may open the way to dissecting the heterogeneity of the RNA structurome

Design and Synthesis of a cADPR Mimic as a Novel Tool for Monitoring the Intracellular Ca2+ Concentration

Cyclic ADP-ribose (cADPR, 1, Figure 1) is a naturally occurring metabolite of NAD+ capable of mobilizing Ca2+ ions from intracellular stores. It was firstly isolated from sea urchin egg extract, but it was later established that it is also produced in many other mammalian cells, including pancreatic β-cells, T-lymphocytes, smooth and cardiac muscle cells, and cerebellar neurons, acting as a Ca2+-mobilizing agent. For this activity, cADPR has been classified as a second messenger that, by activating the ryanodine receptors of the sarcoplasmatic reticulum, is able to mobilize the calcium ions from intracellular stores. cADPR is involved in many physiological processes related to variation in the Ca2+ concentration, such as synaptic homeostasis in neurons as well as fertilization and cellular proliferation. This cyclic nucleotide, characterized by a very labile glycosidic bond at N1, is also rapidly hydrolysed in neutral aqueous solutions to inactive ADP-ribose. Matsuda and co-workers [1] were the first to synthesize new analogues of cADPR in which the adenine base is replaced by a hypoxanthine ring. This kind of modification produced the cyclic inosine diphosphate ribose (cIDPR), which proved to be stable in hydrolytic physiological conditions and showed significant Ca2+ mobilizing activity. Many modifications regarding the northern and southern ribose, as well as the purine base of cADPR, have been proposed so far. In our laboratories, we have synthesized several analogues of cIDPR [2–7]. In particular, the analogue with the northern ribose replaced by a pentyl chain (cpIDP) showed interesting Ca2+ mobilizing activity on the neuronal PC12 cell line [2]. Starting from these results, we report here the synthesis of the novel analogue 2, in which the “northern” ribose of cIDPR is replaced by a 2″,3″-dihydroxy pentyl chain. The effect of the presence of the diol moiety on the intracellular Ca2+ release will be assessed in due course