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Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previous work using proteomic analysis showed that most UHCAs constitute a homogeneous subtype associated with overexpression of argininosuccinate synthase (ASS1). To clarify the use of ASS1 in the HCA classification and avoid misinterpretations of the immunohistochemical staining, the aims of this work were to study (1) the link between shHCA and ASS1 overexpression and (2) the clinical relevance of ASS1 overexpression for diagnosis. Molecular, proteomic, and immunohistochemical analyses were performed in UHCA cases of the Bordeaux series. The clinico‐pathological features, including ASS1 immunohistochemical labeling, were analyzed on a large international series of 67 cases. ASS1 overexpression and the shHCA subgroup were superimposed in 15 cases studied by molecular analysis, establishing ASS1 overexpression as a hallmark of shHCA. Moreover, the ASS1 immunomarker was better than prostaglandin D2 synthase and only found positive in 7 of 22 shHCAs. Of the 67 UHCA cases, 58 (85.3%) overexpressed ASS1, four cases were ASS1 negative, and in five cases ASS1 was noncontributory. Proteomic analysis performed in the case of doubtful interpretation of ASS1 overexpression, especially on biopsies, can be a support to interpret such cases. ASS1 overexpression is a specific hallmark of shHCA known to be at high risk of bleeding. Therefore, ASS1 is an additional tool for HCA classification and clinical diagnosis., ShHCA is a new HCA subgroup with a high risk of bleeding with PTGDS and ASS1 proposed as immunomarkers, with conflicting results and interpretations in the literature. By molecular, proteomic, and immunohistochemistry analyses, we established that ASS1 overexpression was a specific hallmark of shHCA. Having shown that PTGDS was not a good marker, we demonstrated, using a large cohort of UHCAs, the sensitivity of ASS1 immunomarker and its clinical relevance. Therefore, ASS1 is an additional tool for HCA classification, clinical diagnosis of shHCA, and appropriate management.

Objective: To compare the effects of Pilates®, a 30 s static stretching protocol and elastic bands resistance training on lower and hand-grip strength, rachis morphology, flexibility and body balance among RRMS patients. Methods: Twenty-two subjects affected by relapsing-remitting multiple sclerosis (RRMS, EDSS ≤ 6) were randomly divided into 3 groups whose members each performed 16 weeks of training. Stabilometry, rachis morphology, sit and reach, handgrip and sit to stand tests were performed three times: T0, after a month of learning training protocols; T1, after eight weeks of training; and T2, after sixteen weeks of training. Results: Static stretching group. Spinal Mouse (inclination line between ThSp1 and S1 from a standing position): T0 vs. T2, -55%; Sit and Reach test: T0 vs. T2, +15%. Pilates group. Sit and Reach test: T0 vs. T2, +15%; Sit to Stand test: T0 vs. T2, +31%. Elastic group. Stabilometry with eyes open: T0 vs. T1, -51%; stabilometry with eyes closed: T0 vs. T1, -52%; sit to stand test: T0 vs. T2, +39%. Conclusion: Static stretching, Pilates and resistance training are useful to increase the autonomy in the daily life of people with MS thanks to the adoption of these three different training methods.

International audience; A great number of organic compounds spontaneously form unstable peroxides by reaction of the carbon chain with molecular oxygen in a process of auto-oxidation, the so-called "peroxidation". This is a free-radical and self-propagating reaction that may generate a wide variety of peroxide molécules

Introduction The three effective, commercially available drugs for the treatment of erectile dysfunction—sildenafil, vardenafil, and tadalafil—inhibit the same substrate, the erectolytic enzyme phosphodiesterase type 5 (PDE5). Although there are pharmacological differences between these three compounds, few comparative studies have been conducted to date. Aim The aim of this study was to determine the efficacy of sildenafil, tadalafil, and vardenafil in a randomly assigned 8-week fixed regimen. Methods This was a spontaneous, open-label, randomized, multicenter, crossover study where the patients were randomized to receive sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, or vardenafil 20 mg. Main Outcome Measures The primary outcome included the posttreatment analysis of erectile function domains of the abridged International Index of Erectile Function (IIEF5+1). The secondary objectives included the analysis of peak-systolic velocities (PSVs), end-diastolic velocities (EDVs), and resistive index (RI), and the estimate of the percentage of men with normal penile hemodynamic parameters after each treatment. Results In all groups of patients taking sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, and vardenafil 20 mg at a frequency reflecting the common treatment regimens in real life, there was a statistically significant baseline-to-end point improvement in subjective perception of erectile function measured by IIEF5+1. When the four groups were compared, the treatments were not different in modifying IIEF5+1 and penile flow parameters. However, the within-group analysis showed that PSV improved in the sildenafil 50 mg group and that PSV together with RI significantly ameliorated in patients receiving 100 mg of sildenafil. Regression analysis confirmed an independent effect of sildenafil on hemodynamic efficacy parameters. Conclusions An overall equivalence was demonstrated in the subjective perception of treatment benefits for all the PDE5i tested. However, sildenafil, in a dose-dependent manner, was the unique PDE5i able to ameliorate some of the penile flow parameters within the 8-week treatment period. These findings should be interpreted conservatively because of the observational nature of the study. Jannini EA, Isidori AM, Gravina GL, Aversa A, Balercia G, Bocchio M, Boscaro M, Carani C, Corona G, Fabbri A, Foresta C, Forti G, Francavilla S, Granata ARM, Maggi M, Mansani R, Palego P, Spera G, Vetri M, and Lenzi A on behalf of the Endotrial Study Group. The ENDOTRIAL study: A spontaneous, open-label, randomized, multicenter, crossover study on the efficacy of sildenafil, tadalafil, and vardenafil in the treatment of erectile dysfunction. J Sex Med 2009;6:2547–2560.