Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.

Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage.RCUK Cancer Research UK ERC H2020 Wellcome Trus

A large asymptomatic portal vein aneurysm in an old man

Ultrasound (US) is a useful tool in diagnosis and follow-up of portal vein aneurysms (PVA). In the absence of international surgical guidelines on PVAs, US can be effectively used in follow-up of asymptomatic patients not suitable for surgery

Vimentin-typing in diagnostic surgical pathology: a comparative study using four antibodies after different fixations

Vimentin-typing was carried out on various normal and neoplastic tissues using four anti-vimentin antibodies in order to evaluate the effect of different fixation treatments on tissue reactivity in comparison to the results obtained on frozen sections. All antisera were reactive on frozen material; on paraffin embedded material staining of tissues depended on the type of fixation method applied (formalin, methacarn or absolute alcohol) and each antibody behaved differently in relation to the fixative used. Only mesenchymal normal structures were revealed on frozen material whilst on paraffin embedded material three of the four antibodies reacted also with non-mesenchymal normal structures (epithelia, central and peripheral nervous system cells). All four antibodies decorated, regardless of treatment, neoplastic cells of mesenchymal and non-mesenchymal derivation, but not germ cells or germ cell tumors. The reactivity of vimentin to its specific antibodies depends on the fixative used: therefore, in routine pathology more than one antiserum should be available for testing. Furthermore, given the variety of non-mesenchymal structures stained by the anti-vimentin antibodies, the differential diagnosis of undifferentiated tumors must not be based on vimentin positivity alone. The expression of vimentin by non-mesenchymal neoplastic cells seems to parallel that of normal tissues during embryogenesis; therefore, this intermediate filament appears to be not only a marker of mesenchymal cells but also of many immature elements

Interaction of HDL cholesterol concentrations on the relationship between physical function and inflammation in community-dwelling older persons

Background: the existence of a relationship among inflammation, high-density lipoprotein cholesterol (HDL-C) and physical function has been suggested. Objective: the aim of the study is to investigate the possible interaction of HDL-C on inflammation and physical function. Design: cross-sectional study. Setting: town of Tuscania (Italy). Subjects: all the 329 community-dwelling older persons aged 6575years (mean age 79.8\ub15.2years, women 56.2%). Methods: HDL-C, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and interleukin-6 (IL-6) were measured. Activities of daily living (ADL), instrumental ADL (IADL) and 4-m walking speed were assessed. Linear regression models were performed. Results: given the multiple significant interactions, models were stratified according to HDL-C concentrations. In participants with normal HDL-C concentrations, only IL-6 showed a significant association with IADL (\u3b2=-0.439, SE=0.176, P=0.01). In participants with low HDL-C concentrations, all three inflammatory biomarkers were significantly associated with 4-m walking speed and IADL. IL-6 was also significantly associated with ADL (\u3b2=-0.755, SE=0.259, P=0.006), whereas borderline significances were reported for CRP and ESR. Conclusions: the association between inflammation and physical function is particularly enhanced in elders with low HDL-C concentrations. Though HDL-C may merely act as a wellbeing index, HDL-C concentrations should be considered in studies evaluating inflammation and physical function

Bone marrow uptake of 18F-FDG PET/CT and bone marrow biopsy in initial staging of diffuse large B-cell lymphoma patients

Objective: To develop a method to fuse lymphoscintigraphic images with an adaptable anatomical vector profile and to evaluate its role in the clinical practice. Methods: We used Adobe Illustrator CS6 to create different vector profiles, we fused those profiles, using Adobe Photoshop CS6, with lymphoscintigraphic images of the patient. We processed 197 lymphoscintigraphies performed in patients with cutaneous melanomas, breast cancer or delayed lymph drainage. Results: Our models can be adapted to every patient attitude or position and contain different levels of anatomical details ranging from external body profiles to the internal anatomical structures like bones, muscles, vessels, and lymph nodes. If needed, more new anatomical details can be added and embedded in the profile without redrawing them, saving a lot of time. Details can also be easily hidden, allowing the physician to view only relevant information and structures. Fusion times are about 85 s. The diagnostic confidence of the observers increased significantly. The validation process showed a slight shift (mean 4.9 mm). Conclusions: We have created a new, practical, inexpensive digital technique based on commercial software for fusing lymphoscintigraphic images with built-in anatomical reference profiles. It is easily reproducible and does not alter the original scintigraphic image. Our method allows a more meaningful interpretation of lymphoscintigraphies, an easier recognition of the anatomical site and better lymph node dissection planning. © 2013 The Japanese Society of Nuclear Medicine

Sindrome Metabolica e tumori: il ruolo dell’obesità

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Models for the integration of psychology and primary health care: Towards the concrete construction of primary care psychological treatment?

This review highlights the need to improve SSN to face adequately the growing mental health care demands. Previous research bearing on the topic show that the integration of different professional skills is necessary to achieve this target. A stepped care model, composed by a low-intensity intervention with high level of specificity, is the proposed tool. The introduction of psychologist in primary care system and in particular \uabLo Psicologo nella Casa della Salute\ubb project seems to answer this requirements