Autoimmunity and Extrahepatic Manifestations in Treatment-Naïve Children with Chronic Hepatitis C Virus Infection

Hepatitis C virus (HCV) infection has been associated with autoimmunity and extrahepatic manifestations in adults. Few data are available on these topics in children. Nonorgan specific auto-antibodies development is part of the natural course of chronic hepatitis C in children. Smooth muscle autoantibody is the most common autoantibody found, while liver-kidney microsomal type-1 antibody positivity is the most peculiar autoimmune feature of children with HCV infection. The clinical significance of non-organ specific autoantibodies in the course of paediatric chronic hepatitis C is still debated. Autoantibody positivity can be considered neutral for most patients, while it can be associated with negative connotations for others, especially those positive for liver-kidney microsomal type-1 autoantibody. Subclinical hypothyroidism but not autoimmune thyroiditis has been demonstrated in HCV infection in children, while only few cases of HCV-associated membranoproliferative glomerulonephritis have been described. Single reports are available in the literature reporting the anecdotal association between chronic hepatitis C and other extrahepatic manifestations such as myopathy and opsoclonus-myoclonus syndrome. Despite the low incidence of extrahepatic manifestations of chronic hepatitis C in children, overall, available data suggest a careful monitoring

Enhancing PFI Prediction with GDS-MIL: A Graph-based Dual Stream MIL Approach

Whole-Slide Images (WSI) are emerging as a promising resource for studying biological tissues, demonstrating a great potential in aiding cancer diagnosis and improving patient treatment. However, the manual pixel-level annotation of WSIs is extremely time-consuming and practically unfeasible in real-world scenarios. Multi-Instance Learning (MIL) have gained attention as a weakly supervised approach able to address lack of annotation tasks. MIL models aggregate patches (e.g., cropping of a WSI) into bag-level representations (e.g., WSI label), but neglect spatial information of the WSIs, crucial for histological analysis. In the High-Grade Serous Ovarian Cancer (HGSOC) context, spatial information is essential to predict a prognosis indicator (the Platinum-Free Interval, PFI) from WSIs. Such a prediction would bring highly valuable insights both for patient treatment and prognosis of chemotherapy resistance. Indeed, NeoAdjuvant ChemoTherapy (NACT) induces changes in tumor tissue morphology and composition, making the prediction of PFI from WSIs extremely challenging. In this paper, we propose GDS-MIL, a method that integrates a state-of-the-art MIL model with a Graph ATtention layer (GAT in short) to inject a local context into each instance before MIL aggregation. Our approach achieves a significant improvement in accuracy on the ``Ome18'' PFI dataset. In summary, this paper presents a novel solution for enhancing PFI prediction in HGSOC, with the potential of significantly improving treatment decisions and patient outcomes

Retinoids and cancer: antitumoral effects of ATRA, 9-cis RA and the new retinoid IIF on the HL-60 leukemic cell line.

Objective: To compare the antitumoral effects of all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) with those of 5-OH,11-O-hydrophenanthrene (IIF), a new derivative of retinoic acid. Materials and Methods: The effect of retinoids was tested on cell line HL-60. Cell differentiation and apoptosis were evaluated by morphological and biochemical analysis as bcl-2 protein and by DNA fragmentation assay. The ability to activate retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) and to modulate gene expression was determined by transactivation assay. Results: With cell line HL-60, the antiproliferative effect of IIF was stronger than that of ATRA and 9-cis RA. Following retinoid treatment, cells appeared to differentiate and apoptotic cells were observed. The appearance of DNA laddering and a decrease in the amount of bcl-2 protein confirmed apoptosis. IIF transcriptionally activated RXR-γ more than RAR-α. Conclusion: The findings indicate that IIF transcriptionally activates RXR-γ preferentially, induces apoptosis and has a more antiproliferative activity than ATRA and 9-cis RA on cell line HL-60

Growing Strong and Healthy with Mister Bone: An Educational Program to Have Strong Bones Later in Life.

Optimal peak bone mass and bone health later in life are favored by a sufficient calcium intake in infancy, childhood and adolescence. The purpose of this study was to test a new educational program created to monitor and to improve calcium and vitamin D intake in children. Nutritional habits in children were evaluated through a food frequency questionnaire (FFQ) to assess the intake of calcium, vitamin D, dairy products, and total caloric energy at baseline and after seven months of exposure to a unique educational program applied between November 2013 and May 2014 in 176 schoolchildren (48% male, 52% female) attending the fourth and fifth grades of two selected primary schools in Florence, Italy. A significant increase of calcium (from 870 ± 190 to 1100 ± 200 mg/day, p < 0.05), and vitamin D (from 3.6 ± 1.53 to 4.1 ± 2 µg/day) intake in children was documented after the educational program. The amount of specific foods important for bone health consumed, such as milk and vegetables, increased significantly, both in male and female children (p < 0.05). The proposed educational program appears to be effective in modifying calcium intake in children, with a significant increase in the consumption of dairy products and vegetables, but without a significant change in the total caloric intake

Prevalence, molecular epidemiology and intra-hospital acquisition of Klebsiella pneumoniae strains producing carbapenemases in an Italian teaching hospital from January 2015 to September 2016.

Objectives: We described Klebsiella pneumoniae producing carbapenemase (CPKP) spread from 01/01/2015 to 13/09/16 in a tertiary level hospital. Methods: The first positive surveillance rectal swab (SRS) or clinical sample (CS) collected in the medical department (MD), surgical department (SD) and intensive care department (ICD) were included in the study. A validated in-house Real-Time PCR method was used to detect carbapenemases; multilocus sequence typing (MLST) was used for further characterization of the strains. Results: 21535 patients were included: 213 CPKP strains from surveillance rectal swab (SRS) and 98 from clinical samples (CS) were collected. The percentage of CPKP detected in SRS with respect to CS increased in the medical MD from 2015 to 2016 (p = 0.01) and in ICD from 2012 to 2015 (p = 0.0001), while it decreased in SD from 2014 to 2016 (p = 0.003); 68.5% of the positive SRS had a previous negative SRS; CPKP was more frequently identified in CS than in SRS in MD. Twelve strains harboured more than one carbapenemase gene. Many other species harbouring a carbapenemase gene were collected. Conclusions: MDs need more inclusive surveillance criteria. The late detection of positive SRS underlined the risk of colonization during hospitalization