Background: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. Methods: In 1996 an IBD register of disease onset was established on a national scale. Results: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohn's disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996–2003 an increase of IBD incidence from 0.89 to 1.39/105 inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. Conclusions The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD. (Inflamm Bowel Dis 2008)

Summary Within the interleukin 1 (IL-1) cytokine family, IL-1 receptor accessory protein (IL-1RAcP) is the co-receptor for eight receptor:cytokine pairs, including cytokines IL-1β and IL-33. Unlike for IL-1β, no structure of the IL-33 signaling complex exists that includes both its cognate receptor, ST2, and the shared co-receptor IL-1RAcP, which we now present here. Although the IL-1β and IL-33 complexes shared structural features and engaged identical molecular surfaces of IL-1RAcP, these cytokines had starkly different strategies for co-receptor engagement and signal activation. Our data suggested that IL-1β bound to IL-1RI to properly present the cytokine to IL-1RAcP, while IL-33 bound to ST2 in order to conformationally constrain the cognate receptor in an IL-1RAcP-receptive state. These findings indicated that IL-1 family cytokines use distinct molecular mechanisms to signal through their shared co-receptor, and provide the foundation from which to design new therapies to target IL-33 signaling.

Chemotherapy treatments are considered essential tools to defeat cancer progression and dissemination to improve patients’ quality of life and survival. Although most malignancies initially respond to chemotherapeutic treatments, after an unpredictable period, tumor cells develop mechanisms of resistance to the treatment. Different cell compartments are involved in the mechanism of chemoresistance, and multiple mechanisms can be activated by single cells at different times of the cancer progression. Alteration of drug metabolism, derangement of intracellular pathways’ signaling, cross-talk between different membrane receptors, and modification of apoptotic signaling and interference with cell replication are all mechanisms that the cell uses to overcome the effect of pharmacological compounds. In this review, we describe different adaptation, mostly at the level of the proteome, which cancer cells use to develop resistance to cancer treatment.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited and very often, ineffective medical and surgical therapeutic options. The treatment of patients with advanced unresectable PDAC is restricted to systemic chemotherapy, a therapeutic intervention to which most eventually develop resistance. Recently, nab-paclitaxel has been added to the arsenal of first line therapies, and the combination of gemcitabine and nab-paclitaxel has modestly prolonged median overall survival. However, patients almost invariably succumb to the disease, and little is known about the mechanisms underlying nab-paclitaxel (n-PTX) resistance. Using the conditionally reprogrammed (CR) cell approach, we established and verified continuously growing cell cultures from treatment-naive PDAC patients. To study the mechanisms of primary drug resistance, nab-paclitaxel-resistant (n-PTX-R) cells were generated from primary cultures and drug resistance was verified in vivo, both in zebrafish and in athymic nude mouse xenograft models. Molecular analyses identified the sustained induction of c-MYC in the nab-paclitaxelresistant cells. Depletion of c-Myc restored nab-paclitaxel sensitivity, as did treatment with either the MEK inhibitor, trametinib, or a small molecule activator of protein phosphatase 2a (SMAP). Implications: The strategies we have devised, including the patient-derived primary cells and the unique, drug resistant isogenic cells, are rapid and easily applied in vitro and in vivo platforms to better understand the mechanisms of drug resistance and for defining effective therapeutic options on a patient by patient basis.

At the molecular level, the evolution of life is driven by the generation and diversification of adaptation mechanisms. A universal description of adaptation-capable chemical reaction network (CRN) structures has remained elusive until now, since currently-known criteria for adaptation apply only to a tiny subset of possible CRNs. While adaptation is known to require some form of embedded integral control, current approaches can only identify an internal integral structure in simple special cases. Here we identify the definitive structural requirements that characterize all adaptation-capable collections of interacting molecules, however large or complex. We show that these network structures implement a form of integral control in which multiple independent integrals can collaborate to confer the capacity for adaptation on specific molecules. We present a universal method to test for adaptation capacity, and for detecting the adaptation-conferring integrals, in any CRN. Using this new approach, we demonstrate the existence of embedded integrals in a variety of biologically important CRNs that have eluded previous methods, and for which adaptation has been observed experimentally. This definitive picture of biological adaptation at the level of intermolecular interactions represents a blueprint for adaptation-capable signalling networks across all domains of life, and for the design of synthetic biosystems.

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PurposeThe purpose of this article is to present images from simulated breast microcalcifications and assess the pattern of the microcalcifications with a technical development called “depth 3-dimensional (D3D) augmented reality”.Materials and methodsA computer, head display unit, joystick, D3D augmented reality software, and an in-house script of simulated data of breast microcalcifications in a ductal distribution were used. No patient data was used and no statistical analysis was performed.ResultsThe D3D augmented reality system demonstrated stereoscopic depth perception by presenting a unique image to each eye, focal point convergence, head position tracking, 3D cursor, and joystick fly-through.ConclusionThe D3D augmented reality imaging system offers image viewing with depth perception and focal point convergence. The D3D augmented reality system should be tested to determine its utility in clinical practice.

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