Colonic phenotype of the ileum in Crohn's disease: A prospective study before and after ileocolonic resection

Background: Colonic metaplasia has been described in pouchitis. In a prospective study, we investigated whether colonic phenotype may develop in Crohn's disease (CD) ileum. The expression of sulfomucins (colonic mucin), sialomucins, and CD10 (small intestine mucin and phenotype) was evaluated before and after ileocolonic resection for CD. Methods: From February 2007 to March 2010, 22 patients with CD undergoing surgery were enrolled. Clinical (Crohn's Disease Activity Index >150) and endoscopic recurrence (Rutgeerts score ≥1) rates were assessed at 6 and 12 months. Ileal samples were taken at surgery (T0), at 6 (T1), and 12 months (T2) for histology, histochemistry (High Iron Diamine-Alcian Blue), and immunohistochemistry (anti-CD10). Results: In 22 patients, recurrence was assessed at 6 and 12 months (clinical recurrence 9% and 18%; endoscopic recurrence 73% and 77%). In all 22 patients, ileal samples were taken at 6 and 12 months (involved area in patients with recurrence). In 19 of 22 (86.3%) patients, the involved ileum was also studied at surgery. At T0, T1, and T2, the expression of sialomucins and CD10 (small intestine mucin and phenotype) was comparable and higher (P < 0.0001) than the expression of sulfomucins (colonic mucin) (mean [range], T0:82 [35-100] versus 75 [0-100] versus 16 [0-50]; T1:96 [60-100] versus 94.7 [50-100] versus 3.89 [0-40]; T2:93.3 [60-100] versus 88.1 [25-100] versus 6.6 [0-40]). The expression of small-intestine mucin and phenotype was higher at T1 (P = 0.025) versus T0 (P = 0.026). Differently, the expression of colonic mucin was lower at T1 versus T0 (P = 0.027). Conclusions: In CD, the ileum involved by severe/established lesions develops a "metaplastic" colonic mucosa phenotype. Differently, CD ileum with no lesions or with early recurrence maintains the "native" small intestine type mucin secretion and phenotype

Infrared properties of randomly oriented silver nanowires

We experimentally investigated the infrared properties of a set of randomly oriented silver nanowires films deposited onto glass substrate. Infrared emission of the obtained films was characterized in the long infrared range, i.e., 8–12 μm, by observing their temperature evolution under heating regime with a focal plane array infrared camera as well as a thermocouple. The obtained experimental results showed that the infrared emission from a mesh composed of silver nanowires might be tailored by opportunely assessing preparation condition, such as the metal filling factor. From the theoretical point of view, the real and imaginary part of the electrical permittivity components were retrieved from the calculations of effective permittivities of in-plane randomly oriented metallic wires, thus giving the refractive index and extinction coefficients for the four different silver nanowires meshes. Due to the correspondence between emissivity and absorbance, the experimental results are interpreted with the reconstructed corresponding absorbance spectra, thus suggesting that these coatings are suitable for infrared signature reduction applications.Peer reviewe

Surface Roughness and Effective Stick-Slip Motion

The effect of random surface roughness on hydrodynamics of viscous incompressible liquid is discussed. Roughness-driven contributions to hydrodynamic flows, energy dissipation, and friction force are calculated in a wide range of parameters. When the hydrodynamic decay length (the viscous wave penetration depth) is larger than the size of random surface inhomogeneities, it is possible to replace a random rough surface by effective stick-slip boundary conditions on a flat surface with two constants: the stick-slip length and the renormalization of viscosity near the boundary. The stick-slip length and the renormalization coefficient are expressed explicitly via the correlation function of random surface inhomogeneities. The effective stick-slip length is always negative signifying the effective slow-down of the hydrodynamic flows by the rough surface (stick rather than slip motion). A simple hydrodynamic model is presented as an illustration of these general hydrodynamic results. The effective boundary parameters are analyzed numerically for Gaussian, power-law and exponentially decaying correlators with various indices. The maximum on the frequency dependence of the dissipation allows one to extract the correlation radius (characteristic size) of the surface inhomogeneities directly from, for example, experiments with torsional quartz oscillators.Comment: RevTeX4, 14 pages, 3 figure

Entry mode deviation: a behavioral approach to internalization theory

We explore when and why decision makers choose international entry modes (e.g., hierarchies or markets) that deviate from internalization theory’s predictions. By applying a cognitive perspective on entry mode decision making, we propose that the performance of prior international activities influences decision makers’ behavior in different ways than assumed in internalization theory. More specifically, due to a representativeness bias, underperforming (overperforming) past ventures influence the decision to change (continue using) the previous entry mode choice, which may result in an entry mode deviation. In addition, the propensity to deviate from theoretical predictions is stronger when the experience is recent and/or salient due to an availability bias. In conclusion, we argue that internalization theory can benefit from incorporating more systematically important behavioral assumptions on how firms enter international markets. In so doing, we contribute to the recent conversation on how variations in human behavior influence internalization theory

Molecular epidemiology of a hepatitis C virus epidemic in a haemodialysis unit: outbreak investigation and infection outcome

<p>Abstract</p> <p>Background</p> <p>HCV is a leading cause of liver chronic diseases all over the world. In developed countries the highest prevalence of infection is reported among intravenous drug users and haemodialysis (HD) patients. The present report is to identify the pathway of HCV transmission during an outbreak of HCV infection in a privately run haemodialysis (HD) unit in Italy in 2005.</p> <p>Methods</p> <p>Dynamics of the outbreak and infection clinical outcomes were defined through an ambi-directional cohort study. Molecular epidemiology techniques were used to define the relationships between the viral variants infecting the patients and confirm the outbreak. Risk analysis and auditing procedures were carried out to define the transmission pathway(s).</p> <p>Results</p> <p>Of the 50 patients treated in the HD unit 5 were already anti-HCV positive and 13 became positive during the study period (AR = 28.9%). Phylogenic analysis identified that, all the molecularly characterized incident cases (10 out of 13), were infected with the same viral variant of one of the prevalent cases. The multivariate analysis and the auditing procedure disclosed a single event of multi-dose vials heparin contamination as the cause of transmission of the infection in 11 out of the 13 incident cases; 2 additional incident cases occurred possibly as a result of inappropriate risk management.</p> <p>Discussion</p> <p>More than 30% of all HCV infections in developed countries results from poor application of standard precautions during percutaneous procedures. Comprehensive strategy which included: educational programmes, periodical auditing on standard precaution, use of single-dose vials whenever possible, prospective surveillance for blood-borne infections (including a system of prompt notification) and risk assessment/management dedicated staff are the cornerstone to contain and prevent outbreaks in HD</p> <p>Conclusions</p> <p>The outbreak described should serve as a reminder to HD providers that patients undergoing dialysis are at risk for HCV infection and that HCV may be easily transmitted whenever standard precautions are not strictly applied.</p

Leukotriene D(4)-induced activation of smooth-muscle cells from human bronchi is partly Ca(2+)-independent

Cysteine-containing leukotrienes (cysteinyl-LTs) are potent bronchoconstrictors and play a key role in asthma. We found that histamine and LTD, markedly constrict strips of human bronchi (HB) with similar efficacy. However, in human airway smooth-muscle (HASM) cells, LTD(4), at variance with histamine, elicited only a small, transient change in intracellular calcium ion concentration. HASM cells express both Ca(2+)-dependent and -independent isoforms of protein kinase C (PKC) (i.e., PKC-alpha and PKC-epsilon). Western blot analysis showed that PKC-alpha is activated by histamine and, to a lesser extent, by LTD(4), whereas only LTD(4) translocates PKC-epsilon. This translocation was specifically inhibited by the LTD4 antagonist pobilukast. Phorbol-dibutyrate ester (PDBu) (a PKC activator) contracted HE strips to the same extent in the presence as in the absence of extra- and intracellular Ca(2+). In the absence of Ca(2+), LTD(4) contracted HB strips to the same extent as did PDBu, suggesting the involvement of a Ca(2+)-independent PKC in LTD(4)-mediated signal transduction. PDBu-induced desensitization and the PKC inhibitor H7 abolished the slow and sustained LTD(4)-triggered contraction of HE strips in the absence of Ca(2+), although H7 did not greatly affect the response in the presence of the ion. Thus, in human airways, we identified a novel LTD(4) transduction mechanism linked to bronchial smooth-muscle contraction, which is partly independent of Ca(2+) and involves the activation of PKC-epsilon

dp53 Restrains Ectopic Neural Stem Cell Formation in the Drosophila Brain in a Non-Apoptotic Mechanism Involving Archipelago and Cyclin E

Accumulating evidence suggests that tumor-initiating stem cells or cancer stem cells (CSCs) possibly originating from normal stem cells may be the root cause of certain malignancies. How stem cell homeostasis is impaired in tumor tissues is not well understood, although certain tumor suppressors have been implicated. In this study, we use the Drosophila neural stem cells (NSCs) called neuroblasts as a model to study this process. Loss-of-function of Numb, a key cell fate determinant with well-conserved mammalian counterparts, leads to the formation of ectopic neuroblasts and a tumor phenotype in the larval brain. Overexpression of the Drosophila tumor suppressor p53 (dp53) was able to suppress ectopic neuroblast formation caused by numb loss-of-function. This occurred in a non-apoptotic manner and was independent of Dacapo, the fly counterpart of the well-characterized mammalian p53 target p21 involved in cellular senescence. The observation that dp53 affected Edu incorporation into neuroblasts led us to test the hypothesis that dp53 acts through regulation of factors involved in cell cycle progression. Our results show that the inhibitory effect of dp53 on ectopic neuroblast formation was mediated largely through its regulation of Cyclin E (Cyc E). Overexpression of Cyc E was able to abrogate dp53′s ability to rescue numb loss-of-function phenotypes. Increasing Cyc E levels by attenuating Archipelago (Ago), a recently identified transcriptional target of dp53 and a negative regulator of Cyc E, had similar effects. Conversely, reducing Cyc E activity by overexpressing Ago blocked ectopic neuroblast formation in numb mutant. Our results reveal an intimate connection between cell cycle progression and NSC self-renewal vs. differentiation control, and indicate that p53-mediated regulation of ectopic NSC self-renewal through the Ago/Cyc E axis becomes particularly important when NSC homeostasis is perturbed as in numb loss-of-function condition. This has important clinical implications