Pancreatic cystosis in cystic fibrosis. Sometimes a bike ride can help you decide

Pancreatic cystosis (PC) is an uncommon manifestation of pancreas involvement in cystic fibrosis (CF), characterized by the presence of multiple macrocysts partially or completely replacing pancreas. Only few reports are available from literature and management (surgery vs follow up) is commonly based on the presence of symptoms or complications due to local mass effect, although evidence-based recommendations are still not available. We here report the case of a young adult CF patient with PC, in which cardiopulmonary exercise testing (CPET) provided important information to be integrated to the radiological finding of inferior vena cava compression by the multicystic pancreas complex. Through the analysis of oxygen kinetic cardiodynamic phase pattern, CPET may be helpful to safely exclude significant mass effects on blood venous return and to improve the decision-making process on whether to consider surgery or not in patients with PC

The psoriatic shift induced by interleukin 17 is promptly reverted by a specific anti-IL-17A agent in a three-dimensional organotypic model of normal human skin culture

Interleukin 17A (IL-17A), mainly produced by the T helper subclass Th17, plays a key role in the psoriatic plaque formation and progression. The clinical effectiveness of anti-IL-17A agents is documented, but the early and specific mechanisms of their protection are not identified yet. The challenge of the present study is to investigate the possible reversal exerted by a specific anti-IL-17A agent on the psoriatic events induced by IL-17A in a three-dimensional organotypic model of normal human skin. Bioptic skin fragments obtained after aesthetic surgery of healthy women (n=5) were incubated with i) IL-17A biological inhibitor (anti-IL-17A), ii) IL-17A, iii) a combination of IL-17A and its specific IL-17A biological inhibitor (COMBO). A Control group was in parallel cultured and incubation lasted for 24 and 48 h epidermal-side-up at the air-liquid interface. All subjects were represented in all experimental groups at all considered time-points. Keratinocyte proliferation and the presence of epidermal Langerhans cells were quantitatively estimated. In parallel with transmission electron microscopy analysis, immunofluorescence studies for the epidermal distribution of keratin (K)10, K14, K16, K17, filaggrin/occludin, Toll-like Receptor 4, and Nuclear Factor kB were performed. IL-17A inhibited cell proliferation and induced K17 expression, while samples incubated with the anti-IL-17A agent were comparable to controls. In the COMBO group the IL-17A-induced effects were almost completely reverted. Our study, for the first time, elucidates the most specific psoriatic cellular events that can be partially affected or completely reverted by a specific anti-IL-17A agent during the early phases of the plaque onset and progression. On the whole, this work contributes to expand the knowledge of the psoriatic tableau

Ultrastructural features in organotypic cultures of normal human skin in an in vitro microenvironment mimicking atopic dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease charactided by chronic, systemic inflammation, early age of onset, persistent itch, marked redness, cracking, and dryness of the skin. Skin infections occur frequently in AD, contribute to the disordered immune activity and are probably related to disruption of skin barrier by inhibiting lipids, tight junctions, and antimicrobial peptide formation. Among the several cytokines involved in the AD pathogenesis interleukin (IL) -4, IL- 1 3 and IL22 play a key role. The present study is focused on the early effects of pro-inflammatory cytokines on ultrastructural changes using transmission electron microscopy (TEM) in a well standardized 3D model of normal human skin organotypic culture. Skin explants obtained from plastic surgery of healthy 20-40 yearold women (n = 5) after informed consent were cultured ovemight in Dulbecco's modified Eagle's medium and treated with 50 nglml IL-4, 50 nglml IL-13 and 100 nglml IL-22 alone or in combination (TRIS). Samples were then harvested 24 and 48 hours after the cytokine incubation. In all samples exposed to cytokines, desmosomes appeared well preserved, comparable to controls. TEM analysis revealed that, starting from24 hours of culture, the exposure toIL-4, but not to IL13, caused a marked enlargement of intercellular spaces and chromatin condensation. In TRIS treated samples, these alterations were less evident, however, we have observed condensation of cytoskeletal filaments. Altogether, this present study strongly suggest that this experimental approach useful for studying the early, direct, and specific effects of pro-inflammatory AD cytokines and may be useful for assessing new biological drugs directed against a specific cytokine

Effects of cytokines involved in a microenvironment mimicking atopic dermatitis in a well standardized three-dimensional model of normal human skin

Atopic dermatitis (AD) is one of the most common chronic skin inflammatory disorders, driven by several pro-inflammatory cytokines among which interleukin (IL)-4, IL-13, and IL-22 are the most involved mediators. Tight junctions (TJs) are targeted in AD from both a morphological and a molecular level, leading an epidermal barrier disruption, which is one of the clinical manifestations of AD. TJs seal adjacent keratinocytes in the granular layer and are composed by transmembrane proteins such as occludin and claudins, in addition to cytosolic scaffold proteins. The present study was aimed at evaluating the early effects of IL-4 and IL-13 using a well-standardized three-dimensional model of normal human skin. Skin explants were obtained from plastic surgery of healthy women (n=5) 20-40 years old after informed consent, and cultured overnight in Dulbecco\u2019s modified Eagle\u2019s medium and treated with 50 ng/mL IL-4, 50 ng/mL IL-13. Secondly, the samples were harvested 24 hours after the cytokine incubation and in parallel processed for morphological and molecular biology analysis through both Western Blot. Compared to control samples, a decrease of the expression of occludin was found in samples incubated with either IL-4 or IL-13. TEM analysis revealed an increase of the intercellular spaces and chromatine condensation only in samples treated with IL-4, with well preserved desmosomes. Conversely, samples incubated with IL-13 showed similar features as control ones. All these results suggest the usefulness of this experimental model, which could be used in order to study and evaluate the early and direct effects of several pro-inflammatory cytokines involved in AD, providing a well and standardize method for pre-clinic dermatology research

Una rettocolite "difficile"

Viene esposto un caso clinico di rettocolite in età pediatrica, interessante sia per la gravità che per la precosità del quadro clinico (la RCU ha un esordio tipico in età adolescente-adulta; i casi in età pediatric, specialmente nei lattanti e durante la prima infanzia, sono invece rari e in genere a prognosi più severa), sia per l'elevato numero di recidive presentate in un lasso di tempo relativamente breve

Role of multiparametric MRI in the diagnosis of prostate cancer: update

Prostate cancer is the most common malignancy of the male gender. The role of magnetic resonance imaging has evolved very rapidly over the years to be currently recognized as a fundamental tool in the diagnosis, treatment and follow-up of prostate cancer

Improvement of prostate cancer detection combining a computer-aided diagnostic system with TRUS-MRI targeted biopsy

Purpose: To validate a novel consensus method, called target-in-target, combining human analysis of mpMRI with automated CAD system analysis, with the aim to increasing the prostate cancer detection rate of targeted biopsies. Methods: A cohort of 420 patients was enrolled and 253 patients were rolled out, due to exclusion criteria. 167 patients, underwent diagnostic 3T MpMRI. Two expert radiologists evaluated the exams adopting PI-RADSv2 and CAD system. When a CAD target overlapped with a radiologic one, we performed the biopsy in the overlapping area which we defined as target-in-target. Targeted TRUS-MRI fusion biopsy was performed in 63 patients with a total of 212 targets. The MRI data of all targets were quantitatively analyzed, and diagnostic findings were compared to pathologist’s biopsy reports. Results: CAD system diagnostic performance exhibited sensitivity and specificity scores of 55.2% and 74.1% [AUC = 0.63 (0.54 ÷ 0.71)] , respectively. Human readers achieved an AUC value, in ROC analysis, of 0.71 (0.63 ÷ 0.79). The target-in-target method provided a detection rate per targeted biopsy core of 81.8 % vs. a detection rate per targeted biopsy core of 68.6 % for pure PI-RADS based on target definitions. The higher per-core detection rate of the target-in-target approach was achieved irrespective of the presence of technical flaws and artifacts. Conclusions: A novel consensus method combining human reader evaluation with automated CAD system analysis of mpMRI to define prostate biopsy targets was shown to improve the detection rate per biopsy core of TRUS-MRI fusion biopsies. Results suggest that the combination of CAD system analysis and human reader evaluation is a winning strategy to improve targeted biopsy efficiency

SMC1 involvement in fragile site expression

Common fragile sites have been involved in neoplastic transformation, although their molecular basis is still poorly understood. Here, we demonstrate that inhibition of the SMC1 by RNAi is sufficient to induce fragile site expression. By investigating normal, ATM- and ATR-deficient cell lines, we provide evidence that the contribution of SMC1 in preventing the collapse of stalled replication fork is an Atr-dependent pathway. Using a fluorescent antibody specific for gamma-H2AX, we show that very rare discrete nuclear foci appear 1 and 2 h after exposure to aphidicolin and/or RNAi-SMC1, but became more numerous and distinct after longer treatment times. In this context, fragile sites might be viewed as an in vitro phenomenon originating from double-strand breaks formed because of a stalled DNA replication that lasted too long to be managed by physiological rescue acting through the Atr/Smc1 axis. We propose that in vivo, following an extreme replication block, rare cells could escape checkpoint mechanisms and enter mitosis with a defect in genome assembly, eventually leading to neoplastic transformation