Multimodality Imaging for Diagnosis and Characterization of a Cardiac Hydatid Cyst.

Here, we report the case of a young patient admitted to the emergency department because of abdominal pain. Computed tomography revealed a mass within her right heart. Through serial multimodality imaging testing, including computed tomography, three-dimensional (2D)- and three-dimensional echocardiography, as well as cardiac magnetic resonance, the diagnosis of cardiac involvement in the course of Echinococcus granulosus infection was hypothesized.

Cultivar-Dependent Anticancer and Antibacterial Properties of Silver Nanoparticles Synthesized Using Leaves of Different Olea Europaea Trees.

The green synthesis of nanoparticles (NPs) is currently under worldwide investigation as an eco-friendly alternative to traditional routes (NPs): the absence of toxic solvents and catalysts make it suitable in the design of promising nanomaterials for nanomedicine applications. In this work, we used the extracts collected from leaves of two cultivars (Leccino and Carolea) belonging to the species Olea Europaea, to synthesize silver NPs (AgNPs) in different pH conditions and low temperature. NPs underwent full morphological characterization with the aim to define a suitable protocol to obtain a monodispersed population of AgNPs. Afterwards, to validate the reproducibility of the mentioned synthetic procedure, we moved on to another Mediterranean plant, the Laurus Nobilis. Interestingly, the NPs obtained using the two olive cultivars produced NPs with different shape and size, strictly depending on the cultivar selected and pH. Furthermore, the potential ability to inhibit the growth of two woman cancer cells (breast adenocarcinoma cells, MCF-7 and human cervical epithelioid carcinoma, HeLa) were assessed for these AgNPs, as well as their capability to mitigate the bacteria concentration in samples of contaminated well water. Our results showed that toxicity was stronger when MCF-7 and Hela cells were exposed to AgNPs derived from Carolea obtained at pH 7 presenting irregular shape; on the other hand, greater antibacterial effect was revealed using AgNPs obtained at pH 8 (smaller and monodispersed) on well water, enriched with bacteria and coliforms.

Is Left Ventricular Noncompaction Only a Morphological Feature? A Case of Disappearance of Noncompaction after Surgical Correction of Aorto-Right Ventricular Fistula, Interventricular Septal Defect and Aortic Stenosis.

A 55-year-old man complaining of worsening dyspnea on exertion was diagnosed with restrictive interventricular septal defect, left ventricular noncompaction (LVNC), mild aortic valve stenosis and aorto-right ventricular fistula. He underwent surgical aortic valve replacement with a mechanical bileaflet valve (St. Jude n. 23) and contextual direct suture of interventricular septal defect and closure of aorto-right ventricular fistula. At 2 years of follow-up, the patient was in good general condition. A complete echocardiographic examination showed normalization of left ventricular dimensions and ejection fraction. Furthermore, left ventricular trabeculations became less evident and no longer met the diagnostic criteria for noncompaction. In our case, the expected left ventricular reverse remodeling after cardiac surgery was associated with a significant reduction in LVNC features. In conclusion, physicians should be careful in avoiding overdiagnosis of LVNC, whose features may indeed reflect only the hypertrabeculated morphology of a normal or pathological heart.

Investigating the relation between stochastic differentiation, homeostasis and clonal expansion in intestinal crypts via multiscale modeling.

Colorectal tumors originate and develop within intestinal crypts. Even though some of the essential phenomena that characterize crypt structure and dynamics have been effectively described in the past, the relation between the differentiation process and the overall crypt homeostasis is still only partially understood. We here investigate this relation and other important biological phenomena by introducing a novel multiscale model that combines a morphological description of the crypt with a gene regulation model: the emergent dynamical behavior of the underlying gene regulatory network drives cell growth and differentiation processes, linking the two distinct spatio-temporal levels. The model relies on a few a priori assumptions, yet accounting for several key processes related to crypt functioning, such as: dynamic gene activation patterns, stochastic differentiation, signaling pathways ruling cell adhesion properties, cell displacement, cell growth, mitosis, apoptosis and the presence of biological noise. We show that this modeling approach captures the major dynamical phenomena that characterize the regular physiology of crypts, such as cell sorting, coordinate migration, dynamic turnover, stem cell niche correct positioning and clonal expansion. All in all, the model suggests that the process of stochastic differentiation might be sufficient to drive the crypt to homeostasis, under certain crypt configurations. Besides, our approach allows to make precise quantitative inferences that, when possible, were matched to the current biological knowledge and it permits to investigate the role of gene-level perturbations, with reference to cancer development. We also remark the theoretical framework is general and may be applied to different tissues, organs or organisms.

Early systemic sclerosis: analysis of the disease course in patients with marker autoantibody and/or capillaroscopic positivity.

OBJECTIVE: To investigate whether patients affected by 1 of the 3 subsets of early systemic sclerosis (SSc; scleroderma), i.e., subset I, Raynaud's phenomenon with SSc marker autoantibodies and typical capillaroscopic findings; subset II, autoantibody positive only; and subset III, capillaroscopy positive only and not satisfying the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for SSc at admission, differ from each other in the time to satisfy the criteria. METHODS: Early SSc patients subdivided into the 3 subsets indicated above consecutively admitted to a rheumatology/angiology center were monitored for 12-102 months (median 36 months). Patients were reevaluated twice yearly to assess whether and when each patient satisfied the new ACR/EULAR classification criteria for SSc. Patients with undifferentiated connective tissue disease (UCTD) served as the comparator group. RESULTS: During followup, 11 (52.3%) of 21 subset I, 10 (66.6%) of 15 subset II, 0 of 24 subset III, and 0 of 44 UCTD patients satisfied the criteria (P = 0.0001). The difference was significant between early SSc and UCTD patients (P = 0.0001) and, within the group of early SSc patients, between each of the 2 autoantibody-positive subsets (subsets I and II) and the capillaroscopic-positive/autoantibody-negative subset (subset I versus III: P = 0.0001; subset II versus III: P = 0.0009). There was no difference between the 2 autoantibody-positive subsets (P = 0.454). In addition to marker autoantibody positivity, preclinical lung or heart involvement was associated with an increased risk to satisfy the criteria during followup. CONCLUSION: Our data demonstrated faster progression of SSc in autoantibody-positive patients, particularly in those with preclinical internal organ involvement at baseline, than in autoantibody-negative patients.

Calamitic and antinematic orientational order produced by the generalized Straley lattice model.

We consider here a classical model, consisting of D_{2h}-symmetric particles in a three-dimensional simple-cubic lattice; the pair potential is isotropic in orientation space, and restricted to nearest neighbors. The simplest potential model is written in terms of the squares of the scalar products between unit vectors describing the three interacting arms of the molecules, as proposed in previous literature. Two predominant antinematic couplings of equal strength (+1) are perturbed by a comparatively weaker calamitic one, parameterized by a coupling constant -z ranging in [-1,0]. This choice rules out thermodynamically stable phases endowed with macroscopic biaxiality. The antinematic terms favor states with the corresponding molecular axes mutually orthogonal. Although the low-temperature phase of the special case with null calamitic term (PP0) is uniaxial and antinematically ordered, in the general case presented here both Monte Carlo and molecular-field approaches show that, for z close to zero, the models exhibit a low-temperature uniaxial nematic phase, followed by an antinematic one, and finally by the orientationally disordered one. On the other hand, for sufficiently large values of z, we only find evidence of uniaxial calamitic behavior, as expected by following the limiting cases.

Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers.

INTRODUCTION: Early systemic sclerosis (SSc) is characterized by Raynaud's phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of SSc. Patients presenting with marker autoantibodies plus a capillaroscopic scleroderma pattern seem to evolve into definite SSc more frequently than patients with either feature. Whether early SSc patients with only marker autoantibodies or capillaroscopic positivity differ in any aspect at presentation is unclear. METHODS: Seventy-one consecutive early SSc patients were investigated for preclinical cardiopulmonary alterations. Out of these, 44 patients and 25 controls affected by osteoarthritis or primary fibromyalgia syndrome were also investigated for serum markers of fibroblast (carboxyterminal propeptide of collagen I), endothelial (soluble E-selectin) and T-cell (soluble IL-2 receptor alpha) activation. RESULTS: Thirty-two of the 71 patients (45.1%) had both a marker autoantibody and a capillaroscopic scleroderma pattern (subset 1), 16 patients (22.5%) had only a marker autoantibody (subset 2), and 23 patients (32.4%) had only a capillaroscopic scleroderma pattern (subset 3). Patients with marker autoantibodies (n = 48, 67.6%) had a higher prevalence of impaired diffusing lung capacity for carbon monoxide (P = 0.0217) and increased serum levels of carboxyterminal propeptide of collagen I (P = 0.0037), regardless of capillaroscopic alterations. Patients with a capillaroscopic scleroderma pattern (n = 55, 77.5%) had a higher prevalence of puffy fingers (P = 0.0001) and increased serum levels of soluble E-selectin (P = 0.0003) regardless of marker autoantibodies. CONCLUSION: These results suggest that the autoantibody and microvascular patterns in early SSc may each be related to different clinical-preclinical features and circulating activation markers at presentation. Longitudinal studies are warranted to investigate whether these subsets undergo a different disease course over time.

A review of spatial computational models for multi-cellular systems, with regard to intestinal crypts and colorectal cancer development.

Colon rectal cancers (CRC) are the result of sequences of mutations which lead the intestinal tissue to develop in a carcinoma following a "progression" of observable phenotypes. The actual modeling and simulation of the key biological structures involved in this process is of interest to biologists and physicians and, at the same time, it poses significant challenges from the mathematics and computer science viewpoints. In this report we give an overview of some mathematical models for cell sorting (a basic phenomenon that underlies several dynamical processes in an organism), intestinal crypt dynamics and related problems and open questions. In particular, major attention is devoted to the survey of so-called in-lattice (or grid) models and off-lattice (off-grid) models. The current work is the groundwork for future research on semi-automated hypotheses formation and testing about the behavior of the various actors taking part in the adenoma-carcinoma progression, from regulatory processes to cell-cell signaling pathways.

Antinematic orientational order produced by an extreme case of the generalized Straley lattice model.

We address here a special, extreme case of the quadratic pair interaction potential between classical, D(2h)-symmetric particles (the generalized Straley model) on a three-dimensional simple cubic lattice. The model involves predominant antinematic couplings and it has been studied by Monte Carlo simulation and a molecular field treatment. The obtained results show a second-order transition between the isotropic phase and the low-temperature one, exhibiting uniaxial antinematic order.

Orientationally ordered phase produced by fully antinematic interactions: a simulation study.

We consider here a classical model, consisting of D(2h) symmetric particles, whose centers of mass are associated with a three-dimensional simple-cubic lattice; the pair potential is isotropic in orientation space, and restricted to nearest neighbors. Two orthonormal triads define orientations of a pair of interacting particles; the simplest potential models proposed in the literature can be written as a linear combination involving the squares of the scalar products between corresponding unit vectors only, thus depending on three parameters, and making the interaction model rather versatile. A coupling constant with negative sign tends to keep the two interacting unit vectors parallel to each other, whereas a positive sign tends to keep them mutually orthogonal (antinematic coupling). We address here a special, extreme case of the above family, involving only antinematic couplings: more precisely, three antinematic terms whose coefficients are set to a common positive value (hence the name PPP model). The model under investigation produces a doubly degenerate pair ground state; the nearest-neighbor range of the interaction and the bipartite character of the lattice can propagate the pair ground state and increase the overall degeneracy, but without producing frustration. The model was investigated by a simplified molecular field treatment as well as by Monte Carlo simulation, whose results suggested a second-order transition to a low-temperature biaxially ordered phase; ground-state configurations producing orientational order have been selected by thermal fluctuations. The molecular field treatment also predicted a continuous transition, and was found to overestimate the transition temperature by a factor 2.

Director libration in nematoacoustics.

We extended the analysis of a variational theory for nematoacoustics recently proposed by Virga [Phys. Rev. E 80, 031705 (2009)] by allowing the nematic director to vibrate about an average orientation at the frequency of a propagating wave, a periodic motion that we call the director libration. The acoustic susceptibilities, two phenomenological parameters that, in this theory, express the coupling between director and acoustic fields, are estimated along with an extra viscosity coefficient by using available experimental data.

Time spent for activation of non-profit studies in oncology in Italy.

AIM: The aim of this paper is to describe the time spent to activate oncological non-profit clinical trials promoted in Italy by the National Cancer Institute of Naples, following the implementation of recent European laws. METHODOLOGY: Data about the process of activation of 5 non-profit multicentre clinical trials were prospectively collected through a web-based system. The impact of European guidelines was assessed by comparing the efficiency of the process between applications started before and after the decree introducing in Italy the Clinical Trial Application form (MD-CTA). Outcomes of the descriptive analyses were the time to EC opinion, the time to administrative agreement signature after a positive EC opinion, and the cumulative percentage of submissions that came to closure (either positive or negative) within four subsequent time cohorts. PRINCIPAL FINDINGS: From March 2007 to October 2009, 202 applications were submitted to 107 centres. Forty-four (59%) applications of those submitted before were successful, compared to 71 (55%) of those submitted after MD-CTA. Most of the failures were due to missing EC response (27% and 22%) or administrative reasons (10% and 16%, before and after, respectively); very few (4% and 7%) were due to EC refusal. The impact of the MD-CTA on time to EC opinion looked positive (median 4.1 vs 2.4 months, before and after, respectively) but a subgroup analysis revealed that the impact was limited to a comparison biased by the selection of EC. After a positive EC opinion, there was no difference before and after MD-CTA in the time to administrative agreement signature (median 3.6 and 3.8 months, respectively). A trend to shortening time to closure of the whole submission process over the time was evident, with 58% of the applications coming to closure within 6 months from submission in the most recent cohort. CONCLUSIONS: In our experience there is reassuring evidence of a trend toward shortening the time spent to activate non-profit clinical trials in Italy, but the whole process still remains inefficient. Efforts should be made to improve the process, also focusing on administrative procedures.

Mesogenic lattice models with partly antinematic interactions producing uniaxial nematic phases.

The present paper considers nematogenic lattice models, involving particles of D_{2h} symmetry, whose centers of mass are associated with a three-dimensional simple cubic lattice; the pair potential is isotropic in orientation space and restricted to nearest neighbors. Let two orthonormal triads define orientations of a pair of interacting particles; the simplest potential models proposed in the literature can be reduced to a linear combination involving the squares of the scalar products between corresponding unit vectors only and depending on three parameters. By now, various sets of potential parameters have been proposed and studied in the literature, some of which capable of producing biaxial orientational order at sufficiently low temperature. On the other hand, in experimental terms, mesogenic biaxial molecules mostly produce uniaxial mesophases; thus we address here two very simple cases, involving a nematic (calamitic) term as well as one (model P0M) or two (model PPM) antinematic ones, whose coefficients are set equal in magnitude; when only one antinematic coefficient is used, the third one is set to zero. The calamitic term favors the alignment of two corresponding molecular axes, whereas antinematic terms or geometric constraints tend to keep two other pairs of axes mutually orthogonal. The models were investigated by molecular-field treatments and Monte Carlo simulation and found to predict a first- or second-order transitions between uniaxial nematic and isotropic phases; the molecular-field treatments yielded results in reasonable agreement with simulation.

Biaxial and uniaxial phases produced by partly repulsive mesogenic models involving D2h molecular symmetries.

The present paper considers biaxial nematogenic lattice models, involving particles of D2h symmetry, whose centers of mass are associated with a three-dimensional simple-cubic lattice. The pair potential is isotropic in orientation space and restricted to nearest neighbors. Let two orthonormal triads define orientations of a pair of interacting particles. The investigated potential models are quadratic with respect to the nine scalar products between the two sets of unit vectors. Actually, based on available geometric identities, these expressions can be reduced to diagonal form containing only the scalar products between corresponding unit vectors and depending on three parameters. Over the years, this comparatively simple functional form has also proven to be rather versatile. By now, various sets of potential parameters capable of producing mesogenic behavior of some kind have been proposed and studied in the literature. A new and simplified form was recently proposed and investigated by Sonnet, Virga, Durand, and De Matteis [A. M. Sonnet, E. G. Virga, and G. E. Durand, Phys. Rev. E 67, 061701 (2003); G. De Matteis and E. G. Virga, Phys. Rev. E 71, 061703 (2005)] and is known to support a biaxial phase at sufficiently low temperature. Following the idea of the above authors, we have studied a more extended range of parameters, including cases where biaxiality cannot be sustained in the pair ground state. In cases where a biaxial phase survives, an appropriate mean-field analysis may predict the existence of a direct second-order transition to the isotropic phase as well as a second-order sequence isotropic-to-uniaxial-to-biaxial. A second-order phase transition is also predicted, which involves isotropic and uniaxial phases only. Monte Carlo simulations have been carried out as well, for a few points in the parameter space, and found to produce results which partly confirm mean-field predictions.

[An atypical case of tako-tsubo syndrome presenting with symptomatic bradycardia]. / Sindrome di tako-tsubo: descrizione di un caso atipico con bradicardia sintomatica all'esordio.

The tako-tsubo syndrome (transient left ventricular apical ballooning with normal coronary arteries), initially described in Japanese patients, is now being increasingly observed worldwide and should be considered in the differential diagnosis of acute coronary syndromes. Angina-like chest pain, electrocardiographic changes and an increase in myocardial markers are often present, as well as history of acute stressful events preceding symptom onset. We report the case of an Asiatic woman in whom typical, reversible abnormalities in left ventricular motion were associated with symptomatic junctional bradycardia. Nevertheless, the patient was completely free from angina and excluded acute pain or emotions in the previous weeks. Coronary angiography showed absence of significant disease and left ventricular function was found to be unremarkable 1 month after the acute event. Although infrequent, atypical presentations of tako-tsubo syndrome have occasionally been reported and, in our opinion, they could provide interesting insights into the ill-defined pathophysiology of the disease.

Universal mean-field phase diagram for biaxial nematics obtained from a minimax principle.

We study a class of quadratic Hamiltonians which describe both fully attractive and partly repulsive molecular interactions, characteristic of biaxial liquid crystal molecules. To treat the partly repulsive interactions we establish a minimax principle for the associated mean-field free energy. We show that the phase diagram described by Sonnet [Phys. Rev. E 67, 061701 (2003)] is universal. Our predictions are in good agreement with the recent observations on both V-shaped and tetrapodal molecules.

Bifurcation analysis and computer simulation of biaxial liquid crystals.

We extend the analysis of a mean-field model for biaxial liquid crystals recently proposed by Sonnet et al. [Phys. Rev. E 67, 061701 (2003)]. In particular, we perform a bifurcation analysis of the equilibrium equations and derive the complete phase diagram. We show that two order parameters suffice to label all equilibrium phases, though they exhibit different bifurcation patterns. A Monte Carlo simulation study is performed as well, confirming qualitatively the predictions of this analysis.

Tricritical points in biaxial liquid crystal phases.

We further pursue the analysis of a mean-field model recently proposed by Sonnet [Phys. Rev. E 67, 061701 (2003)] to describe nematic biaxial phases. This model, which is based on a simplified version of Straley's pair potential, is characterized by the prediction of a tricritical point along the transition line between uniaxial and biaxial phases. We show that the same model predicts another tricritical point, but along the line of the direct isotropic-to-biaxial transition. Our prediction is quantitative, as it stems from an analytical criterion for tricriticality.

Analysis of valve motion after the reimplantation type of valve-sparing procedure (David I) with a new aortic root conduit.

BACKGROUND: The reimplantation type of valve-sparing procedure does not allow proper reconstruction of the sinuses of Valsalva. We assessed the valve motion after a reimplantation type (David I) of valve-sparing procedure using a new Dacron conduit that incorporates sinuses of Valsalva. METHODS: Nine consecutive patients undergoing an aortic valve-sparing procedure using the new conduit were studied using two-dimensional transesophageal echocardiography shortly (2 +/- 1 months) after operation to determine root distensibility, expressed as percent change in radius and as pressure strain of the elastic modulus. Next, monodimensional view was used to assess valve motion in its various phases (rapid valve opening velocity, slow closing leaflet displacement, rapid valve closing velocity, maximal leaflet displacement, and leaflet displacement before valve closure). Seven healthy individuals served as control subjects. RESULTS: Root distensibility was reduced at the level of the annulus and sinotubular junction but was similar to control subjects at the level of the sinuses (percent change in radius, 4.1% +/- 0.8% versus 4.5% +/- 1.2%; pressure strain of the elastic modulus, 1,286 +/- 674 g/cm2 versus 1,195 +/- 628 g/cm2). Rapid valve opening (69 +/- 34.4 cm/s versus 51 +/- 11.9 cm/s) and closing (47.6 +/- 16 cm/s versus 36.4 +/- 9 cm/s) velocity as well as slow closing leaflet displacement (24% +/- 4.7% versus 22.1% +/- 7.9%), maximal leaflet displacement (20.1 +/- 4 mm versus 22.7 +/- 1.9 mm), and leaflet displacement before valve closure (15.2 +/- 3 mm versus 17.6 +/- 0.8 mm) were similar to control subjects. CONCLUSIONS: The new aortic root conduit used in a reimplantation type of valve-sparing procedure allows the anatomic reconstruction of the aortic root with leaflet motion similar to that of normal subjects.