Giorgio Bianciardi

Abnormal vascular network complexity: a new phenotypic marker in hereditary non-polyposis colorectal cancer syndrome

Background: Hereditary non-polyposis colorectal cancer (HNPCC) (Lynch cancer family syndrome I (LCFS1) and II (LCFS2)) is one of the most common hereditary cancer disorders. HNPCC results from dominantly inherited germline mutations in mismatch repair (MMR) genes, leading to genomic instability and cancer. No predictive physical signs of HNPCC are available to date. Aims: Increased complexity in tumour associated vascular growth has been reported. Here, we tested the hypothesis that an increased vascular network complexity is a phenotypic marker for LCFS2. Methods: Fourteen subjects from an LCFS2 kindred (gene carriers, n = 5; non-carriers, n = 9) and 30 controls were examined. Fractal dimension (D) at two scales (D (1–46), and D (1–15), tortuosity (minimum path dimension, Dmin), and relative Lempel-Ziev complexity (L-Z) of the vascular networks from the lower gingival and vestibular oral mucosa were measured. Results: LCFS2 networks exhibited a significantly increased overall complexity at both larger (D (1–46): 1.82 (0.04) v 1.68 (0.08); p<0.0001) and smaller (D (1–15): 1.51 (0.11) v 1.20 (0.09); p<0.0001) scales, increased destructured randomness (L-Z: 0.77 (0.09) v 0.56 (0.03); p<0.0001), and decreased vessel tortuosity (Dmin: 1.02 (0.03) v 1.07 (0.04); p = 0.0005) compared with control patterns. The vascular networks of LCFS2 gene carriers showed higher complexity at the smaller scale (D (1–15): 1.59 (0.12) v 1.47 (0.07); p = 0.034), and higher destructured randomness (L-Z: 0.85 (0.11) v 0.73 (0.05); p = 0.013) than those of non-carriers. Conclusions: Increased oral vascular network complexity is a previously unrecognised phenotypic marker for LCFS2, and is related to gene mutation carrier status.

Fractal Analysis in Human Pathology

Living structures may be described as being in a self-organizing, fluctuating steady-state far from equilibrium.1 Self-organization and a state far from equilibrium are characteristics of chaotic structures. Chaotic structures present fractal geometry, so is not too astonishing that the branching pattern of the airways in the lung or the arterial vascular pattern of the cardiovascular system have been described with fractal properties.2–4 Like coastlines, a tumor examined by light microscopy has a complex, irregular border and retains a similar level of complexity over a range of magnifications.5–7 Euclidean morphometric measurements were found to be invalid outside precisely defined conditions of resolution and magnification.8 In our Institute we are applying fractal dimension analysis to study human tumors at light and ultrastructural levels. Here, we present data obtained studying the epithelial–connective tissue interface in basal cell carcinoma of the skin, the boundaries of invasive bladder carcinomas (urothelial neoplasia), and the lymphocytic nuclear membrane in mycosis fungoides and chronic dermatitis.

Ranking Predatory Journals:Solve the Problem Instead of Removing It!

Predatory journals are a well-known issue for scholarly publishing and they are repositories for bogus research. In recent years, the number of predatory journals has risen and it is necessary to present a solution for this challenge. In this paper, we will discuss about a possible ranking of predatory journals. Our ranking approach is based on Bealls criteria for detection of predatory journals and it can help editors to improve their journals or convert their questionable journals to non-predatory ones. Moreover, our approach could help young editors to protect their journals against predatory practice. Finally, we present a case study to clarify our approach.

Fractal analysis of fluoroangiographic patterns in anterior ischaemic optic neuropathy and optic neuritis: a pilot study

Background:  To evaluate by means of fractal analysis the vascular pattern of the optic nerve head obtained by fluorescein angiogram, in non‐arteritic anterior ischaemic optic neuropathy (NAION) and optic neuritis (ON).

Complexity Analysis of the Viking Labeled Release Experiments

The only extraterrestrial life detection experiments ever conducted were the three which were components of the 1976 Viking Mission to Mars. Of these, only the Labeled Release experiment obtained a clearly positive response. In this experiment 14 C radiolabeled nutrient was added to the Mars soil samples. Active soils exhibited rapid, substantial gas release. The gas was probably CO2 and, possibly, other radiocarbon-containing gases. We have applied complexity analysis to the Viking LR data. Measures of mathematical complexity permit deep analysis of data structure along continua including signal vs. noise, entropy vs.negentropy, periodicity vs. aperiodicity, order vs. disorder etc. We have employed seven complexity variables, all derived from LR data, to show that Viking LR active responses can be distinguished from controls via cluster analysis and other multivariate techniques. Furthermore, Martian LR active response data cluster with known biological time series while the control data cluster with purely physical measures. We conclude that the complexity pattern seen in active experiments strongly suggests biology while the different pattern in the control responses is more likely to be non-biological. Control responses that exhibit relatively low initial order rapidly devolve into near-random noise, while the active experiments exhibit higher initial order which decays only slowly. This suggests a robust biological response. These analyses support the interpretation that the Viking LR experiment did detect extant microbial life on Mars.

Oral Mucosal Microvascular Abnormalities: An Early Marker of Bronchopulmonary Dysplasia

An abnormal pulmonary vasculature has been reported as an important component of bronchopulmonary dysplasia (BPD). We tested the hypothesis of an early abnormal vascular network pattern in infants with BPD. Fifteen infants with BPD (nine boys and six girls; gestational age 27.5 ± 2.0 wk; birth weight 850 ± 125 g) and 15 sex- and gestational age–matched infants (nine boys and six girls; gestational age 27.6 ± 2.6 wk; birth weight 865 ± 135 g) were examined on postnatal days 1 and 28. BPD infants showed a significantly higher prevalence of histologic chorioamnionitis (p = 0.009), as well as higher intubation duration (p = 0.0004), oxygen supplementation (p < 0.0001), and initial illness severity (p = 0.0002) than the BPD-negative population. The lower gingival and vestibular oral mucosa was chosen as the study area. The blood vessel area was determined, and the oral vascular networks were characterized by analyzing their complexity (D, at two scales: D 1–46, D 1–15), tortuosity (Dmin), and randomness (L-Z) of the vascular loops. Infants with BPD showed a significantly lower blood vessel area as well as a higher vascular network complexity (D 1–46, D 1–15, and L-Z) than control subjects (p < 0.0001). Our findings provide a new early clinical sign in BPD and stress the importance of an early disorder in the oral mucosal vascularization process in the disease pathogenesis.

Fractal Dimension of Lymphocytic Nuclear Membrane in Mycosis Fungoides and Chronic Dermatitis

The nuclear outline was measured by using fractal analysis in six cases of early mycosis fungoides (EMF) and in five cases of chronic dermatitis (CD). Ultrastructural images of approximately 30 nuclei for each case were processed by image analysis to obtain the nuclear contour. Fractal dimension (FD) was determined by the box-counting method. The nuclear contour index (NCI) was also calculated. Mean nuclear FD value was higher in EMF than in CD (1.1605 vs. 1.0898). A good correlation was found between FD and NCI. FD was higher in NCI ≥ 7 than in NCI < 7 nuclei, both in EMF and in CD (p < 0.001, p < 0.001). These results show that nuclei of lymphoid cells have an irregular outline that may be described as fractal. FD of malignant nuclei is higher than that of benign nuclei. Investigations are in progress to increase the number of samples and determine the predictive FD value in distinguishing between benign and malignant cases.

Preliminary observations on the ultrastructural modifications of the freeze-cleaved circulating platelets surface in hypercholesterolemic rabbits treated with AD6

Summary Circulating platelets show on their surface some “protuberances” placed among the plasma-membrane particles when examined with FE technique. Statistic tests have shown the significant difference in the average number of such protuberances between platelets of hypercholesterolemic and normocholesterolemic rabbits. After i.v. administration of AD 6 (a substance with supposed anti-aggregating action) the number of the “protuberances” of circulating platelets of the hypercholesterolemic rabbits approaches to the average value of the normocholesterolemic ones. An interpretation of such plasma-membrane protuberances is proposed.

Opportunity Rover's image analysis: Microbialites on Mars?

The Mars Exploration Rover Opportunity investigated plains at Meridiani Planum, where laminated sedimentary rocks are present. The Opportunity rover’s Athena morphological investigation showed microstructures organized in intertwined filaments of microspherules: a texture we have also found on samples of terrestrial (biogenic) stromatolites and other microbialites. We performed a quantitative image analysis to compare images (n=45) of microbialites with the images (n=30) photographed by the rover (corresponding, approximately, to 25,000/15,000 microstructures). Contours were extracted and morphometric indexes were obtained: geometric and algorithmic complexities, entropy, tortuosity, minimum and maximum diameters. Terrestrial and Martian textures present a multifractal aspect. Mean values and confidence intervals from the Martian images overlapped perfectly with those from the terrestrial samples. The probability of this occurring by chance is 1/2 8 , less than p<0.004. Terrestrial abiogenic pseudostromatolites showed a simple fractal structure and different morphometric values from those of the terrestrial biogenic stromatolite images or Martian images with a less ordered texture (p<0.001). Our work shows the presumptive evidence of microbialites in the Martian outcroppings: i.e., the presence of unicellular life on the ancient Mars.

Microvascular abnormalities in Rett syndrome

Rett syndrome (RTT) is a post-natal neurological disorder that represents the second most common cause for mental retardation. The presence of cold hands and feet, and blue, a feature frequently observed in these patients, is one of the non-neurological phenotypes that characterizes RTT, up to now not well explained. We have performed videocapillaroscopy in subjects affected by Rett syndrome. We have observed ramified and bushy capillaries, characteristic features of neoangiogenic capillaries, dilated capillaries and an irregular and chaotic microvascular pattern. To quantify these features and to evaluate the microvascular pattern complexity, we have performed a fractal analysis. Fractal dimension and Lempel-Ziv indexes resulted higher in Rett females than in age-matched healthy females (p < 0.001; p < 0.001). Our findings indicate the presence of previously unrecognized microvascular abnormalities in Rett syndrome.