Echocardiographic evaluation of left ventricular outflow tract obstruction in complete transposition of the great arteries

Subpulmonic stenosis in complete d-transposition of the great arteries (d-TGA) is a frequently associated malformation, the precise diagnosis of which is essential for optimal medical and surgical treatment. Sixteen patients with d-TGA and subpulmonic stenosis have been studied by M-mode and two-dimensional (2DE) echocardiography and cardiac catheterization. Dynamic obstruction was found in six patients and fixed stenosis in 10. Systolic anterior motion of the mitral valve without fixed obstruction of the left ventricular outflow tract (LVOT) was present in patients with dynamic stenosis. Measurements of left ventricular end-diastolic posterior wall thickness to minor semiaxis ratio correlated well (p < 0.001) with the pressure gradient across the LVOT. Various types of anatomic fixed obstruction are described. M-mode echocardiography provides assessment of dynamic obstruction but does not allow quantitative evaluation of the length of the narrowed segment. The latter can be achieved by 2DE, which offers improved definition of different anatomic types

Echocardiographic assessment of congenital mitral stenosis.

To assess the severity and precise anatomy of congenital mitral stenosis (MS), 17 patients with congenital left ventricular inflow obstruction were studied by M-mode and two-dimensional echocardiography (2DE) and by cardiac catheterization. In six patients MS was an isolated lesion and in 11 it was combined with other cardiovascular malformations. The diagnosis was confirmed at operation or autopsy in 15 patients. Twenty normal subjects of the same age and sex were selected as controls. M-mode amplitude and speed of diastolic closure (E-F slope) of the anterior mitral valve leaflet were determined in all patients. Mitral valve areas were traced after careful short-axis 2DE scans in 15 patients. Supravalvar, valvar, or subvalvar obstruction was evaluated in patients with surgical or autopsy documentation. Analysis of M-mode echocardiograms showed a reduction of E-F slope in all patients compared to normal control subjects but a poor correlation between E-F slope and hemodynamic data (mitral valve areas or pressure gradients). Diastolic fluttering of either or both mitral valve leaflets was found in 12 patients. It is concluded that M-mode echocardiography may be useful for qualitative assessment of congenital MS, even in the presence of associated heart defects, but less useful in evaluating its severity. Analysis of 2DE revealed good correlation between mitral valve areas as calculated with 2DE and with the Gorlin formula at cardiac catheterization, despite the complexity of the congenital mitral lesion. Anatomic varieties of congenital left ventricular inflow obstruction, such as stenosing supravalvar mitral ring or parachute deformity of the mitral valve, were recognized at 2DE.(ABSTRACT TRUNCATED AT 250 WORDS

DRUDIT: web-based DRUgs DIscovery Tools to design small molecules as modulators of biological targets.

Abstract Motivation New in silico tools to predict biological affinities for input structures are presented. The tools are implemented in the DRUDIT (DRUgs DIscovery Tools) web service. The DRUDIT biological finder module is based on molecular descriptors that are calculated by the MOLDESTO (MOLecular DEScriptors TOol) software module developed by the same authors, which is able to calculate more than one thousand molecular descriptors. At this stage, DRUDIT includes 250 biological targets, but new external targets can be added. This feature extends the application scope of DRUDIT to several fields. Moreover, two more functions are implemented: the multi- and on/off-target tasks. These tools applied to input structures allow for predicting the polypharmacology and evaluating the collateral effects. Results The applications described in the article show that DRUDIT is able to predict a single biological target, to identify similarities among biological targets, and to discriminate different target isoforms. The main advantages of DRUDIT for the scientific community lie in its ease of use by worldwide scientists and the possibility to be used also without specific, and often expensive, hardware and software. In fact, it is fully accessible through the WWW from any device to perform calculations. Just a click or a tap can start tasks to predict biological properties for new compounds or repurpose drugs, lead compounds, or unsuccessful compounds. To date, DRUDIT is supported by four servers each able to execute 8 jobs simultaneously. Availability and implementation The web service is accessible at the www.drudit.com URL and its use is free of charge. Supplementary information Supplementary data are available at Bioinformatics online

METHYLOMIC SIGNATURE AND MOLECULAR MODELLING TO BETTER UNDERSTAND AUTOPHAGY INDUCED BY PHYTOCHEMICAL IN CACO-2 CELLS

The binomial “autophagy-cancer” is intricate and methylomic studies can help to understand it by changing point of view from a gene level to an -omic one. Recently, autophagy-modulating properties of several phytochemicals have attracted attention in anticancer research. We evaluated whether Indicaxanthin (IND), the peculiar known beneficial phytochemical of prickly pear, seasonally available in the southern Italy, could induce autophagy in Caco2 cells, and whether it results from an epigenomic modification and/or a direct molecular interaction. IND increased autophagy in Caco-2 cells; the methylomic signature, obtained by Reduced Representation Bisulfite Sequencing (15 million of clusters) reported that 14 main genes of autophagy, showed a different methylation consistent with the induction of this phenomenon. Among these: MTOR, ATG13, BECN1, TFEB, ATG3, WIPI2, TECPR1, SNAP29, VPS11, VPS16. By traditional approaches we confirmed the demethylation of BECN1 gene and the increase of Beclin1 levels. By in-silico molecular modelling, we displayed a possible interference of IND, by competitive mechanisms, in the Beclin1-Bcl2 interaction. Methylomic signature and molecular modelling has been helpful to understand autophagy IND-induced in intestinal epithelial tumour cells. Our results suggest that the pro-autophagic action promoted by this phytochemical involves both epigenomic modulation and post-translation mechanisms by direct interaction with key targets of autophagy pathway

Protective effects of melatonin in inflamed intestinal epithelium are associated with reduced NF-κB activation and changes in DNA methylation status

Melatonin is the main product of the pineal gland but is also released in the gastrointestinal tract (GIT). Production of melatonin at GIT is independent of the photoperiod and contributes almost completely to plasma melatonin concentration during daylight hours. The physiological role of melatonin at GIT is poorly characterized but recently anti-inflammatory effects have been reported. In this study, we evaluated the effect of Melatonin in intestinal epithelial cells (IEC) stimulated by Interleukin-1β. Our results clearly show that melatonin at micromolar concentrations inhibits the inflammatory response in IEC. The protective effect is expressed through a marked decrease in release and expression of inflammatory mediators, inhibition of DNA damage, and reduced activation of the NF-κB. Moreover, our results provide evidence that local inhibitor effect of Melatonin can involve an epigenetic mechanism also. In conclusion, our findings suggest that the intake of small amounts of melatonin, comparable with those found in pharmaceutical preparations used for sleep disorders, can also exert beneficial effects to the gastrointestinal physiology

First data on microflora of loggerhead sea turtle (Caretta caretta) nests from the coastlines of Sicily

Caretta caretta is threatened by many dangers in the Mediterranean basin, but most are human-related. The purposes of this research were: (i) to investigate microflora in samples from six loggerhead sea turtle nests located on the Sicilian coast and (ii) to understand microbial diversity associated with nests, with particular attention to bacteria and fungi involved in failed hatchings. During the 2016 and 2018 summers, 456 eggs and seven dead hatchling from six nests were collected. We performed bacteriological and mycological analyses on 88 egg samples and seven dead hatchlings, allowing us to isolate: Fusarium spp. (80.6%), Aeromonas hydrophila (55.6%), Aspergillus spp. (27.2%) and Citrobacter freundii (9%). Two Fusarium species were identified by microscopy and were confirmed by PCR and internal transcribed spacer sequencing. Statistical analyses showed significant differences between nests and the presence/absence of microflora, whereas no significant differences were observed between eggs and nests. This is the first report that catalogues microflora from C. caretta nests/eggs in the Mediterranean Sea and provides key information on potential pathogens that may affect hatching success. Moreover, our results suggest the need for wider investigations over extensive areas to identify other microflora, and to better understand hatching failures and mortality related to microbial contamination in this important turtle species

Competition, Gender Equality, and Doping in Sports in the Red Queen Effect Perspective

The nature of sports is characterized by a strong competitive component that generates inequalities among athletes at different levels, specifically in relation to gender, technology, and doping. These inequalities can be represented according to the Red Queen effect perspective, which has been previously hypothesized in other competitive environments (evolutionary biology and economics, for instance). The Red Queen effect considers each competitive environment to require a constant effort to maintain a position of competitive advantage in order reach the best result possible. Therefore, the aim of the current paper is to provide an innovative perspective for the understanding of competition in sports, identifying factors (i.e., physical appearance for gender equality, socioeconomic status of a sport team for technology, and antidoping rules for doping) influencing athletes’ possibilities to win a competition. Concerning gender differences, the disparity between genders reflects a lower coverage in sports news, and media are more likely to focus on female athletes’ physical appearance than their performance in sports. Therefore, women struggle more with increasing their visibility and in affirming their status as an athlete. On the other hand, the introduction of science and technological innovations in sports has generated economic interests in sport competitions, which reached superior performance levels compared to the past. Teams that cannot afford financial burdens of technological innovation risk being left out from sport competitions. Finally, doping creates a Red Queen environment since antidoping rules catch a small portion of athletes using performance enhancement drugs

Toxic metals in Loggerhead sea turtles (Caretta caretta) stranded freshly dead along Sicilian coasts

Abstract Background: The Loggerhead sea turtle (Caretta caretta) is a marine reptile belonging to a monophyletic group of chelonians. As these animals are long-lived, they have the ability to accumulate pollutants. Aim: To collect epidemiological data on toxic metals in marine Loggerhead sea turtles. Materials and Methods: Forty Loggerhead sea turtles comprising 25 males and 15 females stranded freshly dead between 2013 and 2018 along the coasts of Sicily, Southern Italy, were examined for arsenic, cadmium, and lead accumulation in muscle and adipose tissues by means of a validated ICP-MS method. A modified K index as a growth condition factor, namely Fulton's K index, was used. Samples were tested in duplicate. A Wilcoxon rank sum test was carried out to evaluate metal contents differences between muscle and adipose tissues and between genders. Results: The Fulton's K index suggested a good body condition of the C. caretta recovered with mean values of 5.34±3.40 (n=40; ±SD). Detectable concentrations of lead were found in 70% of the samples analysed with mean values of 0.65±1.67 mg/kg wet weight and 0.51±1.29 mg/kg wet weight in muscle and adipose tissues, respectively. No significant differences in arsenic, cadmium, and lead were detected between genders. In addition, no significant correlation was found between modified K index and concentrations of arsenic, cadmium, and lead. Clinical relevance: Findings on muscle and adipose tissues suggest chronic exposure of Caretta caretta to high concentrations of especially lead which might negatively affect health and welfare of these marine turtles although body condition was good

A non-invasive approach to monitor chronic lymphocytic leukemia engraftment in a xenograft mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI).

This work was supported by: Associazione Italiana Ricerca sul Cancro (AIRC) [Grant 5 x mille n.9980, (to M.F., F.M. and A. N.)]; AIRC I.G. [n. 14,326 (to M.F.)], [n.10136 and 16,722 (A.N.)], [n.15426 (to F.F.)]. AIRC and Fondazione CaRiCal co-financed Multi Unit Regional Grant 2014 [n.16695 (to F.M.)]. Italian Ministry of Health 5 × 1000 funds (to F.F). A.G R. was supported by Associazione Italiana contro le Leucemie-Linfomi-Mielomi (AIL) Cosenza - Fondazione Amelia Scorza (FAS). S.M. C.M., F.V., L. E., S. B., were supported by AIRC.Peer reviewedPostprin

Algorithms for personalized therapy of type 2 diabetes: results of a web-based international survey

In recent years increasing interest in the issue of treatment personalization for type 2 diabetes (T2DM) has emerged. This international web-based survey aimed to evaluate opinions of physicians about tailored therapeutic algorithms developed by the Italian Association of Diabetologists (AMD) and available online, and to get suggestions for future developments. Another aim of this initiative was to assess whether the online advertising and the survey would have increased the global visibility of the AMD algorithms