Clinical utility of gadobenate dimeglumine in contrast-enhanced MRI of the breast: a review

Breast magnetic resonance imaging (MRI) is considered the technique with the highest sensitivity for breast cancer detection. Gadobenate dimeglumine is a gadolinium-based contrast agent (GBCA) that is specifically approved in Europe for breast MRI and which has the highest r1 relaxivity among all GBCAs for this indication. In order to improve the diagnostic performance of breast MRI, several intra-individual crossover studies have evaluated gadobenate dimeglumine as a possible GBCA for this application. This review focuses on the role and advantages of gadobenate dimeglumine as a contrast agent for breast MRI by describing the unique properties of this agent and by summarizing published studies

Impairment of Goodwill: Level of Compliance and Quality of Disclosure during the Crisis-An Analysis of Italian Listed Companies

This paper investigates the level of disclosure on impairment test of goodwill in the Italian context. The research is based on the analysis of the consolidated financial statements 2007\u20132011 of companies listed on FTSE MIB of Milan Stock Exchange at 31st December 2012. The main objective of the research is to verify if financial crisis has impacted on the level of compliance with IAS 36 and Guidelines issued by Italian Authorities. In addition, it tests if there are any relations between the level of disclosure and factors such as market capitalization, the ratio Goodwill on Equity and Impairment loss/Goodwill. Our results show that the quality of disclosure is still incomplete, even if it is clear that there is a significant improvement in the period covered by the analysis. In addition, we observe that, at least in relation to our data, there is no relation between the quality of mandatory disclosure on goodwill and the mentioned factors

Changes in total choline concentration in the breast of healthy fertile young women in relation to menstrual cycle or use of oral contraceptives: a 3-T 1H-MRS study

BACKGROUND: To evaluate changes in total choline (tCho) absolute concentration ([tCho]) in the breast of healthy fertile women in relation to menstrual cycle (MC) or use of oral contraceptives (OC). METHODS: After institutional review board approval, we prospectively evaluated 40 healthy fertile volunteers: 20 with physiological MC, aged 28 ± 3 years (mean ± standard deviation; nOC group); 20 using OC, aged 26 ± 3 years (OC group). Hormonal assays and water-suppressed single-voxel 3-T proton magnetic resonance spectroscopy (1H-MRS) were performed on MC days 7, 14, and 21 in the nOC group and only on MC day 14 in the OC group. [tCho] was measured versus an external phantom. Mann-Whitney U test and Spearman coefficient were used; data are given as median and interquartile interval. RESULTS: All spectra had good quality. In the nOC group, [tCho] (mM) did not change significantly during MC: 0.8 (0.3-2.4) on day 7, 0.9 (0.4-1.2) on day 14, and 0.4 (0.2-0.8) on day 21 (p = 0.963). In the OC group, [tCho] was 0.7 (0.2-1.7) mM. The between-groups difference was not significant on all days (p ≥ 0.411). All hormones except prolactin changed during MC (p ≤ 0.024). In the OC group, [tCho] showed a borderline correlation with estradiol (r = 0.458, p = 0.056), but no correlation with other hormones (p ≥ 0.128). In the nOC group, [tCho] negatively correlated with prolactin (r = -0.587, p = 0.006) on day 7; positive correlation was found with estradiol on day 14 (r = 0.679, p = 0.001). CONCLUSIONS: A tCho peak can be detected in the normal mammary gland using 3-T 1H-MRS. The [tCho] in healthy volunteers was 0.4-0.9 mM, constant over the MC and independent of OC use

Safety at high altitude: the importance of emotional dysregulation on pilots’ risk attitudes during flight

IntroductionAviation psychology is very interested in understanding how personological and psychological variables influence flight performances. Indeed, risk attitudes have been considered as a risk factor for aviation accidents. In this context, emotions and coping style are key variables which could influence concentration by affecting cognition and attention. In addition, the specific training backgrounds seemed to be associated with differences in in-flight accident rates. The aim of the present study was to investigate the association between age, sex, flight experience, emotional dysregulation, coping styles, flight licenses, and pilots’ risk attitudes.MethodsEighty pilots completed an online survey composed of ad hoc questionnaire for sociodemographic and work-related information’s and self-report questionnaires that assessed emotional dysregulation, coping styles, and risk attitudes.ResultsResults showed that older age and emotional dysregulation were associated with higher risk attitudes in pilots. Moreover, emotional dysregulation seemed to promote worse self-confidence. Ultralight pilots appeared to be more risk-oriented and less self-confident than civil pilots, while more flight experience appeared to favorite greater self-confidence.DiscussionIn conclusion, the study suggests the importance of promoting interventions based on sharing pilots’ difficulties and emotions and promoting safe attitudes with special attention to ultralight pilots, age, and sex differences

A pathogenic role for cystic fibrosis transmembrane conductance regulator in celiac disease

Intestinal handling of dietary proteins usually prevents local inflammatory and immune responses and promotes oral tolerance. However, in ~ 1% of the world population, gluten proteins from wheat and related cereals trigger an HLA DQ2/8-restricted TH1 immune and antibody response leading to celiac disease. Prior epithelial stress and innate immune activation are essential for breaking oral tolerance to the gluten component gliadin. How gliadin subverts host intestinal mucosal defenses remains elusive. Here, we show that the \u3b1-gliadin-derived LGQQQPFPPQQPY peptide (P31-43) inhibits the function of cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel pivotal for epithelial adaptation to cell-autonomous or environmental stress. P31-43 binds to, and reduces ATPase activity of, the nucleotide-binding domain-1 (NBD1) of CFTR, thus impairing CFTR function. This generates epithelial stress, tissue transglutaminase and inflammasome activation, NF-\u3baB nuclear translocation and IL-15 production, that all can be prevented by potentiators of CFTR channel gating. The CFTR potentiator VX-770 attenuates gliadin-induced inflammation and promotes a tolerogenic response in gluten-sensitive mice and cells from celiac patients. Our results unveil a primordial role for CFTR as a central hub orchestrating gliadin activities and identify a novel therapeutic option for celiac disease

Profiling of Flavonol Derivatives for the Development of Antitrypanosomatidic Drugs

Flavonoids represent a potential source of new antitrypanosomatidic leads. Starting from a library of natural products, we combined target-based screening on pteridine reductase 1 with phenotypic screening on Trypanosoma brucei for hit identification. Flavonols were identified as hits, and a library of 16 derivatives was synthesized. Twelve compounds showed EC50 values against T. brucei below 10 \u3bcM. Four X-ray crystal structures and docking studies explained the observed structure-activity relationships. Compound 2 (3,6-dihydroxy-2-(3-hydroxyphenyl)-4H-chromen-4-one) was selected for pharmacokinetic studies. Encapsulation of compound 2 in PLGA nanoparticles or cyclodextrins resulted in lower in vitro toxicity when compared to the free compound. Combination studies with methotrexate revealed that compound 13 (3-hydroxy-6-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one) has the highest synergistic effect at concentration of 1.3 \u3bcM, 11.7-fold dose reduction index and no toxicity toward host cells. Our results provide the basis for further chemical modifications aimed at identifying novel antitrypanosomatidic agents showing higher potency toward PTR1 and increased metabolic stability

Insights from Second-Line Treatments for Idiopathic Dilated Cardiomyopathy

Background: Dilated cardiomyopathy (DCM) is an independent nosographic entity characterized by left ventricular dilatation and contractile dysfunction leading to heart failure (HF). The idiopathic form of DCM (iDCM) occurs in the absence of coronaropathy or other known causes of DCM. Despite being different from other forms of HF for demographic, clinical, and prognostic features, its current pharmacological treatment does not significantly diverge. Methods: In this study we performed a Pubmed library search for placebo-controlled clinical investigations and a post-hoc analysis recruiting iDCM from 1985 to 2016. We searched for second-line pharmacologic treatments to reconsider drugs for iDCM management and pinpoint pathological mechanisms. Results: We found 33 clinical studies recruiting a total of 3392 patients of various durations and sizes, as well as studies that tested different drug classes (statins, pentoxifylline, inotropes). A metanalysis was unfeasible, although a statistical significance for changes upon treatment for molecular results, morphofunctional parameters, and clinical endpoints was reported. Statins appeared to be beneficial in light of their pleiotropic effects; inotropes might be tolerated more for longer times in iDCM compared to ischemic patients. General anti-inflammatory therapies do not significantly improve outcomes. Metabolic and growth modulation remain appealing fields to be investigated. Conclusions: The evaluation of drug effectiveness based on direct clinical benefit is an inductive method providing evidence-based insights. This backward approach sheds light on putative and underestimated pathologic mechanisms and thus therapeutic targets for iDCM management

Vulvar rare pathologies

Vulvar-vaginal disorder represent a field of growing interest in clinical, epidemiological and healthcare research. An increase of infectious and immunological vulvar disease is currently being recorded. Improved access to gynecological care and lengthening of life expectancy are the basis of increase incidence of chronic disorders requiring early diagnosis, prolonged treatment and adeguate follow-up, in order to prevent the development of neoplastic disease