Evaluation of temperature- and ethanol-related developmental degree variations by a new scoring system (FETAX-score) applicable to Frog Embryo Teratogenicity Assay: Xenopus.

The aim of the present work is to propose a new quantitative assessment method (FETAX-score) for determining the degree of Xenopus laevis embryo development intended for use in embryotoxicity studies. Inspired by a similar scoring system used to evaluate developmental delays (young-for-age phenotypes) in rat embryos cultured in vitro, the FETAX-score was established by considering seven morphological features (head, naris, mouth, lower jaw, tentacles, intestine, anus) that are easily evaluable in tadpoles during the late stages of development at the conclusion of the test. Given that X.

Effects of combined exposure to two bisphenol plasticizers (BPA and BPB) on Xenopus laevis development.

Due to its endocrine disruptive activity, the plastic additive Bisphenol A (BPA) is classified as substance of very high concern (EU ECHA 2017). A correlation between environmental exposure to BPA and congenital defects has been described in humans and in experimental species including the amphibian Xenopus laevis, where severe branchial defects were associated to lethality. The exposure of X.

Teratogenic and neuro-behavioural toxic effects of bisphenol A (BPA) and B (BPB) on Xenopus laevis development.

Bisphenol A (BPA) is a plastic additive with endocrine disruptive activity, classified in 2017 by EU ECHA as substance of very high concern. A correlation between environmental exposure to BPA and congenital defects has been described in humans and in experimental species, including the amphibian Xenopus laevis. Among BPA analogues, bisphenol B (BPB) is used as alternative in different not-EU countries, including US, but seems to share with BPA its endocrine disruptor properties.

A Bioengineering Strategy to Control ADAM10 Activity in Living Cells.

A Disintegrin and Metalloprotease 10, also known as ADAM10, is a cell surface protease ubiquitously expressed in mammalian cells where it cuts several membrane proteins implicated in multiple physiological processes. The dysregulation of ADAM10 expression and function has been implicated in pathological conditions, including Alzheimer's disease (AD). Although it has been suggested that ADAM10 is expressed as a zymogen and the removal of the prodomain results in its activation, other potential mechanisms for the ADAM10 proteolytic function and activation remain unclear.

Moderate alcohol consumption during pregnancy increases potency of two different drugs (the antifungal fluconazole and the antiepileptic valproate) in inducing craniofacial defects: prediction by the in vitro rat whole embryo culture.

The prenatal exposure to ethanol (Eth), fluconazole (FLUCO) and sodium valproate (VPA) is related to effects on development, producing characteristic syndromic pictures. Among embryotoxic effects described for the three molecules, the alteration on craniofacial morphogenesis is a common feature in humans and animal models, including rodent embryos developed in vitro. The aim of the present work is to evaluate the developmental effects of low Eth serum concentration (17 mM, corresponding to the legal limit to drive in UK, USA, Canada, and many other countries) in mixture with increasing realistic concentrations of the antifungal drug FLUCO (62.

Predictive assays for craniofacial malformations: evaluation in Xenopus laevis embryos exposed to triadimefon.

Craniofacial defects are one of the most frequent abnormalities at birth, but their experimental evaluation in animal models requires complex procedures. The aim of the present work is the comparison of different methodologies to identify dose- and stage-related craniofacial malformations in Xenopus laevis assay (R-FETAX, where the full cartilage evaluation, including flat mount technique, is the gold standard for skeletal defect detection). Different methods (external morphological evaluation of fresh samples, deglutition test, whole mount cartilage evaluation and Meckel-palatoquadrate angle measurements) were applied.

Modified Xenopus laevis approach (R-FETAX) as an alternative test for the evaluation of foetal valproate spectrum disorder.

In compliance to animal welfare 3Rs principle there is a great demand for refined tests alternative to classical mammal teratogenicity tests. We propose a refined alternative amphibian method (R-FETAX) to evaluate chemical induced embryotoxicity. The human foetal valproate spectrum disorder (FVSD) characteristics are morphological defects (including cranio-facial, neural tube defects) and behavioural alterations due to valproate (VPA) exposure in pregnancy.

Post-Translational Modifications Modulate Proteinopathies of TDP-43, FUS and hnRNP-A/B in Amyotrophic Lateral Sclerosis.

It has been shown that protein low-sequence complexity domains (LCDs) induce liquid-liquid phase separation (LLPS), which is responsible for the formation of membrane-less organelles including P-granules, stress granules and Cajal bodies. Proteins harbouring LCDs are widely represented among RNA binding proteins often mutated in ALS. Indeed, LCDs predispose proteins to a prion-like behaviour due to their tendency to form amyloid-like structures typical of proteinopathies.

An adverse outcome pathway on the disruption of retinoic acid metabolism leading to developmental craniofacial defects.

Adverse outcome pathway (AOP) is a conceptual framework that links a molecular initiating event (MIE) via intermediate key events (KEs) with adverse effects (adverse outcomes, AO) relevant for risk assessment, through defined KE relationships (KERs). The aim of the present work is to describe a linear AOP, supported by experimental data, for skeletal craniofacial defects as the AO. This AO was selected in view of its relative high incidence in humans and the suspected relation to chemical exposure.

Impact of bariatric surgery-induced weight loss on circulating PCSK9 levels in obese patients.

Background And Aims: To investigate the effect of obesity and bariatric-induced weight loss on circulating levels of proprotein convertase subtilisin/kexin 9 (PCSK9) in severely obese patients.

Methods And Results: In this non-randomized interventional study, we enrolled 36 severely obese patients (BMI 43.7 ± 5.

Effect of nano-encapsulation of β-carotene on embryos development (FETAX).

Vitamin A plays a vital role during embryo development as most precursor of embryonic retinoic acid, a key morphogen during embryogenesis. Carotenoids, including β-carotene, are important vegetal source of Vitamin A and in contrast to teratogenic potential of animal-derived retinoids, β-carotene is usually considered freed from embryotoxic effects and supplements in pregnancy with β-carotene are suggested. The aim of the present work is to evaluate the effect of bulk and nano-encapsulated β-carotene on embryo development, by using the animal model Frog Embryo Teratogenesis Assay: - FETAX.

Development of an adverse outcome pathway for cranio-facial malformations: A contribution from in silico simulations and in vitro data.

Mixtures of substances sharing the same molecular initiating event (MIE) are supposed to induce additive effects. The proposed MIE for azole fungicides is CYP26 inhibition with retinoic acid (RA) local increase, triggering key events leading to craniofacial defects. Valproic acid (VPA) is supposed to imbalance RA-regulated gene expression trough histone deacetylases (HDACs) inhibition.

Relative potency ranking of azoles altering craniofacial morphogenesis in rats: An in vitro data modelling approach.

Facial malformations represent one of the most frequent abnormality in humans. The adverse outcome pathway involved in facial defects seems to be related to retinoic acid (RA) pathway imbalance. Environmental agents inducing craniofacial malformations in experimental models include pesticides (especially azole fungicides).

The Ascidian Embryo Teratogenicity assay in Ciona intestinalis as a new teratological screening to test the mixture effect of the co-exposure to ethanol and fluconazole.

The aim of this work was to evaluate the Ascidian Embryo Teratogenicity assay (AET) as new alternative invertebrate model to test the developmental effects of the co-exposure to ethanol and fluconazole. Ciona intestinalis embryos were exposed to the azolic fungicide fluconazole, (FLUCO, 7.8-250μM), to ethanol (Eth, 0.

iFR-FFR comparison in daily practice: a single-center, prospective, online assessment.

Aims: To compare the performance of instantaneous wave-free ratio (iFR) with fractional flow reserve (FFR) in a real-life, prospective, single-center, and independent study.

Methods And Results: Fifty-four patients were included and 89 angiographic intermediate lesions underwent functional evaluation with both iFR and FFR. FFR was used as the gold standard, and the patients having FFR values 0.

Clinical factors that predict remission of diabetes after different bariatric surgical procedures: interdisciplinary group of bariatric surgery of Verona (G.I.C.O.V.).

Aims: The aims of the study were to investigate weight loss and glycemic control parameters after different bariatric surgical procedures in type 2 diabetes (T2D) obese patients and identify patients' factors that predict diabetes remission.

Methods: The study included 105 obese T2D patients (66 women and 39 men) who underwent laparoscopic gastric banding (LAGB, 11 subjects, age 47 ± 10 years, BMI 42.3 ± 8.

Improved quality of life after bariatric surgery in morbidly obese patients. Interdisciplinary group of bariatric surgery of Verona (G.I.C.O.V.).

Background: Our aim was to evaluate the changes of health-related Quality of Life (HR-QoL) after bariatric surgery.

Patients And Methods: 110 patients, who underwent laparoscopic bariatric surgery (N=34 gastric banding; N= 69 Roux-en-Y gastric bypass, N=7 sleeve gastrectomy), were evaluated before surgery and after an average of 36±13 months with SF-36 Health Survey.

Results: Mean preoperative age and body mass index (BMI) were 43±12 years and 45±7 kg/m2 respectively.

Improvement in health-related quality of life in first year after laparoscopic adjustable gastric banding.

Background: We analyzed the health-related quality of life (HRQOL) and its determinants in the first year after laparoscopic adjustable gastric banding (LAGB). The setting was 10 Italian public and private bariatric surgery centers.

Methods: Data collected in an ongoing, prospective, 3-year multicenter Italian study on the changes in HRQOL after LAGB were used.

Determinants of health-related quality of life in morbid obese candidates to gastric banding.

Objective: To analyse determinants of self reported health-related quality of life (HR-QoL) in morbid obese patients candidates to laparoscopic adjustable gastric banding (LAGB).

Methods: Determinants of HR-QoL were investigated in 383 morbid obese patients (82 M and 301 F) with BMI≥40 kg/m² (BMI≥35 kg/m² if complicated obesity) and age 18-60 years. HR-QoL was determined with the SF-36 questionnaire.

Psychological characteristics of mothers of patients with anorexia nervosa: implications for treatment and prognosis.

Introduction: The complexity of factors involved in anorexia nervosa (AN) and the recommendations of prominent health organizations underscore the importance of reflecting on therapeutic interventions aimed at patients' family members.

Objective: To expand knowledge about the mother-daughter relationship in AN, with a focus on developing a conceptual framework that is able to improve the treatment of the disorder, reduce factors that perpetuate it and improve prognosis.

Method: A clinical method, anchored by psychodynamic references, was employed in a group of family members of patients with eating disorders.

Comparative pharmacokinetic analysis of 5-fluorouracil and its major metabolite 5-fluoro-5,6-dihydrouracil after conventional and reduced test dose in cancer patients.

The aim of this study was to investigate the clinical pharmacokinetics of 5-fluorouracil (5-FU) and its major metabolite 5-fluoro-5,6-dihydrouracil (5-FDHU) in 20 colorectal cancer patients given two dose levels of 5-FU, 250 and 370 mg/m2, administered by i.v. bolus.

[Epithelioid hemangioendothelioma of the liver. A case report].

One case of epithelioid hemangioendothelioma (EHE) of the liver is reported. The problems of a correct diagnosis of this unusual type of vascular tumor are discussed. A final diagnosis can be established only by histologic examination of appropriate material and may be helped by immunohistochemistry and ultrastructural examination.