The PKU & ME study: A qualitative exploration, through co-creative sessions, of attitudes and experience of the disease among adults with phenylketonuria in Italy

Background: Phenylketonuria (PKU) is a hereditary metabolic disease that can be diagnosed and successfully treated from birth with a lifelong phenylalanine-restricted dietary regimen. However, optimal adherence to diet remains an issue and often progressively decreases after adolescence. The study aimed to explore the experience of adults living with PKU in order to gain insights related to their adherence to diet and engagement in managing their condition. Methods: The study adopted a qualitative methodology in sessions that combined specifically designed co- creation exercises with focus group discussion. Adults with early-treated classic PKU were enrolled for 2 different sessions - one for adherent and one for non-adherent patients. The verbatim notes of both sessions and focus group were analyzed using content analysis. Results: Twelve adherent and nine non-adherent adults with PKU participated. Besides the behavioral dictates of following a strict diet, adherent adults reported a positive mental approach and organizational rigor; they seemed aware of the consequences of high-phenylalanine levels, reporting that it can affect mood and conse- quently social interactions which they value highly. In the non-adherent group, the individuals seemed to not fully accept their disease: they were aware of the consequences of non-adherence in children but not in adults, they felt the management of PKU was an individual burden and they experienced a feeling of \u2018diversity\u2019 in the social context (related to eating) that caused emotional distress. PKU seemed a very influential element of the identity both for adherent and non-adherent adults, but with different consequences for the two groups. Finally, all participants reported the desire to be assisted in a healthcare setting dedicated to adults. Conclusions: The findings expand the understanding of the psychological experience of adult patients with PKU in relation to their disease and its dietary requirements, highlighting specific factors that might drive tailored educational or psychological intervention to improve adherence and engagement in the care process

An embodied and grounded perspective on concepts

By the mainstream view in psychology and neuroscience, concepts are informational units, rather stable, and are represented in propositional format. In the view I will outline, instead, concepts correspond to patterns of activation of the perception, action and emotional systems which are typically activated when we interact with the entities they refer to. Starting from this embodied and grounded approach to concepts, I will focus on different research lines and present some experimental evidence concerning concepts of objects, concepts of actions, and abstract concepts. I will argue that, in order to account for abstract concepts, embodied and grounded theories should be extended

Whey-derived peptides interactions with ACE by molecular docking as a potential predictive tool of natural ACE inhibitors

Several milk/whey derived peptides possess high in vitro angiotensin I-converting enzyme (ACE) inhibitory activity. However, in some cases, poor correlation between the in vitro ACE inhibitory activity and the in vivo antihypertensive activity has been observed. The aim of this study is to gain insight into the structure-activity relationship of peptide sequences present in whey/milk protein hydrolysates with high ACE inhibitory activity, which could lead to a better understanding and prediction of their in vivo antihypertensive activity. The potential interactions between peptides produced from whey proteins, previously reported as high ACE inhibitors such as IPP, LIVTQ, IIAE, LVYPFP, and human ACE were assessed using a molecular docking approach. The results show that peptides IIAE, LIVTQ, and LVYPFP formed strong H bonds with the amino acids Gln 259, His 331, and Thr 358 in the active site of the human ACE. Interestingly, the same residues were found to form strong hydrogen bonds with the ACE inhibitory drug Sampatrilat. Furthermore, peptides IIAE and LVYPFP interacted with the amino acid residues Gln 259 and His 331, respectively, also in common with other ACE-inhibitory drugs such as Captopril, Lisinopril and Elanapril. Additionally, IIAE interacted with the amino acid residue Asp 140 in common with Lisinopril, and LIVTQ interacted with Ala 332 in common with both Lisinopril and Elanapril. The peptides produced naturally from whey by enzymatic hydrolysis interacted with residues of the human ACE in common with potent ACE-inhibitory drugs which suggests that these natural peptides may be potent ACE inhibitors

Odors, words and objects

The paper focuses on concepts and words referring to odors and to objects that have an odor. We argue that odors are an interesting object of study since they are evanescent, and since odor words do not refer to concrete and manipulable objects, but to scents evoked by objects. A second reason why odors are interesting is that some languages, as the Western ones, lack a specific odor lexicon, comparable in richness and variety to the color lexicon, and that performance on odors naming is typically worse than performance in color naming. In this work we discuss three main issues. First, we illustrate literature showing that, even if odor words do not have concrete referents, many languages encode them quite easily: the case of odors suggests that word meaning cannot be exhausted by the relationship with a referent, and highlights the importance of the social sharing of meaning. Second, we have discussed the peculiar status of odor concepts and words. Given their ambiguous status, their simple existence poses problems both to theories according to which concrete and abstract concepts do not differ, and to theories according to which they represent a dichotomy. Finally, we present an experiment in which we show that names of objects evoke their smell, and that these smells evoke approach and avoidance movements, in line with theories according to which words are grounded in both sensorial and motor systems

Dissipation effects in mechanics and thermodynamics

With the discussion of three examples, we aim at clarifying the concept of energy transfer associated with dissipation in mechanics and in thermodynamics. The dissipation effects due to dissipative forces, such as the friction force between solids or the drag force in motions in fluids, lead to an internal energy increase of the system and/or to a heat transfer to the surrounding. This heat flow is consistent with the second law, which states that the entropy of the universe should increase when those forces are present because of the irreversibility always associated with their actions. As far as mechanics is concerned the effects of the dissipative forces are include in the Newton's equations as impulses and pseudo-works.Comment: 18 pages, 3 figure

Caveolin-1 is a risk factor for postsurgery metastasis in preclinical melanoma models

Melanomas are highly lethal skin tumours that are frequently treated by surgical resection. However, the efficacy of such procedures is often limited by tumour recurrence and metastasis. Caveolin-1 (CAV1) has been attributed roles as a tumour suppressor, although in late-stage tumours, its presence is associated with enhanced metastasis. The expression of this protein in human melanoma development and particularly how the presence of CAV1 affects metastasis after surgery has not been defined. CAV1 expression in human melanocytes and melanomas increases with disease progression and is highest in metastatic melanomas. The effect of increased CAV1 expression can then be evaluated using B16F10 murine melanoma cells injected into syngenic immunocompetent C57BL/6 mice or human A375 melanoma cells injected into immunodeficient B6Rag1−/− mice. Augmented CAV1 expression suppresses tumour formation upon a subcutaneous injection, but enhances lung metastasis of cells injected into the tail vein in both models. A procedure was initially developed using B16F10 melanoma cells in C57BL/6 mice to mimic better the situation in patients undergoing surgery. Subcutaneous tumours of a defined size were removed surgically and local tumour recurrence and lung metastasis were evaluated after another 14 days. In this postsurgery setting, CAV1 presence in B16F10 melanomas favoured metastasis to the lung, although tumour suppression at the initial site was still evident. Similar results were obtained when evaluating A375 cells in B6Rag1−/− mice. These results implicate CAV1 expression in melanomas as a marker of poor prognosis for patients undergoing surgery as CAV1 expression promotes experimental lung metastasis in two different preclinical models

How abstract is risk for workers? Expertise, context and introspection in abstract concepts

Two studies were performed to test whether abstract concepts are grounded in experience and activate introspective/linguistic information. In Study 1, four groups of participants, each with different expertise in the domain of safety and security at the workplace (S&S), defined abstract concepts belonging to the S&S domain and differing in degree of abstractness. The definitions included mainly situations, confirming grounding of abstract concepts. In Study 2 the task was performed by students with no experience of S&S. The definitions were modulated by participants’ expertise; the role of introspection increased with more abstract concepts. Results support embodied theories on abstract concept

Hitting is male, giving is female. Automatic imitation and complementarity during action observation

Is somebody going to hurt us? We draw back. The present study investigates using behavioral measures the interplay between imitative and complementary actions activated while observing female/male hands performing different actions. Female and male participants were required to discriminate the gender of biologically and artificially colored hands that displayed both individual (grasping) and social (giving and punching) actions. Biological hands evoked automatic imitation, while hands of different gender activated complementary mechanisms. Furthermore, responses reflected gender stereotypes: giving actions were more associated to females, punching actions to males. Results have implications for studies on social stereotyping, and for research on action observation, showing that the mirror neuron system resonates in both an imitative and complementary fashion

Exosome-mediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma

BACKGROUND: Growing evidence is showing that metastatic cell populations are able to transfer their characteristics to less malignant cells. Exosomes (EXOs) are membrane vesicles of endocytic origin able to convey their cargo of mRNAs, microRNAs (miRs), proteins and lipids from donors to proximal as well as distant acceptor cells. Our previous results indicated that miR-221&222 are key factors for melanoma development and dissemination. The aim of this study was to verify whether the tumorigenic properties associated with miR-222 overexpression can be also propagated by miR-222-containing EXOs. METHODS: EXOs were isolated by UltraCentrifugation or Exoquick-TC(®) methods. Preparations of melanoma-derived vesicles were characterized by using the Nanosight™ technology and the expression of exosome markers analyzed by western blot. The expression levels of endogenous and exosomal miRNAs were examined by real time PCR. Confocal microscopy was used to evaluate transfer and uptake of microvesicles from donor to recipient cells. The functional significance of exosomal miR-222 was estimated by analyzing the vessel-like process formation, as well as cell cycle rates, invasive and chemotactic capabilities. RESULTS: Besides microvesicle marker characterization, we evidenced that miR-222 exosomal expression mostly reflected its abundance in the cells of origin, correctly paralleled by repression of its target genes, such as p27Kip1, and induction of the PI3K/AKT pathway, thus confirming its functional implication in cancer. The possible differential significance of PI3K/AKT blockade was assessed by using the BKM120 inhibitor in miR-222-transduced cell lines. In addition, in vitro cultures showed that vesicles released by miR-222-overexpressing cells were able to transfer miR-222-dependent malignancy when taken-up by recipient primary melanomas. Results were confirmed by antagomiR-221&222 treatments and by functional observations after internalization of EXOs devoid of these miRs

Liver involvement in pediatric celiac disease

Celiac disease (CD) is an intestinal inflammatory disease that manifests in genetically susceptible individuals when exposed to dietary gluten. It is a common chronic disorder, with a prevalence of 1% in Europe and North America. Although the disease primarily affects the gut, the clinical spectrum of CD is remarkably varied, and the disease can affect many extraintestinal organs and systems, including the liver. The hepatic dysfunction presenting in CD ranges from asymptomatic liver enzyme elevations or nonspecific reactive hepatitis (cryptogenic liver disorders), to chronic liver disease. In this article, we review the clinical presentations and possible mechanisms of CD-related liver injury to identify strategies for the diagnosis and treatment of these disorders in childhood