Making the Best in a Bad Job: A Psychoanalytic Perspective on Communication with Children and Adolescents with Severe Physical Condutions.

Ill children/adolescents who suffer from severe organic diseases have to cope with their inner experiences, therapies, and the global burden of the disease. Although sometimes depression, anger, and death anxiety are openly encountered in medical settings, other times they can be partially hidden by a reactive and defensive path. In these scenarios, psychoanalysis is challenged to contribute the best comprehension of the intimate communication, maybe hidden, and the needs of the ill patients to express themselves. The best way a child can talk about himself is through spontaneous creativity. The adult's task is to facilitate the creation of an empty space and to recognize the child's mode of communication. There may be intense emotional reactions that the adult has to tolerate to not move the patient towards an over-adaptation. These over-adaptations entail the child being forced to feel good or have fun, thereby causing them to escape from their inner experience. The loss of the child's reality forms an additional burden to the child. The most valid indicator of this attitude is the ability to not take counterphobic attitudes but to allow the depression to be shared in a contact space between the child's true self and the perceived environment.

Using VEGAHUB Within a Weight-of-Evidence Strategy.

Industrial needs and regulatory requirements have played a significant role in accelerating the use of nontesting methods including in silico tools as alternatives to animal testing. The main interest is not solely on the use of in silico tools, or in read-across, but on better toxicological safety assessment of substances, and for this purpose more advanced, integrated strategies have to be implemented. VEGAHUB wants to promote this broader view, not necessarily focused on a specific approach. Applying multiple tools and complementary approaches instead of one technique may provide more elements for a more robust evaluation, but at the same time it is important to have a conceptual scheme to integrate multiple, heterogeneous lines of evidence. We will show how the user can benefit from the diversity of tools available within the platform VEGAHUB for assessing the biological properties of chemical substances on an example of (non)mutagenicity.

Skin sensitization quantitative QSAR models based on mechanistic structural alerts.

Allergic contact dermatitis is increasingly of interest for the hazard characterization of chemicals. in vivo animal testing is usually adopted but in silico approaches are becoming the new frontier due to their swiftness and economic efficiency. Indeed, in silico models can rationalise the experimental outcomes besides having predictive ability. The aim of the present work was to explore the electrophilic chemical behaviour responsible for allergic contact dermatitis using quantitative QSAR regression models. Eight models were proposed, using an experimental LLNA dataset of 366 chemicals. Each model is unique to encode a type of electrophilic reactivity domain. The models were obtained using autocorrelation, electro-topological and atom centered fragment based on two-dimensional descriptors, which incorporated the electronic and stereochemical features of substances interacting with skin proteins to induce skin cell proliferation. Finally, simple steps were proposed to integrate the eight models for the application on the test chemicals.

Can Antiviral Activity of Licorice Help Fight COVID-19 Infection?

The phytotherapeutic properties of Glycyrrhiza glabra (licorice) extract are mainly attributed to glycyrrhizin (GR) and glycyrrhetinic acid (GA). Among their possible pharmacological actions, the ability to act against viruses belonging to different families, including SARS coronavirus, is particularly important. With the COVID-19 emergency and the urgent need for compounds to counteract the pandemic, the antiviral properties of GR and GA, as pure substances or as components of licorice extract, attracted attention in the last year and supported the launch of two clinical trials. In silico docking studies reported that GR and GA may directly interact with the key players in viral internalization and replication such as angiotensin-converting enzyme 2 (ACE2), spike protein, the host transmembrane serine protease 2, and 3-chymotrypsin-like cysteine protease. In vitro data indicated that GR can interfere with virus entry by directly interacting with ACE2 and spike, with a nonspecific effect on cell and viral membranes. Additional anti-inflammatory and antioxidant effects of GR cannot be excluded. These multiple activities of GR and licorice extract are critically re-assessed in this review, and their possible role against the spread of the SARS-CoV-2 and the features of COVID-19 disease is discussed.

The similarity of inherited diseases (I): clinical similarity within the phenotypic series.

BACKGROUND: Mutations of different genes often result in clinically similar diseases. Among the datasets of similar diseases, we analyzed the 'phenotypic series' from Online Mendelian Inheritance in Man and examined the similarity of the diseases that belong to the same phenotypic series, because we hypothesize that clinical similarity may unveil shared pathogenic mechanisms. METHODS: Specifically, for each pair of diseases, we quantified their similarity, based on both number and information content of the shared clinical phenotypes. Then, we assembled the disease similarity network, in which nodes represent diseases and edges represent clinical similarities. RESULTS: On average, diseases have high similarity with other diseases of their own phenotypic series, even though about one third of diseases have their maximal similarity with a disease of another series. Consequently, the network is assortative (i.e., diseases belonging to the same series link preferentially to each other), but the series differ in the way they distribute within the network. Specifically, heterophobic series, which minimize links to other series, form islands at the periphery of the network, whereas heterophilic series, which are highly inter-connected with other series, occupy the center of the network. CONCLUSIONS: The finding that the phenotypic series display not only internal similarity (assortativity) but also varying degrees of external similarity (ranging from heterophobicity to heterophilicity) calls for investigation of biological mechanisms that might be shared among different series. The correlation between the clinical and biological similarities of the phenotypic series is analyzed in Part II of this study1.

[Psychological interventions in hospital during the first-wave of CoViD-19: an overview of the experiences of the Units of Clinical Psychology in Lombardy, Italy.] / Interventi psicologici in ospedale ai tempi della CoViD-19: una panoramica delle realtà proposte dalle Unità Operative di Psicologia (UOPSI) della Lombardia.

The current CoViD-19 pandemic threatens both physical and psychological well-being. According to the bio-psycho-social model, Units of Clinical Psychology of the Hospitals in Lombardy (Italy) reacted to this risk, offering diversified interventions, described in the present contribution. The medical staff operated on the front line during the emergency: psychologists addressed their needs through individual clinical work, sessions of decompression and debriefing. At the same time, Units of Clinical Psychology supported the hospitalized positive patients by conducting psychological consultations, either on the ward or through devices. Moreover, some hospitals activated helplines to address the needs of the population and family members, who were particularly vulnerable during the relative's illness and after the mourning.

The similarity of inherited diseases (II): clinical and biological similarity between the phenotypic series.

BACKGROUND: Despite being caused by mutations in different genes, diseases in the same phenotypic series are clinically similar, as reported in Part I of this study. Here, in Part II, we hypothesized that the phenotypic series too might be clinically similar. Furthermore, on the assumption that gene mutations indirectly cause clinical phenotypes by directly affecting biological functions, we hypothesized that clinically similar phenotypic series might be biologically similar as well. METHODS: To test these hypotheses, we generated a clinical similarity network and a set of biological similarity networks. In both types of network, the nodes represent the phenotypic series, and the edges linking the nodes indicate the similarity of the linked phenotypic series. The weight of each edge is proportional to a similarity coefficient, which depends on the clinical phenotypes and the biological features that are shared by the linked phenotypic series, in the clinical and biological similarity networks, respectively. RESULTS: After assembling and analyzing the networks, we raised the threshold for the similarity coefficient, to retain edges of progressively greater weight. This way all the networks were gradually split into fragments, composed of phenotypic series with increasingly greater degrees of similarity. Finally, by comparing the fragments from the two types of network, we defined subsets of phenotypic series with varying types and degrees of clinical and biological correlation. CONCLUSIONS: Like the individual diseases, the phenotypic series too are clinically and biologically similar to each other. Furthermore, our findings unveil different modalities of correlation between the clinical manifestations and the biological features of the inherited diseases.

Quantitative analysis of proteins which are members of the same protein complex but cause locus heterogeneity in disease.

It is still largely unknown how mutations in different genes cause similar diseases - a condition known as locus heterogeneity. A likely explanation is that the different proteins encoded by the locus heterogeneity genes participate in the same biological function and, specifically, that they belong to the same protein complex. Here we report that, in up to 30% of the instances of locus heterogeneity, the disease-causing proteins are indeed members of the same protein complex. Moreover, we observed that, in many instances, the diseases and protein complexes only partially intersect. Among the possible explanations, we surmised that some genes that encode proteins in the complex have not yet been reported as causing disease and are therefore candidate disease genes. Mutations of known human disease genes and murine orthologs of candidate disease genes that encode proteins in the same protein complex do in fact often cause similar phenotypes in humans and mice. Furthermore, we found that the disease-complex intersection is not only incomplete but also non-univocal, with many examples of one disease intersecting more than one protein complex or one protein complex intersecting more than one disease. These limits notwithstanding, this study shows that action on proteins in the same complex is a widespread pathogenic mechanism underlying numerous instances of locus heterogeneity.

From the "squiggle game" to "games of reciprocity" towards a creative co-construction of a space for working with adolescents.

The "squiggle game" is, above all, a method for relating and encouraging mutual exchange between the analyst and the patient (no matter if child, adolescent, or adult), enabling him to experience holding and freely explore different communication possibilities. After having explored the "technique" as it has been developed by Winnicott, this study also exposes some theoretical considerations, and some variations in the basic technique, brought together by the crucial role played by reciprocity: "Me a little and you a little." The paper is a clinical case with a Chinese adolescent.

Pathogenic Aß A2V versus protective Aß A2T mutation: Early stage aggregation and membrane interaction.

We investigated the effects of punctual A-to-V and A-to-T mutations in the amyloid precursor protein APP, corresponding to position 2 of Aß1-42. Those mutations had opposite effects on the onset and progression of Alzheimer disease, the former inducing early AD pathology and the latter protecting against the onset of the disease. We applied Static and Dynamic Light Scattering and Circular Dichroism, to study the different mutants in the early stages of the aggregation process, essential for the disease. Comparative results showed that the aggregation pathways differ in the kinetics and extent of the process, in the size of the aggregates and in the evolution of the secondary structure, resulting in fibrils of different morphology, as seen by AFM. Mutated peptides had comparable toxic effects on N2a cells. Moreover, as assessed by X-ray scattering, all of them displayed disordering effects on the internal structure of mixed phospholipids-gangliosides model membranes.

Pain measurement in cancer patients: a comparison of six methods.

A consecutive sample of 53 chronic cancer pain patients were administered 5 different pain intensity scales: a visual analogue scale (VAS), a numerical rating scale from 0 to 10 (NRS), a verbal rating scale (VRS), the Italian Pain Questionnaire (Italian version of the McGill Pain Questionnaire) (PRI), and the Integrated Pain Score (IPS) which is an instrument designed at the Pain Therapy and Palliative Care Division of the National Cancer Institute of Milan to integrate pain intensity and duration in a single measure. These scales were administered before and after a definite therapy change. At the time of the second evaluation the patients were also administered a pain relief scale (IRS). A factor analysis of the scoring properties of these instruments revealed a high degree of association between the variables. A single factor clearly emerged explaining most of the different scales variability. A logistic regression analysis showed that VAS, NRS, VRS were more strongly associated with IRS than PRI and IPS.