Testing an Attachment-Based Parenting Intervention-VIPP-FC/A in Adoptive Families with Post-institutionalized Children: Do Maternal Sensitivity and Genetic Markers Count?

This study investigated the effectiveness of a newly integrated version of an intervention targeting adoptive mothers' positive parenting for promoting children's emotional availability, by testing the moderating role of both two maternal genetic polymorphisms (i.e., 5HTTLPR and DRD4-VNTR) and emotional availability-EA on intervention outcomes. Mothers with their children (N = 80; Mage = 42.73 years, SD = 3.79; Mage = 33.18 months, SD = 16.83 months) participated in a RCT testing the Video-Feedback Intervention to Promote Positive Parenting and Sensitive Discipline-VIPP-FC/A effectiveness. Mixed effects regression models showed a significant improvement in mother-child EA for the VIPP-intervention vs. the dummy intervention condition, with a moderating role of maternal EA on children's outcomes. No significant moderating effect was found for the two genetic polymorphisms inquired. Children's and mother's outcomes obtained are discussed

Testing an Attachment-Based Parenting Intervention-VIPP-FC/A in Adoptive Families with Post-institutionalized Children: Do Maternal Sensitivity and Genetic Markers Count?

This study investigated the effectiveness of a newly integrated version of an intervention targeting adoptive mothers' positive parenting for promoting children's emotional availability, by testing the moderating role of both two maternal genetic polymorphisms (i.e., 5HTTLPR and DRD4-VNTR) and emotional availability-EA on intervention outcomes. Mothers with their children (N = 80; Mage = 42.73 years, SD = 3.79; Mage = 33.18 months, SD = 16.83 months) participated in a RCT testing the Video-Feedback Intervention to Promote Positive Parenting and Sensitive Discipline-VIPP-FC/A effectiveness. Mixed effects regression models showed a significant improvement in mother-child EA for the VIPP-intervention vs. the dummy intervention condition, with a moderating role of maternal EA on children's outcomes. No significant moderating effect was found for the two genetic polymorphisms inquired. Children's and mother's outcomes obtained are discussed

Overcoming challenges in glioblastoma treatment: targeting infiltrating cancer cells and harnessing the tumor microenvironment

Glioblastoma is a highly malignant primary brain tumor with limited treatment options and poor prognosis. Despite current treatment approaches, including surgical resection, radiation therapy, and chemotherapy with temozolomide, glioblastoma remains mostly incurable due to its invasive growth pattern, limited drug penetration beyond the blood-brain barrier, and resistance to conventional therapies. One of the main challenges in glioblastoma treatment is effectively eliminating infiltrating cancer cells that remain in the brain parenchyma after primary tumor resection

I nuovi media come dispositivi semiotecnici. Uno sguardo pedagogico

Sia in ambito umanistico, sia scientifico si continua a parlare di rivoluzione digitale. Il tema merita di essere approfondito per due ordini di ragioni: 1) per l'innegabile influenza che i nuovi media esercitano sulle relazioni sociali, sui comportamenti quotidiani e, in generale, sulle esperienze di vita degli individui; 2) perche le tecnologie emergenti, in uno specifico contesto storico-culturale, non sono semplicemente uno strumento ad uso degli uomini ma un medium attraverso cui si costruiscono significati e realta sociali. In ottica educativa diviene interessante chiedersi come le nuove tecnologie digitali influenzino e ristrutturino le esperienze di vita dei soggetti. A tal fine l'articolo propone una lettura pedagogica dei nuovi media come dispositivi semiotecnici (Foucault, 1976): ovvero insiemi codificati di idee, ideologie e rappresentazioni che influenzano e trasformano – insieme a specifici apparati materiali, attraverso i discorsi e facendo presa sui corpi – comportamenti sociali e processi di costruzione identitaria. Le tecnologie in tal senso sono mediatori esperienziali: esse co-creano routine e azioni quotidiane, modificano i rapporti tra individui, con gli oggetti, lo spazio, il tempo e i corpi, contribuendo a produrre nuove soggettivita

Possible role of glucose-6-phosphatase 3 in the pathogenesis of uterine leiomyomas

Background and aim: Glucose-6-phosphatase catalytic subunit 3 (G6PC3) has been recently described as a metabolite repair enzyme involved in the disposal of the phosphorylated glucose analog 1,5-anhydroglucitol-6-phosphate (1,5AG6P). This function is especially relevant in neutrophils; indeed, G6PC3 deficiency leads to neutropenia as the accumulated metabolite 1,5AG6P inhibits the first step of glycolysis. Like neutrophils, tumoral metabolism also mainly relies on glycolysis, and we wondered if G6PC3 is expressed in uterine leiomyoma samples and if it can eventually have a role in the pathogenesis of these tumors. Understanding the complex pathophysiology of leiomyomas is a prerequisite to develop new therapeutic strategies. Methods: We used human uterine leiomyoma and matched myometrial samples. Immunohistochemistry and quantitative polymerase chain reaction (qPCR) were performed. Results: Immunohistochemical analysis has not evidenced appreciable differences between pathologic versus normal tissue samples. Indeed, qPCR analysis suggests a higher expression of G6PC3 in human uterine leiomyoma than in matched myometrial samples. Conclusion: A targeted therapeutic inhibition of G6PC3 in uterine leiomyoma samples is a potential strategy to slow down tumor growth

Increased Susceptibility to Cortical Spreading Depression in the Mouse Model of Familial Hemiplegic Migraine Type 2

Familial hemiplegic migraine type 2 (FHM2) is an autosomal dominant form of migraine with aura that is caused by mutations of the α2-subunit of the Na,K-ATPase, an isoform almost exclusively expressed in astrocytes in the adult brain. We generated the first FHM2 knock-in mouse model carrying the human W887R mutation in the Atp1a2 orthologous gene. Homozygous Atp1a2R887/R887 mutants died just after birth, while heterozygous Atp1a2+/R887 mice showed no apparent clinical phenotype. The mutant α2 Na,K-ATPase protein was barely detectable in the brain of homozygous mutants and strongly reduced in the brain of heterozygous mutants, likely as a consequence of endoplasmic reticulum retention and subsequent proteasomal degradation, as we demonstrate in transfected cells. In vivo analysis of cortical spreading depression (CSD), the phenomenon underlying migraine aura, revealed a decreased induction threshold and an increased velocity of propagation in the heterozygous FHM2 mouse. Since several lines of evidence involve a specific role of the glial α2 Na,K pump in active reuptake of glutamate from the synaptic cleft, we hypothesize that CSD facilitation in the FHM2 mouse model is sustained by inefficient glutamate clearance by astrocytes and consequent increased cortical excitatory neurotransmission. The demonstration that FHM2 and FHM1 mutations share the ability to facilitate induction and propagation of CSD in mouse models further support the role of CSD as a key migraine trigger

Close linkage with the RET protooncogene and boundaries of deletion mutations in autosomal dominant Hirschsprung disease

Tight linkage with the RET proto-oncogene (Zmax = 3.41 at θ = 0.00), analysis of recombinants and detection of a familial microdeletion in a large pedigree restrict the mapping of the Hirschsprung (HSCR) gene previously localized on proximal 10q. The molecular characterization of the familial microdeletion and of 3 additional cytogenetically visible de novo deletions, isolated in somatic cell hybrids, identify a smallest region of overlap of 250 Kb. This contains the RET proto-oncogene where missense mutations causing multiple endocrine neoplasia type 2A (MEN 2A) phenotype were recently found. The pentagastrin test (which detects preclinical forms of MEN 2A or B) is negative in adult HSCR patients with deletions of the RET gene. This represents a good candidate for the search of mutations causing HSC

Untangling the extracellular matrix of idiopathic epiretinal membrane: a path winding among structure, interactomics and translational medicine

Idiopathic epiretinal membranes (iERMs) are fibrocellular sheets of tissue that develop at the vit-reoretinal interface. iERMs consist of cells and extracellular matrix (ECM) formed by a complex array of structural proteins and a large number of proteins that regulate cell-matrix interaction, matrix deposition and remodelling. Many components of the ECM tend to produce a layered pat-tern that can influence the tractional properties of the membranes. We applied a bioinformatics approach on a list of proteins previously identified with an MS-based proteomic analysis on sam-ples of iERM to report the interactome of some key proteins. The performed pathway analysis highlights interactions occurring among ECM molecules, their cell receptors, and intra or extra-cellular proteins that may play a role in matrix biology, in this special context. In particular, integ-rin β1, cathepsin B, epidermal growth factor receptor, protein-glutamine gam-ma-glutamyltransferase 2, and prolow-density lipoprotein receptor-related protein 1 are key hubs in the outlined protein-protein cross-talks. A section on the biomarkers that can be found in the vitreous humor of patients affected by iERM and that can modulate matrix deposition is also pre-sented. Finally, translational medicine in iERM treatment has been summed up taking stock of the techniques that have been proposed for pharmacologic vitreolysi

MAPK15 controls cellular responses to oxidative stress by regulating NRF2 activity and expression of its downstream target genes

Oxidation processes in mitochondria and different environmental insults contribute to unwarranted accumulation of reactive oxygen species (ROS). These, in turn, rapidly damage intracellular lipids, proteins, and DNA, ultimately causing aging and several human diseases. Cells have developed different and very effective systems to control ROS levels. Among these, removal of excessive amounts is guaranteed by upregulated expression of various antioxidant enzymes, through activation of the NF-E2-Related Factor 2 (NRF2) protein. Here, we show that Mitogen Activated Protein Kinase 15 (MAPK15) controls the transactivating potential of NRF2 and, in turn, the expression of its downstream target genes. Specifically, upon oxidative stress, MAPK15 is necessary to increase NRF2 expression and nuclear translocation, by inducing its activating phosphorylation, ultimately supporting transactivation of cytoprotective antioxidant genes. Lungs are continuously exposed to oxidative damages induced by environmental insults such as air pollutants and cigarette smoke. Interestingly, we demonstrate that MAPK15 is very effective in supporting NRF2-dependent antioxidant transcriptional response to cigarette smoke of epithelial lung cells. Oxidative damage induced by cigarette smoke indeed represents a leading cause of disability and death worldwide by contributing to the pathogenesis of different chronic respiratory diseases and lung cancer. Therefore, the development of novel therapeutic strategies able to modulate cellular responses to oxidative stress would be highly beneficial. Our data contribute to the necessary understanding of the molecular mechanisms behind such responses and identify new potentially actionable targets

Co-Expression of Podoplanin and CD44 in Proliferative Vitreoretinopathy Epiretinal Membranes

Epiretinal membranes (ERMs) are sheets of tissue that pathologically develop in the vitreoretinal interface leading to progressive vision loss. They are formed by different cell types and by an exuberant deposition of extracellular matrix proteins. Recently, we reviewed ERMs’ extracellular matrix components to better understand molecular dysfunctions that trigger and fuel the onset and development of this disease. The bioinformatics approach we applied delineated a comprehensive overview on this fibrocellular tissue and on critical proteins that could really impact ERM physiopathology. Our interactomic analysis proposed the hyaluronic-acid-receptor cluster of differentiation 44 (CD44) as a central regulator of ERM aberrant dynamics and progression. Interestingly, the interaction between CD44 and podoplanin (PDPN) was shown to promote directional migration in epithelial cells. PDPN is a glycoprotein overexpressed in various cancers and a growing body of evidence indicates its relevant function in several fibrotic and inflammatory pathologies. The binding of PDPN to partner proteins and/or its ligand results in the modulation of signaling pathways regulating proliferation, contractility, migration, epithelial–mesenchymal transition, and extracellular matrix remodeling, all processes that are vital in ERM formation. In this context, the understanding of the PDPN role can help to modulate signaling during fibrosis, hence opening a new line of therap