Dissipative quantum mechanics and Kondo-like impurities on noncommutative two-tori

In a recent paper, by exploiting the notion of Morita equivalence for field theories on noncommutative tori and choosing rational values of the noncommutativity parameter $\theta$ (in appropriate units), a general one-to-one correspondence between the $m$-reduced conformal field theory (CFT) describing a quantum Hall fluid (QHF) at paired states fillings $\nu =\frac{m}{pm+2}$ and an Abelian noncommutative field theory (NCFT) has been established . That allowed us to add new evidence to the relationship between noncommutativity and quantum Hall fluids\cite% {ncmanybody}. On the other hand, the $m$-reduced CFT is equivalent to a system of two massless scalar bosons with a magnetic boundary interaction as introduced by Callan et al., at the so called ``magic''\ points. We are then able to describe, within such a framework, the dissipative quantum mechanics of a particle confined to a plane and subject to an external magnetic field normal to it. Here we develop such a point of view by focusing on the case $m=2$ which corresponds to a quantum Hall bilayer. The key role of a localized impurity which couples the two layers is emphasized and the effect of noncommutativity in terms of generalized magnetic translations (GMT) is fully exploited. As a result, general GMT operators are introduced, in the form of a tensor product, which act on the QHF and defect space respectively, and a comprehensive study of their rich structure is performed.Comment: 18 pages, 1 figure, accepted for publication in International Journal of Modern Physics

Clinical and genetic characterization of patients with hypertrophic cardiomyopathy and right atrial enlargement

AIMS: Prevalence and clinical significance of right atrial enlargement (RAE) has been poorly characterized in hypertrophic cardiomyopathy. METHODS: One hundred and sixty consecutive patients with hypertrophic cardiomyopathy (35.5 ± 20 years; 64% men) were studied. They underwent clinical examination, standard ECG, M-mode, 2D and Doppler echocardiography, stress test and ECG Holter monitoring. Major adverse cardiac events were considered: cardiac death (sudden death, heart failure death); cardiac transplant; resuscitated cardiac arrest or appropriate implantable cardioverter defibrillator discharge. Genetic analysis of eight sarcomeric genes was performed using Sanger sequencing. RESULTS: RAE was observed in 22 patients (14%), associated with left atrial enlargement in all cases. Patients with RAE were likely to have restrictive mitral pattern (P < 0.001) and had higher New York Heart Association (P < 0.001), N-terminal prohormone of brain natriuretic peptide (P < 0.001), left atrial volume index (P < 0.001), lateral (P = 0.04) and septal (P = 0.002) E/e', systolic pulmonary artery pressure (P < 0.001) and lower ejection fraction (all P < 0.001). On cardiopulmonary exercise testing, peak VO2 was lower and VE/VCO2 higher in patients with RAE (P < 0.001). During a mean follow-up of 4 ± 2.1 years, 30 major adverse cardiac events in 24 patients (15%) were observed. Cox proportional hazards regression analysis identified RAE as an independent predictor of major adverse cardiac events (odds ratio = 2.6; confidence interval 1.5-4.6; P = 0.001). In patients with RAE who were genetically tested, there was a higher prevalence of sarcomeric gene mutations (68%), double mutations (16%) and troponin T mutations (21%). CONCLUSION: RAE is present in a small subset of patients with hypertrophic cardiomyopathy, and largely reflects increased pulmonary pressures because of severe diastolic and/or systolic left ventricular dysfunction. Patients with RAE had a higher prevalence of sarcomeric gene mutations, troponin T mutations and complex genotypes. In conclusion, RAE may serve as a very useful marker of disease progression and adverse outcome in patients with sarcomeric hypertrophic cardiomyopathy

Neuroendocrine tumors: From anatomopathology to clinical presentation

Anatomopathological classification of Neuroendocrine tumors (NETs), today, covers a pivotal role in correctly identifying the disease and establish the right diagnostic and therapeutic approach it is needed in order to manage the patient. Depending on its grading and staging, NENs can have very different prognostic perspectives. Basing on WHO 2017 classification, in this paper will be explored their main characteristics, diving into main histotypes, dividing them into functional and non-functional tumors, keeping in mind their main locations: gastroenteropancreatic tract and lungs. Their typical clinical presentation and diagnostic strategies will be explained, mainly focusing on nuclear medicine and the importance of receptor overexpression (especially represented by somatostatin receptors, or SSTRs). This is the knowledge on which is based the diagnostic and therapeutic approach with peptide radiopharmaceuticals, especially 68Ga-DOTA-peptides (today, the gold standard in well-differentiated neuroendocrine neoplasms, only with the exception of insulinoma, that shows a low density of these molecules on its cellular surface)

Assessment of Executive Functions in Children with Sensorineural Hearing Loss and in Children with Specific Language Impairment: Preliminary Reports

Executive functions (EFs) are related abilities, associated with the frontal lobes functions, that allow individuals to modify behavioral patterns when they become unsatisfactory. The aim of this study was to assess EFs in children with sensorineural hearing loss (SNHL) and in children with "specific language impairment" (SLI), compared with a control group of children with normal development, to identify specific skill deficits. Three groups of preschool children aged between 2 and 6 years were assessed: 19 children with normal hearing, cognitive, and language development, 10 children with SNHL, and 20 children with SLI. The FE-PS 2-6 Battery was used for the assessment of preschool EFs, supplemented with the Modified Bell Test for the analysis of selective attention. Statistically significant differences were found between the two experimental groups and the control one, regarding the investigated skills. Children with SNHL showed a clear deficit in flexibility, whereas children with SLI had greater problems in self-regulation and management of waiting for gratification. Selective attention was found to be deficient in all three groups, with no statistically significant differences. This study shows that the skills investigated were found to be deficient in both SNHL and SLI patients. It is essential to start targeted exercises based on specific deficient skills as part of the rehabilitation program. It is of great importance to understand the consequences of EF deficit in preschool children to achieve an accurate diagnosis and carry out customized rehabilitation programs

Can the AGE/RAGE/ERK signalling pathway and the epithelial-to-mesenchymal transition interact in the pathogenesis of chronic rhinosinusitis with nasal polyps?

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent sinonasal mucosa inflammatory disease with still unclear pathophysiologic mechanisms that imply events of tissue repair and structural remodelling. Several cascades seem to have a considerable role in the onset and progression of mucosa hyperproliferation in nasal polyps including transforming growth factor β/Small mother against decapentaplegic (TGFβ/Smads), mitogenactivated protein kinases (MAPKs), advanced glycosylation end-products (AGEs) together with epithelial-tomesenchymal transition (EMT). Since many inflammatory mediators are reported to play important roles in the development of nasal polyps (NP) disease, this study aimed to analyse the correlation between the AGEs/receptor of advanced glycosylation end-products (RAGE)/extracellular signal-regulated kinase (ERK) signalling pathway and the main markers of EMT to better understand the influence that they exert on the remodelling of nasal mucous membranes in patients affected by CRSwNP vs normal controls. A total of 30 patients were enrolled in this study. Immunohistochemical analysis, using AGE, RAGE, p-ERK, MMP-3, TGF-β1, Smad2/3, Collagen I-III, α-SMA, E-cadherin, IL-6 and Vimentin antibodies, was performed. AGE, RAGE, ERK, p-ERK and MMP3 were also evaluated using western blot analysis. We observed an overexpression of the AGE/RAGE/p-ERK and the main mesenchymal markers of EMT (Vimentin and IL-6) in CRSwNP vs controls whereas the TGF-β/Smad3 pathway did not show any significant differences between the two groups of patients. These observations suggest a complex network of processes in the pathogenesis of NP, and the AGE/RAGE/ERK pathway and EMT might work together in promoting tissue remodelling in the formation of CRSwNP

Cortical and Subcortical Network Dysfunction in a Female Patient With NEXMIF Encephalopathy

The developmental and epileptic encephalopathies (DEE) are the most severe group of epilepsies. Recently, NEXMIF mutations have been shown to cause a DEE in females, characterized by myoclonic–atonic epilepsy and recurrent nonconvulsive status. Here we used advanced neuroimaging techniques in a patient with a novel NEXMIF de novo mutation presenting with recurrent absence status with eyelid myoclonia, to reveal brain structural and functional changes that can bring the clinical phenotype to alteration within specific brain networks. Indeed, the alterations found in the patient involved the visual pericalcarine cortex and the middle frontal gyrus, regions that have been demonstrated to be a core feature in epilepsy phenotypes with visual sensitivity and eyelid myoclonia with absences

Vesicular glutamate release from feeder-free hiPSC-derived neurons

Human-induced pluripotent stem cells (hiPSCs) represent one of the main and powerful tools for the in vitro modeling of neurological diseases. Standard hiPSC-based protocols make use of animal-derived feeder systems to better support the neuronal differentiation process. Despite their efficiency, such protocols may not be appropriate to dissect neuronal specific properties or to avoid interspecies contaminations, hindering their future translation into clinical and drug discovery approaches. In this work, we focused on the optimization of a reproducible protocol in feeder-free conditions able to generate functional glutamatergic neurons. This protocol is based on a generation of neuroprecursor cells differentiated into human neurons with the administration in the culture medium of specific neurotrophins in a Geltrex-coated substrate. We confirmed the efficiency of this protocol through molecular analysis (upregulation of neuronal markers and neurotransmitter receptors assessed by gene expression profiling and expression of the neuronal markers at the protein level), morphological analysis, and immunfluorescence detection of pre-synaptic and post-synaptic markers at synaptic boutons. The hiPSC-derived neurons acquired Ca2+-dependent glutamate release properties as a hallmark of neuronal maturation. In conclusion, our study describes a new methodological approach to achieve feeder-free neuronal differentiation from hiPSC and adds a new tool for functional characterization of hiPSC-derived neurons

Loss of Wwox Perturbs Neuronal Migration and Impairs Early Cortical Development

Mutations in the WWOX gene cause a broad range of ultra-rare neurodevelopmental and brain degenerative disorders, associated with a high likelihood of premature death in animal models as well as in humans. The encoded Wwox protein is a WW domain-containing oxidoreductase that participates in crucial biological processes including tumor suppression, cell growth/differentiation and regulation of steroid metabolism, while its role in neural development is less understood. We analyzed the exomes of a family affected with multiple pre- and postnatal anomalies, including cerebellar vermis hypoplasia, severe neurodevelopmental impairment and refractory epilepsy, and identified a segregating homozygous WWOX mutation leading to a premature stop codon. Abnormal cerebral cortex development due to a defective architecture of granular and molecular cell layers was found in the developing brain of a WWOX-deficient human fetus from this family. A similar disorganization of cortical layers was identified in lde/lde rats (carrying a homozygous truncating mutation which disrupts the active Wwox C-terminal domain) investigated at perinatal stages. Transcriptomic analyses of Wwox-depleted human neural progenitor cells showed an impaired expression of a number of neuronal migration-related genes encoding for tubulins, kinesins and associated proteins. These findings indicate that loss of Wwox may affect different cytoskeleton components and alter prenatal cortical development, highlighting a regulatory role of the WWOX gene in migrating neurons across different species

Expanding Phenotype of Poirier\u2013Bienvenu Syndrome: New Evidence from an Italian Multicentrical Cohort of Patients

Background: Poirier\u2013Bienvenu Neurodevelopmental Syndrome (POBINDS) is a rare disease linked to mutations of the CSNK2B gene, which encodes for a subunit of caseinkinase CK2 involved in neuronal growth and synaptic transmission. Its main features include early-onset epilepsy and intellectual disability. Despite the lack of cases described, it appears that POBINDS could manifest with a wide range of phenotypes, possibly related to the different mutations of CSNK2B. Methods: Our multicentric, retrospective study recruited nine patients with POBINDS, detected using next-generation sequencing panels and whole-exome sequencing. Clinical, laboratory, and neuroimaging data were reported for each patient in order to assess the severity of phenotype, and eventually, a correlation with the type of CSNK2B mutation. Results: We reported nine unrelated patients with heterozygous de novo mutations of the CSNK2B gene. All cases presented epilepsy, and eight patients were associated with a different degree of intellectual disability. Other features detected included endocrinological and vascular abnormalities and dysmorphisms. Genetic analysis revealed six new variants of CSNK2B that have not been reported previously. Conclusion: Although it was not possible to assess a genotype\u2013phenotype correlation in our patients, our research further expands the phenotype spectrum of POBINDS patients, identifying new mutations occurring in the CSNK2B gene