Effectiveness of Flax-TRM composites under traction

The scientific research in the field of masonry structures is increasingly welcoming the adoption of innovative and sustainable rehabilitation techniques aimed at the safeguarding of the Built Cultural Heritage. Textile Reinforced Matrix (TRM) composites are the most widely investigated strengthening systems for ancient masonry structures, thanks to their high compatibility level with the material substrates in terms of fire resistance, chemical/physical aspects, reversibility property, little impact on dimensions, stiffness and weight. Nevertheless, in the last years, the growing concern on sustainability increased the interest in products with low environmental impact, for promoting circular economy approaches in the design of the structural interventions. In particular, efforts have been done to replace the most common composites with materials less harmful to the environment, such as natural fibres, for developing compatible and sustainable rehabilitation techniques for masonry structures. This paper presents the preliminary results of experimental tests conducted by the authors on specimens of TRM composites made with natural, vegetable, flax-fibre grids and natural hydraulic lime mortar. The mechanical characterization tests aimed at detecting the tensile behaviour of the natural TRM system compared to the results available in the literature on different vegetable-fibre composites and TRMs made with natural basalt fibres. The experimental tests highlighted the promising mechanical effectiveness of natural TRM systems under traction and offered a hint to further research aimed at improving their mechanical strength and stiffness

Brain Organoids as Model Systems for Genetic Neurodevelopmental Disorders

Neurodevelopmental disorders (NDDs) are a group of disorders in which the development of the central nervous system (CNS) is disturbed, resulting in different neurological and neuropsychiatric features, such as impaired motor function, learning, language or non-verbal communication. Frequent comorbidities include epilepsy and movement disorders. Advances in DNA sequencing technologies revealed identifiable genetic causes in an increasingly large proportion of NDDs, highlighting the need of experimental approaches to investigate the defective genes and the molecular pathways implicated in abnormal brain development. However, targeted approaches to investigate specific molecular defects and their implications in human brain dysfunction are prevented by limited access to patient-derived brain tissues. In this context, advances of both stem cell technologies and genome editing strategies during the last decade led to the generation of three-dimensional (3D) in vitro-models of cerebral organoids, holding the potential to recapitulate precise stages of human brain development with the aim of personalized diagnostic and therapeutic approaches. Recent progresses allowed to generate 3D-structures of both neuronal and non-neuronal cell types and develop either whole-brain or region-specific cerebral organoids in order to investigate in vitro key brain developmental processes, such as neuronal cell morphogenesis, migration and connectivity. In this review, we summarized emerging methodological approaches in the field of brain organoid technologies and their application to dissect disease mechanisms underlying an array of pediatric brain developmental disorders, with a particular focus on autism spectrum disorders (ASDs) and epileptic encephalopathies

Coarsening on percolation clusters: out-of-equilibrium dynamics versus non linear response

We analyze the violations of linear fluctuation-dissipation theorem (FDT) in the coarsening dynamics of the antiferromagnetic Ising model on percolation clusters in two dimensions. The equilibrium magnetic response is shown to be non linear for magnetic fields of the order of the inverse square root of the number of sites. Two extreme regimes can be identified in the thermoremanent magnetization: (i) linear response and out-of-equilibrium relaxation for small waiting times (ii) non linear response and equilibrium relaxation for large waiting times. The function $X(C)$ characterizing the deviations from linear FDT cross-overs from unity at short times to a finite positive value for longer times, with the same qualitative behavior whatever the waiting time. We show that the coarsening dynamics on percolation clusters exhibits stronger long-term memory than usual euclidian coarsening.Comment: 17 pages, 10 figure

Raising awareness of non-hodgkin lymphoma in HIV-infected adolescents: Report of 2 cases in the HAART era

Human immunodeficiency virus (HIV) chronically infected patients are at increased risk of developing non-Hodgkin lymphoma compared with the general population. Highly active antiretroviral therapy has had a dramatic effect on the natural history of HIV infection, reducing the incidence of acquired immunodeficiency syndrome-related non-Hodgkin lymphoma and improving overall survival. However, problems related to adherence to treatment, frequently experienced during adolescence, may increase the risk of acquired immunodeficiency syndrome-related cancers. Optimizing highly active antiretroviral therapy and monitoring noncompliant patients with persisting HIV replication should be considered by physicians who take care of these patients. We herein report 2 cases of relapsed/progressive Burkitt lymphoma in HIV vertically infected adolescents

Off Equilibrium Study of the Fluctuation-Dissipation Relation in the Easy-Axis Heisenberg Antiferromagnet on the Kagome Lattice

Violation of the fluctuation-dissipation theorem (FDT) in a frustrated Heisenberg model on the Kagome lattice is investigated using Monte Carlo simulations. The model exhibits glassy behaviour at low temperatures accompanied by very slow dynamics. Both the spin-spin autocorrelation function and the response to an external magnetic field are studied. Clear evidence of a constant value of the fluctuation dissipation ratio and long range memory effects are observed for the first time in this model. The breakdown of the FDT in the glassy phase follows the predictions of the mean field theory for spin glasses with one-step replica symmetry breaking.Comment: 4 pages, 4 figure

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

PRRT2 controls neuronal excitability by negatively modulating Na+ channel 1.2/1.6 activity

Proline-rich transmembrane protein 2 (PRRT2) is the causative gene for a heterogeneous group of familial paroxysmal neurological disorders that include seizures with onset in the first year of life (benign familial infantile seizures), paroxysmal kinesigenic dyskinesia or a combination of both. Most of the PRRT2 mutations are loss-of-function leading to haploinsufficiency and 80% of the patients carry the same frameshift mutation (c.649dupC; p.Arg217Profs*8), which leads to a premature stop codon. To model the disease and dissect the physiological role of PRRT2, we studied the phenotype of neurons differentiated from induced pluripotent stem cells from previously described heterozygous and homozygous siblings carrying the c.649dupC mutation. Singlecell patch-clamp experiments on induced pluripotent stem cell-derived neurons from homozygous patients showed increased Na+ currents that were fully rescued by expression of wild-type PRRT2. Closely similar electrophysiological features were observed in primary neurons obtained from the recently characterized PRRT2 knockout mouse. This phenotype was associated with an increased length of the axon initial segment and with markedly augmented spontaneous and evoked firing and bursting activities evaluated, at the network level, by multi-electrode array electrophysiology. Using HEK-293 cells stably expressing Nav channel subtypes, we demonstrated that the expression of PRRT2 decreases the membrane exposure and Na+ current of Nav1.2/Nav1.6, but not Nav1.1, channels. Moreover, PRRT2 directly interacted with Nav1.2/Nav1.6 channels and induced a negative shift in the voltage-dependence of inactivation and a slow-down in the recovery from inactivation. In addition, by co-immunoprecipitation assays, we showed that the PRRT2-Nav interaction also occurs in brain tissue. The study demonstrates that the lack of PRRT2 leads to a hyperactivity of voltage-dependent Na+ channels in homozygous PRRT2 knockout human and mouse neurons and that, in addition to the reported synaptic functions, PRRT2 is an important negative modulator of Nav1.2 and Nav1.6 channels. Given the predominant paroxysmal character of PRRT2-linked diseases, the disturbance in cellular excitability by lack of negative modulation of Na+ channels appears as the key pathogenetic mechanism

Epilepsy with auditory features: A heterogeneous clinico-molecular disease

Objective: To identify novel genes implicated in epilepsy with auditory features (EAF) in phenotypically heterogeneous families with unknown molecular basis. Methods: We identified 15 probands with EAF in whom an LGI1 mutation had been excluded. We performed electroclinical phenotyping on all probands and available affected relatives. We used whole-exome sequencing (WES) in 20 individuals with EAF (including all the probands and 5 relatives) to identify single nucleotide variants, small insertions/deletions, and copy number variants. Results: WES revealed likely pathogenic variants in genes that had not been previously associated with EAF: a CNTNAP2 intragenic deletion, 2 truncating mutations of DEPDC5, and a missense SCN1A change. Conclusions: EAF is a clinically and molecularly heterogeneous disease. The association of EAF with CNTNAP2, DEPDC5, and SCN1A mutations widens the phenotypic spectrum related to these genes. CNTNAP2 encodes CASPR2, a member of the voltage-gated potassium channel complex in which LGI1 plays a role. The finding of a CNTNAP2 deletion emphasizes the importance of this complex in EAF and shows biological convergence

Middle Fossa Extension of Posterior Fossa Meningiomas is Associated with Poorer Clinical Outcomes

Introduction: Progression of posterior fossa meningiomas (PFMs) can lead to extension into the middle cranial fossa. Pre-operative imaging allows for quantification of middle fossa extension (MFE). We aimed to determine the clinical impact of MFE on surgical and clinical outcomes during resection of PFMs. Methods: Craniotomies for meningiomas performed at a large single center academic institution from January 2012 to December 2018 were identified. Preoperative MRI and CT imaging was reviewed to determine the presence of MFE of posterior fossa meningiomas and correlated to post-operative outcomes. Results: 65 PFMs were identified and mean follow-up was 28.8 ± 20.1 months. 13/65 PFMs showed MFE preoperatively. Average size of PFMs with MFE (36.1 cm ± 12.1 cm) was similar to PFMs without MFE (33.5 cm ± 9.2 cm, p \u3e 0.05). 9/13 PFMs with MFE were petrous or petroclival, and 4/13 involved the cavernous sinus. Retrosigmoid craniotomy was the most utilized approach for both isolated PFMs (51.9%) and PFMs with MFE (76.9%). Anterior approaches were used in 2/13 PFMs with MFE. Presence of MFE was strongly associated with decreased rates of GTR (RR= 0.1; p \u3c 0.05). MFE wasn’t associated with longer LOS or rates of readmission within 30 days of discharge, but was associated with a significantly higher rate of overall mortality at last follow-up (RR=5.3; 95%; p \u3c 0.05). Conclusion: PFMs with MFE are easily identifiable and are associated with decreased rates of GTR and overall prognosis and may suggest the need for anterior or combined approaches