Detection of circulating miRNAs in serum in a mouse model of Collagen VI deficiency

Collagen VI is the main extracellular matrix (ECM) protein synthesized and secreted mainly by fibroblasts that forms a structurally network of microfilaments. Collagen VI binds several cell surface receptors and ECM components, suggesting that collagen VI is an important mechanical link between muscle cells and surrounding ECM. [1] Mutations related to COL6A1, COL6A2 and COL6A3 genes encoding for the three main collagen VI chains, cause the collagen VI-related myopathy, a specific subtype of congenital muscular dystrophy (CMD). In particular Ullrich congenital muscular dystrophy (UCMD) is a severe form characterized by progressive muscle wasting leading to loss of ambulation around ten years of age and respiratory problems in late childhood or young adulthood. Bethlem Miopathy (BM) is a mild-form characterized by a slow course usually without respiratory symptoms where around 50% of patients lose ambulation in the fifth decade. [2] Being the genetic test aimed to find mutations in COL6A genes expensive and time consuming mainly because the large size of the three genes, (106 coding exons in total [2]) the diagnosis of collagen VI-related myopathies is based on the clinical signs assessment coupled to the muscular biopsy which is useful to highlight any dystrophic or myopathic changes in the muscle fibers of the patient. The aim of the present work has been to identify a panel of miRNAs significantly dysregulated in col6a1-/- mice, the animal model of Bethlem myopathy and Ullrich congenital muscular dystrophy. miRNAs represent an ideal biomarker because they are easy to detect, well preserved in serum and non invasive. The findings of this work can be translated, in a further step, in a cohort of affected patients in order to become a powerful tool for the diagnosis and the follow-up of collagen VI-related myopathy. Research projects aimed to link the differential miRNA expression to pathological conditions are increasing and this suggests how miRNAs could be used as powerful tool to track disease related changes on a large scale in the forthcoming years. In order to identify differentially expressed miRNAs in knock-out col6a1-/- (KO) mice serum, a miRNAs expression profiling analysis by SYBR Green-based real-time PCR of 752 miRNAs in 5 col6a1+/+(WT) and 6 col6a1-/- has been performed. Fifty one (6.5%) of the 333 miRNAs expressed in col6a1-/- mice serum, showed a significant dysregulation between col6a1-/- and WT mice serum. The statistical analysis revealed 17/51 miRNAs up-regulated and 34/51 down-regulated. To further characterized the dysregulated miRNAs we checked their involvement in disease related pathways coupled with literature analysis. These analyses showed that mmu-miR-195a-5p, mmu-miR-26a-5p, mmu-let-7c-5p and mmu-let-7b-5p are up-regulated in col6a1-/- mice serum, whereas mmu-miR-29b-3p and mmu-miR-29a-3p are downregulated ofd of. These observations are quite interesting because these miRNAs could play an important role in the collagen VI-related myopathies linking genes involved in essential signalling pathway for skeletal muscle cells development, differentiation or coding for ECM proteins. In particular miRNAs targets interfere with ERBb, MAPK, PIK3/Akt, mTOR, ECM-receptors, actin cytoskeleton, focal adhesion and calcium signalling. In conclusion, this project has identified 6 dysregulated microRNAs (mmu-miR-195a-5p, mmu-miR-26a-5p, mmu-let-7c-5p, mmu-let-7b-5p, mmu-miR-29b-3p and mmu-miR-29a-3p) that could be used in future studies as biomarkers and possibly as a tool for the diagnosis and the follow-up of collagen VI-related myopathies. Further analyses in larger cohorts of BM and UCMD patients are needed in order to validate the data obtained in mice models

Ceramic Materials as an Alternative to Titanium for Dental Implant Fabrication

Titanium is the gold standard material to produce dental implants from more than 30 years, showing high success rate in different clinical scenarios. Zirconia implants were recently introduced to overwhelm some aesthetic and biological problems that can arise from titanium. Preclinical studies show that, from a mechanical point of view, zirconia may be a suitable substitute for titanium in implant fabrication. Three-dimensional finite element analysis (FEA) models found no difference between titanium and titanium-zirconium alloy implants, neither for early nor conventional functional loading. Nevertheless, zirconia presents the same osseoconductive properties of the titanium, even if the few clinical studies show survival and success rates slightly inferior for zirconia implants comparing to titanium ones, and long-term follow-ups are missing. For these reasons, the majority of authors agree to be cautious for proposing zirconia implants as widespread substitute of titanium implants

Second-Generation Antipsychotics' Effectiveness and Tolerability: A Review of Real-World Studies in Patients with Schizophrenia and Related Disorders

Despite methodological limitations, real-world studies might support clinicians by broadening the knowledge of antipsychotics' (APs) effectiveness and tolerability in different clinical scenarios and complement clinical trials. We conducted an extensive literature search in the PubMed database to evaluate the effectiveness and tolerability profiles of second-generation antipsychotics (SGAs) from real-world studies to aid clinicians and researchers in selecting the proper treatment for patients with schizophrenia and related disorders. The present review evidenced that SGAs demonstrated superior effectiveness over first-generation antipsychotics (FGAs) in relapse-free survival and psychiatric hospitalization rate and for treating negative symptoms. Persistence and adherence to therapy were higher in SGAs than FGAs. Most studies concluded that switching to long-acting injectables (LAIs) was significantly associated with a lower treatment failure rate than monotherapy with oral SGAs. Considerable improvements in general functionality, subjective well-being, and total score on global satisfaction tests, besides improved personal and social performance, were reported in some studies on patients treated with LAI SGAs. Clozapine was also associated with the lowest rates of treatment failure and greater effectiveness over the other SGAs, although with more severe side effects. Effectiveness on primary negative symptoms and cognitive deficits was rarely measured in these studies. Based on the data analyzed in the present review, new treatments are needed with better tolerability and improved effectiveness for negative, affective, and cognitive symptoms

Caratterizzazione dei processi di formazione della miscela e di combustione in motori ad accensione comandata ed iniezione diretta mediante diagnostiche non convenzionali

Da molti anni l’iniezione diretta nei motori ad accensione comandata è considerata una delle tecnologie più promettenti per il raggiungimento degli obiettivi di basso consumo di combustibile, nel rispetto dei limiti di emissione, e miglioramento delle prestazioni degli attuali propulsori. I motori DISI hanno mostrato, finora, ottime prospettive di sviluppo purtroppo ancora in parte disattese, vista la varietà e complessità dei parametri che sono implicati nell’ottimizzazione del sistema nel suo complesso. Da questo scaturisce l’opportunità di approfondire la conoscenza dei processi termo fluido-dinamici che avvengono nel cilindro e in particolar modo della metodologia di formazione della carica stratificata, mediante i potenti strumenti di indagine offerti dai motori otticamente accessibili e attraverso una sinergica attività numerico-sperimentale. L’attività di dottorato è stata focalizzata sullo studio dei fenomeni che caratterizzano i motori DISI, con particolare riferimento alla formazione della miscela e alla combustione in condizioni di carica omogenea e stratificata, mediante diagnostiche convenzionali e non convenzionali. A questo scopo è stato, in primo luogo, realizzato e messo a punto un motore otticamente accessibile pluricilindrico, derivato da un motore commerciale DISI, cercando di mantenere inalterate il più possibile le sue caratteristiche funzionali. In seguito, grazie al motore strumentato opportunamente, è stata condotta un'estesa attività sperimentale, con lo scopo di approfondire la conoscenza dei fenomeni chiave che caratterizzano questa tipologia di motori, anche riguardo l’utilizzo di combustibili alternativi, quali il bio-etanolo in forma pura e in miscela. Questo studio ha mostrato come il tipo di combustibile abbia un ruolo importante nella formazione della miscela, incidendo sia sulle prestazioni sia sulle emissioni di idrocarburi incombusti e di particolato sotto forma di particelle nanometriche. In particolare, ha evidenziato la grande dipendenza dalla condizione operativa del comportamento dell’etanolo e delle sue miscele con la benzina, in special modo in condizioni di carica stratificata. Mentre nella condizione al minimo, l’etanolo puro ha mostrato di migliorare sia variabilità ciclica sia emissioni grazie ad una migliore miscelazione, in condizioni di carico medio le differenze con la benzina in termini di prestazioni sono risultate inferiori. Per quanto riguarda le miscele, è stato osservato che, l’attesa diminuzione delle emissioni di particolato, non si verifica sempre al crescere della percentuale di etanolo e in tutte le condizioni operative. Ma l'aggiunta di etanolo può creare condizioni favorevoli per la formazione di particelle di soot dai composti pesanti della benzina e che questo effetto è esaltato, inoltre, dai tempi limitati per l’evaporazione e il mescolamento e dagli effetti di impingement dei getti. Pertanto, al fine di ottenere i miglioramenti promessi dai motori DISI, un ruolo molto importante è svolto dall’ottimizzazione congiunta dei sistemi, delle strategie di iniezione e della composizione del combustibile, anche attraverso una stretta collaborazione tra modellazione CFD e misure ottiche ad alta risoluzione spaziale e temporale in camera di combustione

Generalized Blonder-Tinkham-Klapwijk theory and conductance spectra with particle-hole mixing interface potential

We extend the Blonder-Tinkham-Klapwijk treatment including particle-hole mixing boundary conditions in the Bogoliubov-de Gennes scattering problem to describe anomalous conductance features often reported in normal-metal/superconductor junctions. We calculate the differential conductance spectra and show that conductance dips, not expected in the standard formulation, can be explained in terms of a phase π-shift between the bulk and the interface order parameter. A tight-binding model is also introduced to give a quantitative description of the phase-shift in terms of the transparency and polarization of the interface. We characterize the physics arising from particle-hole mixing boundary conditions at the interface and its effects on the conductance anomalies in superconductor-normal heterostructures

The New Elderly Patient: A Necessary Upgrade

The elderly individual is becoming the most common patient in clinical practice due to the increasing average life span, especially in developed countries. The current elderly patients are different from those of some decades ago. They usually have an active social life, want to be informed, and are actively involved in the current society with consequent high expectations for medical and dental treatment. However, not all the elderly patients are like this. Some of them show limited financial resources, reduced mental and manual skills, and poor motivation. The purpose of this communication is to make a brief characterization of the new elderly population in view of prosthetic and dental management

Delirium and Psychiatric Sequelae Associated to SARS-CoV-2 in Asymptomatic Patients With Psychiatric History and Mild Cognitive Impairment as Risk Factors: Three Case Reports

Human coronaviruses have neuroinvasive and neurotropic abilities that might explain psychiatric outcomes in affected patients. We hypothesized that delirium might be the sole clinical manifestation or even the prodrome of a psychiatric episode consistent with the mental history of a few infected patients with a preexisting diagnosed cognitive impairment. We examined three patients with preexisting mild cognitive impairment and delirium at admission for suspected SARS-CoV-2 infection. We diagnosed delirium using DSM-5 and Confusion Assessment Method (CAM) and measured consciousness level by the Glasgow Coma Scale. All the patients had no history of fever, respiratory complications, anosmia or ageusia, meningitis, and negative cerebrospinal fluid analysis for SARS-CoV-2. Our first patient had no psychiatric history, the second reported only a depressive episode, and the third had a history of bipolar disorder dated back to 40 years before. In the first patient, delirium resolved 2 days following the admission. The other two patients recovered in 4 and 14 days, and delirium appeared as the prodrome of a new psychiatric episode resembling past events. Clinicians should monitor the possibility that SARS-CoV-2 presence in the brain might clinically manifest in the form of delirium and acute psychiatric sequelae, even without other systemic symptoms. Psychiatric history and preexisting mild cognitive impairment are to be considered as predisposing factors for COVID-19 sequelae in delirium patients

Developmental Dental Defects and Tooth Wear: Pathological Processes Relationship

Many conditions or pathologies can modify teeth surfaces and cause several functional and esthetic problems. Congenital dental defects and tooth wear are two of the most important reasons of dental tissue changes. Nowadays, the prevalence of tooth wear is increasing because of a high incidence of non-physiological tooth wear especially in young people. However, distinguishing dental defects originated from tooth wear or developmental dental defects is crucial to plan the most suitable treatment. Then the aim of this work is to present the different pathological conditions caused by these two etiological factors as well as the underlying biochemical mechanisms and incorrect habits related

3D Imaging of Buried Dielectric Targets with a Tomographic Microwave Approach Applied to GPR Synthetic Data

Effective diagnostics with ground penetrating radar (GPR) is strongly dependent on the amount and quality of available data as well as on the efficiency of the adopted imaging procedure. In this frame, the aim of the present work is to investigate the capability of a typical GPR system placed at a ground interface to derive three-dimensional (3D) information on the features of buried dielectric targets (location, dimension, and shape). The scatterers can have size comparable to the resolution limits and can be placed in the shallow subsurface in the antenna near field. Referring to canonical multimonostatic configurations, the forward scattering problem is analyzed first, obtaining a variety of synthetic GPR traces and radargrams by means of a customized implementation of an electromagnetic CAD tool. By employing these numerical data, a full 3D frequency-domain microwave tomographic approach, specifically designed for the inversion problem at hand, is applied to tackle the imaging process. The method is tested here by considering various scatterers, with different shapes and dielectric contrasts. The selected tomographic results illustrate the aptitude of the proposed approach to recover the fundamental features of the targets even with critical GPR settings