Targeted next-generation sequencing analysis in Italian patients with keratoconus.

Objective: To report variants in 26 candidate genes and describe the clinical features of Italian patients with keratoconus (KC).

Subjects/methods: Sixty-four patients with a confirmed diagnosis of KC were enrolled in this genetic association study. Patients were classified into two study groups according to whether they had a confirmed diagnosis of progressive or stable KC.

Longitudinal Changes of Cornea Volume Measured by Means of Anterior Segment-Optical Coherence Tomography in Patients with Stable and Progressive Keratoconus.

Keratoconus is a corneal disease which results in progressive thinning and protrusion of the cornea leading to irregular astigmatism. The purpose of this study was to evaluate longitudinal changes in corneal volume (CV) occurring over time in keratoconus eyes. Consecutive patients affected by keratoconus were evaluated by means of anterior segment-optical coherence tomography (AS-OCT) at two different time points: baseline (T0) and after 1 year (T1).

Combined RNA interference and gene replacement therapy targeting MFN2 as proof of principle for the treatment of Charcot-Marie-Tooth type 2A.

Mitofusin-2 (MFN2) is an outer mitochondrial membrane protein essential for mitochondrial networking in most cells. Autosomal dominant mutations in the MFN2 gene cause Charcot-Marie-Tooth type 2A disease (CMT2A), a severe and disabling sensory-motor neuropathy that impacts the entire nervous system. Here, we propose a novel therapeutic strategy tailored to correcting the root genetic defect of CMT2A.

Impact of topographic localization of corneal ectasia on the outcomes of deep anterior lamellar keratoplasty employing large (9 mm) versus conventional diameter (8 mm) grafts.

Objectives: Visual and topographic outcomes of large (9.0 mm) versus conventional (8.0 mm) deep anterior lamellar keratoplasty (DALK) for the treatment of keratoconus (KC) were compared in relation to the different localization of the corneal ectasia (within or beyond the central 8.

Artificial Intelligence in Hypertension Management: An Ace up Your Sleeve.

Arterial hypertension (AH) is a progressive issue that grows in importance with the increased average age of the world population. The potential role of artificial intelligence (AI) in its prevention and treatment is firmly recognized. Indeed, AI application allows personalized medicine and tailored treatment for each patient.

Zebrafish Tric-b is required for skeletal development and bone cells differentiation.

Introduction: Trimeric intracellular potassium channels TRIC-A and -B are endoplasmic reticulum (ER) integral membrane proteins, involved in the regulation of calcium release mediated by ryanodine (RyRs) and inositol 1,4,5-trisphosphate (IPRs) receptors, respectively. While TRIC-A is mainly expressed in excitable cells, TRIC-B is ubiquitously distributed at moderate level. TRIC-B deficiency causes a dysregulation of calcium flux from the ER, which impacts on multiple collagen specific chaperones and modifying enzymatic activity, leading to a rare form of osteogenesis imperfecta (OI Type XIV).

Adult hippocampal neurogenesis and social behavioural deficits in the R451C Neuroligin3 mouse model of autism are reverted by the antidepressant fluoxetine.

Neuron generation persists throughout life in the hippocampus but is altered in animal models of neurological and neuropsychiatric diseases, suggesting that disease-associated decline in cognitive and emotional hippocampal-dependent behaviours might be functionally linked with dysregulation of postnatal neurogenesis. Depletion of the adult neural stem/progenitor cell (NSPCs) pool and neurogenic decline have been recently described in mice expressing synaptic susceptibility genes associated with autism spectrum disorder (ASDs). To gain further insight into mechanisms regulating neurogenesis in mice carrying mutations in synaptic genes related to monogenic ASDs, we used the R451C Neuroligin3 knock-in (Nlgn3 KI) mouse, which is characterized by structural brain abnormalities, deficits in synaptic functions and reduced sociability.

Structure, evolution and expression of zebrafish cartilage oligomeric matrix protein (COMP, TSP5). CRISPR-Cas mutants show a dominant phenotype in myosepta.

COMP (Cartilage Oligomeric Matrix Protein), also named thrombospondin-5, is a member of the thrombospondin family of extracellular matrix proteins. It is of clinical relevance, as in humans mutations in COMP lead to chondrodysplasias. The gene encoding zebrafish Comp is located on chromosome 11 in synteny with its mammalian orthologs.

An electrochemical sensor-based carbon black associated with a modified mixed oxide (SiO/TiO/SbO) for direct determination of thiamethoxam in raw honey and water samples.

The study aimed to develop an electrochemical sensor based on glassy carbon, mixed oxide (SiO/TiO/SbO), and carbon black. The material was synthesized, characterized, and used to determine thiamethoxam in raw honey and water. The morphologic structure and electrochemical performance of the sensor was characterized by scanning electron microscopy and cyclic voltammetry.

Characterization of the impact of the gene and rs3809849 on asparaginase sensitivity and cellular functions.

To investigate the role of gene and rs3809849 in pancreatic cancer (PANC1) and lymphoblastic leukemia (NALM6) cell lines and their response to asparaginase treatment. The authors applied CRISPR-Cas9 to produce knock-out (KO) and rs3809849 knock-in (KI) cell lines. The authors also interrogated rs3809849's impact on PANC1 cells through allele-specific overexpression.

Targeting PTB for Glia-to-Neuron Reprogramming In Vitro and In Vivo for Therapeutic Development in Neurological Diseases.

In vivo cell reprogramming of glial cells offers a promising way to generate new neurons in the adult mammalian nervous system. This approach might compensate for neuronal loss occurring in neurological disorders, but clinically viable tools are needed to advance this strategy from bench to bedside. Recently published work has described the successful neuronal conversion of glial cells through the repression of a single gene, polypyrimidine tract-binding protein 1 (), which encodes a key RNA-binding protein.

Clinical and multi-modality imaging approach in the selection of patients for left atrial appendage closure.

Atrial fibrillation (AF) can lead to embolic stroke and in subjects with non-valvular AF most of thrombi are sited in the left atrial appendage (LAA). LAA is a structure located in the free wall of heart with a wide variable and complex anatomy. LAA occlusion (LAAO) could be taken in consideration in subjects with non-valvular AF and who cannot have long-term anticoagulant therapy.

Incremental value of compression ultrasound sonography in the emergency department.

The quick evaluation of venous thromboembolism is a key point of modern medicine since the delayed diagnosis is associated with a worse prognosis. Venous ultrasound (VU) is a sensitive and rapidly performed test in cases of suspected deep venous thrombosis. Various protocols have been proposed for its execution, such as the study of the whole deep venous circulation of the lower limb or the analysis of the femoral-popliteal area.

Knocking out TMEM38B in human foetal osteoblasts hFOB 1.19 by CRISPR/Cas9: A model for recessive OI type XIV.

Osteogenesis imperfecta (OI) type XIV is a rare recessive bone disorder characterized by variable degree of severity associated to osteopenia. It is caused by mutations in TMEM38B encoding for the trimeric intracellular cation channel TRIC-B, specific for potassium and ubiquitously present in the endoplasmic reticulum (ER) membrane. OI type XIV molecular basis is largely unknown and, due to the rarity of the disease, the availability of patients' osteoblasts is challenging.

Serum Uric Acid and Left Ventricular Mass in Essential Hypertension.

Serum uric acid (sUA) has been associated with cardiovascular risk. Although the recent mechanistic hypothesis poses the basis for the association between sUA and left ventricular mass index (LVMi), the issue remains poorly investigated in a clinical setup. Through a retrospective analysis of the database of the departmental Hypertension Clinic of University Hospital of Salerno Medical School, we identified 177 essential hypertensives (age 60.

Role of comorbidities in heart failure prognosis Part 2: Chronic kidney disease, elevated serum uric acid.

Despite improvements in pharmacotherapy, morbidity and mortality rates in community-based populations with chronic heart failure still remain high. The increase in medical complexity among patients with heart failure may be reflected by an increase in concomitant non-cardiovascular comorbidities, which are recognized as independent prognostic factors in this population. Heart failure and chronic kidney disease share many risk factors, and often coexist.

A Novel HGF/SF Receptor (MET) Agonist Transiently Delays the Disease Progression in an Amyotrophic Lateral Sclerosis Mouse Model by Promoting Neuronal Survival and Dampening the Immune Dysregulation.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease with no effective treatment. The Hepatocyte Growth Factor/Scatter Factor (HGF/SF), through its receptor MET, is one of the most potent survival-promoting factors for motor neurons (MN) and is known as a modulator of immune cell function. We recently developed a novel recombinant MET agonist optimized for therapy, designated K1K1.

Animal Models of CMT2A: State-of-art and Therapeutic Implications.

Charcot-Marie-Tooth disease type 2A (CMT2A), arising from mitofusin 2 (MFN2) gene mutations, is the most common inherited axonal neuropathy affecting motor and sensory neurons. The cellular and molecular mechanisms by which MFN2 mutations determine neuronal degeneration are largely unclear. No effective treatment exists for CMT2A, which has a high degree of genetic/phenotypic heterogeneity.

Neural Stem Cell Transplantation for Neurodegenerative Diseases.

Neurodegenerative diseases are disabling and fatal neurological disorders that currently lack effective treatment. Neural stem cell (NSC) transplantation has been studied as a potential therapeutic approach and appears to exert a beneficial effect against neurodegeneration via different mechanisms, such as the production of neurotrophic factors, decreased neuroinflammation, enhanced neuronal plasticity and cell replacement. Thus, NSC transplantation may represent an effective therapeutic strategy.

Transcriptional regulation of adult neural stem/progenitor cells: tales from the subventricular zone.

In rodents, well characterized neurogenic niches of the adult brain, such as the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampus, support the maintenance of neural/stem progenitor cells (NSPCs) and the production of new neurons throughout the lifespan. The adult neurogenic process is dependent on the intrinsic gene expression signatures of NSPCs that make them competent for self-renewal and neuronal differentiation. At the same time, it is receptive to regulation by various extracellular signals that allow the modulation of neuronal production and integration into brain circuitries by various physiological stimuli.

Crtap and p3h1 knock out zebrafish support defective collagen chaperoning as the cause of their osteogenesis imperfecta phenotype.

Prolyl 3-hydroxylation is a rare collagen type I post translational modification in fibrillar collagens. The primary 3Hyp substrate sites in type I collagen are targeted by an endoplasmic reticulum (ER) complex composed by cartilage associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1) and prolyl cis/trans isomerase B, whose mutations cause recessive forms of osteogenesis imperfecta with impaired levels of α1(I)3Hyp986. The absence of collagen type I 3Hyp in wild type zebrafish provides the unique opportunity to clarify the role of the complex in vertebrate.

Increased serum uric acid level predicts poor prognosis in mildly severe chronic heart failure with reduced ejection fraction. An analysis from the MECKI score research group.

Background: Hyperuricemia prognostic impact on clinical outcomes in chronic heart failure (HF) patients has been investigated with inconclusive results.

Objectives: Aim of the study was to evaluate the prognostic impact of serum uric acid (SUA) on long-term clinical outcomes in HF.

Methods: An analysis of MECKI (Metabolic Exercise Cardiac Kidney Index) database, with median follow-up of 3.

Molecular Mechanisms of Neurogenic Aging in the Adult Mouse Subventricular Zone.

In the adult rodent brain, the continuous production of new neurons by neural stem/progenitor cells (NSPCs) residing in specialized neurogenic niches and their subsequent integration into pre-existing cerebral circuitries supports odour discrimination, spatial learning, and contextual memory capabilities. Aging is recognized as the most potent negative regulator of adult neurogenesis. The neurogenic process markedly declines in the aged brain, due to the reduction of the NSPC pool and the functional impairment of the remaining NSPCs.