Cognitive, Neuropsychological and Biological Effects of Oxygen-Ozone Therapy on Frailty: A Study Protocol for a 5-Week, Randomized, Placebo-Controlled Trial.

Cognitive frailty (CF) is a heterogeneous syndrome that is becoming one of the most serious health problems as the world's population age is increasing. Elucidating its biological mechanisms as well as prevention and treatments is becoming increasingly significant, particularly in view of the associated health costs. We presented the study protocol of a research project funded by the Italian Ministry of Health (grant number RF-2016-02363298) aiming to investigate the cognitive and neuropsychological effects of a 5-week treatment with therapy based on the regenerative properties of ozone (O) in a cohort of subjects stratified according to CF scores.

Time- and Region-specific Effect of Vortioxetine on Central LPS-induced Transcriptional Regulation of NLRP3 Inflammasome.

Background: Inflammasome overactivation, multiprotein complexes that trigger inflammatory responses, plays a critical role in Major Depressive Disorder (MDD) pathogenesis and treatment responses. Indeed, different antidepressants alleviate depression-related behaviours by specifically counteracting the NLRP3 inflammasome signalling pathway. The immunomodulatory effects of vortioxetine (VTX), a multimodal antidepressant with cognitive benefits, were recently revealed to counter memory impairment induced by a peripheral lipopolysaccharide (LPS) injection 24 hours (h) postchallenge.

Validation of the Italian Version of the Daily Spiritual Experience Scale Among Psychiatric Patients.

Spiritual experience can represent an important aspect of mental health. The purpose of the current study was to validate the Italian version of the Daily Spiritual Experience Scale (DSES-IT) in a population of patients with different psychiatric disorders. It involved 209 patients enrolled in four facilities within the network of IRCCS Centro San Giovanni di Dio Fatebenefratelli Research Institute in Italy.

Promising Intervention Approaches to Potentially Resolve Neuroinflammation And Steroid Hormones Alterations in Alzheimer's Disease and Its Neuropsychiatric Symptoms.

Neuroinflammation is a biological process by which the central nervous system responds to stimuli/injuries affecting its homeostasis. So far as this reactive response becomes exacerbated and uncontrolled, it can lead to neurodegeneration, compromising the cognitive and neuropsychiatric domains. Parallelly, modifications in the hypothalamic signaling of neuroprotective hormones linked also to the inflammatory responses of microglia and astrocytes can exacerbate these processes.

Intermediate lengths of the hexanucleotide repeat expansion may synergistically contribute to attention deficit hyperactivity disorder in child and his father: case report.

We have summarized the abstract section as follows: "We report a son and his father affected by Attention Deficit Hyperactivity Disorder (ADHD). They belonged to a larger cohort (116 ADHD children, 20 related parents, 77 controls) wholly genotyped forexpansion. Ten ADHD susceptibility genes were further investigated in the family.

Behavioral and Psychological Symptoms of Dementia (BPSD): Clinical Characterization and Genetic Correlates in an Italian Alzheimer's Disease Cohort.

Background: The occurrence of Behavioral and Psychological Symptoms of Dementia (BPSD) in Alzheimer's Disease (AD) patients hampers the clinical management and exacerbates the burden for caregivers. The definition of the clinical distribution of BPSD symptoms, and the extent to which symptoms are genetically determined, are still open to debate. Moreover, genetic factors that underline BPSD symptoms still need to be identified.

MiRNA Profiling in Plasma Neural-Derived Small Extracellular Vesicles from Patients with Alzheimer's Disease.

Small extracellular vesicles (EVs) are able to pass from the central nervous system (CNS) into peripheral blood and contain molecule markers of their parental origin. The aim of our study was to isolate and characterize total and neural-derived small EVs (NDEVs) and their micro RNA (miRNA) cargo in Alzheimer's disease (AD) patients. Small NDEVs were isolated from plasma in a population consisting of 40 AD patients and 40 healthy subjects (CTRLs) using high throughput Advanced TaqMan miRNA OpenArrays, which enables the simultaneous determination of 754 miRNAs.

Molecular mechanisms in cognitive frailty: potential therapeutic targets for oxygen-ozone treatment.

In the last decade, cognitive frailty has gained great attention from the scientific community. It is characterized by high inflammation and oxidant state, endocrine and metabolic alterations, mitochondria dysfunctions and slowdown in regenerative processes and immune system, with a complex and multifactorial aetiology. Although several treatments are available, challenges regarding the efficacy and the costs persist.

The Missing Heritability of Sporadic Frontotemporal Dementia: New Insights from Rare Variants in Neurodegenerative Candidate Genes.

Frontotemporal dementia (FTD) is a common form of dementia among early-onset cases. Several genetic factors for FTD have been revealed, but a large proportion of FTD cases still have an unidentified genetic origin. Recent studies highlighted common pathobiological mechanisms among neurodegenerative diseases.

Genome Wide Association Study and Next Generation Sequencing: A Glimmer of Light Toward New Possible Horizons in Frontotemporal Dementia Research.

Frontotemporal Dementia (FTD) is a focal neurodegenerative disease, with a strong genetic background, that causes early onset dementia. The present knowledge about the risk loci and causative mutations of FTD mainly derives from genetic linkage analysis, studies of candidate genes, Genome-Wide Association Studies (GWAS) and Next-Generation Sequencing (NGS) applications. In this review, we report recent insights into the genetics of FTD, and, specifically, the results achieved thanks to GWAS and NGS approaches.

Next Generation Sequencing Analysis in Early Onset Dementia Patients.

Background: Early onset dementias (EOD) are rare neurodegenerative dementias that present before 65 years. Genetic factors have a substantially higher pathogenetic contribution in EOD patients than in late onset dementia.

Objective: To identify known and/or novel rare variants in major candidate genes associated to EOD by high-throughput sequencing.

Altered Expression of Circulating Cdc42 in Frontotemporal Lobar Degeneration.

The term frontotemporal lobar degeneration (FTLD) defines a group of heterogeneous conditions histologically characterized by neuronal degeneration, inclusions of various proteins, and synaptic loss. However, the molecular mechanisms contributing to these alterations are still unknown. As the Rho-GTPase family member Cell division cycle 42 (Cdc42) plays a key role in the regulation of actin cytoskeleton dynamics and spine formation, we investigated whether Cdc42 protein levels were altered in the disease.

Serum C-Peptide, Visfatin, Resistin, and Ghrelin are Altered in Sporadic and GRN-Associated Frontotemporal Lobar Degeneration.

Frontotemporal lobar degeneration (FTLD) is a group of complex neurodegenerative disease characterized by progressive deterioration of the frontal and anterior temporal lobes of the brain resulting in different heterogeneous conditions, mainly characterized by personality changes, behavioral disturbances, such as binge eating, and deficits in language and executive functions. Null mutations in progranulin gene (GRN) are one of the most frequent genetic determinants in familial frontotemporal dementia. Recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance revealing its metabolic function.

The Heritability of Frontotemporal Lobar Degeneration: Validation of Pedigree Classification Criteria in a Northern Italy Cohort.

A large portion of frontotemporal lobar degeneration (FTLD) patients has a family history of disease and the presence of a pathogenic mutation confirms the clinical diagnosis. Recently, standardized criteria to evaluate FTLD pedigree, based on first- and second-degree affected relatives, their age at onset, and clinical phenotype, were proposed and validated in an American cohort. Herein we applied these criteria to 402 Italian FTLD pedigrees and assessed mutation frequencies in GRN, C9orf72, and MAPT genes with the aim of validating these criteria.

Digital Detection of Exosomes by Interferometric Imaging.

Exosomes, which are membranous nanovesicles, are actively released by cells and have been attributed to roles in cell-cell communication, cancer metastasis, and early disease diagnostics. The small size (30-100 nm) along with low refractive index contrast of exosomes makes direct characterization and phenotypical classification very difficult. In this work we present a method based on Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) that allows multiplexed phenotyping and digital counting of various populations of individual exosomes (>50 nm) captured on a microarray-based solid phase chip.

Progranulin Mutations Affects Brain Oscillatory Activity in Fronto-Temporal Dementia.

Background: Mild cognitive impairment (MCI) is a clinical stage indicating a prodromal phase of dementia. This practical concept could be used also for fronto-temporal dementia (FTD). Progranulin (PGRN) has been recently recognized as a useful diagnostic biomarker for fronto-temporal lobe degeneration (FTLD) due to GRN null mutations.

Loss of exosomes in progranulin-associated frontotemporal dementia.

Many cells of the nervous system have been shown to release exosomes, a subclass of secreted vesicles of endosomal origin capable of transferring biomolecules among cells: this transfer modality represents a novel physiological form of intercellular communication between neural cells. Herein, we demonstrated that progranulin (PGRN), a protein targeted to the classical secretory pathway, is also secreted in association with exosomes by human primary fibroblasts. Moreover, we demonstrated that null mutations in the progranulin gene (GRN), a major cause of frontotemporal dementia, strongly reduce the number of released exosomes and alter their composition.

Molecular Pathways Bridging Frontotemporal Lobar Degeneration and Psychiatric Disorders.

The overlap of symptoms between neurodegenerative and psychiatric diseases has been reported. Neuropsychiatric alterations are commonly observed in dementia, especially in the behavioral variant of frontotemporal dementia (bvFTD), which is the most common clinical FTD subtype. At the same time, psychiatric disorders, like schizophrenia (SCZ), can display symptoms of dementia, including features of frontal dysfunction with relative sparing of memory.

Combined mass quantitation and phenotyping of intact extracellular vesicles by a microarray platform.

The interest towards extracellular vesicles (EVs) has grown exponentially over the last few years; being involved in intercellular communication and serving as reservoirs for biomarkers for tumors, they have a great potential for liquid biopsy development, possibly replacing many costly and invasive tissue biopsies. Here we propose, for the first time, the use of a Si/SiO2 interferometric, microarray platform for multiparametric intact EVs analysis combining label-free EVs mass quantitation and high sensitivity fluorescence based phenotyping. Label free interferometric measurement allows to quantify the amount of vesicles captured by printed antibodies while, on the same chip, EVs are also detected by fluorescence in a sandwich immunoassay.

Can APOE and MTHFR polymorphisms have an influence on the severity of cardiovascular manifestations in Italian Pseudoxanthoma elasticum affected patients?

Background: The clinical phenotype of Pseudoxanthoma elasticum (PXE) affected patients, although progressive with age, is very heterogeneous, even in the presence of identical mutations, thus suggesting the occurrence of modifier genes. Beside typical skin manifestations, the cardiovascular (CV) system, and especially the peripheral vasculature, is frequently and prematurely compromised.

Methods And Results: A cohort of 119 Italian PXE patients has been characterized for apolipoprotein E () and methylenetetrahydrofolate reductase () gene polymorphisms by PCR.