24-h continuous non-invasive multiparameter home monitoring of vitals in patients with Rett syndrome by an innovative wearable technology: evidence of an overlooked chronic fatigue status.

Background: Sleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting female patients (prevalence 7.1/100,000 female patients) linked to pathogenic variations in the X-linked methyl-CpG-binding protein 2 () gene. Autonomic nervous system dysfunction with a predominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PSNS) is reported in RTT, along with exercise fatigue and increased sudden death risk.

Epilepsy phenotypes across the different age-ranges in IQSEC2-related encephalopathy: An Italian multicentre retrospective cohort study.

Background: Epilepsy is a hallmark of IQSEC2-related encephalopathy within a phenotypic variability ranging between early onset epileptic and developmental encephalopathy and X-linked intellectual disability with epilepsy.

Patients And Methods: Data including demographic aspects, gene variants, seizure semiology and timing, EEG features, neuroimaging and response to therapy were retrospectively collected in patients with IQSEC2-related epilepsy referring to 8 Italian tertiary centres.

Results: The reported cohort included 11 patients (8 males and 3 females).

Natural Course of -Related Encephalopathy: An Italian National Structured Survey.

Pathogenic loss-of-function variants in the IQ motif and SEC7 domain containing protein 2 () gene cause intellectual disability with Rett syndrome (RTT)-like features. The aim of this study was to obtain systematic information on the natural history and extra-central nervous system (CNS) manifestations for the Italian population (>90%) by using structured family interviews and semi-quantitative questionnaires. encephalopathy prevalence estimate was 7.

A novel mini-invasive finger-prick protocol for preparing blood micro-samples for morphological analysis of human erythrocytes by scanning electron microscopy.

Here we describe the development and optimization of a new protocol for the preparation and surface imaging by scanning electron microscope of human erythrocytes from blood micro-samples obtained by finger prick. By testing several key pre-analytical conditions for blood sampling, erythrocyte preservation, storage and imaging, we designed a rapid new minimally-invasive reproducible method for obtaining uniform deposition of an adequate number of erythrocytes with well-preserved morphology on a substrate. The possibility of obtaining reliable reproducible high resolution morphometric data on peripheral erythrocytes makes this protocol valuable for diagnostic and basic research purposes.

Breathing Abnormalities During Sleep and Wakefulness in Rett Syndrome: Clinical Relevance and Paradoxical Relationship With Circulating Pro-oxidant Markers.

Background: Breathing abnormalities are common in Rett syndrome (RTT), a pervasive neurodevelopmental disorder almost exclusively affecting females. RTT is linked to mutations in the methyl-CpG-binding protein 2 () gene. Our aim was to assess the clinical relevance of apneas during sleep-wakefulness cycle in a population with RTT and the possible impact of apneas on circulating oxidative stress markers.

Isoprostanoid Plasma Levels Are Relevant to Cerebral Adrenoleukodystrophy Disease.

Cerebral adrenoleukodystrophy (ALD) is a rare neuroinflammatory disorder characterized by progressive demyelination. Mutations within the gene result in very long-chain fatty acid (VLCFA) accumulation within the peroxisome, particularly in the brain. While this VLCFA accumulation is known to be the driving cause of the disease, oxidative stress can be a contributing factor.

F-Neuroprostanes: A Role in Sperm Capacitation.

F-neuroprostanes (F-NeuroPs), derived from the oxidative metabolization of docosahexaenoic acid (DHA), are considered biomarkers of oxidative stress in neurodegenerative diseases. Neurons and spermatozoa display a high DHA content. NeuroPs might possess biological activities.

Tissue Antioxidant Status and Lipid Peroxidation Are Related to Dietary Intake of n-3 Polyunsaturated Acids: A Rabbit Model.

Polyunsaturated fatty acid (PUFA) metabolism and tissue distribution is modulated by the oxidation of these molecules. This research aimed to investigate the implication of dietary n-3 PUFA supplementation (precursor and long-chain PUFA) on the PUFA profile and oxidative status of the liver, testis, and brain of adult rabbit bucks. Twenty New Zealand White rabbit bucks were divided into four experimental groups ( = 5 per group) and were fed different diets for 110 days: control (CNT), standard diet containing 50 mg/kg alpha-tocopheryl acetate (vitamin E); CNT+, standard diet + 200 mg/kg vitamin E; FLAX, standard diet + 10% flaxseed + 200 mg/kg vitamin E; or FISH, standard diet + 3.

Circulating 4-F-Neuroprostane and 10-F-Neuroprostane Are Related to Gene Mutation and Natural History in Rett Syndrome.

Neuroprostanes, a family of non-enzymatic metabolites of the docosahexaenoic acid, have been suggested as potential biomarkers for neurological diseases. Objective biological markers are strongly needed in Rett syndrome (RTT), which is a progressive X-linked neurodevelopmental disorder that is mainly caused by mutations in the methyl-CpG binding protein 2 () gene with a predominant multisystemic phenotype. The aim of the study is to assess a possible association between mutations or RTT disease progression and plasma levels of 4()-4-F-neuroprostane (4-F-NeuroP) and 10()-10-F-neuroprostane (10-F-NeuroP) in typical RTT patients with proven gene mutation.

Protective role of mirtazapine in adult female Mecp2 mice and patients with Rett syndrome.

Background: Rett syndrome (RTT), an X-linked neurodevelopmental rare disease mainly caused by MECP2-gene mutations, is a prototypic intellectual disability disorder. Reversibility of RTT-like phenotypes in an adult mouse model lacking the Mecp2-gene has given hope of treating the disease at any age. However, adult RTT patients still urge for new treatments.

OPERA: a novel method to reduce ghost and aliasing artifacts.

Objective: A method for Orthogonal Phase Encoding Reduction of Artifact (OPERA) was developed and tested.

Materials And Methods: Because the position of ghosts and aliasing artifacts is predictable along columns or rows, OPERA combines the intensity values of two images acquired using the same parameters, but with swapped phase-encoding directions, to correct the artifacts. Simulations and phantom experiments were conducted to define the efficacy, robustness, and reproducibility.

Defective proteasome biogenesis into skin fibroblasts isolated from Rett syndrome subjects with MeCP2 non-sense mutations.

Rett Syndrome (RTT) is a rare X-linked neurodevelopmental disorder which affects about 1: 10000 live births. In >95% of subjects RTT is caused by a mutation in Methyl-CpG binding protein-2 (MECP2) gene, which encodes for a transcription regulator with pleiotropic genetic/epigenetic activities. The molecular mechanisms underscoring the phenotypic alteration of RTT are largely unknown and this has impaired the development of therapeutic approaches to alleviate signs and symptoms during disease progression.

Effect of Dietary -3 Source on Rabbit Male Reproduction.

In the last two decades, the human sperm count linearly decreased in Western countries. Health problems, lifestyle, pollutants, and dietary behaviours are considered as the main risk factors, and the unbalance of dietary -6/-3 fatty acids is one of the most relevant. The aim of the present research is to study the effect of different dietary sources of -3 polyunsaturated fatty acids (PUFA) on reproductive traits using rabbit buck as the animal model.

Brain protein changes in Mecp2 mouse mutant models: Effects on disease progression of Mecp2 brain specific gene reactivation.

Rett syndrome (RTT) is a leading cause of severe intellectual disability in females, caused by de novo loss-of function mutations in the X-linked methyl-CpG binding protein 2 (MECP2). To better investigate RTT disease progression/pathogenesis animal models of Mecp2 deficiency have been developed. Here, Mecp2 mouse models are employed to investigate the role of protein patterns in RTT.

Increased isoprostanoid levels in brain from murine model of Krabbe disease - Relevance of isoprostanes, dihomo-isoprostanes and neuroprostanes to disease severity.

Krabbe disease (KD) is a rare and devastating pediatric leukodystrophy caused by mutations in the galactocerebrosidase (GALC) gene. The disease leads to impaired myelin formation and extensive myelin damage in the brain. Oxidative stress is implicated in the pathogenesis of KD but insofar few information is available.

Isoprostanoids in Clinical and Experimental Neurological Disease Models.

Isoprostanoids are a large family of compounds derived from non-enzymatic oxidation of polyunsaturated fatty acids (PUFAs). Unlike other oxidative stress biomarkers, they provide unique information on the precursor of the targeted PUFA. Although they were discovered about a quarter of century ago, the knowledge on the role of key isoprostanoids in the pathogenesis of experimental and human disease models remains limited.

Intestinal Candida parapsilosis isolates from Rett syndrome subjects bear potential virulent traits and capacity to persist within the host.

Background: Rett syndrome (RTT) is a neurological disorder mainly caused by mutations in MeCP2 gene. It has been shown that MeCP2 impairments can lead to cytokine dysregulation due to MeCP2 regulatory role in T-helper and T-reg mediated responses, thus contributing to the pro-inflammatory status associated with RTT. Furthermore, RTT subjects suffer from an intestinal dysbiosis characterized by an abnormal expansion of the Candida population, a known factor responsible for the hyper-activation of pro-inflammatory immune responses.

Clinical biomarkers for cancer recognition and prevention: A novel approach with optical measurements.

Cancer is the most important cause of death worldwide, and early cancer detection is the most fundamental factor for efficacy of treatment, prognosis, and increasing survival rate. Over the years great effort has been devoted to discovering and testing new biomarkers that can improve its diagnosis, especially at an early stage. Here we report the potential usefulness of new, easily applicable, non-invasive and relatively low-cost clinical biomarkers, based on abnormalities of oral mucosa spectral reflectance and fractal geometry of the vascular networks in several different tissues, for identification of hereditary non-polyposis colorectal cancer carriers as well for detection of other tumors, even at an early stage.

Relevance of 4-F-neuroprostane and 10-F-neuroprostane to neurological diseases.

F-neuroprostanes (F-NeuroPs) are non-enzymatic oxidized products derived from docosahexaenoic acid (DHA) and are suggested to be oxidative damage biomarkers of neurological diseases. However, 128 isomers can be formed from DHA oxidation and among them, 4(RS)-4-F-NeuroP (4-F-NeuroP) and 10(RS)-10-F-NeuroP (10-F-NeuroP) are the most studied. Here, we report the identification and the clinical relevance of 4-F-NeuroP and 10-F-NeuroP in plasma of four different neurological diseases, including multiple sclerosis (MS), autism spectrum disorders (ASD), Rett syndrome (RTT), and Down syndrome (DS).

Dysphagia in Rett Syndrome: A Descriptive Study.

Objectives: Rett syndrome (RS) is a neurodevelopmental disorder and the second major cause of mental retardation in females. The aim of this study was to evaluate swallowing problems of RS patients by endoscopic assessment and compile a list of suggestions for managing feeding and preventing complications.

Methods: The sample consisted of 61 female patients (mean age = 13.

Persistent Unresolved Inflammation in the -308 Female Mutated Mouse Model of Rett Syndrome.

Rett syndrome (RTT) is a rare neurodevelopmental disorder usually caused by mutations in the X-linked gene (). Several mutant mouse lines have been developed recapitulating part of the clinical features. In particular, -308 female heterozygous mice, bearing a truncating mutation, are a validated model of the disease.

New evidences on the altered gut microbiota in autism spectrum disorders.

Background: Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by social and behavioural impairments. In addition to neurological symptoms, ASD subjects frequently suffer from gastrointestinal abnormalities, thus implying a role of the gut microbiota in ASD gastrointestinal pathophysiology.

Results: Here, we characterized the bacterial and fungal gut microbiota in a cohort of autistic individuals demonstrating the presence of an altered microbial community structure.

Oxygen exchange and energy metabolism in erythrocytes of Rett syndrome and their relationships with respiratory alterations.

Rett syndrome (RTT) is a neurodevelopmental disorder, mainly affecting females, which is associated to a mutation on the methyl-CpG-binding protein 2 gene. In the pathogenesis and progression of classic RTT, red blood cell (RBC) morphology has been shown to be an important biosensor for redox imbalance and chronic hypoxemia. Here we have evaluated the impact of oxidation and redox imbalance on several functional properties of RTT erythrocytes.

Proteomic analysis of the Rett syndrome experimental model mecp2 mutant zebrafish.

Unlabelled: Rett syndrome (RTT) is a severe genetic disorder resulting from mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Recently, a zebrafish carrying a mecp2-null mutation has been developed with the resulting phenotypes exhibiting defective sensory and thigmotactic responses, and abnormal motor behavior reminiscent of the human disease. Here, we performed a proteomic analysis to examine protein expression changes in mecp2-null vs.

Skeletal dysplasia with bowing long bones: Proposed flowchart for prenatal diagnosis with case demonstration.

Objective: Skeletal dysplasia with bowing long bones is a rare group of multiple characterized congenital anomalies.

Materials And Methods: We introduce a simple, practical diagnostic flowchart that may be helpful in identifying the appropriate pathway of obstetrical management.

Results: Herein, we describe four fetal cases of bent bony dysplasia that focus on ultrasound findings, phenotype, molecular tests, distinctive X-ray features, and chondral growth plate histology.