Search results for "Disorder"

The Role of Next-Generation Sequencing in the Diagnosis of Lysosomal Storage Disorders

2016

Next-generation sequencing (NGS) panels are used widely in clinical diagnostics to identify genetic causes of various monogenic disease groups including neurometabolic disorders and, more recently, lysosomal storage disorders (LSDs). Many new challenges have been introduced through these new technologies, both at the laboratory level and at the bioinformatics level, with consequences including new requirements for interpretation of results, and for genetic counseling. We review some recent examples of the application of NGS technologies, with purely diagnostic and with both diagnostic and research aims, for establishing a rapid genetic diagnosis in LSDs. Given that NGS can be applied in a w…

PFN1 and integrin‐β1/mTOR axis involvement in cornea differentiation of fibroblast limbal stem cells

2019

Abstract Ex vivo limbal stem cell transplantation is the main therapeutic approach to address a complete and functional re‐epithelialization in corneal blindness, the second most common eye disorder. Although important key points were defined, the molecular mechanisms involved in the epithelial phenotype determination are unclear. Our previous studies have demonstrated the pluripotency and immune‐modulatory of fibroblast limbal stem cells (f‐LSCs), isolated from the corneal limbus. We defined a proteomic profile especially enriched in wound healing and cytoskeleton‐remodelling proteins, including Profilin‐1 (PFN1). In this study we postulate that pfn‐1 knock down promotes epithelial lineage…

CNS-Targeting Therapies for Lysosomal Storage Diseases: Current Advances and Challenges.

2020

During the past decades, several therapeutic approaches have been developed and made rapidly available for many patients afflicted with lysosomal storage disorders (LSDs), inborn organelle disorders with broad clinical manifestations secondary to the progressive accumulation of undegraded macromolecules within lysosomes. These conditions are individually rare, but, collectively, their incidence ranges from 1 in 2,315 to 7,700 live-births. Most LSDs are manifested by neurological symptoms or signs, including developmental delay, seizures, acroparesthesia, motor weakness, and extrapyramidal signs. The chronic and later-onset clinical forms are at one end of the continuum spectrum and are char…

Natural visibility graphs for diagnosing attention deficit hyperactivity disorder (ADHD)

2016

“NOTICE: this is the author’s version of a work that was accepted for publication in Electronic Notes in Discrete Mathematics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Electronic Notes in Discrete Mathematics, [Volume 54, October 2016, Pages 337-342] DOI 10.1016/j.endm.2016.09.058 ¨

Text mining and expert curation to develop a database on psychiatric diseases and their genes

2017

Psychiatric disorders constitute one of the main causes of disability worldwide. During the past years, considerable research has been conducted on the genetic architecture of such diseases, although little understanding of their etiology has been achieved. The difficulty to access up-to-date, relevant genotype-phenotype information has hampered the application of this wealth of knowledge to translational research and clinical practice in order to improve diagnosis and treatment of psychiatric patients. PsyGeNET (http://www.psygenet.org/) has been developed with the aim of supporting research on the genetic architecture of psychiatric diseases, by providing integrated and structured accessi…

2019

Epileptic activity without visible convulsions is common in Alzheimer's disease (AD) and may contribute adversely to the disease progress and symptoms. Transgenic mice with amyloid plaque pathology also display epileptic seizures, but those are too infrequent to assess the effect of anti-epileptic treatments. Besides spontaneous seizures, these mice also display frequent epileptic spiking in epidural EEG recordings, and these have provided a means to test potential drug treatment to AD-related epilepsy. However, the origin of EEG spikes in transgenic AD model mice has remained elusive, which makes it difficult to relate electrophysiology with underlying pathology at the cellular and molecul…

Implications of SARS-COV-2 infection in the diagnosis and management of the pediatric gastrointestinal disease

2021

AbstractGastrointestinal diseases such as celiac disease, functional gastrointestinal disorders (FGIDs), inflammatory bowel disease (IBDs) and acute or chronic diarrhea are quite frequent in the pediatric population. The approach, the diagnosis and management can be changed in the 2019 coronavirus disease (COVID-19) pandemic era. This review has focused on: i) the current understanding of digestive involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected children and adolescents and the clinical implications of COVID-19 for pediatric gastroenterologists, ii) the impact of COVID-19 on the clinical approach to patients with pre-existing or onset diseases, including…

Coffee and metabolic impairment: An updated review of epidemiological studies

2016

Abstract Background Coffee is one of the most consumed beverages worldwide. In the last years, coffee consumption has been associated with a number of beneficial effects against metabolic impairment. The aim of this narrative review was to report the most updated and comprehensive evidence from epidemiological and experimental studies as well as mechanisms of action of coffee on metabolic impairment. Methods A search in electronic databases (PUBMED and EMBASE) was performed to retrieve systematic and pooled analyses on coffee and diabetes, hypertension, and dyslipidemia. Furthermore, the most accredited hypotheses and mechanisms of action of coffee have been described. Results Coffee consum…

Changes in the Peripheral Endocannabinoid System as a Risk Factor for the Development of Eating Disorders

2017

BACKGROUND AND OBJECTIVE Eating Disorder (ED) is characterized by persistently and severely disturbed eating behaviours. They arise from a combination of long-standing behavioural, emotional, psychological, interpersonal, and social factors and result in insufficient nutrient ingestion and/or adsorption. The three main EDs are: anorexia nervosa, bulimia nervosa, and binge eating disorder. We review the role of peripheral endocannabinoids in eating behaviour. DISCUSSION The neuronal pathways involved in feeding behaviours are closely related to catecholaminergic, serotoninergic and peptidergic systems. Accordingly, feeding is promoted by serotonin, dopamine, and prostaglandin and inhibited b…

Diacylglycerol lipase alpha in astrocytes is involved in maternal care and affective behaviors.

2021

Genetic deletion of cannabinoid CB1 receptors or diacylglycerol lipase alpha (DAGLa), the main enzyme involved in the synthesis of the endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG), produced profound phenotypes in animal models of depression-related behaviors. Furthermore, clinical studies have shown that antagonists of CB1 can increase the incidence and severity of major depressive episodes. However, the underlying pathomechanisms are largely unknown. In this study, we have focused on the possible involvement of astrocytes. Using the highly sensitive RNAscope technology, we show for the first time that a subpopulation of astrocytes in the adult mouse brain expresses Dagla, albeit at …