Developing Allosteric Chaperones for -Associated Disorders-An Integrated Computational and Experimental Approach.

Mutations in the gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are associated with Gaucher disease and increased risk of Parkinson's disease. This study describes the discovery and characterization of novel allosteric pharmacological chaperones for GCase through an innovative computational approach combined with experimental validation. Utilizing virtual screening and structure-activity relationship optimization, researchers identified several compounds that significantly enhance GCase activity and stability across various cellular models, including patient-derived fibroblasts and neuronal cells harboring mutations.

Discovery of allosteric regulators with clinical potential to stabilize alpha-L-iduronidase in mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal disease caused by lowered activity of the enzyme alpha-L-iduronidase (IDUA). Current therapeutic options show limited efficacy and do not treat some important aspects of the disease. Therefore, it may be advantageous to identify strategies that could improve the efficacy of existing treatments.

Validation of a highly sensitive HaloTag-based assay to evaluate the potency of a novel class of allosteric β-Galactosidase correctors.

Site-directed Enzyme Enhancement Therapy (SEE-Tx®) technology is a disease-agnostic drug discovery tool that can be applied to any protein target of interest with a known three-dimensional structure. We used this proprietary technology to identify and characterize the therapeutic potential of structurally targeted allosteric regulators (STARs) of the lysosomal hydrolase β-galactosidase (β-Gal), which is deficient due to gene mutations in galactosidase beta 1 (GLB1)-related lysosomal storage disorders (LSDs). The biochemical HaloTag cleavage assay was used to monitor the delivery of wildtype (WT) β-Gal and four disease-related β-Gal variants (p.

[Epidemiology of multiple sclerosis in Spain].

Introduction: Multiple sclerosis is a chronic autoimmune, inflammatory and neurodegenerative disease of the central nervous system and the most common non-traumatic disabling neurological disease in young adults. In the latest decades, multiple sclerosis is increasing worldwide, especially in women. The latitudinal distribution has been progressively attenuated.

Multiple sclerosis prevalence and incidence in San Vicente del Raspeig, Spain.

Background: Changes in the demographic epidemiology of multiple sclerosis (MS) may challenge the view of a latitudinal gradient in the distribution of MS. The objective of this study was to assess the incidence and prevalence of MS in addition to information on MS phenotypes and the use of disease modifying therapies (DMTs) in San Vicente del Raspeig in south eastern Spain.

Methods: This was a prospective epidemiological study of MS in San Vicente del Raspeig (population of 57,175 inhabitants based on the 2017 census) from 2005 to 2018.

A Prominent Role of the Human Cytomegalovirus UL8 Glycoprotein in Restraining Proinflammatory Cytokine Production by Myeloid Cells at Late Times during Infection.

Human cytomegalovirus (HCMV) persistence in infected individuals relies on a plethora of mechanisms to efficiently reduce host immune responses. To that end, HCMV uses a variety of gene products, some of which have not been identified yet. Here we characterized the gene, which consists of two exons, sharing the first with the HCMV RL11 family member UL8 is a transmembrane protein with an N-terminal immunoglobulin (Ig)-like domain in common with UL7 but with an extended stalk and a distinctive cytoplasmic tail.

[Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in the province of Alicante].

Introduction: Post-authorisation studies are important to confirm whether the outcomes of clinical trials are reproduced in usual clinical practice.

Aims: To evaluate the effectiveness and safety of fingolimod in clinical practice in the province of Alicante.

Patients And Methods: A retrospective multi-centre study was conducted with remitting multiple sclerosis patients treated with fingolimod.

Signaling Lymphocytic Activation Molecule Family Receptor Homologs in New World Monkey Cytomegaloviruses.

Unlabelled: Throughout evolution, large DNA viruses have been usurping genes from their hosts to equip themselves with proteins that restrain host immune defenses. Signaling lymphocytic activation molecule (SLAM) family (SLAMF) receptors are involved in the regulation of both innate and adaptive immunity, which occurs upon engagement with their ligands via homotypic or heterotypic interactions. Here we report a total of seven SLAMF genes encoded by the genomes of two cytomegalovirus (CMV) species, squirrel monkey CMV (SMCMV) and owl monkey CMV (OMCMV), that infect New World monkeys.

Migraine education brochures and patient-perceived satisfaction.

Introduction: Brochures are commonly used as educational tools in daily neurological practice. They are provided to increase the general population's knowledge of a specific disease and also to combat sources of erroneous information. Surveys are the most commonly used method of ascertaining user satisfaction with services received.

Cytomegalovirus m154 hinders CD48 cell-surface expression and promotes viral escape from host natural killer cell control.

Receptors of the signalling lymphocyte-activation molecules (SLAM) family are involved in the functional regulation of a variety of immune cells upon engagement through homotypic or heterotypic interactions amongst them. Here we show that murine cytomegalovirus (MCMV) dampens the surface expression of several SLAM receptors during the course of the infection of macrophages. By screening a panel of MCMV deletion mutants, we identified m154 as an immunoevasin that effectively reduces the cell-surface expression of the SLAM family member CD48, a high-affinity ligand for natural killer (NK) and cytotoxic T cell receptor CD244.

Switching from natalizumab to fingolimod: an observational study.

Background: Multiple sclerosis patients who discontinue using natalizumab are at risk of a rebound in disease activity. However, the optimal alternative therapy is not currently known.

Aims Of The Study: We report on clinical and MRI data and patient safety in a group of relapsing-remitting multiple sclerosis patients who tested seropositive for the JC virus and who have switched from natalizumab to fingolimod because of concerns regarding PML risks.

Human cytomegalovirus UL7, a homologue of the SLAM-family receptor CD229, impairs cytokine production.

Human cytomegalovirus (HCMV), the β-herpesvirus prototype, has evolved a wide spectrum of mechanisms to counteract host immunity. Among them, HCMV uses cellular captured genes encoding molecules capable of interfering with the original host function or of fulfilling new immunomodulatory tasks. Here, we report on UL7, a novel HCMV heavily glycosylated transmembrane protein, containing an Ig-like domain that exhibits remarkable amino acid similarity to CD229, a cell-surface molecule of the signalling lymphocyte-activation molecule (SLAM) family involved in leukocyte activation.

[The phenomenon of immigration within the European Community and its impact on neurological care in the Marina Baixa area, Alicante].

Introduction: Immigration is shaping a new model of society, with new needs and demands, whose characteristics must guide health-care policies. AIM. To determine the repercussions of the phenomenon of immigration on the extra-hospital neurological care carried out in Department 16 of the Agencia Valenciana de Salud (Valencian Health Service) and how language problems affect visits.

[Multiple mononeuropathy associated to treatment with pravastatin].

Introduction: The first reports of neuropathy due to treatment with statins appeared in 1994, although it is an infrequent complication. It usually consists of an axonal polyneuropathy, which is predominantly sensory, distal and symmetric, and may be subacute or chronic. We present here the second case reported in the literature of multiple mononeuropathy associated to the use of statins.

[Ambulatory neurological care in the Marina Baixa area, Alicante].

Introduction: The demand for neurological care depends on the type of population to be attended, among other variables. The Marina Baixa area, which includes towns such as Altea and Benidorm, has its own peculiar characteristics due to its being one of the places that is often chosen by pensioners from northern and central Spain and Europe to set up residence.

Aim: The aim of this study was to determine the characteristics of the ambulatory neurological care in our health area.

[Serous otitis media. Comparative study of carbinoxamine- pseudoephedrine vs astemizole-pseudoephedrine].

They were studied 48 children of 3 to 8 years old, of two sex (30 male and 18 female), that attended the external service of otolaryngology of the Hospital of the ISSSTE of Nuevo Laredo, Tamaulipas (Mexico) and the private practice of the Allergy Clinic and Otolaringol in Nuevo Laredo, Tamaulipas, of the month of November of 1995 to April of 1996. Some of the side effects observed in the patients treated in the group A (carbinoxamine-P) were: mild sedation and in some instances hyperexcitability and irritability. However, it was not necessary to discontinue the medication or to modify the dose.

[Hyperinsulinism probably caused by diffuse pancreatic hyperplasia].

A case history of a two years seven months old boy with hyperinsulinism and marked psychomotor retardation is presented. In this patient, biochemical analysis revealed persistent hypoglycemia. Basal insulin levels (RIA) were consistently superior to 10 mU/ml.