Development of a clinical algorithm for the early diagnosis of mucopolysaccharidosis III

Mucopolysaccharidosis III (MPS III) is a rare inherited metabolic disease primarily affecting the central nervous system, leading to developmental and/or speech regression. Early diagnosis of the disease is important to introduce appropriate management measures and to optimize therapeutic outcomes. The diagnosis of MPS III is often significantly delayed due to the rarity of the disease, the more attenuated somatic presentation compared to other MPS types, and the symptom overlap with other developmental disorders. To shorten the time to diagnosis, a list of eight early signs and symptoms was identified through an expert system approach by a global, multidisciplinary working group of 13 specialists with expertise in various aspects of MPS and developmental disorders and three parents of MPS III patients. Coarse facial features and persistent hirsutism or prominent, thick eyebrows were identified as the most important MPS III early signs. The list of eight early MPS III signs and symptoms is the first step towards the development of a clinical algorithm aiming to identify neonates and infants with MPS III before the onset of neurocognitive damage, ultimately shortening the diagnostic journey of MPS III patients

Cell adhesive peptides functionalized on CoCr alloy stimulate endothelialization and prevent thrombogenesis and restenosis

Immobilization of bioactive peptide sequences on CoCr surfaces is an effective route to improve endothelialization, which is of great interest for cardiovascular stents. In this work, we explored the effect of physical and covalent immoblization of RGDS, YIGSR and their equimolar combination peptides on endothelial cells (EC) and smooth muscle cell (SMC) adhesion and on thrombogenicity. We extensively investigated using RT-qPCR, the expression by ECs cultured on functionalised CoCr surfaces of different genes. Genes relevant for adhesion (ICAM-1 and VCAM-1), vascularization (VEGFA, VEGFR-1 and VEGFR-2) and anti-thrombogenicity (tPA and eNOS) were over-expressed in the ECs grown to covalently functionalized CoCr surfaces compared to physisorbed and control surfaces. Pro-thrombogenic genes expression (PAI-1 and vWF) decreased over time. Cell co-cultures of ECs/SMCs found that functionalization increased the amount of adhered ECs onto modified surfaces compared to plain CoCr, independently of the used peptide and the strategy of immobilization. SMCs adhered less compared to ECs in all surfaces. All studied peptides showed a lower platelet cell adhesion compared to TCPS. Covalent functionalization of CoCr surfaces with an equimolar combination of RGDS and YIGSR represented prevailing strategy to enhance the early stages of ECs adhesion and proliferation, while preventing SMCs and platelet adhesion.Postprint (author's final draft

Patrimoni científic escolar

Fem una crida a que es valori el patrimoni que cada centre ha acumulat pel sol fet del temps que ha passat des de la seva inauguració

Early disease progression of Hurler syndrome

Abstract Background Newborn screening for mucopolysaccharidosis type I (MPS I) shows promise to improve outcomes by facilitating early diagnosis and treatment. However, diagnostic tests for MPS I are of limited value in predicting whether a child will develop severe central nervous system disease associated with Hurler syndrome, or minimal or no central nervous system involvement associated with the attenuated phenotypes (Hurler–Scheie and Scheie syndromes). Given that the optimal treatment differs between Hurler syndrome and the attenuated MPS I phenotypes, the absence of a reliable prognostic biomarker complicates clinical decision making for infants diagnosed through newborn screening. Information about the natural history of Hurler syndrome may aid in the management of affected infants, contribute to treatment decisions, and facilitate evaluation of treatment effectiveness and prognosis. Thus, the aim of this study was to characterize the progression and timing of symptom onset in infants with Hurler syndrome. Results Clinical data from 55 patients evaluated at a single center were retrospectively reviewed. Information about each child’s medical history was obtained following a standardized protocol including a thorough parent interview and the review of previous medical records. All patients underwent systematic physical and neurodevelopmental evaluations by a multidisciplinary team. Nearly all patients (98%) showed signs of disease during the first 6 months of life. Common early disease manifestations included failed newborn hearing screen, respiratory symptoms, difficulty latching, and otitis media. Other symptoms such as kyphosis, corneal clouding, cardiac disease, joint restrictions, and enlarged head circumference typically appeared slightly later (median age, 8–10 months). During the first 12 months, gross motor development was the most severely affected area of functioning, and a significant number of patients also experienced language delays. Cognition was typically preserved during this period. Conclusions In this large cohort of patients with Hurler syndrome, the vast majority showed signs and symptoms of disease during the first months of life. More research is needed to determine the extent to which early clinical manifestations of MPS I can predict phenotype and treatment outcomes

treatment of brain disease in the mucopolysaccharidoses

Abstract The mucopolysaccharidosis (MPS) disorders are a group of lysosomal storage diseases caused by lysosomal enzyme deficits that lead to glycosaminoglycan accumulation, affecting various tissues throughout the body based on the specific enzyme deficiency. These disorders are characterized by their progressive nature and a variety of somatic manifestations and neurological symptoms. There are established treatments for some MPS disorders, but these mostly alleviate somatic and non-neurological symptoms and do not cure the disease. Patients with MPS I, II, III, and VII can present with neurological manifestations such as neurocognitive decline and behavioral problems. Treatment of these neurological manifestations remains challenging due to the blood-brain barrier (BBB) that limits delivery of therapeutic agents to the central nervous system (CNS). New therapies that circumvent this barrier and target brain disease in MPS are currently under development. They primarily focus on facilitating penetration of drugs through the BBB, delivery of recombinant enzyme to the brain by gene therapy, or direct CNS administration. This review summarizes existing and potential future treatment approaches that target brain disease in MPS. The information in this review is based on current literature and presentations and discussions during a closed meeting by an international group of experts with extensive experience in managing and treating MPS

Improved Brain Pathology and Progressive Peripheral Neuropathy in a 15 Year Old Survivor of Infantile Krabbe Disease Treated With Umbilical Cord Transplantation

ObjectiveKrabbe disease is a fatal leukodystrophy caused by deficiency in galactocerebrosidase enzyme activity. The only currently available therapy is hematopoietic stem cell transplantation with bone marrow or umbilical cord blood (UCBT), which leads to increased lifespan and functional abilities when performed in the preclinical stage. While stabilization of white matter disease has been seen on serial MRI studies, neuropathological changes following transplantation have not been documented so far.Materials and MethodsWe report the first postmortem examination of a 15-year-old female patient with infantile Krabbe disease after UCBT in infancy.ResultsIn contrast to an untreated Krabbe disease brain, which showed severe myelin and oligodendrocyte loss with occasional globoid cells, the transplanted brain displayed markedly improved myelin preservation, but not reaching normal myelination levels. Consistent with the transplanted patient’s clinical presentation of pronounced deficits in gross motor skills, corticospinal tracts were most severely affected. No globoid cells or evidence of active demyelination were observed in the central nervous system, indicative of at least partially successful functional restoration. This was corroborated by the identification of male donor-derived cells in the brain by in situ hybridization. Unlike the observed disease stabilization in the central nervous system, the patient experienced progressive peripheral neuropathy. While diminished macrophage infiltration was seen postmortem, peripheral nerves exhibited edema, myelin and axon loss and persistent Schwann cell ultrastructural inclusions.ConclusionUmbilical cord blood transplantation was able to alter the natural disease progression in the central but less so in the peripheral nervous system, possibly due to limited cross-correction of Schwann cells

Mobile Usability: An Experiment to Check Whether Current Mobile Devices are Ready to Support Frames and iFrames

Frames have traditionally been identified as a usability issue in websites for computers. Literature points out that they may also be a problem for mobile websites but no studies have been carried out to prove it. Since mobile devices have changed a lot in recent years, it is necessary to check whether frames are still a problem for those devices. In this paper we have performed an experiment with twenty-two mobile devices, to test whether the content can be showed in their browsers, as well as their behavior with different configuration of frames and iframes and whether behavior of bookmarks and the back button is correct or not. The results show that frames and iframes should be avoided in mobile devices because they can cause many problems, which are explained in detail in this paper

Una sociedad para todas las edades: curso monográfico de ejercicio físico

 The population trend changes (e.g., increased life expectancy or life-long learning) highlight the need to implement intervention policies that fit the needs and expectations of older people. With that objective, this text presents the design of a monographic course of physical exercise for students over 45 years of the Universidad Abierta de Personas Mayores, in the University of Burgos. The intervention will take place over one academic year, and consists of 15 sessions. It will be led by university students in grades Social Education, Early Childhood Education and Pedagogy, thus promoting intergenerational culture. In order to assess the results of the implementation of this training program, two evaluations will be conducted (pre and post intervention), with SF-36 Health Survey, which evaluates the quality of life. We conclude that many studies show healthy benefits for this group after the continued practice of physical exercise, besides preventing dependency and increasing the quality of life. Los cambios de tendencia de la población (como mayor esperanza de vida o el aprendizaje a lo largo de la vida) ponen de manifiesto la necesidad de implementar políticas de intervención que se ajusten a las necesidades y las expectativas de las personas mayores. Con tal objetivo, se presenta el diseño de un curso monográfico de ejercicio físico para los alumnos mayores de 45 años de la Universidad Abierta de Personas Mayores de la Universidad de Burgos. La intervención se llevará a cabo a lo largo de un curso académico, y consta de 15 sesiones. Será conducido por estudiantes universitarios de los grados de Educación Social, Educación Infantil y Pedagogía, para fomentar de esta forma la cultura intergeneracional. Con el fin de valorar los resultados de la aplicación del programa de entrenamiento, se llevarán a cabo dos evaluaciones (pre-post intervención) con el Cuestionario de Salud SF-36, el cual valora la calidad de vida. Concluimos que numerosos estudios evidencian los beneficios saludables que reporta para este colectivo la práctica continuada del ejercicio físico, además de prevenir la dependencia física y aumentar la calidad de vida

Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood

Apixaban is a new oral anticoagulant with a specific inhibitory action on FXa. No information is available on the reversal of the antihemostatic action of apixaban in experimental or clinical settings. We have evaluated the effectiveness of different factor concentrates at reversing modifications of hemostatic mechanisms induced by moderately elevated concentrations of apixaban (200 ng/ml) added in vitro to blood from healthy donors (n = 10). Effects on thrombin generation (TG) and thromboelastometry (TEM) parameters were assessed. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with blood circulating through damaged vascular surfaces, at a shear rate of 600 s−1. The potential of prothrombin complex concentrates (PCCs; 50 IU/kg), activated prothrombin complex concentrates (aPCCs; 75 IU/kg), or activated recombinant factor VII (rFVIIa; 270 μg/kg), at reversing the antihemostatic actions of apixaban, were investigated. Apixaban interfered with TG kinetics. Delayed lag phase, prolonged time to peak and reduced peak values, were improved by the different concentrates, though modifications in TG patterns were diversely affected depending on the activating reagents. Apixaban significantly prolonged clotting times (CTs) in TEM studies. Prolongations in CTs were corrected by the different concentrates with variable efficacies (rFVIIa≥aPCC>PCC). Apixaban significantly reduced fibrin and platelet interactions with damaged vascular surfaces in perfusion studies (p<0.05 and p<0.01, respectively). Impairments in fibrin formation were normalized by the different concentrates. Only rFVIIa significantly restored levels of platelet deposition. Alterations in hemostasis induced by apixaban were variably compensated by the different factor concentrates investigated. However, effects of these concentrates were not homogeneous in all the tests, with PCCs showing more efficacy in TG, and rFVIIa being more effective on TEM and perfusion studies. Our results indicate that rFVIIa, PCCs and aPCCs have the potential to restore platelet and fibrin components of the hemostasis previously altered by apixaban