a single blinded randomized pilot study of botulinum toxin type a combined with non pharmacological treatment for spastic foot

OBJECTIVE: To explore the effect of treatment after botulinum toxin type A combined with treatments for the spastic foot. DESIGN: Single-blind, randomized trial, with 3-month follow-up. SUBJECTS: Twenty-three chronic hemiplegic adult patients with spastic equinus foot. METHODS: Following botulinum toxin type A injection at the medial and lateral gastrocnemius, patients were assigned randomly to 3 groups, and treated with taping, electrical stimulation or stretching. They were evaluated before treatment (t0), and at 10 (t1), 20 (t2) and 90 (t3) days after treatment. Outcome measures were: Modified Ashworth Scale; passive range of motion at the ankle; measurement of muscle action potential at the gastrocnemius medialis; and measurement of maximum ankle dorsiflexion angle in stance using gait analysis. RESULTS: The group treated with electrical stimulation performed better at t1 on the Modified Ashworth Scale. The taping and electrical stimulation groups performed better in all outcome measures at t3. The taping group performed better mainly for maximum ankle dorsiflexion angle in stance. The stretching group showed a less durable result, with some worsening at the t3 evaluation compared with the assessment performed before treatment. CONCLUSIONS: This pilot study indicates that combining botulinum toxin type A administration for the ankle plantar flexors with taping and electrical stimulation might be beneficial

Robust Generation of Oligodendrocyte Progenitors from Human Neural Stem Cells and Engraftment in Experimental Demyelination Models in Mice

Cell-based therapy holds great promises for demyelinating diseases. Human-derived fetal and adult oligodendrocyte progenitors (OPC) gave encouraging results in experimental models of dysmyelination but their limited proliferation in vitro and their potential immunogenicity might restrict their use in clinical applications. Virtually unlimited numbers of oligodendroglial cells could be generated from long-term self-renewing human (h)-derived neural stem cells (hNSC). However, robust oligodendrocyte production from hNSC has not been reported so far, indicating the need for improved understanding of the molecular and environmental signals controlling hNSC progression through the oligodendroglial lineage. The aim of this work was to obtain enriched and renewable cultures of hNSC-derived oligodendroglial cells by means of epigenetic manipulation.We report here the generation of large numbers of hNSC-derived oligodendroglial cells by concurrent/sequential in vitro exposure to combinations of growth factors (FGF2, PDGF-AA), neurotrophins (NT3) and hormones (T3). In particular, the combination FGF2+NT3+PDGF-AA resulted in the maintenance and enrichment of an oligodendroglial cell population displaying immature phenotype (i.e., proliferation capacity and expression of PDGFRalpha, Olig1 and Sox10), limited self-renewal and increased migratory activity in vitro. These cells generate large numbers of oligodendroglial progeny at the early stages of maturation, both in vitro and after transplantation in models of CNS demyelination.We describe a reliable method to generate large numbers of oligodendrocytes from a renewable source of somatic, non-immortalized NSC from the human foetal brain. We also provide insights on the mechanisms underlying the pro-oligodendrogenic effect of the treatments in vitro and discuss potential issues responsible for the limited myelinating capacity shown by hNSC-derived oligodendrocytes in vivo

Existence and multiplicity for elliptic problems with quadratic growth in the gradient

We show that a class of divergence-form elliptic problems with quadratic growth in the gradient and non-coercive zero order terms are solvable, under essentially optimal hypotheses on the coefficients in the equation. In addition, we prove that the solutions are in general not unique. The case where the zero order term has the opposite sign was already intensively studied and the uniqueness is the rule.Comment: To appear in Comm. PD

Tackling amyloidogenesis in Alzheimer's disease with A2V variants of Amyloid-β

We developed a novel therapeutic strategy for Alzheimer’s disease (AD) exploiting the properties of a natural variant of Amyloid-β (Aβ) carrying the A2V substitution, which protects heterozygous carriers from AD by its ability to interact with wild-type Aβ, hindering conformational changes and assembly thereof. As prototypic compound we designed a six-mer mutated peptide (Aβ1-6A2V), linked to the HIV-related TAT protein, which is widely used for brain delivery and cell membrane penetration of drugs. The resulting molecule [Aβ1-6A2VTAT(D)] revealed strong anti-amyloidogenic effects in vitro and protected human neuroblastoma cells from Aβ toxicity. Preclinical studies in AD mouse models showed that short-term treatment with Aβ1-6A2VTAT(D) inhibits Aβ aggregation and cerebral amyloid deposition, but a long treatment schedule unexpectedly increases amyloid burden, although preventing cognitive deterioration. Our data support the view that the AβA2V-based strategy can be successfully used for the development of treatments for AD, as suggested by the natural protection against the disease in human A2V heterozygous carriers. The undesirable outcome of the prolonged treatment with Aβ1-6A2VTAT(D) was likely due to the TAT intrinsic attitude to increase Aβ production, avidly bind amyloid and boost its seeding activity, warning against the use of the TAT carrier in the design of AD therapeutics

Survey of ixodid ticks, vectors of Rickettsia parkeri, Buenos Aires province, Argentina

In America, rickettsiae have aroused greater interest in public health. Categorized as emerging zoonotic diseases called "Spotted Fever" (FM), this group of diseases are transmitted to humans essentially by hematophagous arthropods such as Ixodidae ticks. This problem exists in Argentina, where the main vector of the Rickettsia parkeri bacterium (within FM), in areas of the Plata Hydrographic Basin, is the hard tick of the Amblyomma triste species. The aim of this study is to survey the species of ticks, mainly of the genus Amblyomma spp., both in urban (UA) and natural (NA) areas, in municipalities that are part of the Plata River basin and its sub-basins, in order to make new contributions to its epidemiology and surveillance, during the period from September 2021 to March 2022. A descriptive, quantitative, observational and cross-sectional study was carried out to survey the different species of ticks in NA and UA, in the Plata River Hydrographic Basin.Para acceder a la videoconferencia completa, hacer clic en "Enlace externo".Sociedad Latinoamericana de Ecología de Vectore

A novel nonsense ATP7A pathogenic variant in a family exhibiting a variable occipital horn syndrome phenotype

We report on a family with occipital horn syndrome (OHS) diagnosed in the proband's late fifties. A novel ATP7A pathogenic variant (c.4222A > T, p.(Lys1408*)), representing the first nonsense variant and the second late truncation causing OHS rather than classic Menkes disease, was found to segregate in the family. The predicted maintenance of transmembrane domains is consistent with a residual protein activity, which may explain the mild clinical presentation

Allá lejos la seguridad y la justicia : Los barrios y los problemas de la seguridad y la justicia

El libro lleva por título central: Allá lejos la seguridad y la justicia. Tal vez, no es una manera habitual de titular tratándose de una compilación de capítulos escritos por investigadoras/es e invitadas especiales que, en su tarea como tales, relevaron durante mas de tres años de investigación teórica y de campo las representaciones sociales de los vecinos/as vinculadas a la seguridad y la organización judicial. El título es anticipatorio del pensamiento que nos expresaron las personas entrevistadas y encuestadas, que desde sus diferentes posiciones socio-económicas y lugares de residencia, nos manifestaron su escepticismo y malestar en cuanto a los problemas vinculados a la seguridad/inseguridad y la insuficiente atención por parte de los gobiernos, como así también una sensación de lejanía y tal vez de resignación, cuando de acceso a la justicia se trata. Saben que los hechos de (in)seguridad existen, se ven, se sufren, se escuchan y, que la organización judicial, existe pero es lejana. Admiten que la seguridad y el acceso a la justicia son cuestiones no resueltas en la sociedad argentina, que están aún lejos de alcanzarse.Facultad de Ciencias Jurídicas y Sociale

Allá lejos la seguridad y la justicia : Los barrios y los problemas de la seguridad y la justicia

El libro lleva por título central: Allá lejos la seguridad y la justicia. Tal vez, no es una manera habitual de titular tratándose de una compilación de capítulos escritos por investigadoras/es e invitadas especiales que, en su tarea como tales, relevaron durante mas de tres años de investigación teórica y de campo las representaciones sociales de los vecinos/as vinculadas a la seguridad y la organización judicial. El título es anticipatorio del pensamiento que nos expresaron las personas entrevistadas y encuestadas, que desde sus diferentes posiciones socio-económicas y lugares de residencia, nos manifestaron su escepticismo y malestar en cuanto a los problemas vinculados a la seguridad/inseguridad y la insuficiente atención por parte de los gobiernos, como así también una sensación de lejanía y tal vez de resignación, cuando de acceso a la justicia se trata. Saben que los hechos de (in)seguridad existen, se ven, se sufren, se escuchan y, que la organización judicial, existe pero es lejana. Admiten que la seguridad y el acceso a la justicia son cuestiones no resueltas en la sociedad argentina, que están aún lejos de alcanzarse.Facultad de Ciencias Jurídicas y Sociale

GPR126 is a specifier of blood-brain barrier formation in the mouse central nervous system

Data availability. RNA sequencing data are available through the European Molecular Biology Laboratory–European Bioinformatics Institute (EMBL-EBI) ArrayExpress BioStudies portal with accession number E-MTAB-13914. All supporting data are provided in the Supporting Data Values file.The blood-brain barrier (BBB) acquires unique properties to regulate neuronal function during development. The formation of the BBB, which occurs in tandem with angiogenesis, is directed by the Wnt/β-catenin signaling pathway. Yet the exact molecular interplay remains elusive. Our study reveals the G protein–coupled receptor GPR126 as a critical target of canonical Wnt signaling, essential for the development of the BBB’s distinctive vascular characteristics and its functional integrity. Endothelial cell–specific deletion of the Gpr126 gene in mice induced aberrant vascular morphogenesis, resulting in disrupted BBB organization. Simultaneously, heightened transcytosis in vitro compromised barrier integrity, resulting in enhanced vascular permeability. Mechanistically, GPR126 enhanced endothelial cell migration, pivotal for angiogenesis, acting through an interaction between LRP1 and β1 integrin, thereby balancing the levels of β1 integrin activation and recycling. Overall, we identified GPR126 as a specifier of an organotypic vascular structure, which sustained angiogenesis and guaranteed the acquisition of the BBB properties during development.This study was supported by the European Research Council (ERC; 742922) and AIRC (18683 and 21320) to ED; ITN BtRAIN (675619) and CARIPLO Foundation (2016-0461) to MG; and AIRC (26183) and Horizon 2020 (964481) to DI. KB was funded by the Francis Crick Institute (FC001751). AP is funded by the Engineering and Physical Sciences Research Council (EP/S030964/1). SS was supported by the ERC (grant 101002280) and AIRC (grant 24415). MDG is supported by the Armenise Harvard Foundation, ERC (101116224), and AIRC (27564). MI is supported by the ERC (725038), AIRC (19891 and 22737), and Italian Ministry for University and Research (INF-ACT and PRIN 2022FMESXL)