La democracia mexicana en el camino de la estabilidad

El actual proceso electoral mexicano se desarrolla en condiciones de elevada competitividad y una real confrontación entre los partidos políticos, que algunos consideran arriesgada para la estabilidad política del país. Los anteriores procesos electorales presidenciales, el marco legal e institucional vigente y las nuevas medidas adoptadas para esta elección constituyen los elementos que nos permiten afirmar que dichas previsiones no tienen sustento y forman parte de la agenda de los actores políticos durante el desarrollo de las campañas electorales y no una amenaza real e inminente a la estabilidad política nacional

Resilience: New Utopia or New Tyranny? Reflection about the Potentials and Limits of the Concept of Resilience in Relation to Vulnerability Reduction Programmes

Resilience is becoming influential in development and vulnerability reduction sectors such as social protection, disaster risk reduction and climate change adaptation. Policy makers, donors and international development agencies are now increasingly referring to the term. In that context, the objective of this paper was to assess in a critical manner the advantages and limits of resilience. While the review highlights some positive elements –in particular the ability of the term to foster integrated approach across sectors– it also shows that resilience has important limitations. In particular it is not a pro-poor concept, and the objective of poverty reduction cannot simply be substituted by resilience building

Brasil, Colombia y México. Políticas curriculares recientes para la enseñanza de la historia y las ciencias sociales en la educación básica y la formación inicial del profesorado

El texto sintetiza una investigación documental comparativa sobre los propósitos que orientan las propuestas curriculares para la enseñanza de la historia y las ciencias sociales en Brasil, Colombia y México, desde finales del siglo XX y durante el siglo XXI, evidenciando que estas han estado supeditadas a políticas de gobierno y a reformas que responden más a miradas hegemónicas y disputas entre las disciplinas, que a las finalidades de la formación de los ciudadanos de este siglo. Se hace un análisis de las políticas para la formación inicial del profesorado en estas mismas disciplinas en los tres países, las cuales responden a recomendaciones de organismos internacionales, que menoscaban la importancia de la formación para la docencia en estos campos del conocimiento. Finalmente, en la búsqueda de relaciones entre los resultados de los dos análisis anteriores se identifican pocos puntos de encuentro. Falta investigación sobre la formación inicial de docentes de historia y de ciencias sociales que aporte, no solo a la formación inicial del profesorado, sino también a su enseñanza en la educación básica

Nomenclature of Genetic Movement Disorders:Recommendations of the International Parkinson and Movement Disorder Society Task Force – An Update

In 2016, the Movement Disorder Society Task Force for the Nomenclature of Genetic Movement Disorders presented a new system for naming genetically determined movement disorders and provided a criterion-based list of confirmed monogenic movement disorders. Since then, a substantial number of novel disease-causing genes have been described, which warrant classification using this system. In addition, with this update, we further refined the system and propose dissolving the imaging-based categories of Primary Familial Brain Calcification and Neurodegeneration with Brain Iron Accumulation and reclassifying these genetic conditions according to their predominant phenotype. We also introduce the novel category of Mixed Movement Disorders (MxMD), which includes conditions linked to multiple equally prominent movement disorder phenotypes. In this article, we present updated lists of newly confirmed monogenic causes of movement disorders. We found a total of 89 different newly identified genes that warrant a prefix based on our criteria; 6 genes for parkinsonism, 21 for dystonia, 38 for dominant and recessive ataxia, 5 for chorea, 7 for myoclonus, 13 for spastic paraplegia, 3 for paroxysmal movement disorders, and 6 for mixed movement disorder phenotypes; 10 genes were linked to combined phenotypes and have been assigned two new prefixes. The updated lists represent a resource for clinicians and researchers alike and they have also been published on the website of the Task Force for the Nomenclature of Genetic Movement Disorders on the homepage of the International Parkinson and Movement Disorder Society (https://www.movementdisorders.org/MDS/About/Committees--Other-Groups/MDS-Task-Forces/Task-Force-on-Nomenclature-in-Movement-Disorders.htm). © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society

Frequency and phenotypic spectrum of KMT2B dystonia in childhood: A single‐center cohort study

Background: Childhood-onset dystonia is often genetically determined. Recently, KMT2B variants have been recognized as an important cause of childhood-onset dystonia. Objective: To define the frequency of KMT2B mutations in a cohort of dystonic patients aged less than 18 years at onset, the associated clinical and radiological phenotype, and the natural history of disease. Methods: Whole-exome sequencing or customized gene panels were used to screen a cohort of sixty-five patients who had previously tested negative for all other known dystonia-associated genes. Results: We identified fourteen patients (21.5%) carrying KMT2B variants, of which one was classified as a Variant of Unknown Significance (VUS). We also identified two additional patients carrying pathogenic mutations in GNAO1 and ATM. Overall, we established a definitive genetic diagnosis in 23% of cases. We observed a spectrum of clinical manifestations in KMT2B variant carriers, ranging from generalized dystonia to short stature or intellectual disability alone, even within the same family. In 78.5% of cases, dystonia involved the lower limbs at onset, with later caudo-cranial generalization. Eight patients underwent pallidal Deep Brain Stimulation with a median decrease of BFMDRS-M score of 38.5% in the long term. We also report four asymptomatic carriers, suggesting that some KMT2B mutations may be associated with incomplete disease penetrance. Conclusions: KMT2B mutations are frequent in childhood-onset dystonia and cause a complex neurodevelopmental syndrome often featuring growth retardation and intellectual disability as additional phenotypic features. A dramatic and long-lasting response to Deep Brain Stimulation is characteristic of DYT-KMT2B dystonia

Low specificity and sensitivity of smell identification testing for the diagnosis of Parkinson?s disease

Objective: The aim of this study is to determine if the University of Pennsylvania’s Smell Identification Test (UPSIT) is an accurate diagnostic tool for olfactory dysfunction in Parkinson’s disease (PD). Method: We included 138 non-demented PD subjects and 175 control subjects matched by gender. Smell identification was tested using UPSIT. Results: The mean number of UPSIT items correctly identified by controls was 27.52±5.88; the mean score for PD subjects was 19.66±6.08 (p=<0.001). UPSIT sensitivity was 79.7% with a specificity of 68.5% using a cut-off score of ≤25. The overall accuracy for the diagnosis of PD was of 75.3%. Conclusion: UPSIT accuracy and specificity were lower than what has been previously reported. Our data demonstrates that 17.5% of items of the UPSIT were not well identified by healthy controls. Further research of the identification of a truly cross-cultural test is warranted

Bi-allelic variants in TSPOAP1, encoding the active zone protein RIMBP1, cause autosomal recessive dystonia

Dystonia is a debilitating hyperkinetic movement disorder, which can be transmitted as a monogenic trait. Here, we describe homozygous frameshift, nonsense and missense variants in TSPOAP1, encoding the active zone RIM-binding protein 1 (RIMBP1), as a novel genetic cause of autosomal recessive dystonia in seven subjects from three unrelated families. Subjects carrying loss-of-function variants presented with juvenile-onset progressive generalized dystonia, associated with intellectual disability and cerebellar atrophy. Conversely, subjects carrying a pathogenic missense variant (p.Gly1808Ser) presented with isolated adult-onset focal dystonia. In mice, complete loss of RIMBP1, known to reduce neurotransmission, led to motor abnormalities reminiscent of dystonia, decreased Purkinje cell dendritic arborization, and reduced numbers of cerebellar synapses. In vitro analysis of the p.Gly1808Ser variant showed larger spike-evoked calcium transients and enhanced neurotransmission, suggesting that RIMBP1-linked dystonia can be caused by either reduced or enhanced rates of spike-evoked release in relevant neural networks. Our findings establish a direct link between dysfunction of the presynaptic active zone and dystonia and highlight the critical role played by well-balanced neurotransmission in motor control and disease pathogenesis

Study in Parkinson’s disease of exercise phase 3 (SPARX3): study protocol for a randomized controlled trial

Background: To date, no medication has slowed the progression of Parkinson’s disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility. This study will determine the efficacy of high-intensity endurance exercise as first-line therapy for persons diagnosed with PD within 3 years, and untreated with symptomatic therapy at baseline. Methods: This is a multicenter, randomized, evaluator-blinded study of endurance exercise training. The exercise intervention will be delivered by treadmill at 2 doses over 18 months: moderate intensity (4 days/week for 30 min per session at 60–65% maximum heart rate) and high intensity (4 days/week for 30 min per session at 80–85% maximum heart rate). We will randomize 370 participants and follow them at multiple time points for 24 months. The primary outcome is the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor score (Part III) with the primary analysis assessing the change in MDS-UPDRS motor score (Part III) over 12 months, or until initiation of symptomatic antiparkinsonian treatment if before 12 months. Secondary outcomes are striatal dopamine transporter binding, 6-min walk distance, number of daily steps, cognitive function, physical fitness, quality of life, time to initiate dopaminergic medication, circulating levels of C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF). Tertiary outcomes are walking stride length and turning velocity. Discussion: SPARX3 is a Phase 3 clinical trial designed to determine the efficacy of high-intensity, endurance treadmill exercise to slow the progression of PD as measured by the MDS-UPDRS motor score. Establishing whether high-intensity endurance treadmill exercise can slow the progression of PD would mark a significant breakthrough in treating PD. It would have a meaningful impact on the quality of life of people with PD, their caregivers and public health. Trial registration: ClinicalTrials.govNCT04284436. Registered on February 25, 2020

MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia

The Mediator multiprotein complex functions as a regulator of RNA polymerase II-catalyzed gene transcription. In this study, exome sequencing detected biallelic putative disease-causing variants in MED27, encoding Mediator complex subunit 27, in 16 patients from 11 families with a novel neurodevelopmental syndrome. Patient phenotypes are highly homogeneous, including global developmental delay, intellectual disability, axial hypotonia with distal spasticity, dystonic movements, and cerebellar hypoplasia. Seizures and cataracts were noted in severely affected individuals. Identification of multiple patients with biallelic MED27 variants supports the critical role of MED27 in normal human neural development, particularly for the cerebellum. ANN NEUROL 2021Peer reviewe