Potenciar la proteína RAC1 podría compensar los efectos asociados a la enfermedad de Parkinson

The Small GTPase RAC1/CED-10 Is Essential in Maintaining Dopaminergic Neuron Function and Survival Against α-Synuclein-Induced Toxicity

Abstract

Parkinson’s disease is associated with intracellular α-synuclein accumulation and ventral midbrain dopaminergic neuronal death in the Substantia Nigra of brain patients. The Rho GTPase pathway, mainly linking surface receptors to the organization of the actin and microtubule cytoskeletons, has been suggested to participate to Parkinson’s disease pathogenesis. Nevertheless, its exact contribution remains obscure. To unveil the participation of the Rho GTPase family to the molecular pathogenesis of Parkinson’s disease, we first used C elegans to demonstrate the role of the small GTPase RAC1 (ced-10 in the worm) in maintaining dopaminergic function and survival in the presence of alpha-synuclein. In addition, ced-10mutant worms determined an increase of alpha-synuclein inclusions in comparison to control worms as well as an increase in autophagic vesicles. We then used a human neuroblastoma cells (M17)

Nuevo fenotipo de la enfermedad de Pompe infantil

A new phenotype of infantile-onset Pompe disease

Abstract

Infantile-onset Pompe disease is a kind of glycogenosis resulting from a deficit of the enzyme acid alpha-glucosidase. Before specific enzyme replacement therapy (ERT) became available, the classic form was fatal during the first two years of life. ERT increases survival and improves cardiac, respiratory and motor functioning.Case 1: 2-month-old infant with predominantly axial hypotonia who required the use of a nasogastric tube as a result of difficulties in sucking and swallowing. Myopathy and hypertrophic cardiomyopathy were observed. The patient was diagnosed with Pompe disease, ERT was established and improved heart and motor functioning were noted. Nevertheless, she presented recurring respiratory infections that finally made it necessary to perform a tracheostomy. She is currently still undergoing ERT, walks with a walker and presents a mild ventricular dysfunction. Case 2: 3-week-old infant who was taken to see his paediatrician for a routine check-up. The examination revealed a systolic bruit and axial and proximal hypotonia. Cardiology tests revealed hypertrophic cardiomyopathy. The patient was sent to a referral centre, where he was diagnosed with Pompe disease and a cross-reactive immunological material-negative status. The patient received immunomodulator treatment and ERT. Progress was favourable, although he presented frequent respiratory infections. The patient is currently capable of walking by himself, although the gait is unsteady.Both cases illustrate the new phenotype of infantile-onset Pompe disease treated with ERT. Despite the motor limitations and respiratory involvement presented by the patients, both survival and autonomy have increased.

Psicoterapias de apoyo a jóvenes con autismo

Cognitive enhancement therapy for adult autism spectrum disorder: Results of an 18‐month randomized clinical trial

Abstract

Cognitive remediation is a promising approach to treating core cognitive deficits in adults with autism, but rigorously controlled trials of comprehensive interventions that target both social and non‐social cognition over a sufficient period of time to impact functioning are lacking. This study examined the efficacy of cognitive enhancement therapy (CET) for improving core cognitive and employment outcomes in adult autism. Verbal adult outpatients with autism spectrum disorder (N = 54) were randomized to an 18‐month, single‐blind trial of CET, a cognitive remediation approach that integrates computer‐based neurocognitive training with group‐based training in social cognition, or an active enriched supportive therapy (EST) comparison focused on psychoeducation and condition management. Primary outcomes were composite indexes of neurocognitive and social‐cognitive change. Competitive employment was a secondary outcome. Intent‐to‐treat analyses indicated that CET produced significant differential increases in neurocognitive function relative to EST (d = .46, P = .013). Both CET and EST were associated with large social‐cognitive improvements, with CET demonstrating an advantage at 9 (d = .58, P = 0.020), but not 18 months (d = .27, P = 0.298). Effects on employment indicated that participants treated with CET were significantly more likely to gain competitive employment than those in EST, OR = 6.21, P = 0.023, which was mediated by cognitive improvement. CET is a feasible and potentially effective treatment for core cognitive deficits in adult autism spectrum disorder. The treatment of cognitive impairments in this population can contribute to meaningful improvements in adult outcomes. Autism Res 2018, 11: 519–530. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Cognitive enhancement therapy (CET), an 18‐month cognitive remediation intervention designed to improve thinking and social understanding, was found to be more effective than supportive therapy at improving mental quickness, attention, and employment in adults living with autism. Social understanding was equally improved in CET and supportive therapy. Cognitive remediation interventions are feasible and may confer significant functional benefits to adults with autism.

Autismo, trastorno bipolar y esquizofrenia comparten similitudes genéticas

Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap

Abstract

Recent large-scale studies have identified multiple genetic risk factors for mental illness and indicate a complex, polygenic, and pleiotropic genetic architecture for neuropsychiatric disease. However, little is known about how genetic variants yield brain dysfunction or pathology. We use transcriptomic profiling as an unbiased, quantitative readout of molecular phenotypes across 5 major psychiatric disorders, including autism (ASD), schizophrenia (SCZ), bipolar disorder (BD), depression (MDD), and alcoholism (AAD), compared with carefully matched controls. We identify a clear pattern of shared and distinct gene-expression perturbations across these conditions, identifying neuronal gene co-expression modules downregulated across ASD, SCZ, and BD, and astrocyte related modules most prominently upregulated in ASD and SCZ. Remarkably, the degree of sharing of transcriptional dysregulation was strongly related to polygenic (SNP-based) overlap across disorders, indicating a significant genetic component. These findings provide a systems-level view of the neurobiological architecture of major neuropsychiatric illness and demonstrate pathways of molecular convergence and specificity.

Se constata disparidad en la atención escolar al trastorno por déficit de atención/hiperactividad entre las comunidades españolas

School assistance for attention deficit hyperactivity disorder in the Spanish autonomous regions

Abstract

In recent years different Spanish autonomous regions have presented policies on school assistance for attention deficit hyperactivity disorder (ADHD) or coordination between the educational and healthcare services, which result in protocols, instructions or guidelines of action.To determine and compare the proposals put forward by the different Spanish regions with respect to school assistance for ADHD.After searching for the documents that contain these policies, the information therein was analysed with the aim of being able to compare them in several different areas: document, scope of application, detection of ADHD, diagnosis, school measures, follow-up of the proposals of the Guidelines on clinical practice in attention deficit hyperactivity disorder, grounds and resources offered.The Valencian Region is the only one for which no documents were found. The document for the Balearic Islands was not analysed because it is not public, and in the other regions differences were found in the degree of compliance with the criteria assessed in each area. The policies in Extremadura, Galicia, Catalonia and Navarra are the ones that meet the largest number of criteria. All the regions with policies on ADHD propose some kind of school measures and resources such as bibliographical references, contacts or models of documents or screening tools. All of them, except Madrid, offer information about the detection and diagnosis of ADHD.There are differences among the proposals for school assistance for ADHD in Spain, and those of Extremadura, Galicia, Catalonia and Navarra are found to be the most complete.

Nuevo enfoque para la aplicación de la optogenética en trastornos cerebrales

Near-infrareddeep brain stimulation via upconversion nanoparticle–mediated optogenetics

Abstract

Optogenetics has revolutionized the experimental interrogation of neural circuits and holds promise for the treatment of neurological disorders. It is limited, however, because visible light cannot penetrate deep inside brain tissue. Upconversion nanoparticles (UCNPs) absorb tissue-penetrating near-infrared (NIR) light and emit wavelength-specific visible light. Here, we demonstrate that molecularly tailored UCNPs can serve as optogenetic actuators of transcranial NIR light to stimulate deep brain neurons. Transcranial NIR UCNP-mediated optogenetics evoked dopamine release from genetically tagged neurons in the ventral tegmental area, induced brain oscillations through activation of inhibitory neurons in the medial septum, silenced seizure by inhibition of hippocampal excitatory cells, and triggered memory recall. UCNP technology will enable less-invasive optical neuronal activity manipulation with the potential for remote therapy.

Factores de riesgo de ictus en mujeres

Stroke RiskFactors Unique to Women

Stroke is the third leading cause of death in women in the United States and is a leading cause of disability. Each year 55 000 more women than men have a stroke, a discrepancy largely driven by longer life expectancy in women (www.stroke.org). Although the majority of stroke incidence can be attributed to traditional vascular risk factors that occur in both men and women, including hypertension, hyperlipidemia, diabetes mellitus, smoking, and atrial fibrillation, there are several stroke risk factors that are specific to women. Specifically, differences in sex hormones, exogenous estrogens, and pregnancy exposures are factors exclusively experienced by women. In this review, we will summarize the current state of the literature with regards to women-specific factors, such as endogenous hormone levels, exogenous hormone therapy, pregnancy, parity, timing of age at menarche, and menopause in relation to stroke risk.

Methods

The following terms were searched with women and stroke in PubMed and Google Scholar, mainly for original articles and meta-analysis/systematic reviews: estrogens, estradiol, testosterone, DHEAS, menarche, menopause, oophorectomy, postmenopausal hormone therapy, oral contraception, transgender, transmen, transwomen, pregnancy, peripartum, postpartum, and parity The following search was also performed: therapy OR treatment OR secondary prevention AND pregnancy AND stroke. The resultant literature was reviewed by the authors, and the data covering the topics outlined below were reviewed in this manuscript.

Endogenous Estrogen State

Endogenous Hormone Levels

Data on the relationship of endogenous sex hormones and risk of stroke in women are relatively limited. Estrogen levels fluctuate dramatically in women with the menstrual cycle and then drop dramatically in the menopausal transition and in post-menopause. In data from the Copenhagen City Study, neither high nor low estradiol levels were associated with increased risk of ischemic stroke.1 In premenopausal women, those in the lowest 10th percentile of estradiol had a >2-fold increased risk of ischemic stroke, but this was based on …

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La prevalencia del síndrome alcohólico fetal podría ser mayor de lo que se pensaba

Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities

Abstract

Importance  Fetal alcohol spectrum disorders are costly, life-long disabilities. Older data suggested the prevalence of the disorder in the United States was 10 per 1000 children; however, there are few current estimates based on larger, diverse US population samples.

Objective  To estimate the prevalence of fetal alcohol spectrum disorders, including fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder, in 4 regions of the United States.

Design, Setting, and Participants  Active case ascertainment methods using a cross-sectional design were used to assess children for fetal alcohol spectrum disorders between 2010 and 2016. Children were systematically assessed in the 4 domains that contribute to the fetal alcohol spectrum disorder continuum: dysmorphic features, physical growth, neurobehavioral development, and prenatal alcohol exposure. The settings were 4 communities in the Rocky Mountain, Midwestern, Southeastern, and Pacific Southwestern regions of the United States. First-grade children and their parents or guardians were enrolled.

Exposures  Alcohol consumption during pregnancy.

Main Outcomes and Measures  Prevalence of fetal alcohol spectrum disorders in the 4 communities was the main outcome. Conservative estimates for the prevalence of the disorder and 95% CIs were calculated using the eligible first-grade population as the denominator. Weighted prevalences and 95% CIs were also estimated, accounting for the sampling schemes and using data restricted to children who received a full evaluation.

Results  A total of 6639 children were selected for participation from a population of 13 146 first-graders (boys, 51.9%; mean age, 6.7 years [SD, 0.41] and white maternal race, 79.3%). A total of 222 cases of fetal alcohol spectrum disorders were identified. The conservative prevalence estimates for fetal alcohol spectrum disorders ranged from 11.3 (95% CI, 7.8-15.8) to 50.0 (95% CI, 39.9-61.7) per 1000 children. The weighted prevalence estimates for fetal alcohol spectrum disorders ranged from 31.1 (95% CI, 16.1-54.0) to 98.5 (95% CI, 57.5-139.5) per 1000 children.

Conclusions and Relevance  Estimated prevalence of fetal alcohol spectrum disorders among first-graders in 4 US communities ranged from 1.1% to 5.0% using a conservative approach. These findings may represent more accurate US prevalence estimates than previous studies but may not be generalizable to all communities.

El «hombre de la mano seca»: ¿iconografía de la parálisis saturnínica?

The man with the withered hand': iconography of the saturnine palsy?

INTRODUCTION:

The synoptic gospels tell about a man who cannot extend his hand, that appeared dried. The description is consistent with radial palsy. Christian artists depicted this gospel story producing a rich material, unexplored from the medical point of view.

AIM:

To analyze the mentioned iconography verifying the depicted lesions and their possible causes.

DEVELOPMENT:

Six representations of the evangelical text pertaining to the period comprehended between 10th and 17th centuries were selected. Four belong to illuminated gospels, one is a mosaic and the other one is a fresco. In three of them the figure with the palsy hand appeared holding the affected member with the opposite hand; another one has a foot drop. The description of postures that are characteristic of extensor palsies points out that these artists must have known real patients. Saturnism, frequent in Europe during the period in which these works were created, was probably the cause of the paralysis in these cases. Another hypothesis was that the artists could have suffered themselves saturnism, caused by manipulating paints with high lead content; this could not be confirmed.

CONCLUSIONS:

The iconographies of 'the man with the withered hand' are realistic representations of motor paralysis consistent with saturnine neuropathy. These works preceded for a long time the best medical descriptions of such condition.

La eliminación de células senescentes podría prevenir la enfermedad de Parkinson

Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinson’s Disease

Summary

Exposure to the herbicide paraquat (PQ) is associated with an increased risk of idiopathic Parkinson’s disease (PD). Therapies based on PQ’s presumed mechanisms of action have not, however, yielded effective disease therapies. Cellular senescence is an anticancer mechanism that arrests proliferation of replication-competent cells and results in a pro-inflammatory senescence-associated secretory phenotype (SASP) capable of damaging neighboring tissues. Here, we demonstrate that senescent cell markers are preferentially present within astrocytes in PD brain tissues. Additionally, PQ was found to induce astrocytic senescence and an SASP in vitro and in vivo, and senescent cell depletion in the latter protects against PQ-induced neuropathology.

Las mujeres tienen una peor recuperación que los hombres tras un ictus

Focused Update of Sex Differences inPatient Reported Outcome Measures After Stroke

Women experience worse outcomes after stroke than men despite their lower age-adjusted incidence of stroke. Previous reviews of sex differences in select stroke outcomes, including activity limitations, participation restriction, poststroke depression (PSD), and health-related quality of life (HRQoL), demonstrated that women had worse outcomes than men across many of these measures. Women’s greater age and stroke severity, as well as poorer prestroke function, seem to contribute to the sex difference in outcomes, but data on other contributing factors are limited. Existing reviews included studies published >5 years ago, and given the rapid increase in the number of studies addressing sex differences in stroke outcomes, an updated review is warranted.

Methods

Full details of our methods are provided in the online-only Data Supplement. A previous review included studies up to 2007, so we reviewed studies from 2007 onwards that examined sex differences in patient reported outcome measures (PROMs) at ≤12 months after stroke, including activity limitations, HRQoL, participation restriction, impaired cognition, and mood. Full results tables are shown in the online-only Data Supplement.

Results

Activity Limitations

Of 1875 articles identified, 22 studies (3 population based) that were designed to examine sex differences (Results and Table I in the online-only Data Supplement) met criteria for inclusion. The most common instrument to assess activity limitations was the modified Rankin Scale, followed by the Barthel Index.

In 8 studies including ischemic and hemorrhagic strokes, unadjusted estimates showed that women had more activity limitations than men through significantly lower odds of good outcome (odds ratio [OR] range: 0.44–0.61)7–9 or greater odds of poor outcome (OR range: 1.29–1.62). In multivariable adjusted analyses, women had worse outcome than men with significantly lower odds of good outcome (OR range: 0.37–0.75).

La prevalencia del síndrome alcohólico fetal podría ser mayor de lo que se pensaba

Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities

Abstract

Importance  Fetal alcohol spectrum disorders are costly, life-long disabilities. Older data suggested the prevalence of the disorder in the United States was 10 per 1000 children; however, there are few current estimates based on larger, diverse US population samples.

Objective  To estimate the prevalence of fetal alcohol spectrum disorders, including fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder, in 4 regions of the United States.

Design, Setting, and Participants  Active case ascertainment methods using a cross-sectional design were used to assess children for fetal alcohol spectrum disorders between 2010 and 2016. Children were systematically assessed in the 4 domains that contribute to the fetal alcohol spectrum disorder continuum: dysmorphic features, physical growth, neurobehavioral development, and prenatal alcohol exposure. The settings were 4 communities in the Rocky Mountain, Midwestern, Southeastern, and Pacific Southwestern regions of the United States. First-grade children and their parents or guardians were enrolled.

Exposures  Alcohol consumption during pregnancy.

Main Outcomes and Measures  Prevalence of fetal alcohol spectrum disorders in the 4 communities was the main outcome. Conservative estimates for the prevalence of the disorder and 95% CIs were calculated using the eligible first-grade population as the denominator. Weighted prevalences and 95% CIs were also estimated, accounting for the sampling schemes and using data restricted to children who received a full evaluation.

Results  A total of 6639 children were selected for participation from a population of 13 146 first-graders (boys, 51.9%; mean age, 6.7 years [SD, 0.41] and white maternal race, 79.3%). A total of 222 cases of fetal alcohol spectrum disorders were identified. The conservative prevalence estimates for fetal alcohol spectrum disorders ranged from 11.3 (95% CI, 7.8-15.8) to 50.0 (95% CI, 39.9-61.7) per 1000 children. The weighted prevalence estimates for fetal alcohol spectrum disorders ranged from 31.1 (95% CI, 16.1-54.0) to 98.5 (95% CI, 57.5-139.5) per 1000 children.

Conclusions and Relevance  Estimated prevalence of fetal alcohol spectrum disorders among first-graders in 4 US communities ranged from 1.1% to 5.0% using a conservative approach. These findings may represent more accurate US prevalence estimates than previous studies but may not be generalizable to all communities.

Un traumatismo craneoencefálico grave aumentaría el riesgo de demencia décadas más tarde

Traumatic brain injury and the risk of dementia diagnosis: A nationwide cohort study

Abstract

Background

Traumatic brain injury (TBI) has been associated with dementia. The questions of whether the risk of dementia decreases over time after TBI, whether it is similar for different TBI types, and whether it is influenced by familial aggregation are not well studied.

Methods and findings

The cohort considered for inclusion comprised all individuals in Sweden aged ≥50 years on December 31, 2005 (n = 3,329,360). Diagnoses of dementia and TBI were tracked through nationwide databases from 1964 until December 31, 2012. In a first cohort, individuals diagnosed with TBI (n = 164,334) were matched with up to two controls. A second cohort consisted of subjects diagnosed with dementia during follow-up (n = 136,233) matched with up to two controls. A third cohort consisted of 46,970 full sibling pairs with discordant TBI status. During a mean follow-up period of 15.3 (range, 0–49) years, 21,963 individuals in the first cohort (6.3% with TBI, 3.6% without TBI) were diagnosed with dementia (adjusted odds ratio [OR], 1.81; 95% confidence interval [CI], 1.75–1.86). The association was strongest in the first year after TBI (OR, 3.52; 95% CI, 3.23–3.84), but the risk remained significant >30 years (OR, 1.25; 95% CI, 1.11–1.41). Single mild TBI showed a weaker association with dementia (OR, 1.63; 95% CI, 1.57–1.70) than did more severe TBI (OR, 2.06; 95% CI, 1.95–2.19) and multiple TBIs (OR, 2.81; 95% CI, 2.51–3.15). These results were in general confirmed in the nested case-control cohort. TBI was also associated with an increased risk of dementia diagnosis in sibling pairs with discordant TBI status (OR, 1.89; 95% CI, 1.62–2.21). A main limitation of the present study is the observational design. Thus, no causal inferences can be made based on the associations found.

Conclusions

The risk of dementia diagnosis decreased over time after TBI, but it was still evident >30 years after the trauma. The association was stronger for more severe TBI and multiple TBIs, and it persisted after adjustment for familial factors.

Citation: Nordström A, Nordström P (2018) Traumatic brain injury and the risk of dementia diagnosis: A nationwide cohort study. PLoS Med 15(1): e1002496. https://doi.org/10.1371/journal.pmed.1002496

Academic Editor: David Menon, University of Cambridge, UNITED KINGDOM

Las respuestas neuronales son similares entre amigos

Similar neural responses predict friendship

Abstract

Human social networks are overwhelmingly homophilous: individuals tend to befriend others who are similar to them in terms of a range of physical attributes (e.g., age, gender). Do similarities among friends reflect deeper similarities in how we perceive, interpret, and respond to the world? To test whether friendship, and more generally, social network proximity, is associated with increased similarity of real-time mental responding, we used functional magnetic resonance imaging to scan subjects’ brains during free viewing of naturalistic movies. Here we show evidence for neural homophily: neural responses when viewing audiovisual movies are exceptionally similar among friends, and that similarity decreases with increasing distance in a real-world social network. These results suggest that we are exceptionally similar to our friends in how we perceive and respond to the world around us, which has implications for interpersonal influence and attraction.

Introduction

The notion that people tend to resemble their friends is an enduring intuition, as evidenced by the centuries-old adage, “birds of a feather flock together”1.

Nueva interfaz cerebro-máquina para restaurar la funcionalidad de las manos

Recruitment of additional corticospinal pathways in the human brain with state-dependent paired associative stimulation

Abstract

Standard brain stimulation protocols modify human motor cortex excitability by modulating the gain of the activated corticospinal pathways. However, the restoration of motor function following lesions of the corticospinal tract requires also the recruitment of additional neurons to increase the net corticospinal output. For this purpose, we investigated a novel protocol based on brain state-dependent paired associative stimulation.

Motor imagery (MI)-related electroencephalography was recorded in healthy males and females for brain state-dependent control of both cortical and peripheral stimulation in a brain–machine interface environment. State-dependency was investigated with concurrent, delayed, and independent stimulation relative to the MI task. Specifically, sensorimotor event-related desynchronization (ERD) in the β-band (16–22 Hz) triggered peripheral stimulation through passive hand opening by a robotic orthosis and transcranial magnetic stimulation to the respective cortical motor representation, either synchronously or subsequently. These MI-related paradigms were compared with paired cortical and peripheral input applied independent of the brain state. Cortical stimulation resulted in a significant increase in corticospinal excitability only when applied brain state-dependently and synchronously to peripheral input. These gains were resistant to a depotentiation task, revealed a nonlinear evolution of plasticity, and were mediated via the recruitment of additional corticospinal neurons rather than via synchronization of neuronal firing. Recruitment of additional corticospinal pathways may be achieved when cortical and peripheral inputs are applied concurrently, and during β-ERD. These findings resemble a gating mechanism and are potentially important for developing closed-loop brain stimulation for the treatment of hand paralysis following lesions of the corticospinal tract.

SIGNIFICANCE STATEMENT 

The activity state of the motor system influences the excitability of corticospinal pathways to external input. State-dependent interventions harness this property to increase the connectivity between motor cortex and muscles. These stimulation protocols modulate the gain of the activated pathways, but not the overall corticospinal recruitment. In this study, a brain–machine interface paired peripheral stimulation through passive hand opening with transcranial magnetic stimulation to the respective cortical motor representation during volitional β-band desynchronization. Cortical stimulation resulted in the recruitment of additional corticospinal pathways, but only when applied brain state-dependently and synchronously to peripheral input. These effects resemble a gating mechanism and may be important for the restoration of motor function following lesions of the corticospinal tract.

• corticospinal pathways
• event-related desynchronization
• motor imagery
• paired associative stimulation
• state-dependent stimulation
• transcranial magnetic stimulation

La secuenciación completa del exoma permite el diagnóstico de un síndrome asociado a rasgos autistas

A De Novo FOXP1 Truncating Mutation in a Patient Originally Diagnosed as C Syndrome

Abstract

De novo FOXP1 mutations have been associated with intellectual disability (ID), motor delay, autistic features and a wide spectrum of speech difficulties. C syndrome (Opitz C trigonocephaly syndrome) is a rare and genetically heterogeneous condition, characterized by trigonocephaly, craniofacial anomalies and ID. Several different chromosome deletions and and point mutations in distinct genes have been associated with the disease in patients originally diagnosed as Opitz C. By whole exome sequencing we identified a de novo splicing mutation in FOXP1 in a patient, initially diagnosed as C syndrome, who suffers from syndromic intellectual disability with trigonocephaly. The mutation (c.1428 + 1 G > A) promotes the skipping of exon 16, a frameshift and a premature STOP codon (p.Ala450GLyfs*13), as assessed by a minigene strategy. The patient reported here shares speech difficulties, intellectual disability and autistic features with other FOXP1 syndrome patients, and thus the diagnosis for this patient should be changed. Finally, since trigonocephaly has not been previously reported in FOXP1 syndrome, it remains to be proved whether it may be associated with the FOXP1 mutation.

Convierten células madre en interneuronas sensoriales para restaurar el sentido del tacto

Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells

Summary

Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro-derived sensory interneurons (INs), which permit perception of the environment. Here, we report on the development of a directed differentiation protocol to derive sensory INs for both hESCs and hiPSCs. Two developmentally relevant factors, retinoic acid in combination with bone morphogenetic protein 4, can be used to generate three classes of sensory INs: the proprioceptive dI1s, the dI2s, and mechanosensory dI3s. Critical to this protocol is the competence state of the neural progenitors, which changes over time. This protocol will facilitate developing cellular replacement therapies to reestablish sensory connections in injured patients.

Introduction

The somatosensory system mediates the perception of touch (mechanosensation), pain (nociception), heat (thermosensation), and the position of the body in space

El bilingüismo podría aumentar la flexibilidad cognitiva de niños con trastornos del espectro autista

Can Bilingualism MitigateSet‐Shifting Difficulties in Children With Autism Spectrum Disorders?

Abstract

This study investigated the effects of bilingualism on set‐shifting and working memory in children with autism spectrum disorders (ASD). Bilinguals with ASD were predicted to display a specific bilingual advantage in set‐shifting, but not working memory, relative to monolinguals with ASD. Forty 6‐ to 9‐year‐old children participated (20 ASD, 20 typically‐developing). Set‐shifting was measured using a computerized dimensional change card sort (DCCS) task, and by parent report of executive functioning in daily life. Results showed an advantage for bilingual relative to monolingual children with ASD on the DCCS task, but not for set‐shifting in daily life. Working memory was similar for bilinguals and monolinguals with ASD. These findings suggest that bilingualism may mitigate some set‐shifting difficulties in children with ASD.

The impact of bilingualism on cognition is an ongoing topic of debate.

La tartamudez neurógena, una entidad poco definida y caracterizada

Neurogenic stuttering: areview of the literature.

Abstract

Neurogenic stuttering is a disorder of neurologic origin in the rhythm of speech during which the patient knows exactly what he wants to say but is unable to because of an involuntary prolongation, cessation or repetition of a sound.To assemble new insights regarding the epidemiology, pathophysiology, diagnosis, evaluation and treatment of neurogenic stuttering.A review of all PubMed and Scopus published articles between January 2000 and September 2016 was performed. Thirty-three publications were analyzed. Neurogenic stuttering is a rare entity whose epidemiological incidence is yet not fully established. It is correlated with several neurological diseases and with several possible localizations within the nervous system. Notwithstanding the recent advances in the understanding of the underlying mechanism, it is not yet possible to establish a single pathophysiological mechanism of neurogenic stuttering. The differential diagnosis is complex and requires the detailed knowledge of other language disorders. The treatment is currently based on specific speech language therapy strategies.Neurogenic stuttering is a complex disorder which is not fully understood. Additional studies might help to better explain the underlying pathophysiological mechanism and to open doors to novel therapeutic methods.

Investigan cómo el colesterol contribuye al deterioro neuronal relacionado con la edad

Defective cholesterol clearance limits remyelination in the aged central nervous system

Abstract

Age-associated decline in regeneration capacity limits the restoration of nervous system functionality after injury. In a model for demyelination, we found that old mice fail to resolve the inflammatory response initiated after myelin damage. Aged phagocytes accumulated excessive amounts of myelin debris, which triggered cholesterol crystal formation, phagolysosomal membrane rupture, and stimulated inflammasomes. Myelin debris clearance required cholesterol transporters including apolipoprotein E. Remarkably, stimulation of reverse cholesterol transport was sufficient to restore the capacity of old mice to remyelinate lesioned tissue. Thus, cholesterol-rich myelin debris can overwhelm the efflux capacity of phagocytes, resulting in a phase transition of cholesterol into crystals thereby inducing a maladaptive immune response that impedes tissue regeneration.

La estimulación cerebral profunda podría ayudar a reducir los tics en el síndrome de Tourette

Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome

Abstract

Importance  Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome.

Objective  To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome.

Design, Setting, and Participants  The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide.

Exposures  Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]).

Main Outcomes and Measures  Scores on the Yale Global Tic Severity Scale and adverse events.

Results  The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P < .001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P < .001), and the mean (SD) phonic tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P < .001). The overall adverse event rate was 35.4% (56 of 158 patients), with intracranial hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events (3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation-induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]).

Conclusions and Relevance  Deep brain stimulation was associated with symptomatic improvement in patients with Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.

Posibles biomarcadores de enfermedad de Parkinson y atrofia multisistémica

New Approaches to Exciting Exergame-Experiences for People with Motor Function Impairments

Abstract

 : 

The work presented here suggests new ways to tackle exergames for physical rehabilitation and to improve the players’ immersion and involvement. The primary (but not exclusive) purpose is to increase the motivation of children and adolescents with severe physical impairments, for doing their required exercises while playing. The proposed gaming environment is based on the Kinect sensor and the Blender Game Engine. A middleware has been implemented that efficiently transmits the data from the sensor to the game. Inside the game, different newly proposed mechanisms have been developed to distinguish pure exercise-gestures from other movements used to control the game (e.g., opening a menu). The main contribution is the amplification of weak movements, which allows the physically impaired to have similar gaming experiences as the average population. To test the feasibility of the proposed methods, four mini-games were implemented and tested by a group of 11 volunteers with different disabilities, most of them bound to a wheelchair. Their performance has also been compared to that of a healthy control group. Results are generally positive and motivating, although there is much to do to improve the functionalities. There is a major demand for applications that help to include disabled people in society and to improve their life conditions. This work will contribute towards providing them with more fun during exercise.

Keywords:

 exergames; rehabilitation; Kinect; gamification; serious games; physical disability; muscle weakness; middleware; children; adolescents; adaptation

Videojuegos para la rehabilitación de niños y adolescentes con movilidad reducida

New Approaches to Exciting Exergame-Experiences for People with Motor Function Impairments

Abstract

: 

The work presented here suggests new ways to tackle exergames for physical rehabilitation and to improve the players’ immersion and involvement. The primary (but not exclusive) purpose is to increase the motivation of children and adolescents with severe physical impairments, for doing their required exercises while playing. The proposed gaming environment is based on the Kinect sensor and the Blender Game Engine. A middleware has been implemented that efficiently transmits the data from the sensor to the game. Inside the game, different newly proposed mechanisms have been developed to distinguish pure exercise-gestures from other movements used to control the game (e.g., opening a menu). The main contribution is the amplification of weak movements, which allows the physically impaired to have similar gaming experiences as the average population. To test the feasibility of the proposed methods, four mini-games were implemented and tested by a group of 11 volunteers with different disabilities, most of them bound to a wheelchair. Their performance has also been compared to that of a healthy control group. Results are generally positive and motivating, although there is much to do to improve the functionalities. There is a major demand for applications that help to include disabled people in society and to improve their life conditions. This work will contribute towards providing them with more fun during exercise.

Keywords:

 exergames; rehabilitation; Kinect; gamification; serious games; physical disability; muscle weakness; middleware; children; adolescents; adaptation

Demuestran la acción neuroprotectora de dos ácidos grasos omega 3

Markers of neuroprotection of combined EPA and DHA provided by fish oil are higher than those of EPA (Nannochloropsis) and DHA (Schizochytrium) from microalgae oils in Wistar rats

Abstract

Background
To overcome the current overexploitation of fish rich in n-3 long chain polyunsaturated fatty acids (LCPUFA), microalgae have become a promising marine lipid source. The purpose of this study was to assess eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), isolated or combined from distinct marine origins, on the promotion of neuroprotective effects.

Methods

The experiment lasted for 10 weeks and involved 32 Wistar rats, divided into 4 diets (n = 8): a diet rich in milk fat was taken as control (Milk Fat) and compared to n-3 LCPUFA enriched diets, either in EPA + DHA form through fish oil (Fish Oil), or EPA through Nannochloropsis oil (Nanno), or DHA through Schizochytrium oil (Schyzo), while maintaining Milk Fat incorporation.

Results

Plasma lipid profile and dopamine levels were more beneficial in Fish Oil diet. In addition, n-3 LCPUFA incorporation was found increased in liver and erythrocytes from Fish Oil fed rats, suggesting that fish oil is a better dietary source for fatty acids deposition in the organism than microalgae. The Forced Swimming Test revealed a positive behavioural action of EPA + DHA, in opposition to Milk Fat and Nanno diets, which had higher immobile times. mRNA levels of serotonin receptors, HT1A and HT2A along with CREB, the transmission factor for learning and memory, were higher in the hippocampus of rats fed n-3 LCPUFA diets comparative to Milk Fat.

Conclusion
Taken together, the combination of EPA and DHA from fish oil can counteract the undesirable health effects of saturated fat based diets and benefit, in the long run, neurological function.

Keywords

Fish oil - Microalgae - Fatty acid composition - Forced swimming test - Transcriptional profile

Vinculan los suplementos vitamínicos antes y durante el embarazo con un menor riesgo de autismo

Association of Maternal Use of Folic Acid and Multivitamin Supplements in the Periods Before and During Pregnancy With the Risk of Autism Spectrum Disorder in Offspring

Key Points

Question  Does maternal folic acid and/or multivitamin supplement use before and/or during pregnancy increase the risk of autism spectrum disorder in offspring?

Findings  In this case-control cohort study of 45 300 offspring, statistically significant associations between maternal vitamin supplement use before and/or during pregnancy and reduced risk of autism spectrum disorder in offspring were observed.

Meaning  A reduced risk of autism spectrum disorder in children born to women who used the specified vitamin supplements before and during pregnancy has important public health implications; possible mechanisms include epigenetic modifications.

Abstract

Importance  The association of maternal use of folic acid and multivitamin supplements before and during pregnancy with the risk of autism spectrum disorder (ASD) in offspring is unclear.

Objective  To examine the associations between the use of maternal folic acid and multivitamin supplements before and during pregnancy and the risk of ASD in offspring.

Design, Setting, and Participants  A case-control cohort study of 45 300 Israeli children born between January 1, 2003, and December 31, 2007, were followed up from birth to January 26, 2015, for the risk of ASD. The cases were all children diagnosed with ASD and the controls were a random sample of 33% of all live-born children.

Exposures  Maternal vitamin supplements were classified for folic acid (vitamin B₉), multivitamin supplements (Anatomical Therapeutic Chemical A11 codes vitamins A, B, C, and D), and any combination thereof exposed in the intervals before and during pregnancy.

Main Outcomes and Measures  The association between maternal vitamin supplementation and the risk of ASD in offspring was quantified with relative risks (RRs) and their 95% CIs fitting Cox proportional hazards regression models adjusted for confounders. Sensitivity analyses were performed to test the robustness of the results.

Results  Of the 45 300 children in the study (22 090 girls and 23 210 boys; mean [SD] age, 10.0 [1.4] years at the end of follow-up), 572 (1.3%) received a diagnosis of ASD. Maternal exposure to folic acid and/or multivitamin supplements before pregnancy was statistically significantly associated with a lower likelihood of ASD in the offspring compared with no exposure before pregnancy (RR, 0.39; 95% CI, 0.30-0.50; P < .001). Maternal exposure to folic acid and/or multivitamin supplements during pregnancy was statistically significantly associated with a lower likelihood of ASD in offspring compared with no exposure during pregnancy (RR, 0.27; 95% CI, 0.22-0.33; P < .001). Corresponding RRs were estimated for maternal exposure to folic acid before pregnancy (RR, 0.56; 95% CI, 0.42-0.74; P = .001), maternal exposure to folic acid during pregnancy (RR, 0.32; 95% CI, 0.26-0.41; P < .001), maternal exposure to multivitamin supplements before pregnancy (RR, 0.36; 95% CI, 0.24-0.52; P < .001), and maternal exposure to multivitamin supplements during pregnancy (RR, 0.35; 95% CI, 0.28-0.44; P < .001). The results generally remained statistically significant across sensitivity analyses.

Conclusions and Relevance  Maternal exposure to folic acid and multivitamin supplements before and during pregnancy is associated with a reduced risk of ASD in the offspring compared with the offspring of mothers without such exposure.