Early Medial Temporal Atrophy Scale (EMTA)

186 p.[ES]La atrofia del lóbulo temporal medial puede ser medida a través del uso de escalas de atrofia visual tales como la escala de atrofia del lóbulo temporal medial (MTA). La escala MTA ha sido diseñada y validada para el estudio de pacientes con Enfermedad de Alzheimer moderada (EA). Sin embargo, la MTA no ha sido diseñada para medir los cambios de atrofia de bajo grado que ocurren en la etapa precoz y media del proceso de envejecimiento. El objetivo de este estudio fue desarrollar y validar una nueva MTA; La “Goiz” (en Euskera) GMTA o “Early” (en ingles) EMTA, una nueva escala diseñada para la valoración de la atrofia precoz del lóbulo temporal medial que tiene la capacidad de medir los cambios de atrofia de bajo grado.[EN]Medial temporal lobe atrophy can be measured through visual rating scales such us the medial temporal lobe atrophy scale (MTA). MTA has been designed and validated for the study of patients with mild to moderate Alzheimer disease (AD). However, MTA has not been designed to measure the low-grade atrophy changes that occur at the early and middle aging process. The aim of this study was develop and validate a new MTA; the early (“Goiz” in Basque language) medial temporal lobe atrophy scale (EMTA) that has the capability to measure the low-grade atrophy changes

Selection criteria for overlapping binary models-a simulation study

This paper deals with the problem of choosing the optimum criterion for selecting the best model out of a set of overlapping binary models. The criteria we studied were the well-known AIC and SBIC, and a third one called C-2. Special attention was paid to the setting where neither of the competing models was correctly specified. This situation has not been studied very much but it is the most common case in empirical works. The theoretical study we carried out allowed us to conclude that, in general terms, all criteria perform well. A Monte Carlo exercise corroborated those results

ERTE y COVID-19, desarrollo normativo e interpretación jurídica

Vamos a hablar en el siguiente trabajo de un tema no poco candente que ha sido el uso del Expediente deRegulación de Trabajo Temporal (ERTE) como herramienta de contención y protección social y laboral, quesupuso la implantación de una nueva causa para implantarlos que desencadenó en una ola de expectacióne incertidumbre ya bien por el tardío cobro por parte del Servicio Público de Empleo Estatal (SEPE) y por lacrisis económica derivada y lenta recuperación. Por todo ello, vamos a intentar esclarecer dudas y explicarpuntos concretos legislativos.<br /

La Inspección Educativa en la Comunidad Foral de Navarra

Navarra, is a uniprovincial community, with an approximate population of 620,000 habitants. 43% live in Pamplona and its region. The immigrant population accounts for approximately 10% of the total population.One of its hallmarks of this Community is to have two official languages depending on the geographical areas. The D.F. 159/88, develops the Law of the Basque language defining for non-university education the linguistic models A, B and D. In the aforementioned&nbsp;decree law the models A, B, D are authorized for the Basque-speaking area, therefore, the teaching of the Basque language is mandatory; for the mixed zone the models A, B, D and G and for the non-Basque-speaking area the models A and G.Navarra, es una comunidad uniprovincial, con una población aproximada de 620.000 habitantes. El 43% vive en Pamplona y su comarca. La población inmigrante supone aproximadamente un 10% de la población total. Una de sus señas de identidad de esta Comunidad es la de tener dos lenguas oficiales dependiendo de las zonas geográficas. El D.F. 159/88, desarrolla la Ley del vascuence definiendo para la enseñanza no universitaria los modelos lingüísticos A, B y D. En el citado decreto se autorizan para la zona vascófona los modelos A, B, D, siendo obligatoria por tanto la enseñanza de la lengua vasca; para la zona mixta los modelos A, B, D y G y para la zona no vascófona los modelos A y G

Neurodegeneration trajectory in pediatric and adult/late DM1: A follow‐up MRI study across a decade

Objective: To characterize the progression of brain structural abnormalities in adults with pediatric and adult/late onset DM1, as well as to examine the potential predictive markers of such progression. Methods: 21 DM1 patients (pediatric onset: N = 9; adult/late onset: N = 12) and 18 healthy controls (HC) were assessed longitudinally over 9.17 years through brain MRI. Additionally, patients underwent neuropsychological, genetic, and muscular impairment assessment. Inter-group comparisons of total and voxel-level regional brain volume were conducted through Voxel Based Morphometry (VBM); cross-sectionally and longitudinally, analyzing the associations between brain changes and demographic, clinical, and cognitive outcomes. Results: The percentage of GM loss did not significantly differ in any of the groups compared with HC and when assessed independently, adult/late DM1 patients and their HC group suffered a significant loss in WM volume. Regional VBM analyses revealed subcortical GM damage in both DM1 groups, evolving to frontal regions in the pediatric onset patients. Muscular impairment and the outcomes of certain neuropsychological tests were significantly associated with follow-up GM damage, while visuoconstruction, attention, and executive function tests showed sensitivity to WM degeneration over time. Interpretation: Distinct patterns of brain atrophy and its progression over time in pediatric and adult/late onset DM1 patients are suggested. Results indicate a possible neurodevelopmental origin of the brain abnormalities in DM1, along with the possible existence of an additional neurodegenerative process. Fronto-subcortical networks appear to be involved in the disease progression at young adulthood in pediatric onset DM1 patients. The involvement of a multimodal integration network in DM1 is discussed.CIBERNED609 Eusko JaurlaritzaPRE_ 2016_1_0187PRE_2019_1_0070SAIO08- PE08BF01 Institute of Health Carlos III cofounded by Fondo Europeo de Desarrollo Regional-FEDERPI17/01231 PI17/0184

Shedding light on motor premanifest myotonic dystrophy type 1: A molecular, muscular and central nervous system follow-up study

Background and purpose Myotonic dystrophy type 1 (DM1) is a hereditary and multisystemic disease that is characterized by heterogeneous manifestations. Although muscular impairment is central to DM1, a premanifest DM1 form has been proposed for those characterized by the absence of muscle signs in precursory phases. Nevertheless, subtle signs and/or symptoms related to other systems, such as the central nervous system (CNS), may emerge and progress gradually. This study aimed to validate the premanifest DM1 concept and to characterize and track affected individuals from a CNS centred perspective. Methods Retrospective data of 120 participants (23 premanifest DM1, 25 manifest DM1 and 72 healthy controls) were analysed transversally and longitudinally (over 11.17 years). Compiled data included clinical, neuropsychological and neuroradiological (brain volume and white matter lesion, WML) measures taken at two time points. Results Manifest DM1 showed significantly more molecular affectation, worse performance on neuropsychological domains, lower grey and white matter volumes and a different pattern of WMLs than premanifest DM1. The latter was slightly different from healthy controls regarding brain volume and WMLs. Additionally, daytime sleepiness and molecular expansion size explained 50% of the variance of the muscular deterioration at follow-up in premanifest individuals. Conclusions Premanifest DM1 individuals showed subtle neuroradiological alterations, which suggests CNS involvement early in the disease. Based on follow-up data, a debate emerges around the existence of a ‘non-muscular DM1’ subtype and/or a premanifest phase, as a precursory stage to other DM1 manifestations.This work was supported by the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (Ref: 609), from the Institute of Health Carlos III co-founded by Fondo Europeo de Desarrollo Regional (PI17/01231 to A.S.; PI17/01841 to A.L.); Basque Government (S-PE13UN030 to A.S.); and University of the Basque Country (UPV/EHU) (PIF 20/238 to J.G.; GU 20/057 to J.G., G.L. and A.S.)

White matter integrity changes and neurocognitive functioning in adult-late onset DM1: a follow-up DTI study

[EN] Myotonic Dystrophy Type 1 (DM1) is a multisystemic disease that affects gray and white matter (WM) tissues. WM changes in DM1 include increased hyperintensities and altered tract integrity distributed in a widespread manner. However, the precise temporal and spatial progression of the changes are yet undetermined. MRI data were acquired from 8 adult- and late-onset DM1 patients and 10 healthy controls (HC) at two different timepoints over 9.06 years. Fractional anisotropy (FA) and mean diffusivity (MD) variations were assessed with Tract-Based Spatial Statistics. Transversal and longitudinal intra- and intergroup analyses were conducted, along with correlation analyses with clinical and neuropsychological data. At baseline, reduced FA and increased MD values were found in patients in the uncinate, anterior-thalamic, fronto-occipital, and longitudinal tracts. At follow-up, the WM disconnection was shown to have spread from the frontal part to the rest of the tracts in the brain. Furthermore, WM lesion burden was negatively correlated with FA values, while visuo-construction and intellectual functioning were positively correlated with global and regional FA values at follow-up. DM1 patients showed a pronounced WM integrity loss over time compared to HC, with a neurodegeneration pattern that suggests a progressive anterior–posterior disconnection. The visuo-construction domain stands out as the most sensitive neuropsychological measure for WM microstructural impairment.The present study has been supported by funding from the Institute of Health Carlos III co-founded by Fondo Europeo de Desarrollo Regional-FEDER [Grant Numbers PI17/01231 and PI17/01841], CIBERNED (Grant Number: 609), the Basque Government [SAIO08-PE08BF01] and the University of the Basque Country (Neurosciences group: GIU20-057). BC was supported by a predoctoral grant from the Basque Government [PRE-2020-1-0187]. AJM was supported by a predoctoral grant from the Basque Government [PRE-2019-1-0070]. JG was supported by a predoctoral grant from the University of the Basque Country [PIF20/238]

Cerebrospinal Fluid 7-Ketocholesterol Level is Associated with Amyloid-β42 and White Matter Microstructure in Cognitively Healthy Adults

Background:Abnormal cholesterol metabolism changes the neuronal membrane and may promote amyloidogenesis. Oxysterols in cerebrospinal fluid (CSF) are related to Alzheimer’s disease (AD) biomarkers in mild cognitive impairment and dementia. Cholesterol turnover is important for axonal and white matter (WM) microstructure maintenance. Objective:We aim to demonstrate that the association of oxysterols, AD biomarkers, and WM microstructure occurs early in asymptomatic individuals. Methods:We studied the association of inter-individual variability of CSF 24-hydroxycholesterol (24-OHC), 27-hydroxycholesterol (27-OHC), 7-ketocholesterol (7-KC), 7β-hydroxycholesterol (7β-OHC), amyloid-β42 (Aβ42), total-tau (t-tau), phosphorylated-tau (p-tau), neurofilament (NfL), and WM microstructure using diffusion tensor imaging, generalized linear models and moderation/mediation analyses in 153 healthy adults. Results:Higher 7-KC levels were related to lower Aβ42, indicative of greater AD pathology (p = 0.041) . Higher 7-KC levels were related to lower fractional anisotropy (FA) and higher mean (MD), axial (AxD), and radial (RD) diffusivity. 7-KC modulated the association between AxD and NfL in the corpus callosum splenium (B = 39.39, p = 0.017), genu (B = 68.64, p = 0.000), and fornix (B = 10.97, p = 0.000). Lower Aβ42 levels were associated to lower FA and higher MD, AxD, and RD in the fornix, corpus callosum, inferior longitudinal fasciculus, and hippocampus. The association between AxD and Aβ42 was moderated by 7K-C (p = 0.048). Conclusion:This study adds clinical evidence to support the role of 7K-C on axonal integrity and the involvement of cholesterol metabolism in the Aβ42 generation process

PR-LncRNA Signature Regulates Glioma Cell Activity Through Expression of SOX Factors

Long non-coding RNAs (LncRNAs) have emerged as a relevant class of genome regulators involved in a broad range of biological processes and with important roles in tumor initiation and malignant progression. We have previously identified a p53-regulated tumor suppressor signature of LncRNAs (PR-LncRNAs) in colorectal cancer. Our aim was to identify the expression and function of this signature in gliomas. We found that the expression of the four PR-LncRNAs tested was high in human low-grade glioma samples and diminished with increasing grade of disease, being the lowest in glioblastoma samples. Functional assays demonstrated that PR-LncRNA silencing increased glioma cell proliferation and oncosphere formation. Mechanistically, we found an inverse correlation between PR-LncRNA expression and SOX1, SOX2 and SOX9 stem cell factors in human glioma biopsies and in glioma cells in vitro. Moreover, knock-down of SOX activity abolished the effect of PR-LncRNA silencing in glioma cell activity. In conclusion, our results demonstrate that the expression and function of PR-LncRNAs are significantly altered in gliomagenesis and that their activity is mediated by SOX factors. These results may provide important insights into the mechanisms responsible for glioblastoma pathogenesis.PA, JA-I and AS-A were recipients of a predoctoral fellowship from the Spanish Association Against Cancer (AECC Gipuzkoa), Basque Government and Instituto Salud Carlos III. This work was supported by grants from the Carlos III Institute of Health and the European Regional Development Fund (PI13/02277, CP16/00039, DTS16/084, and PI16/01580) and Industry and Health Departments of the Basque Country

Smelling fit: scent marking exposes parasitic infection status in the banded mongoose

Preference for uninfected mates is presumed beneficial as it minimizes one’s risk of contracting an infection and infecting one’s offspring. In avian systems, visual ornaments are often used to indicate parasite burdens and facilitate mate choice. However, in mammals, olfactory cues have been proposed to act as a mechanism allowing potential mates to be discriminated by infection status. The effect of infection upon mammalian mate choice is mainly studied in captive rodents where experimental trials support preference for the odors of uninfected mates and some data suggest scent marking is reduced in individuals with high infection burdens. Nevertheless, whether such effects occur in nonmodel and wild systems remains poorly understood. Here, we investigate the interplay between parasite load (estimated using fecal egg counts) and scent marking behavior in a wild population of banded mongooses Mungos mungo. Focusing on a costly protozoan parasite of the genus Isospora and the nematode worm Toxocara, we first show that banded mongooses that engage in frequent, intensive scent marking have lower Isospora loads, suggesting marking behavior may be an indicator trait regarding infection status. We then use odor presentations to demonstrate that banded mongooses mark less in response to odors of opposite sexed individuals with high Isospora and Toxocara loads. As both of these parasites are known to have detrimental effects upon the health of preweaned young in other species, they would appear key targets to avoid during mate choice. Results provide support for scent as an important ornament and mechanism for advertising parasitic infection within wild mammals