Skin does not care about crisis

OBJETIVO: Evaluar los productos hidratantes ofertados en las grandes superficies comerciales según la relación coste/efectividad y sus indicaciones

Challenges associated with biomarker-based classification systems for Alzheimer's disease

Altres ajuts: This work was also supported by research grants from the Carlos III Institute of Health, Spain and the CIBERNED program (Program 1, Alzheimer Disease to Alberto Lleó and SIGNAL study, www.signalstudy.es), partly funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, "Una manera de hacer Europa". This work has also been supported by a "Marató TV3" grant (20141210 to Juan Fortea and 044412 to Rafael Blesa) and by Generalitat de Catalunya and a grant from the Fundació Bancaria La Caixa to Rafael Blesa. I. Illán-Gala is supported by the i-PFIS grant from the FIS, Instituto de Salud Carlos III and the Rio Hortega grant (CM17/00074) from "Acción estratégica en Salud 2013-2016" and the European Social Fund. USPHS NIH grants awarded to M.J.d.L. include: AG13616, AG022374, AG12101, and AG057570.We aimed to evaluate the consistency of the A/T/N classification system. We included healthy controls, mild cognitive impairment, and dementia patients from Alzheimer's disease Neuroimaging Initiative. We assessed subject classification consistency with different biomarker combinations and the agreement and correlation between biomarkers. Subject classification discordance ranged from 12.2% to 44.5% in the whole sample; 17.3%-46.4% in healthy controls; 11.9%-46.5% in mild cognitive impairment, and 1%-35.7% in dementia patients. Amyloid, but not neurodegeneration biomarkers, showed good agreement both in the whole sample and in the clinical subgroups. Amyloid biomarkers were correlated in the whole sample, but not along the Alzheimer's disease continuum (as defined by a positive amyloid positron emission tomography). Neurodegeneration biomarkers were poorly correlated both in the whole sample and along the Alzheimer's disease continuum. The relationship between biomarkers was stage-dependent. Our findings suggest that the current A/T/N classification system does not achieve the required consistency to be used in the clinical setting

APP-derived peptides reflect neurodegeneration in frontotemporal dementia

Altres ajuts: The Catalan frontotemporal initiative (CATFI) is funded by the Health Department of the Government of Catalonia (grant PERIS SLT002/16/00408 to Alberto Lleó and Raquel Sánchez-Valle). This work was also supported by research grants from the CIBERNED Program (Program 1, Alzheimer Disease to Alberto Lleó and SIGNAL study, file://www.signalstudy.es), partly funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, "Una manera de hacer Europa." This work has also been supported by a "Marató TV3" grant (20141210 to Juan Fortea, 044412 to Rafael Blesa, 20143710 to Ricard Rojas-García and 20143810 to Raquel Sánchez-Valle) and Fundación BBVA (grant to A. Lleó) and a grant from the Fundació Bancaria La Caixa to Rafael Blesa. Ignacio Illán-Gala and Sergi Borrego-Écija are supported by the Rio Hortega grant from "Acción estratégica en Salud 2013-2016" and the European Social Fund. Ignacio Illán-Gala is supported by the Global Brain Health Institute (Atlantic Fellow for Equity in Brain Health). We acknowledge all the participants in this study and all the collaborators of the SPIN cohort. We also acknowledge Soraya Torres and Laia Muñoz for technical assistance. We thank EUROIMMUN for providing Aβ1-38 and Aβ1-40 ELISA assays for this study.Objective: We aimed to investigate the relationship between cerebrospinal fluid levels (CSF) of amyloid precursor protein (APP)-derived peptides related to the amyloidogenic pathway, cortical thickness, neuropsychological performance, and cortical gene expression profiles in frontotemporal lobar degeneration (FTLD)-related syndromes, Alzheimer's disease (AD), and healthy controls. Methods: We included 214 participants with CSF available recruited at two centers: 93 with FTLD-related syndromes, 57 patients with AD, and 64 healthy controls. CSF levels of amyloid β (Aβ)1-42, Aβ1-40, Aβ1-38, and soluble β fragment of APP (sAPPβ) were centrally analyzed. We compared CSF levels of APP-derived peptides between groups and, we studied the correlation between CSF biomarkers, cortical thickness, and domain-specific cognitive composites in each group. Then, we explored the relationship between cortical thickness, CSF levels of APP-derived peptides, and regional gene expression profile using a brain-wide regional gene expression data in combination with gene set enrichment analysis. Results: The CSF levels of Aβ1-40, Aβ1-38, and sAPPβ were lower in the FTLD-related syndromes group than in the AD and healthy controls group. CSF levels of all APP-derived peptides showed a positive correlation with cortical thickness and the executive cognitive composite in the FTLD-related syndromes group but not in the healthy control or AD groups. In the cortical regions where we observed a significant association between cortical thickness and CSF levels of APP-derived peptides, we found a reduced expression of genes related to synaptic function. Interpretation: APP-derived peptides in CSF may reflect FTLD-related neurodegeneration. This observation has important implications as Aβ1-42 levels are considered an indirect biomarker of cerebral amyloidosis

Plasma and cerebrospinal fluid glial fibrillary acidic protein levels in adults with Down syndrome: a longitudinal cohort study

Background: The diagnosis of symptomatic Alzheimer's disease is a clinical challenge in adults with Down syndrome. Blood biomarkers would be of particular clinical importance in this population. The astrocytic Glial Fibrillary Acidic Protein (GFAP) is a marker of astrogliosis associated with amyloid pathology, but its longitudinal changes, association with other biomarkers and cognitive performance have not been studied in individuals with Down syndrome. Methods: We performed a three-centre study of adults with Down syndrome, autosomal dominant Alzheimer's disease and euploid individuals enrolled in Hospital Sant Pau, Barcelona (Spain), Hospital Clinic, Barcelona (Spain) and Ludwig-Maximilians-Universität, Munich (Germany). Cerebrospinal fluid (CSF) and plasma GFAP concentrations were quantified using Simoa. A subset of participants had PET 18F-fluorodeoxyglucose, amyloid tracers and MRI measurements. Findings: This study included 997 individuals, 585 participants with Down syndrome, 61 Familial Alzheimer's disease mutation carriers and 351 euploid individuals along the Alzheimer's disease continuum, recruited between November 2008 and May 2022. Participants with Down syndrome were clinically classified at baseline as asymptomatic, prodromal Alzheimer's disease and Alzheimer's disease dementia. Plasma GFAP levels were significantly increased in prodromal and Alzheimer's disease dementia compared to asymptomatic individuals and increased in parallel to CSF Aβ changes, ten years prior to amyloid PET positivity. Plasma GFAP presented the highest diagnostic performance to discriminate symptomatic from asymptomatic groups (AUC = 0.93, 95% CI 0.9−0.95) and its concentrations were significantly higher in progressors vs non-progressors (p < 0.001), showing an increase of 19.8% (11.8–33.0) per year in participants with dementia. Finally, plasma GFAP levels were highly correlated with cortical thinning and brain amyloid pathology. Interpretation: Our findings support the utility of plasma GFAP as a biomarker of Alzheimer's disease in adults with Down syndrome, with possible applications in clinical practice and clinical trials. Funding: AC Immune, La Caixa Foundation, Instituto de Salud Carlos III, National Institute on Aging, Wellcome Trust, Jérôme Lejeune Foundation, Medical Research Council, Alzheimer's Association, National Institute for Health Research, EU Joint Programme–Neurodegenerative Disease Research, Alzheimer's Society, Deutsche Forschungsgemeinschaft, Stiftung für die Erforschung von Verhaltens, Fundación Tatiana Pérez de Guzmán el Bueno & European Union's Horizon 2020 und Umwelteinflüssen auf die menschliche Gesundheit

Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome

Background: Basal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS. Methods: We included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume. Results: In DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance. Discussion: BF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS

Cortical microstructure in primary progressive aphasia: a multicenter study

Cortical mean diffusivity is a novel imaging metric sensitive to early changes in neurodegenerative syndromes. Higher cortical mean diffusivity values reflect microstructural disorganization and have been proposed as a sensitive biomarker that might antedate macroscopic cortical changes. We aimed to test the hypothesis that cortical mean diffusivity is more sensitive than cortical thickness to detect cortical changes in primary progressive aphasia (PPA).In this multicenter, case-control study, we recruited 120 patients with PPA (52 non-fluent, 31 semantic, and 32 logopenic variants; and 5 GRN-related PPA) as well as 89 controls from three centers. The 3-Tesla MRI protocol included structural and diffusion-weighted sequences. Disease severity was assessed with the Clinical Dementia Rating scale. Cortical thickness and cortical mean diffusivity were computed using a surface-based approach.The comparison between each PPA variant and controls revealed cortical mean diffusivity increases and cortical thinning in overlapping regions, reflecting the canonical loci of neurodegeneration of each variant. Importantly, cortical mean diffusivity increases also expanded to other PPA-related areas and correlated with disease severity in all PPA groups. Cortical mean diffusivity was also increased in patients with very mild PPA when only minimal cortical thinning was observed and showed a good correlation with measures of disease severity.Cortical mean diffusivity shows promise as a sensitive biomarker for the study of the neurodegeneration-related microstructural changes in PPA.© 2022. The Author(s)

Espècie aviària: manual lesional de suport per al dictamen de carns fresques

Escorxador; Aviram; Pollastres; Carn: Control oficialMatadero; Aves de corral; Pollos; Carne: Control oficialSlaughterhouse; Poultry; Chickens; Meat: Official controlLa inspecció post mortem de les carns d’aviram que efectua el col·lectiu de veterinaris oficials d’escorxador és una part important dels controls oficials relatius a la carn fresca i, com a tal, és un dels elements que condiciona que es dictamini com a apta o no per al consum humà i que s’hagin de notificar les malalties de declaració obligatòria. Els escorxadors són entorns òptims per observar i registrar les particularitats de la variada patologia animal que s’hi presenta. Aquesta informació, si és compartida, pot esdevenir una eina molt útil i interessant per al col·lectiu de professionals. En conseqüència la comunitat de pràctica (CoP) ha realitzat aquest manual l’autoria del qual és de veterinaris oficials d’escorxador de la Generalitat de Catalunya. El contingut s’ha volgut transmetre per mitjà de fitxes que contenen informació científica, tècnica i legal per a cada una de les malalties i lesions que s’hi descriuen. Alhora, les fitxes s’il·lustren amb imatges obtingudes a diferents escorxadors d’aviram de Catalunya. El propòsit és que les fitxes puguin ser un suport pràctic per a la inspecció post mortem i una ajuda per al dictamen. Per això, s’ha procurat establir un posicionament vers el dictamen de les carns amb els motius desenvolupats de la manera més concreta possible. Cal dir que en alguns casos no ha estat possible obtenir imatges que il·lustrin algunes de les lesions o malalties que s’hi defineixen.La inspección post mortem de las carnes de aves de corral que efectúa el colectivo de veterinarios oficiales de matadero es una parte importante de los controles oficiales relativos a la carne fresca y, como tal, es uno de los elementos que condiciona que se dictamine como a apta o no para el consumo humano y que deban notificarse las enfermedades de declaración obligatoria. Los mataderos son entornos óptimos para observar y registrar las particularidades de la variada patología animal que se presenta. Esta información, si es compartida, puede convertirse en una herramienta muy útil e interesante para el colectivo de profesionales. En consecuencia, la comunidad de práctica (CoP) ha realizado este manual cuya autoría es de veterinarios oficiales de matadero de la Generalitat de Catalunya. El contenido se ha querido transmitir por medio de fichas que contienen información científica, técnica y legal para cada una de las enfermedades y lesiones que se describen. Asimismo, las fichas se ilustran con imágenes obtenidas en diferentes mataderos de aves de corral de Cataluña. El propósito es que las fichas puedan ser un soporte práctico para la inspección post mortem y una ayuda para el dictamen. Por eso, se ha procurado establecer un posicionamiento hacia el dictamen de las carnes con los motivos desarrollados de la forma más concreta posible. Hay que decir que en algunos casos no ha sido posible obtener imágenes que ilustren algunas de las lesiones o enfermedades que se definen.The post mortem inspection of poultry meat carried out by the group of official slaughterhouse veterinarians is an important part of the official controls related to fresh meat and, as such, is one of the elements that determines whether it is ruled as a suitable or not for human consumption and that notifiable diseases must be notified. Slaughterhouses are optimal environments to observe and record the particularities of the varied animal pathology that occurs. This information, if shared, can become a very useful and interesting tool for the group of professionals. Consequently, the community of practice (CoP) has produced this manual authored by official slaughterhouse veterinarians of the Generalitat de Catalunya. The content has been conveyed through sheets containing scientific, technical and legal information for each of the diseases and injuries described. Likewise, the sheets are illustrated with images obtained in different poultry slaughterhouses in Catalonia. The purpose is that the cards can be a practical support for the post mortem inspection and an aid for the opinion. For this reason, an attempt has been made to establish a position towards the opinion of meats with the reasons developed in the most concrete way possible. It must be said that in some cases it has not been possible to obtain images that illustrate some of the injuries or diseases that are defined

The era of reference genomes in conservation genomics

Progress in genome sequencing now enables the large-scale generation of reference genomes. Various international initiatives aim to generate reference genomes representing global biodiversity. These genomes provide unique insights into genomic diversity and architecture, thereby enabling comprehensive analyses of population and functional genomics, and are expected to revolutionize conservation genomics

Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome : a cross-sectional study

Altres ajuts: Instituto de Salud Carlos III, Fundació Bancaria La Caixa, Fundació La Marató de TV3, Medical Research Council, and National Institutes of Health.Alzheimer's disease and its complications are the leading cause of death in adults with Down syndrome. Studies have assessed Alzheimer's disease in individuals with Down syndrome, but the natural history of biomarker changes in Down syndrome has not been established. We characterised the order and timing of changes in biomarkers of Alzheimer's disease in a population of adults with Down syndrome. We did a dual-centre cross-sectional study of adults with Down syndrome recruited through a population-based health plan in Barcelona (Spain) and through services for people with intellectual disabilities in Cambridge (UK). Cognitive impairment in participants with Down syndrome was classified with the Cambridge Cognitive Examination for Older Adults with Down Syndrome (CAMCOG-DS). Only participants with mild or moderate disability were included who had at least one of the following Alzheimer's disease measures: apolipoprotein E allele carrier status; plasma concentrations of amyloid β peptides 1-42 and 1-40 and their ratio (Aβ), total tau protein, and neurofilament light chain (NFL); tau phosphorylated at threonine 181 (p-tau), and NFL in cerebrospinal fluid (CSF); and one or more of PET with 18 F-fluorodeoxyglucose, PET with amyloid tracers, and MRI. Cognitively healthy euploid controls aged up to 75 years who had no biomarker abnormalities were recruited from the Sant Pau Initiative on Neurodegeneration. We used a first-order locally estimated scatterplot smoothing curve to determine the order and age at onset of the biomarker changes, and the lowest ages at the divergence with 95% CIs are also reported where appropriate. Between Feb 1, 2013, and June 28, 2019 (Barcelona), and between June 1, 2009, and Dec 31, 2014 (Cambridge), we included 388 participants with Down syndrome (257 [66%] asymptomatic, 48 [12%] with prodromal Alzheimer's disease, and 83 [21%] with Alzheimer's disease dementia) and 242 euploid controls. CSF Aβ and plasma NFL values changed in individuals with Down syndrome as early as the third decade of life, and amyloid PET uptake changed in the fourth decade. 18 F-fluorodeoxyglucose PET and CSF p-tau changes occurred later in the fourth decade of life, followed by hippocampal atrophy and changes in cognition in the fifth decade of life. Prodromal Alzheimer's disease was diagnosed at a median age of 50·2 years (IQR 47·5-54·1), and Alzheimer's disease dementia at 53·7 years (49·5-57·2). Symptomatic Alzheimer's disease prevalence increased with age in individuals with Down syndrome, reaching 90-100% in the seventh decade of life. Alzheimer's disease in individuals with Down syndrome has a long preclinical phase in which biomarkers follow a predictable order of changes over more than two decades. The similarities with sporadic and autosomal dominant Alzheimer's disease and the prevalence of Down syndrome make this population a suitable target for Alzheimer's disease preventive treatments. Instituto de Salud Carlos III, Fundació Bancaria La Caixa, Fundació La Marató de TV3, Medical Research Council, and National Institutes of Health

Analysis of the P. lividus sea urchin genome highlights contrasting trends of genomic and regulatory evolution in deuterostomes

Sea urchins are emblematic models in developmental biology and display several characteristics that set them apart from other deuterostomes. To uncover the genomic cues that may underlie these specificities, we generated a chromosome-scale genome assembly for the sea urchin Paracentrotus lividus and an extensive gene expression and epigenetic profiles of its embryonic development. We found that, unlike vertebrates, sea urchins retained ancestral chromosomal linkages but underwent very fast intrachromosomal gene order mixing. We identified a burst of gene duplication in the echinoid lineage and showed that some of these expanded genes have been recruited in novel structures (water vascular system, Aristotle's lantern, and skeletogenic micromere lineage). Finally, we identified gene-regulatory modules conserved between sea urchins and chordates. Our results suggest that gene-regulatory networks controlling development can be conserved despite extensive gene order rearrangement