The spanish intergenerational study : beliefs, stereotypes, and metacognition about older people and grandparents to tackle ageism

Funding: The work received support from Memorial Mercedes Llort Sender 2021/80/09241941/4.Ageism can be seen as systematic stereotypes, prejudice, and discrimination of people because of their age. For a long time, society has accepted negative stereotypes as a norm. When referring to older adults, the United Nations Global Report on Ageism warns about a severe impact. The Intergenerational Study for a Healthy Aging, a questionnaire about believes, stereotypes, and knowledge about older people and grandparents, was administered to 326 Spanish biology and medical students. Here we report the results of stereotype analysis through adjective qualification of the youth and older people performed before the survey. Content analysis of two open questions about metacognition at the end of the survey is also presented. The results show that: (1) The questionnaire promoted metacognition; (2) Positive metacognition toward grandparents was higher than for the general old population; (3) Most participants were not conscious about ageism; (4) Gender was a key factor-male students were more ageist than females; (5) The feeling of guilt was higher in the questionnaire about older people; (6) The metacognition exercise elicited thoughts and, in few cases, the need to take action to tackle ageism. In conclusion, both activities promoted active thoughts about older people vs. grandparents and helped participants realize unconscious ageism-specifically toward the older population-serving as an awareness activity that may help tackle ageism

A comprehensive systematic review of CSF proteins and peptides that defne Alzheimer’s disease

Background: During the last two decades, over 100 proteomics studies have identifed a variety of potential bio‑ markers in CSF of Alzheimer’s (AD) patients. Although several reviews have proposed specifc biomarkers, to date, the statistical relevance of these proteins has not been investigated and no peptidomic analyses have been generated on the basis of specifc up- or down- regulation. Herein, we perform an analysis of all unbiased explorative proteom‑ ics studies of CSF biomarkers in AD to critically evaluate whether proteins and peptides identifed in each study are consistent in distribution; direction change; and signifcance, which would strengthen their potential use in studies of AD pathology and progression. Methods: We generated a database containing all CSF proteins whose levels are known to be signifcantly altered in human AD from 47 independent, validated, proteomics studies. Using this database, which contains 2022 AD and 2562 control human samples, we examined whether each protein is consistently present on the basis of reliable statistical studies; and if so, whether it is over- or under-represented in AD. Additionally, we performed a direct analysis of available mass spectrometric data of these proteins to generate an AD CSF peptide database with 3221 peptides for further analysis. Results: Of the 162 proteins that were identifed in 2 or more studies, we investigated their enrichment or depletion in AD CSF. This allowed us to identify 23 proteins which were increased and 50 proteins which were decreased in AD, some of which have never been revealed as consistent AD biomarkers (i.e. SPRC or MUC18). Regarding the analysis of the tryptic peptide database, we identifed 87 peptides corresponding to 13 proteins as the most highly consistently altered peptides in AD. Analysis of tryptic peptide fngerprinting revealed specifc peptides encoded by CH3L1, VGF, SCG2, PCSK1N, FBLN3 and APOC2 with the highest probability of detection in AD. Conclusions: Our study reveals a panel of 27 proteins and 21 peptides highly altered in AD with consistent statistical signifcance; this panel constitutes a potent tool for the classifcation and diagnosis of AD

Performance of Screening Strategies for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease: Results from the ENEIDA Registry of GETECCU

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-gamma-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18-20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50-0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66-0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20-22%] vs. 14% [95% CI 13-16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients

BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 +/- 12 vs. 54 +/- 16 years, p < 0.001), had been diagnosed younger (31 +/- 12 vs. 36 +/- 15 years, p < 0.001), and had a shorter disease duration (14 +/- 7 vs. 18 +/- 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe

El mapa hidrogeológico continuo de la provincia de Granada: una herramienta al servicio de los usuarios

Congreso Ibérico sobre Agua Subterránea, Medio Ambiente, Salud y Patrimonio (2018. Salamanca)En el marco del actual Convenio Específico de Colaboración establecido entre el Instituto Geológico y Minero de España y la Diputación Provincial de Granada se ha realizado el mapa hidrogeológico continuo georreferenciado de la Provincia de Granada. El objetivo ha sido actualizar y mejorar el existente dentro del Atlas Hidrogeológico de la Provincia de Granada elaborado en el año 1990. Este mapa utiliza la base cartográfica geológica del IGME, a escala 1:50.000 del proyecto GEODE, y en él se delimitan las diferentes masas de agua subterránea tanto para la Demarcación Hidrográfica del Guadalquivir como para la Mediterránea Andaluza; se definen las litologías; se establece una leyenda de permeabilidades de los materiales y se incluyen los puntos de agua subterránea más significativos. El mapa está compuesto por archivos con formato shapefile y sus metadatos e incluye un fichero mxd de ArcGis con sus correspondientes capas para la correcta simbolización de los datos. Con este mapa se pone a disposición de los usuarios una herramienta digital, que será acoplada al sistema de información geográfica SIGGRA de la web de la Diputación Provincial de Granada. Próximamente se estudiará su implementación para la consulta desde dispositivos móviles.Unidad de Granada, Instituto Geológico y Minero de España, EspañaDiputación Provincial de Granada, Españ

Biological Significance of the Protein Changes Occurring in the Cerebrospinal Fluid of Alzheimer’s Disease Patients: Getting Clues from Proteomic Studies

The fact that cerebrospinal fluid (CSF) deeply irrigates the brain together with the relative simplicity of sample extraction from patients make this biological fluid the best target for biomarker discovery in neurodegenerative diseases. During the last decade, biomarker discovery has been especially fruitful for the identification new proteins that appear in the CSF of Alzheimer’s disease (AD) patients together with amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau). Thus, several proteins have been already stablished as important biomarkers, due to an increase (i.e., CHI3L1) or a decrease (i.e., VGF) in AD patients’ CSF. Notwithstanding this, only a deep analysis of a database generated with all the changes observed in CSF across multiple proteomic studies, and especially those using state-of-the-art methodologies, may expose those components or metabolic pathways disrupted at different levels in AD. Deep comparative analysis of all the up- and down-regulated proteins across these studies revealed that 66% of the most consistent protein changes in CSF correspond to intracellular proteins. Interestingly, processes such as those associated to glucose metabolism or RXR signaling appeared inversely represented in CSF from AD patients in a significant manner. Herein, we discuss whether certain cellular processes constitute accurate indicators of AD progression by examining CSF. Furthermore, we uncover new CSF AD markers, such as ITAM, PTPRZ or CXL16, identified by this study

Human amyloid-β enriched extracts: evaluation of in vitro and in vivo internalization and molecular characterization

[Background]: Intracerebral inoculation of extracts from post-mortem human Alzheimer’s disease brains into mice produces a prion-like spreading effect of amyloid-β. The differences observed between these extracts and the synthetic peptide, in terms of amyloid-β internalization and seed and cell-to-cell transmission of cytosolic protein aggregates, suggest that brain extracts contain key contributors that enhance the prion-like effect of amyloid-β. Nevertheless, these potential partners are still unknown due to the complexity of whole brain extracts.[Methods]: Herein, we established a method based on sequential detergent solubilization of post-mortem samples of human brains affected by Alzheimer’s disease that strongly enrich amyloid-β aggregates by eliminating 92% of the remaining proteins. Internalization of Aβ1–42 from the enriched AD extracts was evaluated in vitro, and internalization of fluorescent-labeled AD extracts was also investigated in vivo. Furthermore, we carried out a molecular characterization of the Aβ-enriched fraction using label-free proteomics, studying the distribution of representative components in the amygdala and the olfactory cortex of additional human AD brain samples by immunohistochemistry.[Results]: Aβ1–42 from the enriched AD extracts are internalized into endothelial cells in vitro after 48 h. Furthermore, accumulation of fluorescent-labeled Aβ-enriched extracts into mouse microglia was observed in vivo after 4 months of intracerebral inoculation. Label-free proteomics (FDR < 0.01) characterization of the amyloid-β-enriched fraction from different post-mortem samples allowed for the identification of more than 130 proteins, several of which were significantly overrepresented (i.e., ANXA5 and HIST1H2BK; p < 0.05) and underrepresented (i.e., COL6A or FN1; p < 0.05) in the samples with Alzheimer’s disease. We were also able to identify proteins exclusively observed in Alzheimer’s disease (i.e., RNF213) or only detected in samples not affected by the disease (i.e., CNTN1) after the enrichment process. Immunohistochemistry against these proteins in additional tissues revealed their particular distribution in the amygdala and the olfactory cortex in relation to the amyloid-β plaque.[Conclusions]: Identification and characterization of the unique features of these extracts, in terms of amyloid-β enrichment, identification of the components, in vitro and in vivo cell internalization, and tissue distribution, constitute the best initial tool to further investigate the seeding and transmissibility proposed in the prion-like hypothesis of Alzheimer’s disease.Sponsored by the Spanish Ministry of Economy and Competitiveness-FEDER (grant # SAF2016-75768-R) to AMM, MINECO-RETOS (AEI-FEDER) to MDP, and the Autonomous Government of Castilla-La Mancha/FEDER (grant no. SBPLY/ 17/180501/000430) to AMM and DSS.Peer reviewe

Coenzyme Q₁₀ Protects Human Endothelial Cells from β-Amyloid Uptake and Oxidative Stress-Induced Injury

<div><p>Neuropathological symptoms of Alzheimer's disease appear in advances stages, once neuronal damage arises. Nevertheless, recent studies demonstrate that in early asymptomatic stages, ß-amyloid peptide damages the cerebral microvasculature through mechanisms that involve an increase in reactive oxygen species and calcium, which induces necrosis and apoptosis of endothelial cells, leading to cerebrovascular dysfunction. The goal of our work is to study the potential preventive effect of the lipophilic antioxidant coenzyme Q (CoQ) against ß-amyloid-induced damage on human endothelial cells. We analyzed the protective effect of CoQ against Aβ-induced injury in human umbilical vein endothelial cells (HUVECs) using fluorescence and confocal microscopy, biochemical techniques and RMN-based metabolomics. Our results show that CoQ pretreatment of HUVECs delayed Aβ incorporation into the plasma membrane and mitochondria. Moreover, CoQ reduced the influx of extracellular Ca²⁺, and Ca²⁺ release from mitochondria due to opening the mitochondrial transition pore after β-amyloid administration, in addition to decreasing O₂^.− and H₂O₂ levels. Pretreatment with CoQ also prevented ß-amyloid-induced HUVECs necrosis and apoptosis, restored their ability to proliferate, migrate and form tube-like structures <i>in vitro</i>, which is mirrored by a restoration of the cell metabolic profile to control levels. CoQ protected endothelial cells from Aβ-induced injury at physiological concentrations in human plasma after oral CoQ supplementation and thus could be a promising molecule to protect endothelial cells against amyloid angiopathy.</p></div