Alberto Sols Biomedical Research Institute
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Measurement and sampling noise undermine inferences about awareness in location probability learning: A modeling approach
No full textOccasionally, experimental psychologists enter into the realm of psychometrics without being fully aware of the risks involved in the study of individual differences. Here we re-assess the many studies on the interaction between memory and attention in location probability learning that suggest that people can unconsciously learn to suppress salient but irrelevant distractors frequently presented in a certain location. In the additional singleton task, one of the arguments to support this claim is that suppression in memory-guided visual search does not significantly differ between “aware” and “unaware” participants. Although rarely acknowledged, this null interaction could also result if the data are contaminated by measurement and/or sampling noise. Unfortunately, the reliability of the awareness measure cannot be assessed with standard methods, since it is a single-trial test. In the present study we offer model-based estimations of measurement and sampling noise in empirical data. Our goal is to determine how often researchers would mistakenly conclude that learning is unconscious, given data from a model based on the opposite claim (i.e., that learning is conscious) but including noise in participants’ search times and awareness responses. To do so, we fitted this noisy conscious model to a dataset involving 159 participants who performed the additional singleton task. Estimated parameters from this model were used, first, to predict the observed pattern of results and, second, to simulate new responses and participants. Results suggest that, under reasonable measurement noise and sample sizes, simulated evidence from the model can paradoxically but falsely support arguments used to defend the unconscious learning hypothesis. This study serves as an illustration to experimental psychologists – particularly those investigating memory and learning – of the risks of neglecting basic psychometric requirements in individual differences researchAFM was supported by PhD fellowship PRE2021-097654 from the Spanish Ministry of Science and Innovation. FVC was supported by PhD fellowship PRE2018-085148 from Ministerio de Ciencia e Innovación. DRS was supported by grant ES/Y002482/1 from the UK Economic and Social Research Council. MAV was supported by grants PID2020118583 GB-I00 and CNS2022-135346 from Agencia Estatal de Investigación / FEDER U
Unlocking adolescence: A novel approach to approximate the socio-cultural implications of puberty in medieval Spain
No full textIntroduction: The objectives of this investigation were to study puberty in medieval adolescents from northern Spain and use funerary archaeology data to explore the social implications of adolescence within this community.Method: The pubertal development of 37 skeletons (aged 8–25 years) from Marialba de la Ribera (León, Spain, 3rd to 15thcenturies AD) was assessed, with 32 assigned a pubertal stage. Using this information in conjunction with burial location, the relationship between physical maturity and social identity was considered. Results: Onset of the pubertal growth spurt was observed to occur between 10 and 12 years, but delays in reaching the later pubertal stages resulted in extended adolescent growth. Menarche age was placed at 16 years. Developmental patterns observed suggest delays compared with modern adolescents but were similar to other past populations. Regarding cemetery distribution, most individuals who died while prepubescent or in the early puberty stages were buried within the children's section, while those in later puberty or post puberty were not.Conclusion: Growth deceleration appears to have been the point at which individuals were no longer considered children in this population. This stage marks a critical turning point in pubertal development because, although not fully mature, adolescents exhibit physical characteristics resembling those of adults and are able to undertake tasks and fulfill roles typically reserved for adulthood. Exploring social roles shaped by the biological life cycle facilitates a deeper understanding of not only the adolescents themselves but also the communities to which they belonged and may be the only way to truly approximate adolescence in past populationsThe Laboratorio de Poblaciones del Pasado (LAPP) has been supported by the following projects: Leaky Foundation 38360, Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España HAR2017-83004-P, Ministerio de Ciencia, Innovación y Universidades PGC2018- 099405-B-100, HAR2016-74846-P, Ministerio de Economía, Industria y Competitividad HAR2016-78036-P, HAR2017-82755-P, Comunidad de Madrid SI4/PJI/2024-0010
Targeting CB2 receptor with a novel antagonist reverses cognitive decline, neurodegeneration and pyroptosis in a TAU-dependent frontotemporal dementia mouse model
No full textFrontotemporal dementia (FTD) comprises a group of disorders characterized by a progressive decline in behavior or language linked to the degeneration of the frontal and anterior temporal lobes followed by hippocampal atrophy. There are no effective treatments for FTD and for this reason, novel pharmacological targets, such as the endocannabinoid system (ECS), are being explored. Previous results from our laboratory showed a TAUP301L-dependent increase in CB2 receptor expression in hippocampal neurons of a FTD mouse model, alongside the neuroprotective impact of CB2 ablation. In this study, we evaluated the therapeutic potential of a new CB2 antagonist (PGN36) in our TAU-dependent FTD mouse model. Six-month-old mice received stereotaxic injections of an adeno-associated virus expressing human TAUP301L protein (AAV-TAUP301L) into the right hippocampus and were treated daily with PGN36 (5 mg/kg, i.p.) or vehicle for three weeks. By integrating behavioral tests, RNA-seq, qPCR expression analysis, and immunofluorescence in the AAV expressing TAU mouse model, we found that PGN36 treatment reverses key features of the neurodegenerative process triggered by TAUP301L overexpression. PGN36 treatment effectively countered TAUP301L-induced cognitive decline by reducing TAU protein expression levels and restoring markers of synaptic plasticity. Notably, we observed neuroprotection in the dentate gyrus granular layer, which we attribute to the modulation of pyroptosis. This programmed cell death pathway, is triggered by TAUP301L overexpression. PGN36 appears to modulate the pyroptotic cascade, thereby preventing the pyroptosis-induced neuronal loss. These findings collectively underscore the neuroprotective potential of this novel CB2 antagonist treatment against TAU-associated FTDThis work was supported by Fundación Tatiana Pérez de Guzmán el Bueno, MINECO (grants PID2019-105600RB-I00 and PID2022- 137065OB-I00 to I.L-B and PDC2022-133809-I00 to MGL), ISCiii CIBERNED (CB06/05/0089 to I. L-B.) and Community of Madrid ref CAM-P2022/BMD-7230 to MGL. FPU18/00630 contract to E
Middle Cerebral Artery M2 Occlusions: Impact of Segment Dominance and Benefit of Direct Aspiration for the First-Pass Effect
No full textBackground and Purpose: Endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) with M2 segment occlusion of the middle cerebral artery (MCA) is debatable. This study assessed the efficacy, safety, and functional outcomes of EVT in M2 occlusion patients, examining differences in outcomes based on the dominance of the occluded segment (DomM2 vs. Non-DomM2). Methods: A prospective cohort of 108 patients with AIS resulting from M2 segment occlusion of the MCA who underwent EVT was analyzed. We compared demographic, clinical, angiographic, and clinical outcome data (National Institutes of Health Stroke Scale [NIHSS] score at 24 h and modified Rankin Scale [mRS] score at 3 months) between patients with or without DomM2. The primary endpoint was the first-pass effect (FPE), defined as achieving modified Thrombolysis in Cerebral Infarction 2c–3 after one pass. We examined the symptomatic hemorrhagic transformation, 3-month functional outcomes, and mortality rates. Results: Seventy-five patients (69.44%) had DomM2. FPE rates (48.48% for DomM2; 42.66% for Non-DomM2, p = 0.521), final successful recanalization rate, and functional outcomes were comparable between subgroups. Direct aspiration yielded a higher FPE rate (56.25%). FPE was associated with lower NIHSS scores at discharge (median, 2 [interquartile range 0–4] vs. 5 [1–10]; p < 0.001) and higher 3-month functional independence (83.33% vs. 60.34%; p < 0.001). Direct aspiration independently predicted FPE, with a 75% likelihood compared to stent retriever (p = 0.007). Conclusions: EVT is a safe and effective treatment for acute M2 occlusion regardless of the dominance of the M2 segment. Direct aspiration used as a frontline technique increases the likelihood of FP
Prevalence and Economic Impact of Acute Respiratory Failure in the Prehospital Emergency Medical Service of the Madrid Community: Retrospective Cohort Study
No full textBackground: Chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and acute pulmonary edema (APE) are serious illnesses that often require acute care from prehospital emergency medical services (EMSs). These respiratory diseases that cause acute respiratory failure (ARF) are one of the main reasons for hospitalization and death, generating high health care costs. The prevalence of the main respiratory diseases treated in a prehospital environment in the prepandemic period and during the COVID-19 pandemic in Spain is unknown. The Madrid Community EMS is a public service that serves all types of populations and represents an epidemiological reference for supporting a population of 6.4 million inhabitants. The high volume of patients treated by Madrid’s medical advanced life supports (ALSs) allows us to analyze this little-studied problem. Objectives: Our goal was to lay the groundwork for comprehensive data collection and surveillance of respiratory failure, with an emphasis on the most prevalent diseases that cause it, an aspect that has been largely overlooked in previous initiatives. By achieving these objectives, we hope to inform efforts to address respiratory failure and establish a standardized methodology and framework that can facilitate expansion to a continuous community-wide registry in Madrid, driving advances in emergency care and care practices in these pathologies. The aim of this retrospective observational study was to determine the pathologies that have mainly caused respiratory failure in patients and required medicalized ALS and to evaluate the cost of care for these pathologies collected through this pilot registry. Methods: A multicenter descriptive study was carried out in the Madrid Community EMS. The anonymized medical records of patients treated with medical ALS, who received any of the following medical diagnoses, were extracted: ARF not related to chronic respiratory disease, ARF in chronic respiratory failure, exacerbations of COPD, APE, CHF, and bronchospasm (not from asthma or COPD). The prevalence of each pathology, its evolution from 2014 to 2020, and the economic impact of the Medical ALSs were calculated. Results: The study included 96,221 patients. The most common pathology was exacerbation of COPD, with a prevalence of 0.07% in 2014; it decreased to 0.03% in 2020. CHF followed at 0.06% in 2014 and 0.03% in 2020. APE had a prevalence of 0.01% in 2014, decreasing to 0.005% in 2020 with the pandemic. The greatest economic impact was on exacerbation of COPD in 2015, with an annual cost of €2,726,893 (which equals to US 61,832,879)Funding for open-access publishing was provided by the FIIBAP (grant 883345
Propionic acidemia‐induced proarrhythmic electrophysiological alterations in human iPSC‐derived cardiomyocytes
No full textPropionic acidemia (PA) is a metabolic disorder caused by a deficiency of the mitochondrial enzyme propionyl-CoA carboxylase (PCC) due to mutations in the PCCA or PCCB genes, which encode the two PCC subunits. PA may lead to several types of cardiomyopathy and has been linked to cardiac electrical abnormalities such as QT interval prolongation, life-threatening arrhythmias, and sudden cardiac death. To gain insights into the mechanisms underlying PA-induced proarrhythmia, we recorded action potentials (APs) and ion currents using whole-cell patch-clamp in ventricular-like induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) from a PA patient carrying two pathogenic mutations in the PCCA gene (p.Cys616_Val633del and p.Gly477Glufs*9) (PCCA cells) and from a healthy subject (healthy cells). In cells driven at 1 Hz, PCC deficiency increased the latency and prolonged the AP duration (APD) measured at 20% of repolarization, without modifying resting membrane potential or AP amplitude. Moreover, delayed afterdepolarizations appeared at the end of the repolarization phase in unstimulated and paced PCCA cells. PCC deficiency significantly reduced peak sodium current (INa) but increased the late INa (INaL) component. In addition, L-type Ca2+ current (ICaL) density was reduced, while the inward and outward density of the Na+/Ca2+ exchanger current (INCX) was increased in PCCA cells compared to healthy ones. In conclusion, our results demonstrate that at the cellular level, PCC deficiency can modify the ion currents controlling cardiac excitability, APD, and intracellular Ca2+ handling, increasing the risk of arrhythmias independently of the progressive late-onset cardiomyopathy induced by PA diseaseThis work was supported by Propionic Acidemia Foundation, PAF113; Instituto de Salud Carlos III, CB16/11/00303; Ministerio de Ciencia, Innovación y Universidades, PID2020118694RBI00, PID2022137238OB100, PID2023150993OBI00; Comunidad de Madrid, ARCADIA S2022/BMD7229; Fundación Ramón Areces, XX National Call 202
Extractive distillation for separating short-chain alcohols from water using cyclic carbonates as an extractive solvent: Experimental and process simulation
No full textBioethanol has gained increasing importance in recent years due to the potential scarcity of fossil fuels and the urgent need to reduce CO2 emissions. Other light alcohols, such as bioisopropanol, have significant potential, like ethanol, as gasoline additives, while tert-butanol plays a crucial role in the chemical industry. However, a major challenge arises to each alcohol separation from water (the most common impurity) due to the presence of an azeotrope. Among the dehydration technologies for these alcohols, extractive distillation stands out as one of the most efficient operations due to its energy savings. On the other hand, cyclic carbonates derived from CO2 conversion processes have recently become very important as solvents for a wide range of applications. This work proposes the use of cyclic carbonates as extractive agents for separating various mixtures of light alcohol and water through extractive distillation. This work demonstrates the universality of this approach in terms of the cyclic carbonates applicability in a new system as well as their effectiveness for a series of light alcohols, for the first time. After preselecting and characterizing two cyclic carbonates, a whole process was designed to meet two purity levels for the three alcohols evaluated. Glycerol carbonate has shown to be a very competitive solvent, with energy consumption moving from 4000 to 11000 kJ/kg −depending on the alcohol type (tertbutyl alcohol < 2-propanol < ethanol) and purity assessed (0.99 < 0.995)-, confirming that cyclic carbonates are CO2-derived designer solvents capable of working well for polar mixturesThe authors are grateful to Ministerio de Ciencia e Innovación of Spain (project PID2023-150532OB-I00) and Comunidad de Madrid (project TEC-2024/BIO-27) for financial support and Centro de Computación Científica de la Universidad Autónoma de Madrid for computational facilities. A. Belinchón also thanks the Spanish Ministerio de Universidades for awarding him the FPI grant PRE2021-097533. Rubén Santiago thanks UNED-Santander for finantial support through the project: Ayudas a Investigadores Tempranos UNED-SANTANDER 202
Impacto de la valoración geriátrica integral y la presencia de fragilidad en la decisión clínica y la evolución de pacientes mayores intervenidos de cáncer colorrectal
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de Lectura: 04-03-202
Impact of remnant cholesterol and triglycerides on diabetes foot and disease in type 1 diabetes: A propensity score-matched case-control study
Get PDFObjective: Remnant cholesterol is an emerging cardiovascular risk factor; however, its impact on diabetes foot disease (DFD) remains poorly studied. This study evaluates the association between dyslipidaemia and DFD in a cohort of individuals with type 1 diabetes (T1D). Methods: A nested case–control study was conducted within a cohort of 419 individuals with T1D. DFD was defined as a history of peripheral arterial disease—such as prior lower limb revascularization or vascular-origin amputations—or as the presence of diabetic foot according to the Wagner classification. Clinical and sociodemographic data were collected, and a 1:2 propensity score matching was performed based on age, sex, diabetes duration, smoking status, HbA1c, diabetic retinopathy, and nephropathy. Conditional logistic regression models were used to evaluate the association between dyslipidemia and DFD, adjusting for confounding variables. Results: Of the 419 subjects, 56 (13.4 %) had DFD. After matching, 17 subjects were excluded, leaving 39 cases and 78 controls (n = 117). The mean age was 61.6 ± 14.3 years, 40.2 % were women, and the mean diabetes duration was 30.0 ± 14.4 years. Remnant cholesterol was significantly higher in cases (22 ± 10 mg/dL vs. 17 ± 11 mg/dL, p = 0.038), as were triglycerides (111 ± 49 mg/dL vs. 90 ± 65 mg/dL, p = 0.005). In multivariable analysis, remnant cholesterol (OR = 1.15, 95 % CI [1.03–1.27]) and triglycerides (OR = 1.03, 95 % CI [1.01–1.05]) were independently associated with DFD. Conclusion: Remnant cholesterol and triglycerides are associated with DFD in individuals with long-standing T1D and high cardiovascular risk. Prospective studies are needed to confirm these findingsThis work was funded by Proyectos de Investigacion en Salud PI19/ 00584, PI22/01404 and PMP22/00021 (funded by Instituto de Salud Carlos III), iTIRONET - P2022/BMD7379 (funded by Comunidad de Madrid), and co-financed by funds from the European Regional Development Fund (ERDF) to M
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Get PDFCurso de formación organizado por la Biblioteca en formato híbrido: presencial y en línea, dirigido a estudiantes de posgrado y PDI. El objetivo principal de esta formación es adquirir una visión general sobre el panorama actual del acceso abierto, y adquirir unas competencias básicas que le ayuden a seleccionar el mejor medio para publicar sus resultados de investigación en abiert