Emociones políticas y virtudes epidémicas en el siglo XVIII

El proyecto se propone abrir nuevas vías en la enseñanza de las Humanidades en la UCM mediante la práctica de una historia de las ideas del siglo XVIII que atiende a los condicionantes materiales de la cultura y a la valoración de las emociones como índices de construcción de imágenes de lo privado y lo público. El proyecto pretende, por un lado, explorar los mecanismos materiales de producción de ideas y creencias compartidas por la sociedad del siglo XVIII, teniendo en cuenta los diferentes contextos de la Ilustración Francesa, Alemana, Judía y Escocesa, con especial atención a la formación de metáforas políticas y a las emociones estéticamente más aceptadas y difundidas en la época analizada. La otra dimensión estudiada por el proyecto se refiere a los procesos de configuración de lo público y la crítica intelectual del poder, tomando como instrumento de análisis la comunicación de ideas materializada en la correspondencia, en la prensa, en los libros y en el proyecto de la Enciclopedia. Este programa de trabajo tendrá como principal destinatario el alumnado de Grado, Máster y Doctorado de la UCM, al que se invitará a las sesiones de trabajo del equipo, especialmente al matriculado en las asignaturas impartidas durante el curso 2016/17 por la IP. El proyecto reúne a destacados especialistas de la UCM y de otras universidades madrileñas y españolas, además de contar entre sus miembros con estudiantes de doctorado, que propiciarán la difusión de las actividades entre los estudiantes UCM, y con personal de administración y servicios, a los que se asignarán tareas relacionadas con la difusión y transferencia de los resultados del proyecto, a la sociedad, a la comunidad universitaria UCM y a los estudiantes Erasmus que reciba en el curso 2016/17 la Facultad de Filosofía de la UCM

Contrapicados y puntos de fuga. Las otras historias de la historia de la filosofía

Depto. de Lógica y Filosofía TeóricaFac. de FilosofíaFALSEsubmitte

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Improving Early Diagnosis of Child Neglect for a Better Response in Healthcare Settings

Early diagnosis of child neglect is an ongoing challenge with consequences of the child’s safety, health, and effective referral for intervention. This study aims to obtain a selected set of family, maternal, and dyadic variables of the immediate caregiving environment for diagnosis, preventive, and intervention responses in healthcare settings. Mothers and their children under five years old: 51 in the neglected group (NG) and 89 in the non-neglected control group (CG), were recruited through pediatric primary care services and social services in Spain. Family demographics, adverse events, childhood maltreatment, maternal psychopathologies, personality variables, and observed mother–child interactions were assessed. Gradient boosting analyses were applied for the contributor’s relative importance (RI), followed by logistic regression and discriminant analyses for those with higher RI. Parametric analyses showed high diagnostic accuracy (80–82% of NG and 92% of CG) for risky factors of child neglect: having a physically neglected and depressed mother, living in families in need of financial assistance, and large families; and for protective factors: having an older mother and showing higher mother–child emotional availability. Identifying a select group of features makes early diagnosis and preventive intervention more effective for mitigating the impact of child neglect and building mother–child resilience

Vieses na avaliação do choro infantil em negligência materna: o papel da alexitimia

This study analyzes the extent to which the subjective evaluation of infant crying in mothers with severe neglect is altered, and the possible influence of alexithymia on this alteration. Participants were 24 neglectful mothers and 22 control mothers who evaluated the faces of children and adult (crying and neutral) according to their valence and the approximation response elicited by them. The results indicate that both groups evaluate infant faces as more pleasant and with a greater approximation response than adult faces. Two types of bias were obtained: 1) a less pleasant evaluation of the neutral faces, similar to that of crying, in the high levels of alexithymia characteristic of neglectful mothers; and 2) a greater response of approximation to crying in neglectful mothers that is not explained by their high levels of alexithymia, since these generate less approximation response. The resolution of these dissonances must be a therapeutic objective of first order to advance in the promotion of their capacities and favor the preservation or family reunification.Este estudio analiza en qué medida está alterada la evaluación subjetiva del llanto infantil en las madres con negligencia severa, y la posible influencia de la alexitimia en dicha alteración. Participaron 24 madres negligentes y 22 madres controles que evaluaron caras de niños/as y caras adultas (de llanto y neutras) según su valencia y la respuesta de aproximación que éstas elicitan. Los resultados indican que ambos grupos evalúan las caras infantiles como más agradables y con mayor respuesta de aproximación que las caras adultas. Se obtuvieron dos tipos de sesgos: 1) una valoración menos agradable de las caras neutras, similar a la del llanto, en los niveles altos de aleximitia característicos de las madres negligentes; y 2) una mayor respuesta de aproximación ante el llanto en las madres negligentes que no se explica por sus altos niveles de alexitimia, ya que éstos generan menos respuesta de aproximación. La resolución de estas disonancias debe ser un objetivo terapéutico de primer orden para avanzar en la promoción de sus capacidades y favorecer la preservación o la reunificación familiar

Mother adversity and co-residence time impact mother–child similarity in genome-wide and gene-specific methylation profiles

Abstract Background The effects of adverse life events on physical and psychological health, with DNA methylation (DNAm) as a critical underlying mechanism, have been extensively studied. However, the epigenetic resemblance between mother and child in the context of neglectful caregiving, and whether it may be shaped by the emotional impact of maternal stressful events and the duration of co-residence (indexed by child age), remains unknown. The present study examined mother–child similarity in methylation profiles, considering the potential effect of mother adversity, mother empathy, neglect-control group, child age (an index of years of mother–child co-residence), and mother age. Using Illumina Epic arrays, we quantified DNAm in 115 mother–child saliva samples. We obtained a methylation similarity index by computing correlation coefficients between methylation profiles within dyads, for the entire epigenome, and five specific genes related to stress and empathy: NR3C1, FKPB5, OXTR, SCL6A4, and BDNF. Results The methylation profiles of the mother–child familial pairs significantly correlated as compared to mother–child random pairs for the entire epigenome and NR3C1, FKBP5, OXTR and BDNF genes. Next, multiple linear regression models observed associations of mother adversity, child age, and neglect-control group on mother–child methylation similarity, only significant in mother–child familial pairs, after correcting for multiple comparisons. Higher mother adversity was associated with lower mother–child methylation similarity for the epigenome-wide analysis, for the BDNF gene, and in the neglect-control group for the OXTR gene. In turn, being an older child (longer co-residence) was associated with higher mother–child methylation similarity. Conclusions Mother adversity and co-residence time are modulating factors in the intergenerational methylation process that offer a window into development-dependent adaptations that can be affected by both hereditary and environmental factors, significantly observed only in biological dyads. A twofold implication for child well-being emerges, one is positive in that children of mothers exposed to life adversity or neglect did not necessarily inherit their methylation patterns. The other is concerning due to the influence of time spent living together, which affects similarity with the mother and potentially increases the risk of inheriting an epigenetic profile associated with future dysfunctional parenting patterns. This underscores the importance of the 'the earlier, the better' recommendation by the Child Protection System, which is not always followed

The shared mother-child epigenetic signature of neglect is related to maternal adverse events

Studies of DNA methylation have revealed the biological mechanisms by which life adversity confers risk for later physical and mental health problems. What remains unknown is the “biologically embedding” of maternal adverse experiences resulting in maladaptive parenting and whether these epigenetic effects are transmitted to the next generation. This study focuses on neglectful mothering indexed by a severe disregard for the basic and psychological needs of the child. Using the Illumina Human Methylation EPIC BeadChip in saliva samples, we identified genes with differentially methylated regions (DMRs) in those mothers with (n = 51), versus those without (n = 87), neglectful behavior that present similar DMRs patterns in their children being neglected versus non-neglected (n = 40 vs. 75). Mothers reported the emotional intensity of adverse life events. After covariate adjustment and multiple testing corrections, we identified 69 DMRs in the mother epigenome and 42 DMRs in the child epigenome that were simultaneously above the α = 0.01 threshold. The common set of nine DMRs contained genes related to childhood adversity, neonatal and infant diabetes, child neurobehavioral development and other health problems such as obesity, hypertension, cancer, posttraumatic stress, and the Alzheimer’s disease; four of the genes were associated with maternal life adversity. Identifying a shared epigenetic signature of neglect linked to maternal life adversity is an essential step in breaking the intergenerational transmission of one of the most common forms of childhood maltreatment

Reduction in Epigenetic Age Acceleration Is Related to Empathy in Mothers with Neglectful Caregiving

DNA methylation clocks are used as molecular estimators of epigenetic age, but with little evidence in mothers and none in neglectful mothering. We investigated differences in epigenetic age acceleration (EAA) and the role of empathy using the PhenoAge clock. We collected saliva samples from mothers with extreme disregard for their child’s needs (50 in the neglect group, NG) and mothers with non-neglectful caregiving (87 in the control group, CG). Mothers completed an empathy scale, along with questionnaires of their own childhood maltreatment, adverse life events and psychiatric disorders. Sociodemographic variables potentially affecting EAA were also measured. The ANCOVA solution showed a significant increase in EAA in the NG compared to the CG, after adjustment for maternal age, number of pregnancies, financial assistance, adverse events, childhood maltreatment and psychiatric disorder. The group interaction effects showed a reduction in EAA for greater empathic concern and for a higher education level both as positive factors, and an increment in EAA for mothers living in a two-parent family as a risk factor, all in the NG. Our findings open the search for protective factors of EAA associated with caregiver behavior to reduce health vulnerabilities and poor social functioning, especially for mothers at risk of maladaptive caregiving

Lessons learned from a sporadic FUSopathy in a young man: a case report

Abstract Background In frontotemporal dementia (FTD) spectrum, younger patients may correspond to fusopathy cases, and cognitive decline could be rapidly progressive. We present a clinical and neuropathological description of a patient. Case presentation A 37-year-old man, without a family history of neurodegenerative diseases, was brought by his family to consult for dysarthria and behavioural change. Initial exploration showed spastic dysarthria and disinhibition. He progressively worsened with a pseudobulbar syndrome, right-lateralized pyramidal signs, left hemispheric corticobasal syndrome and, finally, lower motor neuron signs in his right arm. He died four years after the initiation of the syndrome from bronchopneumonia. Laboratory tests (including blood and cerebrospinal fluid (CSF)) were normal. Magnetic resonance imaging (MRI) and fluorodeoxyglucose-containing positron emission tomography (PET-18F-FDG) showed left fronto-insular atrophy and hypometabolism. Subsequently, 123I-ioflupane (DaT-SCAN®) single-photon emission computed tomography (SPECT) was pathologic, manifesting bilaterally decreased activity with greater affection on the left side. Only a third electromyogram (EMG) detected denervation in the last year of evolution. No mutations were found in genes such as Tau, progranulin, C9orf72, FUS, TDP-43, CHMP2B, or VCP. In necropsy, severe frontotemporal atrophy with basophilic neuronal cytoplasmic and intranuclear inclusions, negative for tau and TAR DNA binding protein 43 (TDP-43), but positive for fused in sarcoma (FUS) consistent with specifically basophilic inclusions body disease (BIBD) type was found. Conclusions In patients affected by FTD, particularly the youngest, with rapidly progressive decline and early motor affection, fusopathy must be suspected. These cases can include motor signs described in the FTD spectrum. Lower motor neuron affection in EMG could be detected late