Event-related potentials during the ultimatum game in people with symptoms of depression and/or social anxiety

Data of this study cannot be made available because itwould require participants to sign and additional consentform which is not possible to implement at the moment.Code implementing General Linear Mixed Models to analyze ERPs is openly available at: https://github.com/enicolaisen/GLMM_ERPs.gitDepression and social anxiety are common disorders that have a profound impact on social functioning. The need for studying the neural substrates of social interactions in mental disorders using interactive tasks has been emphasized. The field of neuroeconomics, which combines neuroscience techniques and behavioral economics multiplayer tasks such as the Ultimatum Game (UG), can contribute in this direction. We assessed emotions, behavior, and Event-Related Potentials in participants with depression and/or social anxiety symptoms (MD/SA, n = 63, 57 females) and healthy controls (n = 72, 67 females), while they played the UG. In this task, participants received fair, mid-value, and unfair offers from other players. Mixed linear models were implemented to assess trial level changes in neural activity. The MD/SA group reported higher levels of sadness in response to mid-value and unfair offers compared to controls. In controls, the Medial Frontal Negativity associated with fair offers increased over time, while this dynamic was not observed in the MD/SA group. The MD/SA group showed a decreased P3/LPP in all offers, compared to controls. These results indicate an enhanced negative emotional response to unfairness in the MD/SA group. Neural results reveal a blunted response over time to positive social stimuli in the MD/SA group. Moreover, between-group differences in P3/LPP may relate to a reduced saliency of offers and/or to a reduced availability of resources for processing incoming stimuli in the MD/SA group. Findings may shed light into the neural substrates of social difficulties in these disordersAgencia Nacional de Investigación e Innovación. Grant Number: POS_NAC_2015_1_109714, Universidad de la Republica Uruguay, Comisión Sectorial de Investigación Científica, Programa de Desarrollo de las Ciencias Básicas; Comunidad de Madrid in collaboration with the Universidad Autónoma de Madrid, Spain. Grant Numbers: SI1-PJI-2019-00011, 2017-T2/SOC-5569; Ministerio de Ciencia, Innovación y Universidades, Spain. Grant Number: PGC2018-093570-B-I0

Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors

The number of patients diagnosed with chronic bile duct disease is increasing and in most cases these diseases result in chronic ductular scarring, necessitating liver transplantation. The formation of ductular scaring affects liver function; however, scar-generating portal fibroblasts also provide important instructive signals to promote the proliferation and differentiation of biliary epithelial cells. Therefore, understanding whether we can reduce scar formation while maintaining a pro-regenerative microenvironment will be essential in developing treatments for biliary disease. Here, we describe how regenerating biliary epithelial cells express Wnt-Planar Cell Polarity signalling components following bile duct injury and promote the formation of ductular scars by upregulating pro-fibrogenic cytokines and positively regulating collagen-deposition. Inhibiting the production of Wnt-ligands reduces the amount of scar formed around the bile duct, without reducing the development of the pro-regenerative microenvironment required for ductular regeneration, demonstrating that scarring and regeneration can be uncoupled in adult biliary disease and regeneration

A joint SZ-X-ray-optical analysis of the dynamical state of 288 massive galaxy clusters

We use imaging from the first three years of the Dark Energy Survey to characterize the dynamical state of 288 galaxy clusters at $0.1 \lesssim z \lesssim 0.9$ detected in the South Pole Telescope (SPT) Sunyaev-Zeldovich (SZ) effect survey (SPT-SZ). We examine spatial offsets between the position of the brightest cluster galaxy (BCG) and the center of the gas distribution as traced by the SPT-SZ centroid and by the X-ray centroid/peak position from Chandra and XMM data. We show that the radial distribution of offsets provides no evidence that SPT SZ-selected cluster samples include a higher fraction of mergers than X-ray-selected cluster samples. We use the offsets to classify the dynamical state of the clusters, selecting the 43 most disturbed clusters, with half of those at $z \gtrsim 0.5$, a region seldom explored previously. We find that Schechter function fits to the galaxy population in disturbed clusters and relaxed clusters differ at $z>0.55$ but not at lower redshifts. Disturbed clusters at $z>0.55$ have steeper faint-end slopes and brighter characteristic magnitudes. Within the same redshift range, we find that the BCGs in relaxed clusters tend to be brighter than the BCGs in disturbed samples, while in agreement in the lower redshift bin. Possible explanations includes a higher merger rate, and a more efficient dynamical friction at high redshift. The red-sequence population is less affected by the cluster dynamical state than the general galaxy population.Comment: 21 pages, 12 Figures, 4 Tables. Accepted for publication in MNRA

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

publishedVersio

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

COMPUESTOS FENÓLICOS DE TEJOCOTE (Crataegus spp.): SU ACTIVIDAD BIOLÓGICA ASOCIADA A LA PROTECCIÓN DE LA SALUD HUMANA

El tejocote (Crataegus spp.) es un planta ampliamente distribuida en México, donde se le utiliza principalmente como alimento humano y para el ganado. Su uso en la medicina tradicional es bajo, comparado con el que se presenta en otros países. Históricamente, este fruto se ha utilizado para tratar un sinnúmero de padecimientos, que incluyen enfermedades cardiovasculares, las cuales representan una de las principales causas de muerte en México y el mundo. Los estudios científicos atribuyen algunos efectos benéficos del tejocote a los compuestos fenólicos. En la presente revisión, se analizan de manera crítica y sistemática los efectos benéficos atribuidos al tejocote y los mecanismos de acción involucrados, con la finalidad de promover su uso en el tratamiento de diversos padecimientos catalogados en México como problemas de salud pública.</jats:p