The three-dimensional structure of DapE from Enterococcus faecium reveals new insights into DapE/ArgE subfamily ligand specificity.

DapE is a Zn2+-metallohydrolase recognized as a drug target for bacterial control. It is a homodimer that requires the exchange of interface strands by an induced fit essential for catalysis. Identifying novel anti-DapE agents requires greater structural details. Most of the characterized DapEs are from the Gram-negative group. Here, two high-resolution DapE crystal structures from Enterococcus faecium are presented for the first time with novel aspects. A loosened enzyme intermediate between the open and closed conformations is observed. Substrates may bind to loose state, subsequently it closes, where hydrolysis occurs, and finally, the change to the open state leads to the release of the products. Mutation of His352 suggests a role, along with His194, in the oxyanion stabilization in the mono-metalated Zn2+ isoform, while in the di-metalated isoform, the metal center 2 complements it function. An aromatic-π box potentially involved in the interaction of DapE with other proteins, and a peptide flip could determine the specificity in the Gram-positive ArgE/DapE group. Finally, details of two extra-catalytic cavities whose geometry changes depending on the conformational state of the enzyme are presented. These cavities could be a target for developing non-competitive agents that trap the enzyme in an inactive state.

Technological Perception with Rural and Urban Differentiation and Its Influence on the Quality of Life of Older People with Age-Related Macular Degeneration.

The past decade has seen a global increase in population age, especially in developed countries, where aging involves visual diseases such as age-related macular degeneration (AMD), which severely affect quality of life (QoL) and mental health, as well as increase isolation and care costs. This study investigated how persons with AMD perceive the impact of technology use on their QoL, focusing on potential disparities between urban and rural contexts in Spain. Using a cross-sectional observational design, data from the 2020 National Statistics Institute's Disability, Personal Autonomy, and Dependency Situations Survey were analyzed, focusing on QoL aspects based on the WHO items of the WHOQOL-100 scale. The results revealed a generally positive perception of technology among participants, with urban residents perceiving technology's positive impact more favorably. Sex discrepancies in technology perception were also observed, as women exhibited a more positive outlook on technology's influence on QoL. The analysis of QoL aspects, such as 'Visibility', 'Learning', 'Mobility', and 'Domestic life', highlighted distinct challenges faced by rural and urban populations, underscoring the importance of context-specific approaches in technology interventions. However, these perceptions were intertwined with comorbidities, which can exacerbate AMD-related issues. Furthermore, this study explored the role of technology in enhancing QoL among older adults with AMD, examining how it influences daily activities and independence, particularly in the context of AMD management. This study concluded that developing more-inclusive policies tailored to the specific needs of persons with AMD, with special attention to environmental and sex differences, is imperative to enhance the positive impact of technology on their QoL.

Prophylactic Anticoagulation Reduces the Risk of Kidney Graft Venous Thrombosis in Recipients From Uncontrolled Donation After Circulatory Death Donors With High Renal Resistive Index.

Background: Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplantation (KT) at the expense of a higher risk of primary graft nonfunction (PNF). At least half of the cases of PNF are secondary to graft venous thrombosis. The potential benefit from prophylactic anticoagulation in this scenario remains unclear. Methods: In this single-center retrospective study we compared 2 consecutive cohorts of KT from uDCD with increased (≥0.8) renal resistive index (RRI) in the Doppler ultrasound examination performed within the first 24-72 h after transplantation: 36 patients did not receive anticoagulation ("nonanticoagulation group") and 71 patients underwent prophylactic anticoagulation until normalization of RRI in follow-up Doppler examinations ("anticoagulation group"). Results: Anticoagulation was initiated at a median of 2 d (interquartile range, 2-3) after transplantation and maintained for a median of 12 d (interquartile range, 7-18). In 4 patients (5.6%), anticoagulation had to be prematurely stopped because of the development of a hemorrhagic complication. In comparison with the nonanticoagulation group, recipients in the anticoagulation group had a lower 2-wk cumulative incidence of graft venous thrombosis (19.4% versus 0.0%; P < 0.001) and PNF (19.4% versus 2.8%; P = 0.006). The competing risk analysis with nonthrombotic causes of PNF as the competitive event confirmed the higher risk of graft thrombosis in the nonanticoagulation group (P = 0.0001). The anticoagulation group had a higher incidence of macroscopic hematuria (21.1% versus 5.6%; P = 0.049) and blood transfusion requirements (39.4% versus 19.4%; P = 0.050) compared with the nonanticoagulation group. No graft losses or deaths were attributable to complications potentially associated with anticoagulation. Conclusions: Early initiation of prophylactic anticoagulation in selected KT recipients from uDCD with an early Doppler ultrasound RRI of ≥0.8 within the first 24-72 h may reduce the incidence of graft venous thrombosis as a cause of PNF.

Medical students' knowledge about human papillomavirus (HPV), HPV vaccine and head and neck cancer.

The Human Papillomavirus (HPV) is a sexually transmitted infection that significantly affects the population worldwide. HPV preventive methods include vaccination, prophylactics, and education. Different types of cancers associated with HPV usually take years or decades to develop after infections, such as Head and Neck Cancer(HNC). Therefore, HPV prevention can be considered cancer prevention. A sample of medical students in Puerto Rico was evaluated to assess their knowledge about HPV, HPV vaccine, and HNC through two previously validated online questionnaires composed of 38 dichotomized questions, we measured HPV, HPV vaccination(HPVK), and HNC knowledge (HNCK). Out of 104 students surveyed, the mean HPVK score obtained was 20.07/26, SD = 3.86, while the mean score for HNCK was 6.37/12, SD = 1.78. Bidirectional stepwise regression showed study year and HPV Vaccine name had been the most influential variables on HPVK and HNCK. MS1 participants scored lower than MS2-MS4 participants, with no significant difference between MS2-MS4 scores. The results reveal knowledge gaps in HPV/HPV Vaccine and HNC among surveyed medical students. Our findings also suggest an association between knowledge of personal vaccination status, self-perceived risk, and how uncertainty in these factors may affect the medical students' understanding of HPV, HPV vaccination, and associated cancers.

Assessing the effects of pandemic risk on cooperation and social norms using a before-after Covid-19 comparison in two long-term experiments.

How does threat from disease shape our cooperative actions and the social norms that guide such behaviour? To study these questions, we draw on a collective-risk social dilemma experiment that we ran before the emergence of the Covid-19 pandemic (Wave 1, 2018) and compare this to its exact replication, sampling from the same population, that we conducted during the first wave of the pandemic (Wave 2, 2020). Tightness-looseness theory predicts and evidence generally supports that both cooperation and accompanying social norms should increase, yet, we mostly did not find this. Contributions, the probability of reaching the threshold (cooperation), and the contents of the social norm (how much people should contribute) remained similar across the waves, although the strength of these social norms were slightly greater in Wave 2. We also study whether the results from Wave 1 that should not be affected by the pandemic-the relationship between social norms and cooperation and specific behavioural types-replicate in Wave 2 and find that these results generally hold. Overall, our work demonstrates that social norms are important drivers of cooperation, yet, communicable diseases, at least in the short term, have little or no effects on either.

Análisis de eventos adversos en los servicios de cirugía general y aparato digestivo. Estudio multicéntrico / Analysis of adverse events in general surgery: A multicenter study

Introducción: El conocimiento de los eventos adversos (EA) en los hospitales de agudos es un aspecto de especial relevancia en la seguridad del paciente. Su incidencia oscila entre un 3-17% y la cirugía se relaciona con la aparición de entre un 46-65% de todos los EA. Material y métodos: Se realiza un estudio observacional, descriptivo, retrospectivo y multicéntrico, con la participación de 31 hospitales de agudos españoles, para la determinación y análisis de los EA en los servicios de cirugía general. Resultados: La prevalencia de EA fue del 31,53%. Los tipos de EA más frecuentes fueron de tipo infeccioso (35%). Los pacientes con mayores grados de ASA, mayor complejidad y un tipo de ingreso urgente son factores asociados a la presencia de EA. A la mayoría de los pacientes se les atribuyó una categoría de daño F (daño temporal al paciente que requiera iniciar o prolongar la hospitalización) (58,42%). El 14,69% de los EA son considerados graves. El 34,22% de los EA se consideraron evitables. Conclusiones: La prevalencia de EA en los pacientes de cirugía general y del aparato digestivo (CGAD) es elevada. La mayor parte de los EA fueron de tipo infeccioso. El EA más frecuente fue la infección de herida o sitio quirúrgico. Los pacientes con mayores grados de ASA, mayor complejidad y un tipo de ingreso urgente son factores asociados a la presencia de EA. La mayoría de los EA detectados han supuesto un daño leve o moderado sobre los pacientes. Alrededor de un tercio de EA fueron evitables.(AU)

Introduction: Knowledge of adverse events (AE) in acute care hospitals is a particularly relevant aspect of patient safety. Its incidence ranges from 3% to 17%, and surgery is related to the occurrence of 46%-65% of all AE. Material and methods: An observational, descriptive, retrospective, multicenter study was conducted with the participation of 31 Spanish acute-care hospitals to determine and analyze AE in general surgery services. Results: The prevalence of AE was 31.53%. The most frequent types of AE were infectious (35%). Higher ASA grades, greater complexity and urgent-type admission are factors associated with the presence of AE. The majority of patients (58.42%) were attributed a category F event (temporary harm to the patient requiring initial or prolonged hospitalization); 14.69% of AE were considered severe, while 34.22% of AE were considered preventable. Conclusions: The prevalence of AE in General and GI Surgery (GGIS) patients is high. Most AE were infectious, and the most frequent AE was surgical site infection. Higher ASA grades, greater complexity and urgent-type admission are factors associated with the presence of AE. Most detected AE resulted in mild or moderate harm to the patients. About one-third of AE were preventable.(AU)

Modelling social norms: an integration of the norm-utility approach with beliefs dynamics.

We review theoretical approaches for modelling the origin, persistence and change of social norms. The most comprehensive models describe the coevolution of behaviours, personal, descriptive and injunctive norms while considering influences of various authorities and accounting for cognitive processes and between-individual differences. Models show that social norms can improve individual and group well-being. Under some conditions though, deleterious norms can persist in the population through conformity, preference falsification and pluralistic ignorance. Polarization in behaviour and beliefs can be maintained, even when societal advantages of particular behaviours or belief systems over alternatives are clear. Attempts to change social norms can backfire through cognitive processes including cognitive dissonance and psychological reactance. Under some conditions social norms can change rapidly via tipping point dynamics. Norms can be highly susceptible to manipulation, and network structure influences their propagation. Future models should incorporate network structure more thoroughly, explicitly study online norms, consider cultural variations and be applied to real-world processes. This article is part of the theme issue 'Social norm change: drivers and consequences'.

Structural and functional properties of uridine 5'-monophosphate synthase from Coffea arabica.

In higher eukaryotes and plants, the last two sequential steps in the de novo biosynthesis of uridine 5'-monophosphate (UMP) are catalyzed by a bifunctional natural chimeric protein called UMP synthase (UMPS). In higher plants, UMPS consists of two naturally fused enzymes: orotate phosphoribosyltransferase (OPRTase) at N-terminal and orotidine-5'-monophosphate decarboxylase (ODCase) at C-terminal. In this work, we obtained the full functional recombinant protein UMPS from Coffea arabica (CaUMPS) and studied its structure-function relationships. A biochemical and structural characterization of a plant UMPS with its two functional domains is described together with the presentation of the first crystal structure of a plant ODCase at 1.4 Å resolution. The kinetic parameters measured of CaOPRTase and CaODCase domains were comparable to those reported. The crystallographic structure revealed that CaODCase is a dimer that conserves the typical fold observed in other ODCases from prokaryote and eukaryote with a 1-deoxy-ribofuranose-5'-phosphate molecule bound in the active site of one subunit induced a closed conformation. Our results add to the knowledge of one of the key enzymes of the de novo biosynthesis of pyrimidines in plant metabolism and open the door to future applications.

Analysis of adverse events in general surgery. Multicenter study.

INTRODUCTION: Knowledge of adverse events (AE) in acute care hospitals is a particularly relevant aspect of patient safety. Its incidence ranges from 3% to 17%, and surgery is related to the occurrence of 46%-65% of all AE. MATERIAL AND METHODS: An observational, descriptive, retrospective, multicenter study was conducted with the participation of 31 Spanish acute-care hospitals to determine and analyze AE in general surgery services. RESULTS: The prevalence of AE was 31.53%. The most frequent types of AE were infectious (35%). Higher ASA grades, greater complexity and urgent-type admission are factors associated with the presence of AE. The majority of patients (58.42%) were attributed a category F event (temporary harm to the patient requiring initial or prolonged hospitalization); 14.69% of AE were considered severe, while 34.22% of AE were considered preventable. CONCLUSIONS: The prevalence of AE in General and GI Surgery (GGIS) patients is high. Most AE were infectious, and the most frequent AE was surgical site infection. Higher ASA grades, greater complexity and urgent-type admission are factors associated with the presence of AE. Most detected AE resulted in mild or moderate harm to the patients. About one-third of AE were preventable.

Lung microbiome alterations in patients with anti-Jo1 antisynthetase syndrome and interstitial lung disease.

Aim: To characterize the lung microbiome in the bronchoalveolar lavage fluid (BALF) of patients with Antisynthetase Syndrome (ASSD) according to anti-Jo1 autoantibody positivity and evaluate the correlation with differential cell count and other bacterial genera in BALF. Methods: We sequenced the 16S ribosomal RNA gene in the BALF of anti-Jo1-positive (JoP, n=6) and non-Jo1-positive (NJo, n=17) patients, and the differential cell count in BALF was evaluated. The Spearman's correlation was calculated for the quantitative variables and abundance of bacterial species. Results: The Veillonella genus showed a significant decrease (p<0.01) in JoP (2.2%) in comparison to NJo (4.1%) patients. The correlation analysis showed several high (rho ≥ ± 0.7) and significant (p < 0.05) correlations. We analyzed the results obtained for the Veillonella genera and other study variables. The JoP group showed that the abundance of Veillonella had a high negative correlation with macrophages (rho = - 0.77) and a positive correlation with eosinophils (rho = 0.77), lymphocytes (rho = 0.77), and Prevotella (rho = 1). Conclusions: The lung microbiome in ASSD patients differs and may affect cell composition, contributing to lung damage mechanisms. The presence of anti-Jo1 autoantibodies showed a low abundance of Veillonella. This genus had a strong and positive correlation with Prevotella abundance and levels of eosinophils and lymphocytes, and it showed a strong negative correlation with the percentage of macrophages.

Depresión, ansiedad y calidad de sueño en deportistas ante la contingencia sanitaria COVID-19. Estudio exploratorio. / Depression, anxiety and sleep quality in athletes in the face of the COVID-19 health contingency. Exploratory study

Objetivo: Identificar los síntomas de ansiedad, depresión y calidad de sueño ante la contingencia sanitaria en una muestra de deportistas mexicanos, mediante un estudio descriptivo-exploratorio de corte transversal. Método: La muestra del estudio fue 110 deportistas con una media de edad de 24.4 años, los cuales tenían distintos niveles de experiencia: amateur, semi-profesional y profesional. Se aplicaron los siguientes instrumentos: inventario de depresión de Beck, escala de ansiedad de Hamilton y el índice de calidad de sueño de Pittsburg. Resultados: Se mostraron que los deportistas profesionales muestran menores niveles de ansiedad y depresión, respecto a los semi profesionales y amateur. No obstante, su calidad de sueño fue menor. Conclusión: La pandemia de COVID-19 ha hecho evidente la necesidad de cambios en las prácticas profesionales y en la investigación científica de la psicología del deporte que beneficien a la comunidad de atletas, por ello la presencia de especialistas en la salud mental en los equipos deportivos será una necesidad de alta prioridad, que cumplirá con el fortalecimiento de la preparación psicológica y el cuidado de la salud mental. (AU)

T regulatory lymphocytes specific for SARS-CoV-2 display increased functional plasticity.

The study of phenotypic and functional characteristics of immune cells involved in host response to SARS-CoV-2 is relevant for understanding COVID-19 pathogenesis and individual differences in disease progression. We have analyzed chemokine receptor expression in SARS-CoV-2-specific CD4+ T lymphocytes from vaccinated donors, and have found an increase of CCR9+ and CCR6+ cells. CCR9+ specific CD4+ cells are enriched in T regulatory (Treg) lymphocytes. These cells specifically show heterogeneous regulatory activity, associated with different profiles of CCR9/CCR6 expression, individual differences in IL-10 and IL-17 production, and variable FoxP3 and Notch4 expression. A higher heterogeneity in FoxP3 is selectively observed in convalescent individuals within vaccinated population. Accordingly, SARS-CoV-2-specific CD4+ lymphocytes from COVID-19 patients are also enriched in CCR9+ and CCR6+ cells. CCR6+ specific Treg lymphocytes are mainly increased in critically ill individuals, indicating a preferential role for these cells in lung injury pathogenesis. We provide experimental evidence for a SARS-CoV-2-specific Treg population with increased plasticity, which may contribute to the differential pathogenic response against SARS-CoV-2 among individuals, and underlie the development of autoimmune conditions following SARS-CoV-2 infection.

Stability of the personal relationship networks in a longitudinal study of middle school students.

The personal network of relationships is structured in circles of friendships, that go from the most intense relationships to the least intense ones. While this is a well established result, little is known about the stability of those circles and their evolution in time. To shed light on this issue, we study the temporal evolution of friendships among teenagers during two consecutive academic years by means of a survey administered on five occasions. We show that the first two circles, best friends and friends, can be clearly observed in the survey but also that being in one or the other leads to more or less stable relationships. We find that being in the same class is one of the key drivers of friendship evolution. We also observe an almost constant degree of reciprocity in the relationships, around 60%, a percentage influenced both by being in the same class and by gender homophily. Not only do our results confirm the mounting evidence supporting the circle structure of human social networks, but they also show that these structures persist in time despite the turnover of individual relationships-a fact that may prove particularly useful for understanding the social environment in middle schools.

Potential Biomarkers Associated with Prognosis and Trastuzumab Response in HER2+ Breast Cancer.

Breast cancer (BC) is the most common malignancy among women worldwide. Around 15-25% of BC overexpress the human epidermal growth factor receptor 2 (HER2), which is associated with a worse prognosis and shortened disease-free survival. Therefore, anti-HER2 therapies have been developed, such as monoclonal antibodies (trastuzumab, Tz), antibody-drug conjugates (ado-trastuzumab emtansine, T-DM1), and pharmacological inhibitors of tyrosine kinase activity (lapatinib, Lp). Although Tz, the standard treatment, has significantly improved the prognosis of patients, resistance still affects a significant population of women and is currently a major challenge in clinical oncology. Therefore, this study aims to identify potential biomarkers to predict disease progression (prognostic markers) and the efficacy of Tz treatment (predictive markers) in patients with HER2+ BC. We hypothesize that proteins involved in cell motility are implicated in Tz-resistance. We aim to identify alterations in Tz-resistant cells to guide more efficient oncologic decisions. By bioinformatics, we selected candidate proteins and determined how their expression, localization, and the process they modulate were affected by anti-HER2 treatments. Next, using HER2+ BC patients' data, we assessed these proteins as prognostic and predictive biomarkers. Finally, using Tz-resistant cells, we evaluated their roles in Tz response. We identified deregulated genes associated with cell motility in Tz/T-DM1-resistant vs. -sensitive cells. We showed that Tz, T-DM1, and Lp decrease cell viability, and their effect is enhanced in combinations. We determined synergism between Tz/T-DM1 and Lp, making possible a dose reduction of each drug to achieve the same therapeutic effect. We found that combinations (Tz/T-DM1 + Lp) efficiently inhibit cell adhesion and migration. Furthermore, we demonstrated the induction of FAK nuclear and cortactin peri-nuclear localization after T-DM1, Lp, and Tz/T-DM1 + Lp treatments. In parallel, we observed that combined treatments downregulate proteins essential for metastatic dissemination, such as SRC, FAK, and paxillin. We found that low vinculin (VCL) and cortactin (CTTN) mRNA expression predicts favorable survival rates and has diagnostic value to discriminate between Tz-sensible and Tz-resistant HER2+ BC patients. Finally, we confirmed that vinculin and cortactin are overexpressed in Tz-resistance cells, SKBR3-RTz. Moreover, we found that Tz plus FAK/paxillin/cortactin-silencing reduced cell adhesion/migration capacity in Tz-sensitive and -resistant cells. In conclusion, we demonstrate that combined therapies are encouraging since low doses of Tz/T-DM1 + Lp inhibit metastatic processes by downregulating critical protein expression and affecting its subcellular localization. We propose that vinculin and cortactin might contribute to Tz-sensibility/resistance in BC cells. Finally, we identify potential prognostic and predictive biomarkers that are promising for personalized BC management that would allow efficient patient selection in order to mitigate resistance and maximize the safety and efficacy of anti-HER2 therapies.

Novel 1,2,4-oxadiazole compounds as PPAR-α ligand agonists: a new strategy for the design of antitumour compounds.

Modulation of PPAR-α by natural ligands is a novel strategy for the development of anticancer therapies. A series of 16 compounds based on the structure of 3-(pyridin-3-yl)-5-(thiophen-3-yl)-1,2,4-oxadiazole (natural compound) with antitumour potential were designed and synthesised. The cytotoxicity and PPAR agonist activity of these synthetic 1,2,4-oxadiazoles were evaluated in the A-498 and DU 145 tumour cell lines. Preliminary biological evaluation showed that most of these synthetic 1,2,4-oxadiazoles are less cytotoxic (sulforhodamine B assay) than the positive control WY-14643. Regarding the PPAR-α modulation, compound 16 was the most active, with EC50 = 0.23-0.83 µM (PPAR-α). Additionally, compound 16 had a similar activity to the natural compound (EC50 = 0.18-0.77 µM) and was less toxic in the RPTEC and WPMY-1 cell lines (non-tumour cells) (CC50 = 81.66-92.67 µM) than the natural compound. Looking at the link between chemical structure and activity, our study demonstrates that changes to the natural 1,2,4-oxadiazole at the level of the thiophenyl residue can lead to new agonists of PPAR-α with promising anti-tumour activity.

Comparative Analysis of CRISPR-Cas Systems in Pseudomonas Genomes.

Pseudomonas is a bacterial genus with some saprophytic species from land and others associated with opportunistic infections in humans and animals. Factors such as pathogenicity or metabolic aspects have been related to CRISPR-Cas, and in silico studies into it have focused more on the clinical and non-environmental setting. This work aimed to perform an in silico analysis of the CRISPR-Cas systems present in Pseudomonas genomes. It analyzed 275 complete genomic sequences of Pseudomonas taken from the NCBI database. CRISPR loci were obtained from CRISPRdb. The genes associated with CRISPR (cas) and CAS proteins, and the origin and diversity of spacer sequences, were identified and compared by BLAST. The presence of self-targeting sequences, PAMs, and the conservation of DRs were visualized using WebLogo 3.6. The CRISPR-like RNA secondary structure prediction was analyzed using RNAFold and MFold. CRISPR structures were identified in 19.6% of Pseudomonas species. In all, 113 typical CRISPR arrays with 18 putative cas were found, as were 2050 spacers, of which 52% showed homology to bacteriophages, 26% to chromosomes, and 22% to plasmids. No potential self-targeting was detected within the CRISPR array. All the found DRs can form thermodynamically stable secondary RNA structures. The comparison of the CRISPR/Cas system can help understand the environmental adaptability of each evolutionary lineage of clinically and environmentally relevant species, providing data support for bacterial typing, traceability, analysis, and exploration of unconventional CRISPR.

Isolation of Nocuolin A and Synthesis of New Oxadiazine Derivatives. Design, Synthesis, Molecular Docking, Apoptotic Evaluation, and Cathepsin B Inhibition.

Nocuolin A (1), an oxadiazine, was isolated from the cyanobacterium Nostoc sp. Its chemical structure was elucidated using NMR and mass spectroscopic data. From this compound, two new oxadiazines, 3-[(6R)-5,6-dihydro-4,6-dipentyl-2H-1,2,3-oxadiazin-2-yl]-3-oxopropyl acetate (2) and 4-{3-[(6R)-5,6-dihydro-4,6-dipentyl-2H-1,2,3-oxadiazin-2-yl]-3-oxopropoxy}-4-oxobutanoic acid (3), were synthesised. The chemical structures of these two compounds were elucidated by a combination of NMR and MS analysis. Compound 3 showed cytotoxicity against the ACHN (0.73 ± 0.10 µM) and Hepa-1c1c7 (0.91 ± 0.08 µM) tumour cell lines. Similarly, compound 3 significantly decreased cathepsin B activity in ACHN and Hepa-1c1c7 tumour cell lines at concentrations of 1.52 ± 0.13 nM and 1.76 ± 0.24 nM, respectively. In addition, compound 3 showed no in vivo toxicity in a murine model treated with a dose of 4 mg/kg body weight.

Triadic influence as a proxy for compatibility in social relationships.

Networks of social interactions are the substrate upon which civilizations are built. Often, we create new bonds with people that we like or feel that our relationships are damaged through the intervention of third parties. Despite their importance and the huge impact that these processes have in our lives, quantitative scientific understanding of them is still in its infancy, mainly due to the difficulty of collecting large datasets of social networks including individual attributes. In this work, we present a thorough study of real social networks of 13 schools, with more than 3,000 students and 60,000 declared positive and negative relationships, including tests for personal traits of all the students. We introduce a metric-the "triadic influence"-that measures the influence of nearest neighbors in the relationships of their contacts. We use neural networks to predict the sign of the relationships in these social networks, extracting the probability that two students are friends or enemies depending on their personal attributes or the triadic influence. We alternatively use a high-dimensional embedding of the network structure to also predict the relationships. Remarkably, using the triadic influence (a simple one-dimensional metric) achieves the best accuracy, and adding the personal traits of the students does not improve the results, suggesting that the triadic influence acts as a proxy for the social compatibility of students. We postulate that the probabilities extracted from the neural networks-functions of the triadic influence and the personalities of the students-control the evolution of real social networks, opening an avenue for the quantitative study of these systems.

MindReader: Unsupervised Classification of Electroencephalographic Data.

Electroencephalogram (EEG) interpretation plays a critical role in the clinical assessment of neurological conditions, most notably epilepsy. However, EEG recordings are typically analyzed manually by highly specialized and heavily trained personnel. Moreover, the low rate of capturing abnormal events during the procedure makes interpretation time-consuming, resource-hungry, and overall an expensive process. Automatic detection offers the potential to improve the quality of patient care by shortening the time to diagnosis, managing big data and optimizing the allocation of human resources towards precision medicine. Here, we present MindReader, a novel unsupervised machine-learning method comprised of the interplay between an autoencoder network, a hidden Markov model (HMM), and a generative component: after dividing the signal into overlapping frames and performing a fast Fourier transform, MindReader trains an autoencoder neural network for dimensionality reduction and compact representation of different frequency patterns for each frame. Next, we processed the temporal patterns using a HMM, while a third and generative component hypothesized and characterized the different phases that were then fed back to the HMM. MindReader then automatically generates labels that the physician can interpret as pathological and non-pathological phases, thus effectively reducing the search space for trained personnel. We evaluated MindReader's predictive performance on 686 recordings, encompassing more than 980 h from the publicly available Physionet database. Compared to manual annotations, MindReader identified 197 of 198 epileptic events (99.45%), and is, as such, a highly sensitive method, which is a prerequisite for clinical use.

Prevalence of hepatitis C virus infection in patients with chronic mental disorders: The relevance of dual disorders / Prevalencia de la infección por el virus de la hepatitis C en pacientes con trastornos mentales crónicos: la relevancia de la patología dual

Objective: The prevalence of hepatitis C virus (HCV) infection is higher in people with psychiatric disorders compared to the general population. In addition, patients with severe mental illness are frequently affected by substance abuse, which increases the risk of blood-borne viral infections. Epidemiological studies in samples of hospitalised individuals with chronic mental disorders and dual diagnosis (DD) are lacking. The objective of this study was to investigate the prevalence of HCV infection in a sample of in-patients with severe mental illness. Patients and methods: This was a retrospective observational study. All patients meeting selection criteria admitted to the Medium-Term Psychiatric Unit of the University of Salamanca Health Care Complex between 2007 and 2018 were included. The primary endpoint was the prevalence of HCV infection. The secondary endpoint comprised the characteristics influencing the occurrence of HCV infection in these patients. Results: A total of 497 admissions were included and patients’ last admission data were considered for analyses (n=345). The overall prevalence of HCV infection was 3.8% and reached 14.3% among DD patients, who showed a higher prevalence than those without this condition (14.3% versus 3.1%, p=0.009). HCV RNA was detected in 6 individuals at diagnosis who received DAA treatment reaching sustained virological response. Conclusions:The prevalence of HCV infection in our sample was higher than in the general population, especially among DD patients. Despite the multiple barriers to access healthcare by patients with chronic mental illness, efforts to include this population in screening and treatment are mandatory.(AU)

Objetivo: La prevalencia de la infección por el virus de la hepatitis C (VHC) es mayor en las personas con trastornos psiquiátricos que en la población general. Además, los pacientes con enfermedades mentales graves padecen con frecuencia abuso de sustancias, que aumenta el riesgo de infecciones virales transmitidas por la sangre. El objetivo de este estudio fue investigar la prevalencia de la infección por el VHC en una muestra de pacientes hospitalizados con trastornos psiquiátricos graves. Pacientes y métodos: Se trata de un estudio observacional retrospectivo. Se incluyeron todos los pacientes que cumplían los criterios de selección ingresados en la Unidad de Convalecencia del Servicio de Psiquiatría del Complejo Asistencial Universitario de Salamanca entre 2007 y 2018. El criterio de evaluación principal fue la prevalencia de la infección por VHC. El criterio de evaluación secundario abarcó las características que contribuyen a dicha infección en estos pacientes. Resultados: Se consideraron los datos del último ingreso de los pacientes incluidos (n=345). La prevalencia global de la infección por VHC fue del 3,8% y alcanzó el 14,3% entre los pacientes con patología dual, que mostraron una prevalencia mayor que aquellos sin esta condición (14,3 versus 3,1%, p=0,009). Se detectó ARN de VHC en 6 individuos en el momento del diagnóstico, que recibieron tratamiento DAA y alcanzaron una respuesta virológica sostenida. Conclusiones: La prevalencia de infección por VHC en nuestra muestra fue mayor que en la población general, especialmente entre los pacientes con patología dual. A pesar de las barreras que dificultan el acceso a la atención sanitaria de los pacientes con enfermedades mentales crónicas, es imprescindible incluirlos en el cribado y el tratamiento.(AU)