Nrg1 intracellular signaling regulates the development of interhemispheric callosal axons in mice.

Schizophrenia is associated with altered cortical circuitry. Although the schizophrenia risk gene NRG1 is known to affect the wiring of inhibitory interneurons, its role in excitatory neurons and axonal development is unclear. Here, we investigated the role of Nrg1 in the development of the corpus callosum, the major interhemispheric connection formed by cortical excitatory neurons. We found that deletion of Nrg1 impaired callosal axon development in vivo. Experiments in vitro and in vivo demonstrated that Nrg1 is cell-autonomously required for axonal outgrowth and that intracellular signaling of Nrg1 is sufficient to promote axonal development in cortical neurons and specifically in callosal axons. Furthermore, our data suggest that Nrg1 signaling regulates the expression of Growth Associated Protein 43, a key regulator of axonal growth. In conclusion, our study demonstrates that NRG1 is involved in the formation of interhemispheric callosal connections and provides a novel perspective on the relevance of NRG1 in excitatory neurons and in the etiology of schizophrenia.

T-TAS® 01 as a new tool for the evaluation of hemostasis in thrombocytopenic patients after platelet transfusion.

BACKGROUND: Current laboratory tests fail to evaluate the hemostatic function of platelets in patients with thrombocytopenia. We investigated the use of the Total Thrombus-Formation Analysis System (T-TAS® 01 [Fujimori Kogyo Co, Tokyo, Japan]) to evaluate hemostasis under conditions of experimental thrombocytopenia, and in patients before and after platelet transfusion. MATERIALS AND METHODS: Specific T-TAS 01 chips, for thrombocytopenic conditions, were used. The area under the curve (AUC) and occlusion time (OT, min) were measured in: (i) experimentally induced thrombocytopenia (183±15 to 6.3±1.2×103 platelets/µL) in blood samples from healthy donors (No.=13), and (ii) blood from oncohematological thrombocytopenic patients (No.=48), before and after platelet transfusion. The influences of hematocrit and number of transfusions were analyzed in these patients. RESULTS: Progressive reductions of AUC and prolongations of OT related significantly to decreasing platelet counts (p<0.05 for all) in experimental thrombocytopenia. In samples from thrombocytopenic patients, platelet counts, AUC and OT were, respectively, 10.8±0.6×103/µL, 175.2±59, and 27.2±1 min before transfusion; and 22±1.5×103/µL, 400.8±83 and 22.9±1.5 min after platelet transfusion (p<0.01 for all). A hematocrit below 25% or exposure to ten or more previous platelet transfusions had a negative impact on the T-TAS 01 performance in patients. In vitro correction of the hematocrit improved the hemostatic response in thrombocytopenic patients. DISCUSSION: T-TAS 01 measurements were sensitive to low platelet counts in the experimental setting. The technology was sensitive to evaluate the hemostatic capacity of platelet transfusions. Exposure to multiple medications, repeated platelet transfusions and lower hematocrits may interfere with the hemostatic performance in oncohematological patients with thrombocytopenia.

Different Perspectives of Spanish Patients and Professionals on How a Dialysis Unit Should Be Designed.

Aim: The opinion of hemodialysis patients, professionals and family members is rarely considered in the design of a hemodialysis unit. Purpose: To know and compare the opinion and preferences of patients, family members and professionals regarding the design of a dialysis unit and the potential activities they believe should be carried out during the session in order to provide architects with real information for the construction of a dialysis center. Patients and Methods: Anonymous and voluntary survey in electronic format addressed to patients, relatives and professionals belonging to the 18 hemodialysis centers of the renal foundation and to ALCER and its different delegations, in relation to leisure activities to be carried out in the dialysis center and preferred design of the treatment room. The results obtained between the patient-family group and the professionals were compared. Results: We received 331 responses, of which 215 were from patients and family members (65%) and 116 (35%) from professionals. The most represented category among professionals was nursing (53%), followed by assistants (24%) and physicians (12.9%). A higher proportion of patients (66%) preferred rooms in groups of 10-12 patients as opposed to professionals who preferred open-plan rooms (p<0.001). The options that showed the most differences between patients and professionals were chatting with colleagues and intimacy (options most voted by patients/families), versus performing group activities and visibility (professionals). Conclusion: The professionals' view of patients' needs does not always coincide with the patients' perception. The inclusion of the perspective of people with kidney disease continues to be a pending issue in which we must improve both patient organizations and professionals, and the opinion of professionals and patients must be included in the design of a dialysis unit and the activities to be developed in it.

Collision-induced state-changing rate coefficients for cyanogen backbones NCN 3Σ- and CNN 3Σ- in astrophysical environments.

We report quantum calculations involving the dynamics of rotational energy-transfer processes, by collision with He atoms in interstellar environments, of the title molecular species which share the presence of the CN backbone and are considered of importance in those environments. The latter structural feature is taken to be especially relevant for prebiotic chemistry and for its possible role in the processing of the heterocyclic rings of RNA and DNA nucleobases in the interstellar space. We carry out ab initio calculations of their interaction potentials with He atoms and further obtain the state-to-state rotationally inelastic cross sections and rate coefficients over the relevant range of temperatures. The similarities and differences between such species and other similar partners which have been already detected are analyzed and discussed for their significance on internal state populations in interstellar space for the two title molecular radicals.

Potential energy surfaces for singlet and triplet states of the LiH2+ system and quasi-classical trajectory cross sections for H + LiH+ and H+ + LiH.

A new set of six accurate ab initio potential energy surfaces (PESs) is presented for the first three singlet and triplet states of LiH2+ (1,21A', 11A'', 1,23A', and 13A'' states, where four of them are investigated for the first time), which have allowed new detailed studies gaining a global view on this interesting system. These states are relevant for the study of the most important reactions of lithium chemistry in the early universe. More than 45 000 energy points were calculated using the multi-reference configuration interaction level of theory using explicitly correlated methods (ic-MRCI-F12), and the results obtained for each individual electronic state were fitted to an analytical function. Using quasiclassical trajectories and considering the initial diatomic fragment in the ground rovibrational state, we have determined the integral cross sections for the H + LiH+(X2Σ+, C2Π) and H+ + LiH(X1Σ+, B1Π) reactions. In these calculations all available reaction channels were considered: the chemically most important H or H+ transfer/abstraction as well as atom exchange and collision induced dissociation for up to 1.0 eV of collision energy.

Validation of a Reduced Set of High-Performance Triggers for Identifying Patient Safety Incidents with Harm in Primary Care: TriggerPrim Project.

OBJECTIVE: The aim of the study was to construct and validate a reduced set of high-performance triggers for identifying adverse events (AEs) via electronic medical records (EMRs) review in primary care (PC). METHODS: This was a cross-sectional descriptive study for validating a diagnostic test. The study included all 262 PC centers of Madrid region (Spain). Patients were older than 18 years who attended their PC center over the last quarter of 2018. The randomized sample was n = 1797. Main measurements were as follows: ( a ) presence of each of 19 specific computer-identified triggers in the EMR and ( b ) occurrence of an AE. To collect data, EMR review was conducted by 3 doctor-nurse teams. Triggers with statistically significant odds ratios for identifying AEs were selected for the final set after adjusting for age and sex using logistic regression. RESULTS: The sensitivity (SS) and specificity (SP) for the selected triggers were: ≥3 appointments in a week at the PC center (SS = 32.3% [95% confidence interval {CI}, 22.8%-41.8%]; SP = 92.8% [95% CI, 91.6%-94.0%]); hospital admission (SS = 19.4% [95% CI, 11.4%-27.4%]; SP = 97.2% [95% CI, 96.4%-98.0%]); hospital emergency department visit (SS = 31.2% [95% CI, 21.8%-40.6%]; SP = 90.8% [95% CI, 89.4%-92.2%]); major opioids prescription (SS = 2.2% [95% CI, 0.0%-5.2%]; SP = 99.8% [95% CI, 99.6%-100%]); and chronic benzodiazepine treatment in patients 75 years or older (SS = 14.0% [95% CI, 6.9%-21.1%]; SP = 95.5% [95% CI, 94.5%-96.5%]).The following values were obtained in the validation of this trigger set (the occurrence of at least one of these triggers in the EMR): SS = 60.2% (95% CI, 50.2%-70.1%), SP = 80.8% (95% CI, 78.8%-82.6%), positive predictive value = 14.6% (95% CI, 11.0%-18.1%), negative predictive value = 97.4% (95% CI, 96.5%-98.2%), positive likelihood ratio = 3.13 (95% CI, 2.3-4.2), and negative likelihood ratio = 0.49 (95% CI, 0.3-0.7). CONCLUSIONS: The set containing the 5 selected triggers almost triples the efficiency of EMR review in detecting AEs. This suggests that this set is easily implementable and of great utility in risk-management practice.

Decision-support tools to build climate resilience against emerging infectious diseases in Europe and beyond.

Climate change is one of several drivers of recurrent outbreaks and geographical range expansion of infectious diseases in Europe. We propose a framework for the co-production of policy-relevant indicators and decision-support tools that track past, present, and future climate-induced disease risks across hazard, exposure, and vulnerability domains at the animal, human, and environmental interface. This entails the co-development of early warning and response systems and tools to assess the costs and benefits of climate change adaptation and mitigation measures across sectors, to increase health system resilience at regional and local levels and reveal novel policy entry points and opportunities. Our approach involves multi-level engagement, innovative methodologies, and novel data streams. We take advantage of intelligence generated locally and empirically to quantify effects in areas experiencing rapid urban transformation and heterogeneous climate-induced disease threats. Our goal is to reduce the knowledge-to-action gap by developing an integrated One Health-Climate Risk framework.

Spin-Forbidden Addition of Molecular Oxygen to Stable Enol Intermediates-Decarboxylation of 2-Methyl-1-tetralone-2-carboxylic Acid.

The deprotonation of an organic substrate is a common preactivation step for the enzymatic cofactorless addition of O2 to this substrate, as it promotes charge-transfer between the two partners, inducing intersystem crossing between the triplet and singlet states involved in the process. Nevertheless, the spin-forbidden addition of O2 to uncharged ligands has also been observed in the laboratory, and the detailed mechanism of how the system circumvents the spin-forbiddenness of the reaction is still unknown. One of these examples is the cofactorless peroxidation of 2-methyl-3,4-dihydro-1-naphthol, which will be studied computationally using single and multi-reference electronic structure calculations. Our results show that the preferred mechanism is that in which O2 picks a proton from the substrate in the triplet state, and subsequently hops to the singlet state in which the product is stable. For this reaction, the formation of the radical pair is associated with a higher barrier than that associated with the intersystem crossing, even though the absence of the negative charge leads to relatively small values of the spin-orbit coupling.

Is primary care a patient-safe setting? Prevalence, severity, nature, and causes of adverse events: numerous and mostly avoidable.

Knowing the frequency and characteristics of adverse events (AEs) is key to implementing actions that can prevent their occurrence. However, reporting systems are insufficient for this purpose and epidemiological studies are also required. Currently, the reviewing of clinical records is the gold standard method for knowing the frequency and characteristics of AEs. Research on AEs in a primary care setting has been limited and primarily focuses on specific types of events (medication errors, etc.) or patients. Large studies that search for any kind of AE in all patients are scarce. This study aimed to estimate the prevalence of AEs in the primary care setting and their characteristics. SETTING: all 262 primary health-care centres in the Madrid region (Spain) during the last quarter of 2018. DESIGN: cross-sectional descriptive study. Eligible population: subjects over 18 years of age who attended medical consultation over the last year (N = 2 743 719); a randomized sample stratified by age. MAIN OUTCOMES: age, sex, occurrence of an AE, number of consultations in the study period, avoidability, severity, place of occurrence, type of event, and contributory factors. The clinical records were reviewed by three teams, each composed of one doctor and one nurse trained and with expertise in patient safety. The SPSS software package (version 26) was used for the statistical analyses. The evaluators reviewed 1797 clinical records. The prevalence of AEs over the study period was 5.0% [95% confidence interval (CI): 4.0%‒6.0%], with higher values in women (5.7%; 95% CI: 4.6%‒6.8%;P = 0.10) and patients over 75 years of age (10.3%; 95% CI: 8.9%‒11.7%; P < 0.001). The overall occurrence per hundred consultations was estimated to be 1.58% (95% CI: 1.28%‒1.94%). Of the detected AEs, 71.3% (95% CI: 62.1%‒80.5%) were avoidable. Additionally, 60.6% (95% CI: 50.7%‒70.5%) were categorized as mild, 31.9% (95% CI: 22.4%‒41.4%) as moderate, and 7.4% (95% CI: 2.1%‒12.7%) as severe. Primary care was the occurrence setting in 76.6% (95% CI: 68.0%‒85.2%) of cases. The overall incidence of AEs related to medication was 53.2% (95% CI: 50.9%‒55.5%). The most frequent types of AEs were prescription errors (28.7%; 95% CI: 19.5%‒37.9%), followed by drug administration errors by patients (17.0%; 95% CI: 9.4%‒24.6%), and clinical assessment errors (11.7%; 95% CI: 5.2%‒18.2%). The most common contributory factors were those related to the patient (80.6%; 95% CI: 71.1%‒90.1%) and tasks (59.7%; 95% CI: 48.0%‒71.4%). A high prevalence of AEs (1 in 66 consultations) was observed, which was slightly higher than that reported in similar studies. About 3 out of 4 such events were considered to be avoidable and 1 out of 13 was severe. Prescription errors, drug administration errors by patients, and clinical assessment errors were the most frequent types of AEs. Graphical Abstract.

IGF2 interacts with the imprinted gene Cdkn1c to promote terminal differentiation of neural stem cells.

Adult neurogenesis is supported by multipotent neural stem cells (NSCs) with unique properties and growth requirements. Adult NSCs constitute a reversibly quiescent cell population that can be activated by extracellular signals from the microenvironment in which they reside in vivo. Although genomic imprinting plays a role in adult neurogenesis through dose regulation of some relevant signals, the roles of many imprinted genes in the process remain elusive. Insulin-like growth factor 2 (IGF2) is encoded by an imprinted gene that contributes to NSC maintenance in the adult subventricular zone through a biallelic expression in only the vascular compartment. We show here that IGF2 additionally promotes terminal differentiation of NSCs into astrocytes, neurons and oligodendrocytes by inducing the expression of the maternally expressed gene cyclin-dependent kinase inhibitor 1c (Cdkn1c), encoding the cell cycle inhibitor p57. Using intraventricular infusion of recombinant IGF2 in a conditional mutant strain with Cdkn1c-deficient NSCs, we confirm that p57 partially mediates the differentiation effects of IGF2 in NSCs and that this occurs independently of its role in cell-cycle progression, balancing the relationship between astrogliogenesis, neurogenesis and oligodendrogenesis.

The CH-3Σ+ Anion: Inelastic Rate Coefficients from Collisions with He at Interstellar Conditions.

We present accurate ab initio calculations on several properties of a gas-phase system of interest in the interstellar medium (ISM), where the title molecular anion has been often surmised but not yet confirmed by observations. The CH-3Σ+ constitutes the smallest term in the series of longer anionic polyynes which have been observed in the ISM (e.g., C4H- and several others). Hence, its dynamical behavior in collision with He atoms, one of the most abundant atoms in that environment, can provide quantitative indicators on the changes which can occur in the rotational state population of the title anion when driven by this collision dynamics. We therefore report an accurate evaluation of the full potential energy surface (PES) which acts between the molecular anion in its ground vibrational state and the He atom. The relevant inelastic scattering cross sections and the corresponding inelastic rate coefficients are then computed within a quantum treatment of the collisions. We find that the fairly small values of the final inelastic rate coefficients indicate state-changing processes by collisions to be inefficient paths for modifying the rotational state populations of this anion and therefore to aid its possible observation from direct radiative emission in the microwave region.

Post-transcriptional control of a stemness signature by RNA-binding protein MEX3A regulates murine adult neurogenesis.

Neural stem cells (NSCs) in the adult murine subependymal zone balance their self-renewal capacity and glial identity with the potential to generate neurons during the lifetime. Adult NSCs exhibit lineage priming via pro-neurogenic fate determinants. However, the protein levels of the neural fate determinants are not sufficient to drive direct differentiation of adult NSCs, which raises the question of how cells along the neurogenic lineage avoid different conflicting fate choices, such as self-renewal and differentiation. Here, we identify RNA-binding protein MEX3A as a post-transcriptional regulator of a set of stemness associated transcripts at critical transitions in the subependymal neurogenic lineage. MEX3A regulates a quiescence-related RNA signature in activated NSCs that is needed for their return to quiescence, playing a role in the long-term maintenance of the NSC pool. Furthermore, it is required for the repression of the same program at the onset of neuronal differentiation. Our data indicate that MEX3A is a pivotal regulator of adult murine neurogenesis acting as a translational remodeller.

Using latent profile analysis to understand palliative care professionals' quality of life during the COVID-19 pandemic.

Healthcare workers' professional quality of life has been increasingly under the spotlight, even more so during the COVID-19 pandemic, which has posed a genuine challenge for them. This study aims to describe the professional quality of life profiles of a sample of Spanish palliative care professionals during the COVID-19 pandemic, encompassing aspects such as work satisfaction, burnout, compassion fatigue, and compassion satisfaction; while studying the relationships between these profiles and sociodemographic variables, clinical situations experienced during the pandemic, protectors of professional quality of life, the quality of care delivered, and the professionals' wellbeing. Data from a survey of Spanish palliative care professionals were used. The variables measured were professional quality of life, sociodemographic characteristics, COVID-19-related experiences, protectors of professional quality of life, wellbeing, and quality of care. Our research included latent profile analyses, along with chi-squared and t-tests. The results suggested two profiles of professional quality of life, namely low (32.78%) and high (67.22%). The following profile displayed a higher likelihood of having a low professional quality of life: younger professionals, registered nurses, with a decrease in their teamwork, without specific training in palliative care, in coping with death and stress or emotional training and with lower levels of self-care and self-compassion, whose patients were unable to die a dignified death. Similarly, a low professional quality of life profile was associated with reduced wellbeing and poorer quality of care offered. In conclusion, providing professionals with education and training to improve their ability to handle end-of-life care and stress, maintaining cohesive teams and promoting self-care and self-compassion are pivotal to maintaining the quality of life and wellbeing of palliative care professionals and the quality of care that they provide.

Clinical characteristics and indications for blood transfusion in patients with SARS-CoV-2 infection.

Background: There are few data on the clinical characteristics of COVID-19 patients who require blood transfusion. We aimed to investigate the clinical characteristics and indication for transfusion in COVID-19 patients seen during the epidemic's first wave. Material and methods: Cross-sectional study that included all consecutive COVID-19 patients admitted to the Hospital Clínic of Barcelona, Spain, from mid-March to mid-May 2020. Results: A total of 80 patients received 354 RBC units, 116 plasma units, and 48 platelet units. Median age was 71 years (IQR: 62-76), and 59 (74%) were males. In total, 138 of the 261 transfusion episodes that involved RBCs (59%) were related to spontaneous (n = 94) or procedure-related (n = 44) bleeding. Spontaneous bleeding was more frequent in the retroperitoneal space and the gastrointestinal apparatus. Tracheostomy with endotracheal intubation, surgical interventions, and cannulation of femoral vessels were the main procedures behind non-spontaneous bleeding. Most patients (91%) were on anticoagulants, mostly intermediate- or full-dose heparin. Conclusion: Anticoagulation-related bleeding was a leading cause of blood transfusion in COVID-19 patients during the epidemic's first-wave.

Introducción: Las características de los pacientes con COVID-19 transfundidos son poco conocidas. Nuestro objetivo fue investigar el perfil clínico y el motivo de la transfusión en los pacientes con COVID-19 vistos durante la primera ola de la epidemia. Material y métodos: Estudio transversal que incluyó a todos los pacientes con COVID-19 transfundidos en el Hospital Clínic de Barcelona entre marzo y mayo de 2020. Resultados: Ochenta pacientes recibieron 354 unidades de hematíes, 116 de plasma y 48 de plaquetas. La edad mediana fue de 71 años y 59 (74%) eran hombres. En total, 138 de los 261 episodios de transfusión de hematíes (59%) estaban relacionados con hemorragia espontánea (n = 94: principalmente retroperitoneal y gastrointestinal) o con procedimientos invasivos (n = 44: principalmente traqueostomía, cirugía, y canulación de vasos femorales). El 91% de los pacientes recibía tratamiento anticoagulante el día de la transfusión o los dos días previos, sobre todo heparina a dosis intermedia o completa. Conclusión: El sangrado relacionado con la anticoagulación fue el motivo principal de transfusión en los pacientes con COVID-19.

Clinical characteristics and indications for blood transfusion in patients with SARS-CoV-2 infection

Background: There are few data on the clinical characteristics of COVID-19 patients who require blood transfusion. We aimed to investigate the clinical characteristics and indication for transfusion in COVID-19 patients seen during the epidemic's first wave.Material and methodsCross-sectional study that included all consecutive COVID-19 patients admitted to the Hospital Clínic of Barcelona, Spain, from mid-March to mid-May 2020.ResultsA total of 80 patients received 354 RBC units, 116 plasma units, and 48 platelet units. Median age was 71 years (IQR: 62–76), and 59 (74%) were males. In total, 138 of the 261 transfusion episodes that involved RBCs (59%) were related to spontaneous (n=94) or procedure-related (n=44) bleeding. Spontaneous bleeding was more frequent in the retroperitoneal space and the gastrointestinal apparatus. Tracheostomy with endotracheal intubation, surgical interventions, and cannulation of femoral vessels were the main procedures behind non-spontaneous bleeding. Most patients (91%) were on anticoagulants, mostly intermediate- or full-dose heparin.ConclusionAnticoagulation-related bleeding was a leading cause of blood transfusion in COVID-19 patients during the epidemic's first-wave. (AU)

Introducción: Las características de los pacientes con COVID-19 transfundidos son poco conocidas. Nuestro objetivo fue investigar el perfil clínico y el motivo de la transfusión en los pacientes con COVID-19 vistos durante la primera ola de la epidemia.Material y métodosEstudio transversal que incluyó a todos los pacientes con COVID-19 transfundidos en el Hospital Clínic de Barcelona entre marzo y mayo de 2020.ResultadosOchenta pacientes recibieron 354 unidades de hematíes, 116 de plasma y 48 de plaquetas. La edad mediana fue de 71 años y 59 (74%) eran hombres. En total, 138 de los 261 episodios de transfusión de hematíes (59%) estaban relacionados con hemorragia espontánea (n=94: principalmente retroperitoneal y gastrointestinal) o con procedimientos invasivos (n=44: principalmente traqueostomía, cirugía, y canulación de vasos femorales). El 91% de los pacientes recibía tratamiento anticoagulante el día de la transfusión o los dos días previos, sobre todo heparina a dosis intermedia o completa.ConclusiónEl sangrado relacionado con la anticoagulación fue el motivo principal de transfusión en los pacientes con COVID-19. (AU)