Rh(III)‐Catalyzed [5+1] Oxidative Cycloaddition of Arylguanidines with Alkynes: A Novel Access to C4‐Disubstituted 1,4‐ Dihydroquinazolin‐2‐amines

NOTICE: This is the peer reviewed version of the following article: Cajaraville, A., Suárez, J., López, S., Varela. J. A., Saá, C. (2015). Rh(III)‐Catalyzed [5+1] Oxidative Cycloaddition of Arylguanidines with Alkynes: A Novel Access to C4‐Disubstituted 1,4‐ Dihydroquinazolin‐2‐amines. Chem. Commun., 51, 82, 15157-15160. [doi: 10.1039/C5CC06388D]. This article may be used for non-commercial purposes in accordance with The Royal Society of Chemistry Terms and Conditions for self-archivingA novel and mild RhIII-catalyzed [5+1] oxidative cycloaddition between arylguanidines and alkynes efficiently affords C4-disubstituted 1,4-dihydroquinazolin-2-amines. Members of this family of heterocycles, which contain the relevant cyclic guanidine units, have shown interesting pharmacological properties. The mechanism probably involves the formation of an eight-membered rhodacycle in which the imine unit of guanidine is coordinated to the Rh center. This rhodacycle would evolve to give the C-4 disubstituted 1,4-dihydroquinazolin-2-amine skeleton.This work was supported by MICINN (project CTQ2011‐28258), Xunta de Galicia and European Regional Development Fund (projects GRC2014/032 and EM 2012/051). A. C. and J. S. thank Spanish MICINN and Xunta de Galicia for a predoctoral FPI fellowship and postdoctoral contract, respectivelyS

Granger Causality-based Information Fusion Applied to Electrical Measurements from Power Transformers.

In the immediate future, with the increasing presence of electrical vehicles and the large increase in the use of renewable energies, it will be crucial that distribution power networks are managed, supervised and exploited in a similar way as the transmission power systems were in previous decades. To achieve this, the underlying infrastructure requires automated monitoring and digitization, including smart-meters, wide-band communication systems, electronic device based-local controllers, and the Internet of Things. All of these technologies demand a huge amount of data to be curated, processed, interpreted and fused with the aim of real-time predictive control and supervision of medium/low voltage transformer substations. Wiener–Granger causality, a statistical notion of causal inference based on Information Fusion could help in the prediction of electrical behaviour arising from common causal dependencies. Originally developed in econometrics, it has successfully been applied to several fields of research such as the neurosciences and is applicable to time series data whereby cause precedes effect. In this paper, we demonstrate the potential of this methodology in the context of power measures for providing theoretical models of low/medium power transformers. Up to our knowledge, the proposed method in this context is the first attempt to build a data-driven power system model based on G-causality. In particular, we analysed directed functional connectivity of electrical measures providing a statistical description of observed responses, and identified the causal structure within data in an exploratory analysis. Pair-wise conditional G-causality of power transformers, their independent evolution in time, and the joint evolution in time and frequency are discussed and analysed in the experimental section.This work was partly supported by the MINECO/ FEDER under the RTI2018- 098913-B100 project. The authors would like to acknowledge the support of 370 CDTI (Centro para el Desarrollo Tecnologico Industrial, Ministerio de Cien cia, Innovacion y Universidades and FEDER, SPAIN) under the PASTORA project (Ref.: ITC-20181102). and to thank the companies within the PAS TORA consortium: Endesa, Ayesa, Ormaz´abal and Ingelectus. We would like to thank the reviewers for their thoughtful comments and efforts towards im 375 proving our manuscript. Finally, JM Gorriz would like to thank Dr G´omez Exp´osito for his helpful advice and comments

Effectiveness of COVID-19 vaccine booster in the general population and in subjects with comorbidities. A population-based study in Spain

This work was supported by Framework Partnership Agreement between the Consellería de Sanidad de la XUNTA de Galicia and GENVIP-IDIS-2021–2024 (SERGAS-IDIS March 2021; Spain); and consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CB21/06/00103; F.M-T), DIAVIR (Instituto de Salud Carlos III (ISCIII)/DTS19/00049/Cofinanciado FEDER; Proyecto de Desarrollo Tecnológico en Salud), Resvi-Omics (Instituto de Salud Carlos III (ISCIII)/PI19/01039/Cofinanciado FEDER), BI-BACVIR (PRIS-3; Agencia de Conocimiento en Salud (ACIS)—Servicio Gallego de Salud (SERGAS)—Xunta de Galicia; Spain), Programa Traslacional COVID-19 (ACIS—Servicio Gallego de Salud (SERGAS)—XUNTA de Galicia; Spain) and Axencia Galega de Innovación (GAIN; IN607B 2020/08—XUNTA de Galicia; Spain) [A.S]; and ReSVinext (Instituto de Salud Carlos III (ISCIII)/PI16/01569/Cofinanciado FEDER), Enterogen (Instituto de Salud Carlos III (ISCIII)/PI19/01090/Cofinanciado FEDER), and Axencia Galega de Innovación (GAIN; IN845D 2020/23—Xunta de Galicia; Spain) [F.M-T]Background: Research on the effectiveness of COVID-19 booster-based vaccine schedule is ongoing and real-world data on vaccine effectiveness (VE) in comorbid patients are limited. We aimed to estimate booster dose VE against SARS-CoV-2 infection and COVID-19 severity in the general population and in comorbid patients. Method: A retrospective test-negative control study was undertaken in Galicia-Spain (December 2020–November 2021). VE and 95% confidence interval (CI) were estimated using multivariate logistic regression models. Results: 1,512,415 (94.13%) negative and 94,334 (5.87%) positive SARS-CoV-2 test results were included. A booster dose of COVID-19 vaccine is associated with substantially higher protection against SARS-CoV-2 infection than vaccination without a booster [VEboosted = 87% (95%CI: 83%; 89%); VEnon-boosted = 66% (95%CI: 65%; 67%)]. The high VE was observed in all ages, but was more pronounced in subjects older than 65 years. VE against COVID-19 severity was analyzed in a mixed population of boosted and non-boosted individuals and considerable protection was obtained [VE: hospitalization = 72% (95%CI: 68%; 75%); intensive care unit administration = 83% (95%CI: 78%; 88%), in-hospital mortality = 66% (95%CI: 53%; 75%)]. Boosted comorbid patients are more protected against SARS-CoV-2 infection than those who were non-boosted. This was observed in a wide range of major diseases including cancer (81% versus 54%), chronic obstructive pulmonary disease (84% versus 61%), diabetes (84% versus 65%), hypertension (82% versus 65%) and obesity (91% versus 67%), among others. Conclusions: A booster dose of COVID-19 vaccine increases the protection against SARS-CoV-2 infection and COVID-19 severity in the general population and in comorbid patients.S

Effectiveness of family metacognitive training in mothers with psychosis and their adolescent children: a multicenter study protocol

BackgroundMore than half of women with psychosis take care of their children despite the difficulties caused by the disease. Additionally, these kids have a higher risk of developing a mental health disorder. However, no interventions have been developed to meet these needs. Metacognitive Training (MCT) is a psychological intervention that has demonstrated its efficacy in improving cognitive insight, symptom management and social cognition in people with first-episode psychosis (FEP). Additionally, MCT has shown better results in women than men with FEP. This study aims to adapt and evaluate the efficacy of MCT-F in mothers and adolescent children in an online group context with the main purpose of improving family relationships, cognitive awareness and symptoms in women with psychosis and increase their children’s knowledge of the disease and their functioning. As secondary objectives, it also aims to evaluate improvements in metacognition, social cognition, symptoms, protective factors and self-perception of stigma.Materials and methodsA quasi-experimental design with participants acting as their own control will be carried out. Forty-eight mothers with psychosis and their adolescent children (between 12 and 20 years old) recruited from a total of 11 adult mental health care centers will receive MCT-F. Participants will be evaluated 11 weeks before the intervention (T1), at baseline (T2), and post-intervention (T3) with a cognitive insight scale, as a primary outcome. Measures of metacognitive and social cognition, symptoms, cognitive functioning, family and social functioning, protective factors (self-esteem, resilience, and coping strategies) and self-perceived stigma will be addressed as secondary outcomes. Assessment will also address trauma and attachment in mothers and, lastly, the feasibility and acceptability of MCT-F in both participant groups.DiscussionThis will be the first investigation of the efficacy, acceptability, and viability of the implementation of MCT-F. The results of this study may have clinical implications, contributing to improving mothers’ with psychosis and adolescents’ functioning and better understanding of the disease, in addition to the possible protective and preventive effect in adolescents, who are known to be at higher risk of developing severe mental disorders.Clinical trial registration:https://clinicaltrials.gov/, identifier [NCT05358457]

Examining the immune signatures of SARS-CoV-2 infection in pregnancy and the impact on neurodevelopment: Protocol of the SIGNATURE longitudinal study.

The COVID-19 pandemic represents a valuable opportunity to carry out cohort studies that allow us to advance our knowledge on pathophysiological mechanisms of neuropsychiatric diseases. One of these opportunities is the study of the relationships between inflammation, brain development and an increased risk of suffering neuropsychiatric disorders. Based on the hypothesis that neuroinflammation during early stages of life is associated with neurodevelopmental disorders and confers a greater risk of developing neuropsychiatric disorders, we propose a cohort study of SARS-CoV-2-infected pregnant women and their newborns. The main objective of SIGNATURE project is to explore how the presence of prenatal SARS-CoV-2 infection and other non-infectious stressors generates an abnormal inflammatory activity in the newborn. The cohort of women during the COVID-19 pandemic will be psychological and biological monitored during their pregnancy, delivery, childbirth and postpartum. The biological information of the umbilical cord (foetus blood) and peripheral blood from the mother will be obtained after childbirth. These samples and the clinical characterisation of the cohort of mothers and newborns, are tremendously valuable at this time. This is a protocol report and no analyses have been conducted yet, being currently at, our study is in the recruitment process step. At the time of this publication, we have identified 1,060 SARS-CoV-2 infected mothers and all have already given birth. From the total of identified mothers, we have recruited 537 SARS-COV-2 infected women and all of them have completed the mental health assessment during pregnancy. We have collected biological samples from 119 mothers and babies. Additionally, we have recruited 390 non-infected pregnant women

Model of teleconsultation pharmaceutical integrated in the electronic clinical history of the patient

OBJECTIVE: Describe the phases of implementation, scaling and integration of a pharmacy teleconsultation model in electronic history, to coordinate the care transition of patients. METHOD: Descriptive and retrospective study in a health area of 500,000 inhabitants (3 years). In the first phase, a working group was created, a communication platform was designed and a continuity program was piloted between a hospital pharmacist and the 13 primary care pharmacists. The objective was to solve problems related to medications (especially those of sanitary approval) in polymedicated patients hospitalized in the Short Stay Unit- Emergency. In a second phase, the program included all the patients in any unit and all the pharmacists in the hospital. In the third phase, the program was extended to the teleconsultation format within the corporate information systems of the Health Service. Quantitative descriptive variables were recorded (number, motives and resolution of the teleconsultations). RESULTS: In total, more than 470 consultations were registered (118 in the first phase, 158 in the second and 194 in the third), which were resolved in 90% of the cases. The main reasons were discrepancies in type approval drugs, prescribed in the care transition and nutritional assessment. CONCLUSIONS: Teleconsultation allows the coordination of pharmaceutical care between levels, quickly and easily. Increase the visibility and access of professionals. Problems are resolved without displacements or time delays for patients

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case–Control Study (COVID-19-EII)

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case-control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March-July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3-5.9), occupational risk (OR: 2.9; 95%CI: 1.8-4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2-2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09-0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes