Modelo proceso-respuesta de recesión de acantilados por variación del nivel del mar. Aplicación en la Costa de Holderness (Reino Unido).

El desarrollo de modelos predictivos de retroceso de acantilados costeros se encuentra limitado desde el punto de vista geomorfológico debido a la complejidad e interacción de los procesos de desarrollo espacio-temporal que tienen lugar en la zona costera. Los códigos de cálculo existentes en la actualidad incorporan modelos probabilísticos para resolver la estabilidad geomecánica de los materiales. Éstos pueden reproducir tasas de recesión históricas; sin embargo, el comportamiento bajo condiciones variables (cambio climático) no tiene por qué ser el mismo. Se presenta un modelo de proceso-respuesta de retroceso de acantilados costeros que incorpora el comportamiento geomecánico de costas compuestas por tills, incluye la acción protectora de los derrubios presentes al pie del acantilado frente a los procesos erosivos y permite evaluar el efecto del ascenso del nivel medio del mar asociado al cambio climático. Para ello, se acoplan la dinámica marina: nivel medio del mar, mareas y oleaje; con la evolución del terreno: erosión, desprendimiento rocoso y formación de talud de derrubios. La erosión del acantilado se calcula en función del nivel del mar, de las condiciones del oleaje incidente, de la pendiente de la plataforma rocosa y de la resistencia del material rocoso afectado en cada ciclo de marea. Al finalizar cada ciclo, se evalúa la ruptura del acantilado según un criterio geomecánico de roturas por vuelco y en caso de rotura, se genera un talud de derrubios al pie del mismo. El modelo ha sido validado frente a datos reales en la costa de Holderness, Yorkshire, Reino Unido. Los resultados obtenidos presentan un importante avance en los modelos de recesión costera, especialmente en su relación con las condiciones geomecánicas del medio y su respuesta ante condiciones variables del nivel medio del mar producidas por el cambio climático

Aerosol‐Jet‐Printed Donor‐Blocking Layer for Organic Photodiodes

Organic photodiodes (OPDs) are optical sensors combining high performance, lightweight mechanical flexibility, and processability from solution. Their fabrication by industrial printing techniques opens a wide range of innovative applications for emerging fields in sensing and the Internet of Things. They typically consist of printed multilayers with functionalities to absorb light, to extract charges, or to reduce detection noise. However, the printing of such device architecture poses a challenge as the deposition of a material can lead to disruption of film morphology or intermixing of materials if its solvent interacts with the previously deposited layer. This work proposes a process to print multilayers from the same solvent system utilizing the aerosol-jet technique. By fine adjustment of the aerosol properties through the tube temperature (TTube), the drying time of poly(3-hexylthiophene-2,5-diyl) (P3HT) printed layers is significantly reduced. This allows its deposition onto a P3HT-based bulk-heterojunction (BHJ) without negatively affecting its performance. The additional printed P3HT layer, spatially extends the donor region of the BHJ, providing ideal hole extraction and simultaneous noise reduction by the blocking of injected electrons. This donor blocking layer (DBL) yields a noise reduction of two orders of magnitude in OPDs operated under −2 V reverse bias

Role of bacterial community composition as a driver of the small-sized phytoplankton community structure in a productive coastal system

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGWe present here the first detailed description of the seasonal patterns in bacterial community composition (BCC) in shelf waters off the Ría de Vigo (Spain), based on monthly samplings during 2 years. Moreover, we studied the relationship between bacterial and small-sized eukaryotic community composition to identify potential biotic interactions among components of these two communities. Bacterial operational taxonomic unit (OTU) richness and diversity systematically peaked in autumn–winter, likely related to low resource availability during this period. BCC showed seasonal and vertical patterns, with Rhodobacteraceae and Flavobacteriaceae families dominating in surface waters, and SAR11 clade dominating at the base of the photic zone (30 m depth). BCC variability was significantly explained by environmental variables (e.g., temperature of water, solar radiation, or dissolved organic matter). Interestingly, a strong and significant correlation was found between BCC and small-sized eukaryotic community composition (ECC), which suggests that biotic interactions may play a major role as structuring factors of the microbial plankton in this productive area. In addition, co-occurrence network analyses revealed strong and significant, mostly positive, associations between bacteria and small-sized phytoplankton. Positive associations likely result from mutualistic relationships (e.g., between Dinophyceae and Rhodobacteraceae), while some negative correlations suggest antagonistic interactions (e.g., between Pseudo-nitzchia sp. and SAR11). These results support the key role of biotic interactions as structuring factors of the small-sized eukaryotic community, mostly driven by positive associations between small-sized phytoplankton and bacteria.Xunta de Galicia | Ref. EM2013/023Xunta de Galicia | Ref. ED481A-2019/290Xunta de Galicia | Ref. ED431I 2020/03Ministerio de Economía y Competitividad | Ref. CTM2017-83362-RMinisterio de Ciencia e Innovación | Ref. PID2019-110011RB-C3

Phytomelatonin content in Valeriana officinalis L. and some related phytotherapeutic supplements

The use of medicinal plants as an alternative phytotherapeutic remedy against mild illnesses and dysfunctions is increasingly embraced by people. Among these dysfunctions, episodes of nervousness and anxiety due to lack of sleep and insomnia are becoming more and more frequent among the population. To remedy these problems, several plants with sedative activity are recommended. In particular, valerian root (Valeriana officinalis L.) is the most recommended and studied with a significant difference. This study presented a quantification of the phytomelatonin contents in valerian root and several related and recommended herb supplements against nervousness, anxiety, and insomnia. The results showed the presence of phytomelatonin in all the samples analyzed. The high phytomelatonin contents in valerian root and its supplements indicated that, in addition to the known constituents of valerian root such as valerenic acid, phytomelatonin also contributed to the phytotherapeutic activity of this plant since the relaxing and sleep-inducing activity of melatonin is well documented. The recommended daily doses of valerian are analyzed according to their phytomelatonin content, and recommendations are given on the possible synergistic action of the components of valerian as a relaxant and sleep inducer in patients with these dysfunctions. It is also recommended to document the phytomelatonin contents in phytotherapeutic preparations

Early and annual projected savings from anti-CGRP monoclonal antibodies in migraine prevention: a cost-benefit analysis in the working-age population

Anti-CGRP monoclonal antibodies; Migraine prevention; Cost-benefitAnticuerpos monoclonales anti-CGRP; Prevención de la migraña; Costo-beneficioAnticossos monoclonals anti-CGRP; Prevenció de la migranya; Cost-beneficiBackground Migraine is one of the main causes of disability worldwide. Anti-CGRP monoclonal antibodies (MAbs) have proven to be safe and efficacious as preventive migraine treatments. However, their use is restricted in many countries due to their apparently high cost. Cost-benefit studies are needed. Objective To study the cost-benefit of anti-CGRP MAbs in working-age patients with migraine. Methods This is a prospective cohort study of consecutive migraine patients treated with anti-CGRP MAbs (erenumab, fremanezumab and galcanezumab) following National reimbursement policy in a specialized headache clinic. Migraine characteristics and the work impact scale (WPAI) were compared between baseline (M0) and after 3 (M3) and 6 months (M6) of treatment. Using WPAI and the municipal average hourly wage, we calculated indirect costs (absenteeism and presenteeism) at each time point. Direct costs (emergency visits, acute medication use) were also analysed. A cost-benefit study was performed considering the different costs and savings of treating with MAbs. Based on these data an annual projection was conducted. Results From 256 treated working-age patients, 148 were employed (89.2% women; mean age 48.0 ± 8.5 years), of which 41.2% (61/148) were responders (> 50% reduction in monthly headache days (MHD)). Statistically significant reductions between M0 and M3/M6 were found in absenteeism (p < 0.001) and presenteeism (p < 0.001). Average savings in indirect costs per patient at M3 were absenteeism 105.4 euros/month and presenteeism 394.3 euros/month, similar for M6. Considering the monthly cost of anti-CGRP MAbs, the cost-benefit analysis showed savings of 159.8 euros per patient at M3, with an annual projected savings of 639.2 euros/patient. Both responders and partial responders (30–50% reduction in MHD) presented a positive cost-benefit balance. The overall savings of the cohort at M3/M6 compensated the negative cost-benefit balance for non-responders (< 30% reduction in MHD). Conclusion Anti-CGRP MAbs have a positive impact in the workforce significantly reducing absenteeism and presenteeism. In Spain, this benefit overcomes the expenses derived from their use already at 3 months and is potentially sustainable at longer term; also in patients who are only partial responders, prompting reconsideration of current reimbursement criteria and motivating the extension of similar cost-benefit studies in other countries

Intrasaccular Flow Disruptor-Assisted Coiling of Intracranial Aneurysms Using the Novel Contour Neurovascular Systems and NEQSTENT: A Single-Center Safety and Feasibility Study

Brain aneurysms; Endovascular treatment; Intrasaccular devicesAneurismas cerebrales; Tratamiento endovascular; Dispositivos intrasacularesAneurismes cerebrals; Tractament endovascular; Dispositius intrasacularsBackground: Intrasaccular flow disruptors (IFD) have been introduced in the treatment of intracranial aneurysms (IAs) to overcome the low aneurysm occlusion rate and the high recanalization rate of the coiling technique. Among them, the Contour Neurovascular System (CNS) and the Neqstent (NQS) were designed to reconstruct the aneurysmal neck and both can be used as assisting coiling devices. We aimed to report our preliminary experience with the flow disruptor-assisted coiling (IFD-AC) technique. Methods: We performed a retrospective analysis of prospectively collected data of all patients with IAs treated with the IFD-AC. Results: Between February 2021 and April 2022, we treated 15 IAs with the IFD-AC: 10 ruptured and 5 unruptured. The IFD-AC was successfully performed in 13 cases, with a post-operative RROC 1 in 12 cases (92.3%) and RROC 2 in 1 case (7.7%). There was one ischemic event (6.7%) and no hemorrhagic complications. Twelve patients underwent a mid-term radiologic follow-up: Ten IAs (83.4%) presented an adequate occlusion, while 2 (16.7%) had a recurrence. Conclusions: The IFD-AC, both with the CNS and the NQS, seems a safe technique with promising efficacy profile. The IFD-AC has proved to be safe without antiplatelet therapy in ruptured cases. Further studies are needed to confirm our preliminary results

Clinical Outcomes of Severe COVID-19 Patients Admitted to an Intermediate Respiratory Care Unit

Introduction: Many severe COVID-19 patients require respiratory support and monitoring. An intermediate respiratory care unit (IMCU) may be a valuable element for optimizing patient care and limited health-care resources management. We aim to assess the clinical outcomes of severe COVID-19 patients admitted to an IMCU. Methods: Observational, retrospective study including patients admitted to the IMCU due to COVID-19 pneumonia during the months of March and April 2020. Patients were stratified based on their requirement of transfer to the intensive care unit (ICU) and on survival status at the end of follow-up. A multivariable Cox proportional hazards method was used to assess risk factors associated with mortality. Results: A total of 253 patients were included. Of them, 68% were male and median age was 65 years (IQR 18 years). Ninety-two patients (36.4%) required ICU transfer. Patients transferred to the ICU had a higher mortality rate (44.6 vs. 24.2%; p < 0.001). Multivariable proportional hazards model showed that age ≥65 years (HR 4.14; 95%CI 2.31-7.42; p < 0.001); chronic respiratory conditions (HR 2.34; 95%CI 1.38-3.99; p = 0.002) and chronic kidney disease (HR 2.96; 95%CI 1.61-5.43; p < 0.001) were independently associated with mortality. High-dose systemic corticosteroids followed by progressive dose tapering showed a lower risk of death (HR 0.15; 95%CI 0.06-0.40; p < 0.001). Conclusions: IMCU may be a useful tool for the multidisciplinary management of severe COVID-19 patients requiring respiratory support and non-invasive monitoring, therefore reducing ICU burden. Older age and chronic respiratory or renal conditions are associated with worse clinical outcomes, while treatment with systemic corticosteroids may have a protective effect on mortality

The early-life exposome and epigenetic age acceleration in children

The early-life exposome influences future health and accelerated biological aging has been proposed as one of the underlying biological mechanisms. We investigated the association between more than 100 exposures assessed during pregnancy and in childhood (including indoor and outdoor air pollutants, built environment, green environments, tobacco smoking, lifestyle exposures, and biomarkers of chemical pollutants), and epigenetic age acceleration in 1,173 children aged 7 years old from the Human Early-Life Exposome project. Age acceleration was calculated based on Horvath’s Skin and Blood clock using child blood DNA methylation measured by Infinium HumanMethylation450 BeadChips. We performed an exposure-wide association study between prenatal and childhood exposome and age acceleration. Maternal tobacco smoking during pregnancy was nominally associated with increased age acceleration. For childhood exposures, indoor particulate matter absorbance (PMabs) and parental smoking were nominally associated with an increase in age acceleration. Exposure to the organic pesticide dimethyl dithiophosphate and the persistent pollutant polychlorinated biphenyl-138 (inversely associated with child body mass index) were protective for age acceleration. None of the associations remained significant after multiple-testing correction. Pregnancy and childhood exposure to tobacco smoke and childhood exposure to indoor PMabs may accelerate epigenetic aging from an early ageThe study received funding from the European Community’s Seventh Framework Programme (FP7/2007-206) (grant agreement no 308333) (HELIX project), the H2020-EU.3.1.2. - Preventing Disease Programme (grant agreement no 874583) (ATHLETE project), and from the European Union’s Horizon 2020 research and innovation programme (grant Agreement number: 733206) (Early Life stressors and Lifecycle Health (LIFECYCLE)). BiB received funding from the Welcome Trust (WT101597MA), from the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) (MR/N024397/1). INMA was supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU- FP7- HEALTH-2012 Proposal No 308333 HELIX), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011-2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-15). We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. OR was funded by a UKRI Future Leaders Fellowship (MR/S03532X/1). MV-U and CR-A were supported by a FI fellowship from the Catalan Government (FI-DGR 2015 and #016FI_B 00272). MC received funding from Instituto Carlos III (Ministry of Economy and Competitiveness) (CD12/00563 and MS16/00128)S

Direct-acting Antivirals for the Treatment of Kidney Transplant Patients With Chronic Hepatitis C Virus Infection in Spain: A Long-term Prospective Observational Study

Background: Direct-acting antivirals (DAA) allow effective and safe eradication of hepatitis C virus (HCV) in most patients. There are limited data on the long-term effects of all-oral, interferon-free DAA combination therapies in kidney transplant (KT) patients infected with HCV. Here we evaluated the long-term tolerability, efficacy, and safety of DAA combination therapies in KT patients with chronic HCV infection. Methods: Clinical data from KT patients treated with DAA were collected before, during, and after the treatment, including viral response, immunosuppression regimens, and kidney and liver function. Results: Patients (N = 226) were mostly male (65.9%) aged 56.1 +/- 10.9 years, with a median time from KT to initiation of DAA therapy of 12.7 years and HCV genotype 1b (64.6%). Most patients were treated with sofosbuvir-based therapies. Rapid virological response at 1 month was achieved by 89.4% of the patients and sustained virological response by week 12 by 98.1%. Liver function improved significantly after DAA treatment. Tacrolimus dosage increased 37% from the beginning of treatment (2.5 +/- 1.7 mg/d) to 1 year after the start of DAA treatment (3.4 +/- 1.9 mg/d, P < 0.001). Median follow-up was 37.0 months (interquartile range, 28.4-41.9) and death-censored graft survival was 91.1%. Adverse events resulting from DAA treatment, especially anemia, were reported for 31.0% of the patients. Conclusions: Chronic HCV infection can be treated efficiently and safely with DAA therapy in KT patients. Most patients retained stable kidney function and improved liver function. Tacrolimus dose had to be increased in most patients, potentially as a result of better liver function

ERK5 Is a major determinant of chemical sarcomagenesis: implications in human pathology

Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5–KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology.This work has been supported with Grant RTI2018-094093-B-I00 funded by MCIN/AEI/10.13039/501100011033, “ERDF A way of making Europe” to RSP. Also supported with funds from Fundación Leticia Castillejo Castillo, Roche España and ACEPAIN to RSP and MJRH. RSP and MJRH’s Research Institute and the work carried out in their laboratory, received partial support from the European Community through the FEDER. JJ and EAL hold a predoctoral research contract cofounded by the European Social Fund and UCLM. OR holds a contract for accessing the Spanish System of Science, Technology, and Innovation (SECTI) funded by the University of Castilla-La Mancha (UCLM) and received partial support from the European Social Fund (FSE) through its Operative Program for Castilla-La Mancha (2007–2013)