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The treatment of dyslipidemia exhibits wide variability in clinical practice and important limitations that make lipid-lowering goals more difficult to attain. Getting to know the management of these patients in clinical practice is key to understand the existing barriers and to define actions that contribute to achieving the therapeutic goals from the most recent Clinical Practice Guidelines.Observatory where the information gathered is based on routine clinical practice and the experience from the healthcare professionals involved in the treatment of dyslipidemia in Spain. The information is collected by health area through: (i) face-to-face meeting with three different medical specialties and (ii) quantitative information related to hypercholesterolemia patients' management (ad-hoc questionnaire). Information includes patients' profiles, assistance burden, guidelines and protocols used, goal attainment, limitations and opportunities in clinical practice.145 health areas are planned to be included, with the participation of up to 435 healthcare professionals from the 17 Autonomous Regions of Spain. Information collection will result in aggregated data from over four thousand patients.This observatory aims to understand how hypercholesterolemia is being treated in routine clinical practice in Spain. Even though the preliminary results show important improvement areas in the treatment of dyslipidemias, mechanisms to drive a change towards health outcomes optimization are also identified.

Gliomas are stratified by the presence of a hotspot mutation in the enzyme isocitrate dehydrogenase genes (IDH1/2). While mutated IDH (mIDH) correlates with better prognosis, the role of this mutation in antitumor immunity and the response to immunotherapy is not completely understood. Understanding the relationship between the genetic features of these tumors and the tumor immune microenvironment (TIME) may help to develop appropriate therapeutic strategies.In this review we discussed the available literature related to the potential role of IDH mutations as an immunotherapeutic target in gliomas and profiled the immune transcriptome of glioma biopsies. We aimed to shed light on the role of mIDH on the immunological landscape of the different subtypes of gliomas, taking into account the most recent WHO classification of tumors of the central nervous system (CNS). We also discussed different immunotherapeutic approaches to target mIDH tumors and to overcome their immunosuppressive microenvironment.Data presented here indicates that the TIME not only differs in association with IDH mutation status, but also within glioma subtypes, suggesting that the cellular context affects the overall effect of this genetic lesion. Thus, specific therapeutic combinations may help patients diagnosed with different glioma subtypes.

The complex genetics underlying human cardiac disease is evidenced by its heterogenous manifestation, multigenic basis, and sporadic occurrence. These features have hampered disease modeling and mechanistic understanding. Here, we show that 2 structural cardiac diseases, left ventricular noncompaction (LVNC) and bicuspid aortic valve, can be caused by a set of inherited heterozygous gene mutations affecting the NOTCH ligand regulator MIB1 (MINDBOMB1) and cosegregating genes. We used CRISPR-Cas9 gene editing to generate mice harboring a nonsense or a missense MIB1 mutation that are both found in LVNC families. We also generated mice separately carrying these MIB1 mutations plus 5 additional cosegregating variants in the ASXL3, APCDD1, TMX3, CEP192, and BCL7A genes identified in these LVNC families by whole exome sequencing. Histological, developmental, and functional analyses of these mouse models were carried out by echocardiography and cardiac magnetic resonance imaging, together with gene expression profiling by RNA sequencing of both selected engineered mouse models and human induced pluripotent stem cell-derived cardiomyocytes. Potential biochemical interactions were assayed in vitro by coimmunoprecipitation and Western blot. Mice homozygous for the MIB1 nonsense mutation did not survive, and the mutation caused LVNC only in heteroallelic combination with a conditional allele inactivated in the myocardium. The heterozygous MIB1 missense allele leads to bicuspid aortic valve in a NOTCH-sensitized genetic background. These data suggest that development of LVNC is influenced by genetic modifiers present in affected families, whereas valve defects are highly sensitive to NOTCH haploinsufficiency. Whole exome sequencing of LVNC families revealed single-nucleotide gene variants of ASXL3, APCDD1, TMX3, CEP192, and BCL7A cosegregating with the MIB1 mutations and LVNC. In experiments with mice harboring the orthologous variants on the corresponding Mib1 backgrounds, triple heterozygous Mib1 Apcdd1 Asxl3 mice showed LVNC, whereas quadruple heterozygous Mib1 Cep192 Tmx3;Bcl7a mice developed bicuspid aortic valve and other valve-associated defects. Biochemical analysis suggested interactions between CEP192, BCL7A, and NOTCH. Gene expression profiling of mutant mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes revealed increased cardiomyocyte proliferation and defective morphological and metabolic maturation. These findings reveal a shared genetic substrate underlying LVNC and bicuspid aortic valve in which MIB1-NOTCH variants plays a crucial role in heterozygous combination with cosegregating genetic modifiers. This study was supported by grants PID2019-104776RB-I00 and PID2020-120326RB-I00, CB16/11/00399 (CIBER CV) financed by MCIN/AEI/10.13039/501100011033, a grant from the Fundación BBVA (Ref. BIO14_298), and a grant from Fundació La Marató de TV3 (Ref. 20153431) to J.L.d.l.P. M.S.-A. was supported by a PhD contract from the Severo Ochoa Predoctor-al Program (SVP-2014-068723) of the MCIN/AEI/10.13039/501100011033. J.R.G.-B. was supported by SEC/FEC-INV-BAS 21/021. A.R. was funded by grants from MCIN (PID2021123925OB-I00), TerCel (RD16/0011/0024), AGAUR (2017-SGR-899), and Fundació La Marató de TV3 (201534-30). J.M.P.-P. was supported by RTI2018-095410-B-I00 (MCIN) and PY2000443 (Junta de Andalucía). B.I. was supported by the European Commission (H2020-HEALTH grant No. 945118) and by MCIN (PID2019-107332RB-I00). DO’R was sup-ported by the Medical Research Council (MC-A658-5QEB0) and KAMcG by the British Heart Foundation (RG/19/6/34387, RE/18/4/34215). The cost of this publication was supported in part with funds from the European Regional Devel-opment Fund. The Centro Nacional de Investigaciones Cardiovasculares is sup-ported by the ISCIII, the MCIN, and the Pro Centro Nacional de Investigaciones Cardiovasculares Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020001041-S) financed by MCIN/AEI/10.13039/501100011033. For the purpose of open access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising. Sí

Purpose/Aim There are limited studies addressing the knowledge of healthcare professionals (HCPs) on the Medical Science Liaison (MSL) role. The objective of this study was to determine the percentage of HCPs that know the role, and to describe their opinion about the utility of the MSL activities on their clinical practice. Methods An online survey was completed by 107 HCPs between June 2019 and January 2020 through three Scientific Societies. It consisted of 17 or 25 questions, depending on the answers. Results Most HCPs (73.8%) knew the MSL role inside the pharmaceutical industry and were able to differentiate the MSL role from others in marketing/sales departments (77.6%). Support for research projects (70.8%) and training courses (68.1%) were the most valuable activities. Participants scored the credibility of data provided by the MSL with a mean of 7.5 (out of 10), and the added value that the MSL provides to their clinical practice with a mean of 6.9. Among HCPs unfamiliar with the role (26.2%), 60% of them are interested in meeting with the local MSL. Conclusion Our study demonstrates that the MSL role is well-known by HCPs, mostly Key Opinion Leaders, and they agree on the importance of working together in scientific projects on, e.g., disease awareness, medical training, or clinical trials. Given the advance of targeted therapies and the move toward personalized medicine, the MSL role will be in more demand and necessary for HCPs in the years to come.

A systematic review on the topic of automatic detection of COVID-19 using audio signals was performed. A total of 48 papers were obtained after screening 659 records identified in the PubMed, IEEE Xplore, Embase, and Google Scholar databases. The reviewed studies employ a mixture of open-access and self-collected datasets. Because COVID-19 has only recently been investigated, there is a limited amount of available data. Most of the data are crowdsourced, which motivated a detailed study of the various pre-processing techniques used by the reviewed studies. Although 13 of the 48 identified papers show promising results, several have been performed with small-scale datasets (lt;200). Among those papers, convolutional neural networks and support vector machine algorithms were the best-performing methods. The analysis of the extracted features showed that Mel-frequency cepstral coefficients and zero-crossing rate continue to be the most popular choices. Less common alternatives, such as non-linear features, have also been proven to be effective. The reported values for sensitivity range from 65.0% to 99.8% and those for accuracy from 59.0% to 99.8%.

Natural killer (NK) cells recognize and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated human NK cells and their secreted extracellular vesicles (EVs) led to the identification of a specific repertoire of NK-EV-associated microRNAs and their post-transcriptional modifications signature. Several microRNAs of NK-EVs, namely miR-10b-5p, miR-92a-3p, and miR-155-5p, specifically target molecules involved in Th1 responses. NK-EVs promote the downregulation of GATA3 mRNA in CD4+ T cells and subsequent TBX21 de-repression that leads to Th1 polarization and IFN-γ and IL-2 production. NK-EVs also have an effect on monocyte and moDCs (monocyte-derived dendritic cells) function, driving their activation and increased presentation and costimulatory functions. Nanoparticle-delivered NK-EV microRNAs partially recapitulate NK-EV effects in mice. Our results provide new insights on the immunomodulatory roles of NK-EVs that may help to improve their use as immunotherapeutic tools. This manuscript was funded by grants PDI-2020-120412RB-I00 and PDC2021- 121719-I00 (FS-M) and PID2020- 119352RB-I00 (AS) from the Spanish Ministry of Economy and Competitiveness; CAM (S2017/BMD3671-INFLAMUNE-CM) from the Comunidad de Madrid (FS-M). CIBERCV (CB16/11/00272) and BIOIMID PIE13/041 from the Instituto de Salud Carlos. The current research has received funding from 'la Caixa' Foundation under the project code HR17-00016. Grants from Ramón Areces Foundation 'Ciencias de la Vida y de la Salud' (XIX Concurso-2018) and from Ayuda Fundación BBVA y Equipo de Investigación Científica (BIOMEDICINA-2018) (to FSM). The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015–0505). IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, CEX2020-001039-S). SGD is supported by a grant from the Spanish Ministry of Universities. Authors thank Dr Miguel Vicente-Manzanares for critical review and editing. We also thank Dr Francisco Urbano and Dr Covadonga Aguado for their support with EM (TEM facilities, Universidad Autónoma de Madrid). Sí

Aims Vitamin K antagonists (VKAs) are effective drugs reducing the risk for stroke in atrial fibrillation (AF), but the benefits derived from such therapy depend on the international normalized ratio (INR) maintenance in a narrow therapeutic range. Here, we aimed to determine independent variables driving poor anticoagulation control [defined as a time in therapeutic range (TTR) Methods and results The SULTAN registry is a multicentre, prospective study, involving patients with non-valvular AF from 72 cardiology units expert in AF in Spain. At inclusion, all patients naïve for oral anticoagulation were started with VKAs for the first time. For the analysis, the first month of anticoagulation and those patients with Conclusion This study demonstrated that the quality of anticoagulation in AF patients newly starting VKAs is sub-optimal. Previous coronary artery disease and concomitant use of amiodarone were identified as independent variables affecting the poor quality of VKA therapy during the first year.

Background Informal caregivers of patients with multiple chronic conditions are socially good, promoting the sustainability of a large part of home care provision. However, this very demanding activity causes health problems that increase their own need for health services. This study analyses the use of health services by informal carers, comparing it with the use made by the general population with similar characteristics. Methodology Cross-sectional analytical study carried out in the Malaga-Valle Guadalhorce Primary Health Care District (Spain). Healthcare demand and perceived health were measured in the family caregivers, compared to the general population. Strobe Statement for observational studies has been used to strength the report of the results. Results Final sample consisted of 314 family caregivers together with a subsample of 2.290 non-caregivers taken from data of the National Health Survey. This subsample was paired by gender with our sample. Formal caregivers make fewer annual visits to the health services, with respect to the general population, regardless of the perceived level of health. The difference of the means between those who perceive their health as very poor was 0.11 (95% CI: 0.01 to 0.20) consultations with the family doctor, 0.21 (95% CI: 0.15 to 0.26) consultations with medical specialists and 1.70 (95% CI: 1.52 to 1.87) emergency room attention. Three independent factors were identified that predispose to the increased use of health services: background of greater education achievement (OR 8.13, 95% CI: 1.30 to 50.68), non-cohabitation with the care recipient (OR 3.57, 95% CI: 1.16 to 11.11) and a more positive physical quality of life component (OR 1.06; 95% CI: 1.03 to 1.09). Discussion and implications Intrinsic components of the caregiver reveal their independent relationship with the provision of informal care and the use of health services. A broader vision is needed for the factors that influence the health of these caregivers to develop multipurpose interventions and improve the consistency and effectiveness of the health services offered to the caregiver.

Spermatozoa capacitation is a time-dependent physiological process essential for acquiring the fertilizing capacity. In this context, reorganization of spermatozoa surface sugars and tyrosine phosphorylation are some of the most important biochemical changes involved in capacitation. However, the relationship between these 2 biomarkers remains poorly defined. By cytofluorescence we simultaneously characterized the head concanavalin A (ConA)-binding sites and the flagellar tyrosine phosphorylation before capacitation, during different capacitation times (1 and 4 h), and after acrosome reaction induction in human spermatozoa. The results showed a strong connection between ConA-label patterns and tyrosine phosphorylation according to the spermatozoa capacitation time and acrosomal status. Specifically, the spermatozoa subpopulation with phosphotyrosine presented proper sugar location (label in acrosomal and postacrosomal region) just after 1 h of capacitation, while cells without phosphotyrosine needed 4 h to do it. Moreover, after induction of spermatozoa acrosome reaction, phosphorylation was significantly correlated (p < 0.05) with the relocation of ConA-binding residues to the equatorial region, regardless of capacitation time. Overall, these observations provide novel insights regarding spermatozoa subpopulations based on essential physiological events like capacitation and acrosome reaction, which could have potential implications in the improvement of spermatozoa selection techniques. This research was funded by the Human Fertility Cathedra of the University of Alicante and the VIGROB-186.

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The prompt recognition of an acute neurovascular syndrome by the patient or a bystander witnessing the event can directly influence outcome. We aimed to study the predictive value of the medical history and clinical features recognized by the patients’ bystanders to preclassify acute stroke syndromes in prehospital settings. We analyzed 369 patients: 209 (56.6%) with acute ischemic stroke (AIS), 107 (29.0%) with intracerebral hemorrhage (ICH), and 53 (14.4%) with subarachnoid hemorrhage (SAH). All patients had neuroimaging as diagnostic gold standard. We constructed clinical prediction rules (CPRs) with features recognized by the bystanders witnessing the stroke onset to classify the acute neurovascular syndromes before final arrival to the emergency room (ER). In all, 83.2% cases were referred from other centers, and only 16.8% (17.2% in AIS, 15% in ICH, and 18.9% in SAH) had direct ER arrival. The time to first assessment in ≤ 3 h occurred in 72.4% (73.7%, 73.8%, and 64.2%, respectively), and final ER arrival in ≤ 3 h occurred in 26.8% (32.1%, 15.9%, and 28.3%, respectively). Clinical features referred by witnesses had low positive predictive values (PPVs) for stroke type prediction. Language or speech disorder + focal motor deficit showed 63.3% PPV, and 77.0% negative predictive value (NPV) for predicting AIS. Focal motor deficit + history of hypertension had 35.9% PPV and 78.8% NPV for ICH. Headache alone had 27.9% PPV and 95.3% NPV for SAH. In multivariate analyses, seizures, focal motor deficit, and hypertension increased the probability of a time to first assessment in ≤ 3 h, while obesity was inversely associated. Final ER arrival was determined by age and a direct ER arrival without previous referrals. CPRs constructed with the witnesses’ narrative had only adequate NPVs in the prehospital classification of acute neurovascular syndromes, before neuroimaging confirmation.

The aim of this study was to study the role that perceived competence, resilient coping, self-esteem and self-efficacy can have as protective factors of the academic procrastination of nursing students.Participants were 237 nursing students, 202 women and 35 men. The participants answered a questionnaire that contained the Spanish forms of the following instruments: Tuckman Procrastination Scale (TPS), Perceived Personal Competence Scale (PPC), Brief Resilient Coping Scale (BRCS), Rosenberg Self-Esteem Scale (RSES) and General Self-Efficacy Scale (GSE).Significant and negative correlation coefficients (p.01) were obtained between the procrastination scale and the rest of the measures used. The linear regression analysis identified Perceived Competence (PPC) as the only predictive variable of procrastinating behaviour, explaining 21.5% (RThe results of the study show the important protective role that the variables associated with 'positive' psychology have on procrastination. Of special relevance for the theory and practice of teaching is the result that indicates the predictive role of Perceived Competence on the academic procrastination of students.

Aim To measure the Effectiveness of a Diabetes Education Program for people with T2DM, based on Tailored interventions and the Theory of Planned Behaviour. Design Cluster randomized controlled clinical trial. Methods This multicentre study will be carried out at 30 primary healthcare centres, where 436 persons with Type 2 Diabetes Mellitus (T2DM), aged between 18-75 years, will be recruited. The experimental educational program to be applied is modelled using components obtained from a systematic review and prior qualitative analysis. In addition, a taxonomy of nursing practice is used to standardize the program, based on the Theory of Planned Behaviour as a conceptual model. The intervention will be carried out by community nurses, using ADAPP-Ti® , an application developed with FileMaker Pro v.18. The control group will receive usual care and data will be collected at 6, 12, and 18 months, for both groups. The primary outcome considered will be glycosylated haemoglobin and cardiovascular factors, while the secondary ones will be tobacco consumption, body mass index, barriers to self-care, health-related quality of life, and lifestyle modification. The protocol was approved by the Ethics Committee of the Province of Malaga (Spain) in November 2014. Discussion The degree of metabolic control in T2DM is not always associated with healthy lifestyles and significant levels of medication are often prescribed to achieve clinical objectives. An intervention focused on needs, based on the best available evidence and a solid conceptual framework, might successfully consolidate appropriate self-care behaviour in this population. Impact The study will result in the publication of an educational program featuring well-defined interventions and activities that will enable clinicians to tailor health care to the individual's needs and to combat treatment inertia in attending this population.

AIMS AND OBJECTIVES To evaluate the effectiveness of self-care programmes in type 2 diabetes mellitus (T2DM) population in primary health care. BACKGROUND The impact of educational interventions on T2DM has been evaluated in various contexts, but there is uncertainty about their impact in that of primary care. DESIGN Systematic review and meta-analysis. METHODS A search was conducted in PubMed, CINAHL, WOS and Cochrane databases for randomised controlled trials carried out in the period January 2005-December 2017, including studies with at least one face-to-face educational interventions. The quality of the evidence for the primary outcome was evaluated using the GRADE System. A meta-analysis was used to determine the effect achieved although only the results classified as critical or important were taken into consideration. Checklist of Preferred Reporting Items for Systematic Reviews and Meta-analyses has been followed. PROSPERO registration Number: CRD42016038833. RESULTS In total, 21 papers (20 studies) were analysed, representing a population of 12,018 persons with T2DM. For the primary outcome, HbA1 c, the overall reduction obtained was -0.29%, decreasing the effect in long-term follow-up. The quality of the evidence was low/very low due to very serious risk of bias, inconsistency and indirectness of results. Better results were obtained for individual randomised trials versus cluster designs and in those programmes in which nurses leaded the interventions. The findings for other cardiovascular risk factors were inconsistent. CONCLUSIONS Educational interventions in primary care addressing T2DM could be effective for metabolic control, but the low quality of the evidence and the lack of measurement of critical results generates uncertainty and highlights the need for high-quality trials. RELEVANCE TO CLINICAL PRACTICE Most of self-care programmes for T2DM in primary care are focused on metabolic control, while other cardiovascular profile variables with greater impact on mortality or patient-reported outcomes are less intensely addressed.

Objectives Patient repositioning is a recommended intervention to prevent or treat pressure ulcers (PUs). One option under consideration is the tailored repositioning according to patient characteristics, but more knowledge is needed on how different repositioning patterns influence on skin pressure. To determine what degree of inclination of the body in bed generates more pressure in the trochanteric region. Additionally, to analyze the influence of factors such as gender, age and anthropometric characteristics in the variations of this pressure. Methods Analytical cross-sectional study. Body Mass Index (BMI), lean mass and fat mass were measured in healthy volunteers subject to different inclinations (90°, 60° and 30°) in right lateral decubitus. Pressure was measured with a capacitive surface. Results In total, 146 subjects were included, of which 45 were men and 101 women. The results showed pressure differences due to the inclination according to gender and anthropometric values, being statistically significant in men at 90° and 60°, and in women at 30°. (hombres 90° p = 0,026, 60° p = 0,049; mujeres 30° p = 0,036) segun prueba Brown-Forsythe. Conclusions There are differences in the pressures of the trochanteric zone depending on anthropometric factors and by gender, in different body positions. Obese people exerted a higher pressure in the trochanter area at 30° of body inclination than overweight, normal weight and underweight people, respectively. From the clinical point of view, these findings invite to consider a possible differentiation in the repositioning interventions of the patients, according to gender and BMI, as a preventive strategy for PUs.

Globozoospermia is a rare and severe type of teratozoospermia characterized by the presence of round-headed, acrosomeless spermatozoa with cytoskeleton defects. Current data support a negative relationship between globozoospermia and intracytoplasmic sperm injection (ICSI) outcomes, revealing the need to perform exhaustive studies on this type of sperm disorder. The aim of this study was to evaluate different structural, functional and molecular sperm biomarkers in total globozoospermia with proper embryo development after ICSI. The combination of field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) allowed us to identify and correlate eight morphological patterns with both types of microscopy. Additionally, results reported a high percentage of coiled forms, with cytoplasmic retentions around the head and midpiece. By fluorescent microscopy, we detected that most of the sperm showed tubulin in the terminal piece of the flagellum and less than 1% displayed tyrosine phosphorylation in the flagellum. Moreover, we did not detect chaperone Heat shock-related 70 kDa protein 2 (HSPA2) in 85% of the cells. Overall, these findings provide new insights into globozoospermia, which could have potential implications in improving sperm selection methods for assisted reproductive techniques. This research was funded by the Human Fertility Professorship and Departamento de Biotecnología of the Universidad de Alicante (VIGROB-186).

Purpose: New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma. Patients and Methods: In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1–14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1–3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1–21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29). Results: After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3–4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells. Conclusions: R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.

Coronavirus Disease-19 (COVID-19) symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. We carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were present in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis. Co-expression network analysis adds further support to these findings, by detecting modules specifically correlated with severity involved in the abovementioned biological routes; this analysis also provides new candidate genes that might be tested as biomarkers in future studies. We also found tissue specific severity-related signatures mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy This study received support from Instituto de Salud Carlos III (ISCIII): GePEM (PI16/01478/Cofinanciado FEDER; A.S.), DIAVIR (DTS19/00049/Cofinanciado FEDER, A.S.), Resvi-Omics (PI19/01039/Cofinanciado FEDER, A.S.), ReSVinext (PI16/01569/Cofinanciado FEDER, F.M.T.), Enterogen (PI19/01090/Cofinanciado FEDER, F.M.T.); Agencia Gallega para la Gestión del Conocimiento en Salud (ACIS): BI-BACVIR (PRIS-3, A.S.), and CovidPhy (SA 304 C, A.S.); Agencia Gallega de Innovación (GAIN): Grupos con Potencial de Crecimiento (IN607B 2020/08, A.S.), GEN-COVID (IN845D 2020/23, F.M.T.); Framework Partnership Agreement between the Consellería de Sanidad de la XUNTA de Galicia and GENVIP-IDIS - 2021–2024 (SERGAS-IDIS march 2021); and consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CB21/06/00103; F.M.T.). We also thank Aida Freire Valls from Nanostring for her support SI

BACKGROUND Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation. METHODS In this randomised, double-blind, phase 2 dose-finding study, we compared asundexian 20 mg or 50 mg once daily with apixaban 5 mg twice daily in patients aged 45 years or older with atrial fibrillation, a CHA2DS2-VASc score of at least 2 if male or at least 3 if female, and increased bleeding risk. The study was conducted at 93 sites in 14 countries, including 12 European countries, Canada, and Japan. Participants were randomly assigned (1:1:1) to a treatment group using an interactive web response system, with randomisation stratified by whether patients were receiving a direct-acting oral anticoagulant before the study start. Masking was achieved using a double-dummy design, with participants receiving both the assigned treatment and a placebo that resembled the non-assigned treatment. The primary endpoint was the composite of major or clinically relevant non-major bleeding according to International Society on Thrombosis and Haemostasis criteria, assessed in all patients who took at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04218266, and EudraCT, 2019-002365-35. FINDINGS Between Jan 30, 2020, and June 21, 2021, 862 patients were enrolled. 755 patients were randomly assigned to treatment. Two patients (assigned to asundexian 20 mg) never took any study medication, resulting in 753 patients being included in the analysis (249 received asundexian 20 mg, 254 received asundexian 50 g, and 250 received apixaban). The mean age of participants was 73·7 years (SD 8·3), 309 (41%) were women, 216 (29%) had chronic kidney disease, and mean CHA2DS2-VASc score was 3·9 (1·3). Asundexian 20 mg resulted in 81% inhibition of FXIa activity at trough concentrations and 90% inhibition at peak concentrations; asundexian 50 mg resulted in 92% inhibition at trough concentrations and 94% inhibition at peak concentrations. Ratios of incidence proportions for the primary endpoint were 0·50 (90% CI 0·14-1·68) for asundexian 20 mg (three events), 0·16 (0·01-0·99) for asundexian 50 mg (one event), and 0·33 (0·09-0·97) for pooled asundexian (four events) versus apixaban (six events). The rate of any adverse event occurring was similar in the three treatment groups: 118 (47%) with asundexian 20 mg, 120 (47%) with asundexian 50 mg, and 122 (49%) with apixaban. INTERPRETATION The FXIa inhibitor asundexian at doses of 20 mg and 50 mg once daily resulted in lower rates of bleeding compared with standard dosing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with atrial fibrillation. FUNDING Bayer.

Pressure ulcers are a common adverse event in healthcare. To date, no flowmetry studies have been conducted to compare hyperoxygenated fatty acids (HFA) vs. extra-virgin olive oil (EVOO) in alleviating this condition.To determine and evaluate the effect of the application of HFA vs. EVOO on tissue oxygenation and perfusion in heels under pressure, in healthy persons and in hospitalised patients.Two-phase experimental study.Phase 1 will be conducted with healthy subjects, using a randomised, open study design, evaluating an intrasubject control group. Phase 2 will focus on hospitalised subjects, with a randomised, open study group vs. a control group.This Project is undertaken to identify the mechanisms that intervene in the genesis of pressure ulcers and to determine whether there are differences in outcomes between the application of HFA vs. EVOO as a preventive measure The results of this study are of economic importance (due to the price difference between the products used) and will also impact on usual clinical practice for patients with impaired mobility and liable to suffer from pressure ulcers, by considering an alternative to established preventive measures.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an autosomal recessive vascular disorder caused by biallellic variants in HTRA1. Recently, it has been reported that several heterozygous mutations in HTRA1 are responsible for a milder late-onset cerebral small vessel disease (CSVD) with an autosomal dominant pattern of inheritance. The majority of them are missense that affects the Htr1A protease activity due to a dominant-negative effect caused by defective trimerization or monomer activation. The molecular mechanism related to the structural destabilization of the protein supports the practical utility of integrating computational stability predictors to prioritize candidate variants in this gene. In this work, we report a family with several members diagnosed with subcortical ischemic events and progressive cognitive impairment caused by the novel c.820C G, p.(Arg274Gly) heterozygous variant in HTRA1 segregating in an autosomal dominant manner and propose its molecular mechanism by a three-dimensional model of the protein's structure.

International audience; OBJECTIVES: To delineate the clustering of energy balance-related behaviors in adolescents and investigate whether these behaviors are associated with the household socioeconomic status and parental education level. METHODS: Two cross-sectional studies assessed information on sedentary behavior, physical activity, sugar-sweetened beverages and fruit and vegetable consumption, and sleep duration by self-reported questionnaires in adolescents (12.5-17.5 years old) from Maringa/Brazil (BRACAH Study; n = 682) and ten European cities (HELENA Study; n = 1252) from nine different countries. Gender-specific cluster analyses were performed separately for each study, applying a combination of hierarchical and non-hierarchical methods. RESULTS: Girls showed equivalent behaviors: Sedentary; Active; Unhealthy Eating; Healthy Eating; while boys differed (Brazilian: Sedentary; Active; Healthy Eating; European: Sedentary; Healthy; Unhealthy Eating). In Brazil, we found no association between socioeconomic status and parental education. In European girls, the high socioeconomic status and both parents' university degree were associated with Healthy Eating. In European boys, the high socioeconomic status was associated with Unhealthy Eating, and the mothers' university degree was associated with the Healthy cluster. CONCLUSIONS: Adolescents show Sedentary behavior, regardless of their sex, country of origin, or socioeconomic condition.

Background Aortic stenosis (AS) is currently the most frequent heart valve disease. Symptomatic severe AS has a poor prognosis and transcatheter aortic valve implantation (TAVI) is becoming the therapy of choice in these patients. Changes in the conduction tissue after the procedure constitute one of the main limitations of TAVI, with a frequent need for a definitive pacemaker. Interatrial block (IAB) is defined as a prolonged P-wave duration and is related with atrial fibrosis. The presence of IAB could be a marker of conduction tissue abnormalities at other levels. No study has specifically analyzed the role of IAB as a predictor of the need for permanent pacemaker in patients with AS undergoing TAVI. Methods The Baseline Interatrial block and Transcatheter aortic valve implantation (BIT) registry will be performed in approximately 3000 patients with severe AS treated with TAVI. A centralized analysis of baseline ECGs will study the presence and type of IAB and other ECG data (rhythm, P-wave duration, PR and QRS intervals/intraventricular conduction disorders). Clinical follow-up will be carried out by local researchers. The primary endpoint will be the requirement of permanent pacemaker during post-TAVI hospitalization. As secondary objectives, the incidence of new onset AF, stroke, or mortality during follow-up will be analyzed. Secondary endpoints will include the incidence of new onset AF, stroke, or mortality during follow-up. Conclusion The BIT registry will study, for the first time, the influence of previous IAB in the need of permanent pacemaker after TAVI: This large registry will also provide information regarding the association of this and other ECG parameters with prognosis. Sin financiación 0.944 JCR (2019) Q4, 133/138 Cardiac & Cardiovascular Systems 0.448 SJR (2019) Q3, 205/362 Cardiology and Cardiovascular Medicine No data IDR 2019 UEM

INTRODUCTION AND OBJECTIVES To analyze differences between sexes in the clinical management of patients presenting with symptoms of chest pain and/or palpitations within a population-based study. METHODS The OFRECE study included a random sample of 8400 individuals from the Spanish population aged 40 years and older; 1132 (13.5%) had previously consulted for chest pain and 1267 (15.1%) had consulted for palpitations and were included in the present study. We calculated both the crude and adjusted odds ratios (OR) of undergoing certain tests and the results of consultations by sex. Adjustment was performed by classic cardiovascular risk factors, a personal history of cardiovascular disease, and a diagnosis of stable angina or atrial fibrillation confirmed in the OFRECE study in each case. RESULTS No differences were observed in history of consultation for chest pain between women and men (13% vs 14.1%; P=.159) but differences were found in palpitations (19% vs 10.4%, respectively; P

The diagnosis of bacterial infections in hospital settings is currently performed using bacterial culture from sterile site, but they are lengthy and limited. Transcriptomic biomarkers are becoming promising tools for diagnosis with potential applicability in clinical settings. We evaluated a RT-qPCR assay for a 2-transcript host expression signature (FAM89A and IFI44L genes) inferred from microarray data that allow to differentiate between viral and bacterial infection in febrile children. This assay was able to discriminate viral from bacterial infections (P-value = 1.04 × 10−4; AUC = 92.2%; sensitivity = 90.9%; specificity = 85.7%) and showed very high reproducibility regardless of the reference gene(s) used to normalize the data. Unexpectedly, the monogenic IFI44L expression signature yielded better results than those obtained from the 2-transcript test (P-value = 3.59 × 10−5; AUC = 94.1%; sensitivity = 90.9%; specificity = 92.8%). We validated this IFI44L signature in previously published microarray and whole-transcriptome data from patients affected by different types of viral and bacterial infections, confirming that this gene alone differentiates between both groups, thus saving time, effort, and costs. Herein, we demonstrate that host expression microarray data can be successfully translated into a fast, highly accurate and relatively inexpensive in vitro assay that could be implemented in the clinical routine.

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) subtype. The histological transformation (HT) of FL is an event considered frequent in the natural history of this tumor. We studied the transformation rates, predictive factors, and treatment characteristics that may impact in the survival of patients with FL and HT. A total of 1074 patients diagnosed with FL were prospectively enrolled from 1990 to 2016 in a Spanish registry. Sixty-four HTs were recorded based on clinical criteria (55%) or histological confirmation (45%). The cumulative incidence rate of transformation at 5 years is 7.3%. The 5-year overall survival (OS) without HT was 85% (95% confidence interval [CI], 70%-90%) vs 66% (95% CI, 51%-76%; P = 0.0012) with HT. Factors associated with HT were elevated lactate dehydrogenase (LDH) (odds ratio [OR] 1.83), intermediate-high Follicular lymphoma international prognostic index (FLIPI) (OR 2.16-OR 3.21), B symptoms (OR 2.46), or Eastern Cooperative Oncology Group (ECOG) 1 (OR 2.35). Treatment options related to HT were "watch and wait" or no rituximab or anthracyclines initially. A 5-year OS for patients treated with chemotherapy before HT was 55% (95% CI, 38%-69%) versus 81% (95% CI, 53%-93%; P = 0.009) for those who had not received it. The HT rate has decreased after the introduction of rituximab, as has been previously described. The timing of this treatment had an impact on the survival of these patients.

(1) Background: Identifying differences in the competencies of different areas of nursing is a crucial aspect for determining the scope of practice. This would facilitate the creation of a formal structure for clinical practice in advanced and specialised services. The aims of this study are to analyse the distribution of advanced competencies in registered, specialist and advanced practice nurses in Spain, and to determine the level of complexity of the patients attended by these nurses. (2) Methods: A cross-sectional study was developed on registered, specialist and advanced practice nurses, all of whom completed an online survey on their perceived level of advanced competencies and their professional characteristics. (3) Results: In total, 1270 nurses completed the survey. Advanced practice nurses recorded the highest self-perceived level of competency, especially for the dimensions of evidence-based practice, autonomy, leadership and care management. (4) Conclusions: Among registered, specialist and advanced practice nurses, there are significant differences in the level of self-perceived competencies. Patients attended by advanced practice nurses presented the highest levels of complexity. Understanding these differences could facilitate the creation of a regulatory framework for clinical practice in advanced and specialized services.

INTRODUCTION The primary goal of this study was to compare gastrointestinal symptom reduction in patients on bismuth-containing quadruple eradication therapy supplemented with Lactobacillus reuteri strains (DSM 17938 and ATCC PTA 6475) or placebo. MATERIALS AND METHODS This was randomized, double-blind, parallel-arm, placebo-controlled clinical trial. Patients received first-line an eradication regimen based on bismuth subcitrate potassium, metronidazole, tetracycline hydrochloride (three-in-one capsules), and omeprazole 40 mg twice a day for ten days, plus a probiotic or placebo tablet for 30 days. During follow-up gastrointestinal symptoms were assessed using an evaluation scale (GSRS), and adverse events were collected at 0, 14, 28, and 56 days. RESULTS A total of 80 patients were included from February 2018 to May 2019 at a single site. Eradication therapy was effective for 85% of patients, with no differences between treatment arms. In the group receiving the probiotic, abdominal pain decreased in 42% of patients, compared with 19% in the control group (OR: 0.27; CI, 0.13-0.58; p < 0.001), and abdominal distension decreased in 25% versus 17% in the control group (OR: 0.24; IC, 0.19-0.84; p < 0.001); Conclusions: Treatment with L. reuteri only reduced abdominal pain and distension. Further studies are needed to establish the role of probiotics as adjuvant therapy in H. pylori eradication.

The current health crisis resulting from the COVID-19 pandemic increases the stress and anxiety levels in some professions, including social work. The present research aimed to determine the burnout levels of social workers in Spain during the first wave of the pandemic and the predictive variables. The methodological approach used was developed from a quantitative perspective through a simple random sampling from the Maslach Burnout Inventory (MBI) on a sample of Spanish social workers. The results showed high levels of emotional exhaustion (70.1%) and depersonalization (48.5%), although the data related to a reduced sense of personal accomplishment (36.6%) was low. The burnout level was 20.4%, a reduced record considering the values of the first two subscales. In contrast, the logistic regressions carried out showed that teleworking and psychological treatment are predictive variables of emotional exhaustion. With depersonalization, age (41–50 years) and the perception of needing psychological or psychiatric treatment in the future act as predictive variables. In critical scenarios such as a pandemic, work organizations should implement measures to reduce the high percentages of emotional exhaustion, the workload, and the dehumanization of professionals, a consequence linked to depersonalization.

Allan-Herndon-Dudley is an X-linked recessive syndrome caused by pathogenic variants in the SLC16A2 gene. Clinical manifestations are a consequence of impaired thyroid metabolism and aberrant transport of thyroid hormones to the brain. Carrier females are generally asymptomatic and may show subtle symptoms of the disease. We describe a female with a complete Allan-Herndon-Dudley phenotype, carrying a de novo 543-kb deletion of the X chromosome. The deletion encompasses exon 1 of the SLC16A2 gene and JPX and FTX genes; it is known that the latter two genes participate in the X-inactivation process upregulating XIST gene expression. Subsequent studies in the patient demonstrated the preferential expression of the X chromosome with the JPX and FTX deletion.

A recent line of research concerns bedtime procrastination, its effects on sleep quality and duration, and the associated repercussions for health and wellbeing. The Bedtime Procrastination Scale is a brief, self-report instrument developed by Kroese et al. with the aim of evaluating this behavior and exploring its association with insufficient sleep, and hence with health. The aim was to develop and validate a Spanish version of the Bedtime Procrastination Scale (BPS-Sp) and to examine the relationship between bedtime procrastination and both general procrastination and self-control. The original BPS was translated from English into Spanish in accordance with international guidelines on the cross-cultural adaptation of measurement instruments. The sample for the validation study comprised 177 nursing students who completed a questionnaire requesting demographic data and which included the following instruments: the newly developed BPS-Sp, the Tuckman Procrastination Scale, and the Brief Self-Control Scale. Statistical analysis involved tests of normality (Kolmogorov-Smirnov), reliability (Cronbach’s alpha, test-retest), construct validity, and confirmatory factor analysis. Scores on the BPS-Sp showed excellent internal consistency (α = .83) and temporal stability (test-retest r = .84), as well as significant correlations with general procrastination ( r = .26; p

Autism spectrum disorder (ASD) is a prevalent and extremely heterogeneous neurodevelopmental disorder (NDD) with a strong genetic component. In recent years, the clinical relevance of de novo mutations to the aetiology of ASD has been demonstrated. Current guidelines recommend chromosomal microarray (CMA) and a FMR1 testing as first-tier tests, but there is increasing evidence that support the use of NGS for the diagnosis of NDDs. Specifically in ASD, it has not been extensively evaluated and, thus, we performed and compared the clinical utility of CMA, FMR1 testing, and/or whole exome sequencing (WES) in a cohort of 343 ASD patients. We achieved a global diagnostic rate of 12.8% (44/343), the majority of them being characterised by WES (33/44, 75%) compared to CMA (9/44, 20.4%) or FMR1 testing (2/44, 4.5%). Taking into account the age at which genetic testing was carried out, we identified a causal genetic alteration in 22.5% (37/164) of patients over 5 years old, but only in 3.9% (7/179) of patients under this age. Our data evidence the higher diagnostic power of WES compared to CMA in the study of ASD and support the implementation of WES as a first-tier test for the genetic diagnosis of this disorder, when there is no suspicion of fragile X syndrome.

BACKGROUND: Bone volume augmentation is a routine technique used in oral implantology and periodontology. Advances in the surgical techniques and the biomaterials field have allowed a greater accessibility to these treatments. Nevertheless, dehiscence and fenestrations incidence during dental implant procedures are still common in patients with bone loss. OBJECTIVE: The main objective is to evaluate in a pilot experimental study the biological response to mesoporous silica (MS) hybrid scaffolds and its regenerative capacity in different formulations. METHODS: Two defects per rabbit tibia were performed (one for control and other for test) and the biomaterials tested in this study have been used to fill the bone defects, prepared in two different formulations (3D hybrid scaffolds or powdered material, in 100% pure MS form, or 50% MS with 50% hydroxyapatite (HA). Euthanasia was performed 4 months after surgery for bone histopathological study and radiographic images were acquired by computerized microtomography. RESULTS: Results showed that radiographically and histopathologically pure MS formulations lead to a lower biological response, e.g when formulated with HA, the osteogenic response in terms of osteoconduction was greater. CONCLUSIONS: We observed tolerance and lack of toxicity of the MS and HA, without registering any type of local or systemic allergic reaction.

The clinical practice guidelines (CPG) have contributed to the dissemination of scientific information that supports decision-making in different clinical situations. CPGs have become more necessary as scientific information has grown, sometimes offering contradictory data, which makes it difficult for the clinician to easily make the most appropriate decision. In this context, the CPGs summarize and simplify the available scientific information, making it available to the doctor who must make the decisions. The publication of a CPG does not mean that it is applied in practice, much less that it is adopted quickly. In fact, despite the improvement in the quality of the CPGs, it is observed that they have not been fully implemented in a large number of cases, which prevents relevant information from ending up being transferred to clinical practice, with the consequent impact on the quality of care. In this article we will briefly review the strategies adopted to ensure that the scientific recommendations contained in the CPGs end up being transferred to patients and, asa consequence, achieving a reduction in the impact of cardiovascular diseases.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease whose prognosis is associated with clinical features, cell-of-origin and genetic aberrations. Recent integrative, multi-omic analyses had led to identifying overlapping genetic DLBCL subtypes. We used targeted massive sequencing to analyze 84 diagnostic samples from a multicenter cohort of patients with DLBCL treated with rituximab-containing therapies and a median follow-up of 6 years. The most frequently mutated genes were IGLL5 (43%), KMT2D (33.3%), CREBBP (28.6%), PIM1 (26.2%), and CARD11 (22.6%). Mutations in CD79B were associated with a higher risk of relapse after treatment, whereas patients with mutations in CD79B, ETS1, and CD58 had a significantly shorter survival. Based on the new genetic DLBCL classifications, we tested and validated a simplified method to classify samples in five genetic subtypes analyzing the mutational status of 26 genes and BCL2 and BCL6 translocations. We propose a two-step genetic DLBCL classifier (2-S), integrating the most significant features from previous algorithms, to classify the samples as N12-S, EZB2-S, MCD2-S, BN22-S, and ST22-S groups. We determined its sensitivity and specificity, compared with the other established algorithms, and evaluated its clinical impact. The results showed that ST22-S is the group with the best clinical outcome and N12-S, the more aggressive one. EZB2-S identified a subgroup with a worse prognosis among GCB-DLBLC cases.

espanolIntroduccion: la proteina es un nutriente esencial que se puede obtener a traves de diferentes fuentes alimentarias. En los ultimos anos, un creciente desarrollo de la industria alimentaria de productos lacteos con mayor aporte en proteinas ha surgido en el mercado nacional. Metodos: el presente trabajo analizo la informacion nutricional, el contenido proteico y el perfil de aminoacidos de una serie de yogures altos en proteina. Se seleccionaron 5 principales marcas de yogures altos en proteina (YP), una muestra de yogur batido (YBAT) y una de proteina de suero de leche aislado (WP) a las que se realizo un analisis proximal y un perfil de aminoacidos por cromatografia liquida de alto rendimiento (HPLC). Resultados: se pudo observar que el contenido de proteina de los YP analizados vario entre 7,2-15,1 g/porcion, lo que representa del 6,8 al 11 % del contenido total, el doble del contenido del YBAT (3,4 %). Respecto a los hidratos de carbono y grasas, estos se encontraron entre 6,25 y 13,5 g/porcion y 0,9 y 5,3 g/porcion, respectivamente. El contenido de leucina de los YP vario entre 0,6 y 1,5 g/porcion, con valores superiores a los de los YBAT (0,3 g/porcion) e inferiores a los de las WP (2,2 g/porcion). La suma de aminoacidos esenciales se encontro entre 3 y 6,9 g/porcion en los YP, 1,7 g/porcion en los YBAT y 8,5 g/porcion en las WP. Conclusion: estos resultados demuestran que los YP son una buena alternativa para promover una correcta ingesta proteica, semejante a las proteinas de uso deportivo, por lo que su recomendacion podria ser util para promover su consumo en diferentes poblaciones segun sus necesidades. EnglishIntroduction: protein is an essential nutrient that can be obtained through different food sources. In recent years, a growing development in the food industry of dairy products with higher protein content has emerged in the national market. Metodos: the present work analyzed the nutritional information, protein content, and amino acid profile of high protein yogurts. Five main brands of high-protein yogurt (PY) were selected, as was a sample of regular yogurt (RY), and one of whey protein isolate (WP), which underwent a proximal analysis and amino acid profile by high-performance liquid chromatography (HPLC). Results: it was observed that the protein content of the analyzed YP ranged between 7.2 and 15.1 g/portion, representing 6.8 % to 11 % of total content, twice the content of YBAT (3,4 %). Regarding carbohydrates and fats, these were found to range between 6.25 and 13.5 g/serving and 0.9 and 5.3 g/serving, respectively. Leucine content of the PY varied between 0.6 and 1.5 g/portion, which was higher than RY (0.3 g/portion) and lower than WP (2.2 g/portion). The sum of essential amino acids was found to be between 3 and 6.9 g/portion in PY, 1.7 g/serving and 8.5 g/serving in WP. Conclusion: these results show that PYs are a good alternative to promote a correct protein intake, similar to proteins for sports use, so their recommendation could be useful to promote consumption in different populations according to their needs.

Different cell migration modes have been identified in 3D environments, e.g., modes incorporating lamellopodia or blebs. Recently, a new type of cellular migration has been investigated: lobopodia-based migration, which appears only in three-dimensional matrices under certain conditions. The cell creates a protrusion through which the nucleus slips, dividing the cell into two parts (front and rear) with different hydrostatic pressures. In this work, we elucidate the mechanical conditions that favour this type of migration. One of the hypotheses about this type of migration is that it depends on the mechanical properties of the extracellular matrix. That is, lobopodia-based migration is dependent on whether the extracellular matrix is linearly elastic or non-linearly elastic. To determine whether the mechanical properties of the extracellular matrix are crucial in the choice of cell migration mode and which mechanotransduction mechanism the cell might use, we develop a finite element model. From our simulations, we identify two different possible mechanotransduction mechanisms that could regulate the cell to switch from a lobopodial to a lamellipodial migration mode. The first relies on a differential pressure increase inside the cytoplasm while the cell contracts, and the second relies on a change in the fluid flow direction in non-linearly elastic extracellular matrices but not in linearly elastic matrices. The biphasic nature of the cell has been determined to mediate this mechanism and the different behaviours of cells in linearly elastic and non-linearly elastic matrices.

This study was granted by FIS PI18/01585, funded by ISCIII and FEDER, "Una manera de hacer Europa" and by Fundación Mutua Madrileña in the "Convocatoria de Ayudas a la Investigación en Salud 2015". The PLEKHG5 gene encodes a protein that activates the nuclear factor kappa B (NFκB) signaling pathway. Mutations in this gene have been associated with distal spinal muscular atrophy IV and intermediate axonal neuropathy C, both with an autosomal recessive mode of inheritance. Two families with low motor neuron disease (LMND) caused by mutations in PLEKHG5 have been reported to date. We present a third LMND family, the first nonconsanguineous, due to two not previously reported PLEKHG5 mutations. Our results confirm and extend previous findings linking PLEKHG5 mutations to lower motor neuron diseases.

Introduction In recent years, multiple studies have aimed to develop and validate portable technological devices capable of monitoring the motor complications of Parkinson’s disease patients (Parkinson’s Holter). The effectiveness of these monitoring devices for improving clinical control is not known. Methods and analysis This is a single-blind, cluster-randomised controlled clinical trial. Neurologists from Spanish health centres will be randomly assigned to one of three study arms (1:1:1): (a) therapeutic adjustment using information from a Parkinson’s Holter that will be worn by their patients for 7 days, (b) therapeutic adjustment using information from a diary of motor fluctuations that will be completed by their patients for 7 days and (c) therapeutic adjustment using clinical information collected during consultation. It is expected that 162 consecutive patients will be included over a period of 6 months. The primary outcome is the efficiency of the Parkinson’s Holter compared with traditional clinical practice in terms of Off time reduction with respect to the baseline (recorded through a diary of motor fluctuations, which will be completed by all patients). As secondary outcomes, changes in variables related to other motor complications (dyskinesia and freezing of gait), quality of life, autonomy in activities of daily living, adherence to the monitoring system and number of doctor–patient contacts will be analysed. The noninferiority of the Parkinson’s Holter against the diary of motor fluctuations in terms of Off time reduction will be studied as the exploratory objective. Ethics and dissemination approval for this study has been obtained from the Hospital Universitari de Bellvitge Ethics Committee. The results of this study will inform the practical utility of the objective information provided by a Parkinson’s Holter and, therefore, the convenience of adopting this technology in clinical practice and in future clinical trials. We expect public dissemination of the results in 2022. Trial registration NCT04176302;https://clinicaltrials.gov/show/NCT04176302

The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coronavirus has generated a pandemic, in which there are population groups at higher risk and who are potentially fatal victims of the disease. Cancer patients have been considered a group with special susceptibility, particularly patients with lung tumour involvement and haematological neoplasms. The Spanish Lymphoma Oncology Group (GOTEL) carried out a multicenter study of SARS-CoV-2 seroprevalence in patients with lymphoma. Results: A total of 150 patients were included between 22 May and 11 June 2020. The mean age was 65 years (range 17–89), 70 women (46.5%) and 80 men (53, 5%). At the time of diagnosis of lymphoma, 13 cases were stage I (9%), 27 (18%) stage II, 37 (24.5%) stage III, and 73 (48.5%) stage IV, while 6.6% had a primary extranodal origin. A total of 10 cases with positive serology for SARS-CoV-2 were identified, which is a prevalence of 6% in this population. None of the patients required intensive care unit management and all fully recovered from the infection. Conclusion: IgG antibody seroprevalence in lymphoma patients appears similar to that of the general population and does not show greater aggressiveness., This study was supported by the European Union Horizon 2020 research and innovation programme under grant agreement number 875160

The study was supported by the Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias, Spanish Ministry of Health, PI19/01023) (Co-funded by the European Regional Development Fund ‘A way to make Europe’), and Fundación de la Sociedad Española de Alergología e Inmunología Clínica (SEAIC) SI

BackgroundRotavirus (RV) is an enteric pathogen that has devastating impact on childhood morbidity and mortality worldwide. The immunologic mechanism underlying the protection achieved after RV vaccination is not yet fully understood.MethodsWe compared the transcriptome of children affected by community-acquired RV infection and children immunized with a live attenuated RV vaccine (RotaTeq®).ResultsRV vaccination mimics the wild type infection causing similar changes in children’s transcriptome, including transcripts associated with cell cycle, diarrhea, nausea, vomiting, intussusception, and abnormal morphology of midgut. A machine learning approach allowed to detect a combination of nine-transcripts that differentiates vaccinated from convalescent-naturally infected children (AUC: 90%; 95%CI: 70–100) and distinguishes between acute-infected and healthy control children (in both cases, AUC: 100%; 95%CI: 100–100). We identified a miRNA hsa-mir-149 that seems to play a role in the host defense against viral pathogens and may have an antiviral role.DiscussionOur findings might shed further light in the understanding of RV infection, its functional link to intussusception causes, as well as guide development of antiviral treatments and safer and more effective vaccines. The nine-transcript signature may constitute a marker of vaccine protection and helps to differentiate vaccinated from naturally infected or susceptible children.

[enter Abstract Body]The impact of the COVID-19 outbreak on mental health among HIV high-risk populations is not known. We assess the prevalence of depressive symptoms (DS) and explore the association with characteristics related to the COVID-19 pandemic. We conducted an online survey among 881 men who have sex with men (MSM) and transgender women (TGW) assessing the presence of DS using the Center for Epidemiological Studies Depression Scale (CESD-10); results were compared with previously self-reported DS and national data. We applied latent class analysis (LCA) to identify classes of participants with similar COVID-19 related characteristics. The overall prevalence of significant DS was 53.3%. By LCA posterior probabilities we identified three classes: (1) minimal impact of COVID-19 (54.1%), (2) objective risk for COVID-19 (41.5%), and (3) anxiety and economic stress caused by COVID-19 (4.4%). Multivariate logistic regression showed that compared with those in class one, the odds to have significant DS were almost five times higher for those in class three. Our findings suggest high levels of depression among MSM and TGW in Mexico during the COVID-19 pandemic and highlight the need for the provision of targeted psychological interventions to minimize the impacts of COVID-19 on the mental health.

Advances in methods for determining the forces exerted by cells while they migrate are essential for attempting to understand important pathological processes, such as cancer or angiogenesis, among others. Precise data from three-dimensional conditions are both difficult to obtain and manipulate. For this purpose, it is critical to develop workflows in which the experiments are closely linked to the subsequent computational postprocessing. The work presented here starts from a traction force microscopy (TFM) experiment carried out on microfluidic chips, and this experiment is automatically joined to an inverse problem solver that allows us to extract the traction forces exerted by the cell from the displacements of fluorescent beads embedded in the extracellular matrix (ECM). Therefore, both the reconstruction of the cell geometry and the recovery of the ECM displacements are used to generate the inputs for the resolution of the inverse problem. The inverse problem is solved iteratively by using the finite element method under the hypothesis of finite deformations and nonlinear material formulation. Finally, after mathematical postprocessing is performed, the traction forces on the surface of the cell in the undeformed configuration are obtained. Therefore, in this work, we demonstrate the robustness of our computational-based methodology by testing it under different conditions in an extreme theoretical load problem and then by applying it to a real case based on experimental results. In summary, we have developed a new procedure that adds value to existing methodologies for solving inverse problems in 3D, mainly by allowing for large deformations and not being restricted to any particular material formulation. In addition, it automatically bridges the gap between experimental images and mechanical computations.