Search

Proper chromosome segregation is essential to avoid aneuploidy, yet this process fails with increasing age in mammalian oocytes. Here we report a role for the scarcely described protein CENP-V in oocyte spindle formation and chromosome segregation. We show that depending on the oocyte maturation state, CENP-V localizes to centromeres, to microtubule organizing centers, and to spindle microtubules. We find that Cenp-V−/− oocytes feature severe deficiencies, including metaphase I arrest, strongly reduced polar body extrusion, increased numbers of mis-aligned chromosomes and aneuploidy, multipolar spindles, unfocused spindle poles and loss of kinetochore spindle fibres. We also show that CENP-V protein binds, diffuses along, and bundles microtubules in vitro. The spindle assembly checkpoint arrests about half of metaphase I Cenp-V−/− oocytes from young adults only. This finding suggests checkpoint weakening in ageing oocytes, which mature despite carrying mis-aligned chromosomes. Thus, CENP-V is a microtubule bundling protein crucial to faithful oocyte meiosis, and Cenp-V−/− oocytes reveal age-dependent weakening of the spindle assembly checkpoint., Chromosome segregation is essential to avoid aneuploidy, yet in mammalian oocytes it progressively fails in an age-dependent manner. Here the authors identify CENP-V as a microtubule binding and bundling protein crucial to faithful oocyte meiosis, and present Cenp-V−/− oocytes as revealing age-dependent weakening of the spindle assembly checkpoint.

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome., This work was supported by National Plan R+D+I 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministry of Economy, Industry, and Competitiveness, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0009]; cofinanced by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020; and supported by Grants from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Proyectos de Investigación sobre el SARS-CoV-2 y la enfermedad COVID-19 [COV20/00370; COV20/00580]. J.S.C. is a researcher belonging to the program “Nicolás Monardes” (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía, Spain.

Background Worldwide, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases and one of those producing greatest impact on patients’ day-to-day quality of life. Our study aim is to validate the “Living with Chronic Illness Scale” for a Spanish-speaking T2DM population. Methods In this observational, international, cross-sectional study, 582 persons with T2DM were recruited in primary care and outpatient hospital consultations, in Spain and Colombia, during the period from May 2018 to June 2019. The properties analysed were feasibility/acceptability, internal consistency, reliability, precision and (structural) content-construct validity including confirmatory factor analysis. The COSMIN checklist was used to assess the methodological/psychometric quality of the instrument. Results The scale had an adequate internal consistency and test retest reliability (Cronbach’s alpha = 0.90; intraclass correlation coefficient = 0.96, respectively). In addition, the instrument is precise (standard error of measurement = 3.34, with values s = 0.56), quality of life (WHOQOL-BREF) (rs = 0.51–0.30) and ssatisfaction with life (SLS-6) (rs = 0.50–0.38). The original 26-items version of the scale did not support totally the confirmatory factor analysis. The COSMIN checklist is favourable for all the properties analysed, although weaknesses are detected for structural validity. Conclusions The LW-CI-T2DM is a valid, reliable and accurate instrument for use in clinical practice to determine how a person’s life is affected by the presence of diabetes. This instrument correlates well with the associated constructs of social support, quality of life and satisfaction. Additional research is needed to determine how well the questionnaire structure performs when robust factor analysis methods are applied.

[Rationale] SPINOPHILIN (SPN, PPP1R9B) is an important tumor suppressor involved in the progression and malignancy of different tumors depending on its association with protein phosphatase 1 (PP1) and the ability of the PP1-SPN holoenzyme to dephosphorylate retinoblastoma (pRB)., [Methods] We performed a mutational analysis of SPN in human tumors, focusing on the region of interaction with PP1 and pRB. We explored the effect of the SPN-A566V mutation in an immortalized non-tumorigenic cell line of epithelial breast tissue, MCF10A, and in two different p53-mutated breast cancer cells lines, T47D and MDA-MB-468., [Results] We characterized an oncogenic mutation of SPN found in human tumor samples, SPN-A566V, that affects both the SPN-PP1 interaction and its phosphatase activity. The SPN-A566V mutation does not affect the interaction of the PP1-SPN holoenzyme with pocket proteins pRB, p107 and p130, but it affects its ability to dephosphorylate them during G0/G1 and G1, indicating that the PP1-SPN holoenzyme regulates cell cycle progression. SPN-A566V also promoted stemness, establishing a connection between the cell cycle and stem cell biology via pocket proteins and PP1-SPN regulation. However, only cells with both SPN-A566V and mutant p53 have increased tumorigenic and stemness properties., [Conclusions] SPN-A566V, or other equivalent mutations, could be late events that promote tumor progression by increasing the CSC pool and, eventually, the malignant behavior of the tumor., This work was supported by grants from the Ministerio de Ciencia, Innovación y Universidades (MCIU) Plan Estatal de I+D+I 2018, a la Agencia Estatal de Investigación (AEI) y al Fondo Europeo de Desarrollo Regional (MCIU/AEI/FEDER, UE): RTI2018-097455-B-I00 and RTI2018-096735-B-I00 grant from AEI-MICIU/FEDER (RED2018-102723-T); from CIBER de Cáncer (CB16/12/00275), co-funded by FEDER from Regional Development European Funds (European Union); from Consejeria de Salud (PI-0397-2017) and Consejeria of Economía, Conocimiento, Empresas y Universidad of the Junta de Andalucia (P18-RT-2501). Special thanks are also due to the Fundacion AECC and Fundacion Eugenio Rodriguez Pascual for supporting this work.

Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level., German Research Foundation (DFG) AL 1784/3-1, European Commission European Commission Joint Research Centre, International Agency for Research on Cancer, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) (Germany), Federal Ministry of Education & Research (BMBF), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro (AIRC), Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Instituto de Salud Carlos III PI13/00061 PI13/01162, Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain) 6236, Regional Government of Navarra (Spain), Regional Government of Catalonia (Catalan Institute of Oncology -ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK C864/A14136 C8221/A19170, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/N003284/1 MC-UU_12015/1 MR/M012190/1, Projekt DEAL

International Journal of Infectious Diseases, official publication of the International Society for Infectious Diseases Introduction Community-Acquired Pneumonia (CAP) is one of the most frequent causes of hospital admission in children. Our objective is to measure the impact of the introduction of pneumococcal conjugate vaccines on the hospitalization of previously healthy children due to CAP. Method From 2011 to 2016, a partially retrospective, prospective, and descriptive study was carried out on healthy pediatric patients (3 months–14 years old) with CAP, who required hospital admission. Clinical, epidemiological, and demographic characteristics were collected, and vaccination status was obtained from medical records. Results A total of 292 cases were included, with a mean age of 33.4 months, 54% males. There was a progressive and significant 42% decrease in the number of admissions each year, without significant changes in the annual percentage of parapneumonic pleural effusion (PPE). Fifty-six percent of patients were immunized with a pneumococcal conjugate vaccine (PCV). The percentage of children who were not vaccinated decreased by 14%, and the coverage with PCV-13 increased by 46%. This revealed a significant increase of PPE in vaccinated patients with PCV-7 (63%) compared with unvaccinated (45%) and with PCV-13 (57%), without association with the presence of severe PPE. Moreover, no significant differences in severity or hospital stay were observed in unvaccinated patients, compared to those who were vaccinated. In >2-year-olds, we observed a significant increase in PPE (59%) compared to 45% in younger children. Conclusions The increase in vaccination coverage with PCV-13 resulted in a decrease in hospitalizations due to CAP and PPE. Vaccination with PCV-7 is associated in our sample with an increase in PPE but not with severe PPE nor an increase in the hospital stay. There was an epidemiological shift of severe forms of pneumonia and empyema at later ages (>2 years). Yes

Introduction: Ischaemic stroke has been reported in patients with COVID-19, particularly in more severe cases. However, it is unclear to what extent this is linked to systemic inflammation and hypercoagulability secondary to the infection. Materials and methods: We describe the cases of 4 patients with ischaemic stroke and COVID-19 who were attended at our hospital. Patients are classified according to the likelihood of a causal relationship between the hypercoagulable state and ischaemic stroke. We also conducted a review of studies addressing the possible mechanisms involved in the aetiopathogenesis of ischaemic stroke in these patients. Results: The association between COVID-19 and stroke was probably causal in 2 patients, who presented cortical infarcts and had no relevant arterial or cardioembolic disease, but did show signs of hypercoagulability and systemic inflammation in laboratory analyses. The other 2 patients were of advanced age and presented cardioembolic ischaemic stroke; the association in these patients was probably incidental. Conclusions: Systemic inflammation and the potential direct action of the virus may cause endothelial dysfunction, resulting in a hypercoagulable state that could be considered a potential cause of ischaemic stroke. However, stroke involves multiple pathophysiological mechanisms; studies with larger samples are therefore needed to confirm our hypothesis. The management protocol for patients with stroke and COVID-19 should include a complete aetiological study, with the appropriate safety precautions always being observed. Resumen: Introducción: Se ha comunicado la asociación de ictus isquémico y COVID-19, con mayor frecuencia en aquellos pacientes más graves. Sin embargo, se desconoce en qué medida podría estar en relación con la inflamación sistémica e hipercoagulabilidad producidas en el contexto de la infección. Métodos: Descripción de cuatro pacientes atendidos en nuestro Centro por ictus isquémico y diagnóstico de COVID-19, clasificándolos según el grado de probabilidad causal entre el estado de hipercoagulabilidad y el ictus isquémico. Revisión de la literatura sobre los posibles mecanismos implicados en la etiopatogenia del ictus isquémico en este contexto. Resultados: Dos pacientes se consideraron con alta probabilidad causal: presentaban infartos corticales, sin patología cardioembólica ni arterial significativa, con parámetros de inflamación sistémica e hipercoagulabilidad; las otras dos pacientes eran de edad avanzada y el ictus isquémico se consideró cardioembólico, con una probable asociación casual de COVID-19. Conclusiones: La inflamación sistémica, junto con la posible acción directa del virus, provocaría disfunción endotelial, generando un estado de hipercoagulabilidad que podría considerarse una causa potencial de ictus isquémico. Sin embargo, puesto que los mecanismos del ictus pueden ser múltiples, se precisan estudios más amplios que evalúen esta hipótesis. Mientras tanto, el estudio etiológico del ictus en pacientes con COVID-19 debe ser sistemático atendiendo a los protocolos vigentes, con las adaptaciones necesarias en relación con las circunstancias clínicas y epidemiológicas de la actual pandemia.

We developed a predictive score system for 30-day mortality after palliative radiotherapy by using predictors from routine electronic medical record. Patients with metastatic cancer receiving first course palliative radiotherapy from 1 July, 2007 to 31 December, 2017 were identified. 30-day mortality odds ratios and probabilities of the death predictive score were obtained using multivariable logistic regression model. Overall, 5,795 patients participated. Median follow-up was 39.6 months (range, 24.5–69.3) for all surviving patients. 5,290 patients died over a median 110 days, of whom 995 (17.2%) died within 30 days of radiotherapy commencement. The most important mortality predictors were primary lung cancer (odds ratio: 1.73, 95% confidence interval: 1.47–2.04) and log peripheral blood neutrophil lymphocyte ratio (odds ratio: 1.71, 95% confidence interval: 1.52–1.92). The developed predictive scoring system had 10 predictor variables and 20 points. The cross-validated area under curve was 0.81 (95% confidence interval: 0.79–0.82). The calibration suggested a reasonably good fit for the model (likelihood-ratio statistic: 2.81, P = 0.094), providing an accurate prediction for almost all 30-day mortality probabilities. The predictive scoring system accurately predicted 30-day mortality among patients with stage IV cancer. Oncologists may use this to tailor palliative therapy for patients.

Background The Geriatric Oral Health Assessment Index (GOHAI) was developed and validated in 1990 and translated into Spanish in 1999. Since then, the original version has been used in numerous studies, but it has not been re-evaluated in terms of language in the new generations of older adults. The purpose of this study is to confirm the validity of the Spanish version of the Geriatric Oral Health Assessment Index (GOHAI-SP) after three decades to be used as part of an ongoing field trial. Methods The GOHAI-SP was pilot tested in a focus group to confirm linguistic comprehension. A version with minor language changes was administered to individuals with metabolic syndrome aged 55–75 years from one health care district in southern Spain as part of an ongoing field trial (PREDIMED-Plus). Clinical evaluation included assessment of dental and periodontal status. The psychometric properties of the GOHAI-SP were evaluated through stability and internal consistency measures, and concurrent and discriminant validity were assessed. Results The new version of the GOHAI-SP was administered to 100 individuals. The application time was reduced by 7 min. The alpha value for reliability was 0.87. The item-scale correlation coefficients ranged from 0.54 to 0.75, and the test–re-test correlation for the total score was 0.75. There were inverse correlations between GOHAI-SP scores and the number of lost teeth and the decayed-missing-filled teeth index (p Conclusions The GOHAI-SP questionnaire remains a valid and useful tool to assess oral health-related quality of life in primary health care settings. A linguistic update of the questionnaire brought improvements to the instrument application. Trial registration The PREDIMED-Plus trial is registered in the ISRCTN registry with reference number ISRCTN89898870. Registration date: 4th July 2014.

Up to 40% of newly diagnosed cases of HIV-1 infection are late diagnoses, with a profound decrease in CD4 cell counts in many cases. One-third of these individuals do not achieve optimal CD4 cell recovery (OR) after suppressive antiretroviral treatment (ART). This retrospective/longitudinal study of poor recovery (PR) included 79 HIV-1-infected individuals with CD4 count, This work was supported in part by the Spanish AIDS Network “Red de Investigación en Sida (RIS)” RD16/0025/0001; Ayudas contratación de ayudantes de investigación y técnicos de laboratorio, Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid (PEJ15/bio/tl-0064 to MJRL and PEJ17/AI_BMD-6683 to FHW); Health Institute Carlos III, PI18/01216; Junta de Andalucía, Consejería de Economía, Innovación, Ciencia y Empleo, Proyecto de Investigación de Excelencia CTS2593; YMP was supported by the Consejería de Salud y Bienestar Social of Junta de Andalucía through the “Nicolás Monardes” programme (C-0013-2017).

Psoriasis and hidradenitis suppurativa (HS) are chronic inflammatory skin diseases that frequently develop in young women. The aim of this study is to evaluate how hidradenitis suppurativa and psoriasis impact women desiring to conceive, and their influence on fertility and gestation. A systematic review of articles dating from January 2015 to April 2021 was performed using the Scopus (Elsevier) database. The search terms were (psoriasis and (birth or pregnancy or fertility)) and ((hidradenitis suppurativa or acne inversa) and (birth or pregnancy or fertility)). The search was limited to human data. Systematic reviews, case reports, clinical practice guidelines, expert consensus and conference papers were excluded. The impact of HS on pregnancy includes an impaired desire for pregnancy, a decrease in fertility, the worsening of the disease during pregnancy and potential adverse events during pregnancy. Moreover, the pregnancy might imply a change on the treatment of HS. The impact of psoriasis on pregnancy includes a decrease in fertility, potential adverse events during pregnancy and an unpredictable evolution of the disease. Moreover, the pregnancy might imply a change on the treatment of psoriasis, although biologic therapies do not appear to increase the risk of adverse events. In conclusion, both HS and psoriasis have an impact on pregnancy. A decrease of fertility has been reported. Moreover, both diseases have an unpredictable evolution during pregnancy. Pregnant women who are under biologic therapy do not seem to have a higher rate of adverse events. Treatment of both conditions is usually halted during pregnancy since scientific evidence about their safety is not conclusive, or teratogenic risk has been proven. Yes

This research was funded by the Spanish National Research Council (CSIC), project no. 202080E231, and the Agreement with the University of Barcelona and the University of Granada (Official State Gazette 311, on 27 November 2020)., Vulvovaginal candidiasis (VVC) poses a significant problem worldwide affecting women from all strata of society. It is manifested as changes in vaginal discharge, irritation, itching and stinging sensation. Although most patients respond to topical treatment, there is still a need for increase the therapeutic arsenal due to resistances to anti-infective agents. The present study was designed to develop and characterize three hydrogels of chitosan (CTS), Poloxamer 407 (P407) and a combination of both containing 2% caspofungin (CSP) for the vaginal treatment of VVC. CTS was used by its mucoadhesive properties and P407 was used to exploit potential advantages related to increasing drug concentration in order to provide a local effect. The formulations were physically, mechanically and morphologically characterized. Drug release profile and ex vivo vaginal permeation studies were performed. Antifungal efficacy against different strains of Candida spp. was also evaluated. In addition, tolerance of formulations was studied by histological analysis. Results confirmed that CSP hydrogels could be proposed as promising candidates for the treatment of VVC., Spanish National Research Council (CSIC), project no. 202080E231, Agreement with the University of Barcelona and the University of Granada

Background: Pelvic floor dysfunctions affect a third of the adult female population, including a large number of clinical conditions, which can be evaluated through validated questionnaires that inform us of the status and perception of women both objectively and subjectively. The main objective of this study was to review and explain the topics of the validated questionnaires in Spanish on pelvic floor dysfunctions and to review their psychometric properties. Methods: A systematic review was carried out in the PUBMED and WOS databases. The keywords used were in PUBMED: ((((((((“Fecal Incontinence” [Mesh]) OR “Urinary Incontinence” [Mesh]) OR “Pelvic Organ Prolapse” [Mesh]) OR “Pelvic Floor Disorders” [Mesh]) OR “Sexual Dysfunction, Physiological” [Mesh]) OR “Pelvic Girdle Pain” [Mesh]) OR “sexual function” [Title/Abstract]) OR “Prolapse” [Title/Abstract]) AND “Surveys and Questionnaires” [Mesh] AND “Validation” [Title/Abstract] combined with the Boolean operators “AND”/“OR”. In contrast, in WOS, a segregated search was carried out with each of the terms of pelvic floor dysfunction together with “Validation” and “Surveys and Questionnaires”. All articles published up to 19 November 2021 were considered. Methodological quality was assessed with the COSMIN scale. Results: A total of 687 articles were identified, of which 13 were included. The evaluated questionnaires and the structural characteristics and psychometric properties of each of them were collected. Conclusion: The Spanish versions of the questionnaires show good basic structural and psychometric characteristics for the evaluation of patients with pelvic floor dysfunctions and that they resemble other versions of the same questionnaire published in other languages. Yes

This is a retrospective study of data from clinical practice to observe the effect of a high-calorie, high-protein oral nutritional supplement (ONS) with β-hydroxy-β-methylbutyrate (HMB) on nutritional status, body weight, and muscle-related parameters in 283 adult patients with or at risk of malnutrition under standard of care, 63% being cancer patients. They were recommended to increase physical activity and energy and protein intake from regular diet plus two servings per day of a specialized ONS enriched with HMB or standard ONS for up to 6 months. Dietary records, adherence and tolerance to ONS, nutritional status, body composition, handgrip strength, and blood analysis at the beginning and the end of the intervention were recorded. This program improved nutritional status from 100% malnourished or at risk of malnutrition at baseline to 80% well-nourished at final visit. It also increased body weight by 3.6–3.8 kg, fat-free mass by 0.9 to 1.3 kg, and handgrip strength by 4.7 to 6.2 kg. In a subgroup of patients (n = 43), phase angle (PhA), and body cell mass (BCM) increased only in the patients receiving the ONS enriched with HMB (0.95 (0.13) vs. −0.36 (0.4), and 2.98 (0.5) vs. −0.6 (1.5) kg, mean difference (SE) from baseline for PhA and BCM, respectively), suggesting the potential efficacy of this supplement on muscle health.

Alternative splicing; Soluble receptors; IFNAR; Interferon beta; Multiple sclerosis Empalmament alternatiu; Receptors solubles; IFNAR; Interferó beta; Esclerosi múltiple Splicing alternativo; Receptores solubles; IFNAR; Interferón beta; Esclerosis múltiple Purpose: Interferon beta receptor 2 subunit (IFNAR2) can be produced as a transmembrane protein, but also as a soluble form (sIFNAR2) generated by alternative splicing or proteolytic cleavage, which has both agonist and antagonist activities for IFN-β. However, its role regarding the clinical response to IFN-β for relapsing-remitting multiple sclerosis (RRMS) is unknown. We aim to evaluate the in vitro short-term effects and after 6 and 12 months of IFN-β therapy on sIFNAR2 production and their association with the clinical response in MS patients. Methods: Ninety-four RRMS patients were included and evaluated at baseline, 6 and 12 months from treatment onset. A subset of 41 patients were classified as responders and non-responders to IFN-β therapy. sIFNAR2 serum levels were measured by ELISA. mRNA expression for IFNAR1, IFNAR2 splice variants, MxA and proteases were assessed by RT-PCR. The short-term effect was evaluated in PBMC from RRMS patients after IFN-β stimulation in vitro. Results: Protein and mRNA levels of sIFNAR2 increased after IFN-β treatment. According to the clinical response, only non-responders increased sIFNAR2 significantly at both protein and mRNA levels. sIFNAR2 gene expression correlated with the transmembrane isoform expression and was 2.3-fold higher. While MxA gene expression increased significantly after treatment, IFNAR1 and IFNAR2 only slightly increased. After short-term IFN-β in vitro induction of PBMC, 6/7 patients increased the sIFNAR2 expression. Conclusions: IFN-β administration induces the production of sIFNAR2 in RRMS and higher levels might be associated to the reduction of therapeutic response. Thus, levels of sIFNAR2 could be monitored to optimize an effective response to IFN-β therapy. This research was funded by grants from the Instituto de Salud Carlos III and co-funded by European Regional Development Fund (ERDF), Technological Development Project in health DTS/1800045 to BO-M. BO-M holds a contract from Red Andaluza de Investigacion Clínica y Traslacional en Neurología (Neuro-reca) (RIC-0111-2019). PA-G is supported by Promoción de Empleo Joven e Implantación de la Garantía Juvenil 2018 (PEJ2018-002719-A). JR-B is supported by grants from Red Temática de Investigación Cooperativa, Red Española de Esclerosis Multiple REEM (RD16/0015/0010). LL holds a Nicolás Monardes research contract (RC-002-2019) from the Andalusian Ministry of Health and Family. IB-M holds a pFIS contract (FI19/00139) from the Spanish Science and Innovation Ministry.

The integration of physical and high-density genetic maps is a very useful approach to achieve chromosome-level genome assemblies. Here, the genome of a male Senegalese sole (Solea senegalensis) was de novo assembled and the contigs were anchored to a high-quality genetic map for chromosome-level scaffolding. Hybrid assembled genome was 609.3 Mb long and contained 3403 contigs with a N50 of 513 kb. The linkage map was constructed using 16,287 informative SNPs derived from ddRAD sequencing in 327 sole individuals from five families. Markers were assigned to 21 linkage groups with an average number of 21.9 markers per megabase. The anchoring of the physical to the genetic map positioned 1563 contigs into 21 pseudo-chromosomes covering 548.6 Mb. Comparison of genetic and physical distances indicated that the average genome-wide recombination rate was 0.23 cM/Mb and the female-to-male ratio 1.49 (female map length: 2,698.4 cM, male: 2,036.6 cM). Genomic recombination landscapes were different between sexes with crossovers mainly concentrated toward the telomeres in males while they were more uniformly distributed in females. A GWAS analysis using seven families identified 30 significant sex-associated SNP markers located in linkage group 18. The follicle-stimulating hormone receptor appeared as the most promising locus associated with sex within a region with very low recombination rates. An incomplete penetrance of sex markers with males as the heterogametic sex was determined. An interspecific comparison with other Pleuronectiformes genomes identified a high sequence similarity between homologous chromosomes, and several chromosomal rearrangements including a lineage-specific Robertsonian fusion in S. senegalensis. This study was funded by project RTA2017-00054-C03-01 and RTA2017-00054-C03-funded from MCIU/AEI/FEDER, UE and cofunded 80% by Programa Operativo FEDER de Andalucía 2014-2020, project PP.AVA.AVA201601.9 SOLEALGAE. Moreover, the study has received funding from EU H2020 research and innovation program under grant agreement 817992 ERANET-BLUEBIO COFUND project PCI2020-111994 BestBrood/AEI/10.13039/501100011033. IGC is funded by a predoctoral fellowship from INIA. This work would not have been possible without the computer resources and the technical support provided by the Plataforma Andaluza de Bioinformática of the University of Málaga and CNAG.

Gliomas in general and the more advanced glioblastomas (GBM) in particular are the most usual tumors of the central nervous system with poor prognosis. GBM patients develop resistance to distinct therapies, in part due to the existence of tumor cell subpopulations with stem-like properties that participate in trans-differentiation events. Within the complex tumor microenvironment, the involvement of extracellular proteases remains poorly understood. The extracellular protease ADAMTS1 has already been reported to contribute to the plasticity of cancer cells. Accordingly, this basic knowledge and the current availability of massive sequencing data from human gliomas, reinforced the development of this work. We first performed an in silico study of ADAMTS1 and endothelial markers in human gliomas, providing the basis to further assess these molecules in several primary glioblastoma-initiating cells and established GBM cells with the ability to acquire an endothelial-like phenotype. Using a co-culture approach of endothelial and GBM cells, we noticed a relevant function of ADAMTS1 in GBM cells leading the organization of endothelial-like networks and, even more significantly, we found a blockade of the formation of tumor-spheres and a deficient response to hypoxia in the absence of ADAMTS1. Our data support a chief role of this protease modulating the phenotypic plasticity of GBM.

Introduction Neuromuscular diseases include a large group of heterogeneous and rare pathologies that affect different components of the motor unit. It is essential to optimize resources to know the prevalence of comorbidities in the most frequent groups to establish an early multidisciplinary approach in a specialized setting. Patients and methods Retrospective descriptive study of pediatric and adolescent patients with neuromuscular diseases (NMDs). The Inclusion criteria were NMDs patients with motor neuron involvement divided into three groups, depending on the affected component of the motor unit. Group I: involvement of the motor neuron; Group II: peripheral neuropathies; Group III: myopathies. Demographic variables, association with comorbidities, need for respiratory support, and rehabilitative treatment were collected in each group. Results Ninety-six patients who met the inclusion criteria were studied. In group I, when compared to the other two groups, a higher incidence of scoliosis (68.3%, p = 0.011), deformity of the rib cage (31.3%, p = 0.0001), chronic respiratory insufficiency (62.5%, p = 0.001) and bronchial aspiration (12.5%, p = 0.03) was detected. In this group, 50%of the patients required non-invasive mechanical ventilation (p = 0.0001). The in-hospital requirement for respiratory physiotherapy was higher in group I (75%, p = 0.001). We observed a higher incidence of scoliosis in Group III compared to Group II. Conclusions Neuromuscular diseases with motor neuron involvement present more comorbidities and require an early approach after diagnosis to improve prognosis.

Positive psychology is the study of positive subjective experience and individual traits. Identifying deficits in positive psychology regarding fibromyalgia may inform targets for management. Therefore, the aim of the present case-control study was to compare the levels of positive affect, negative affect, satisfaction with life, optimism and emotional repair in a large sample of women with fibromyalgia (cases) and age-matched peers without fibromyalgia (controls). This case-control study included 437 women with fibromyalgia (51.6 & PLUSMN; 7.1 years old) and 206 age-matched women without fibromyalgia (50.6 & PLUSMN; 7.2 years old). Participants self-reported their levels of (i) subjective well-being on the Positive and Negative Affect Schedule and the Satisfaction with Life Scale, (ii) dispositional optimism on the Life Orientation Test-Revised and (iii) emotional repair on the Trait Meta-Mood Scale. Women with fibromyalgia showed lower levels of positive affect, satisfaction with life, optimism and emotional repair and higher levels of negative affect. Large effect sizes were found for positive affect, negative affect and satisfaction with life (all, Cohen's d & GE; 0.80) and small-to-moderate for emotional repair and optimism (both, Cohen's d & GE; 0.50). Women with fibromyalgia experience deficits of positive psychology resources. Thus, developing tailored therapies for fibromyalgia focusing on reducing deficits in positive psychology resources may be of clinical interest, though this remains to be corroborated in future research., This work was supported by the Spanish Ministry of Economy and Competitiveness (I+D+i DEP2010-15639, I+D+I DEP2013-40908); the Spanish Ministry of Education (FPU15/00002), Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). F.E.-L. has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 707404. The funders of this study did not have any role in the study design, data collection and analyses, decision to publish or preparation of the manuscript.

Background: Obesity phenotypes with different metabolic status have been described previously. We analyzed metabolic phenotypes in obese coronary patients during a 5-year follow-up, and examined the factors influencing this evolution. Methods: The CORDIOPREV study is a randomized, long-term secondary prevention study with two healthy diets: Mediterranean and low-fat. All obese patients were classified as either metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO). We evaluated the changes in the metabolic phenotypes and related variables after 5 years of dietary intervention. Results: Initially, 562 out of the 1002 CORDIOPREV patients were obese. After 5 years, 476 obese patients maintained their clinical and dietary visits, 71.8% of MHO patients changed to unhealthy phenotypes (MHO-Progressors), whereas the MHO patients who maintained healthy phenotypes (MHO-Non-Progressors) lost more in terms of their body mass index (BMI) and had a lower fatty liver index (FLI-score) (p &lt, 0.05). Most of the MUO (92%) patients maintained unhealthy phenotypes (MUO-Non-Responders), but 8% became metabolically healthy (MUO-Responders) after a significant decrease in their BMI and FLI-score, with improvement in all metabolic criteria. No differences were found among dietary groups. Conclusions: A greater loss of weight and liver fat is associated with a lower progression of the MHO phenotype to unhealthy phenotypes. Likewise, a marked improvement in these parameters is associated with regression from MUO to healthy phenotypes.

Technological changes have led to important advances in medical diagnoses and treatments that prolong the informal care process. Support from the personal network of informal caregivers is an undervalued resource and the changes that have occurred over time are unknown. The aim of this study was to analyze the changes in personal network support among informal caregivers and to examine the effect of these changes on self-perceived caregiver health, with a focus on differences between men and women and caregivers with high and low levels of burden We also investigated caregiver perceptions and explanations of changes to their support network (losses and additions and no change). Using a mixed-methods approach, data were obtained from 32 caregivers that were intentionally selected in Spain, who were interviewed twice with a one-year interval. In the quantitative phase, personal networks analysis was performed with Egonet software, which obtained data on the composition and functional content in social support from 1600 personal relationships (25 alters for each ego in the two waves). In the qualitative phase, semi-structured interviews were conducted in the two waves with a guide in order to explore the changes in informal support resources over time. The selected men with high levels of burden pointed out a loss of network support with more discouraging reports compared with the low-burden male caregivers. Furthermore, the selected women with low burden levels mentioned losses too, however, their reports were more positive. Women reported improved health, especially those with low burden scores in the first wave and those who did not lose support. Caregivers with a high initial burden and who lost support reported worse health, particularly men and women with a strong sense of duty toward care. Social support from personal networks is important for caregiver health and its effects are influenced by gender roles. Our findings could help by improving the relational and social capital of informal caregivers and adapting them to the new needs of formal home care systems.

Author Correction: Genomic surveillance of enterovirus associated with aseptic meningitis cases in southern Spain, 2015-2018. Sci Rep. 2021 Nov 18;11(1):22899. doi: 10.1038/s41598-021-02194-2. New circulating Enterovirus (EV) strains often emerge through recombination. Upsurges of recombinant non-polio enteroviruses (NPEVs) associated with neurologic manifestations such as EVA71 or Echovirus 30 (E30) are a growing public health concern in Europe. Only a few complete genomes of EVs circulating in Spain are available in public databases, making it difficult to address the emergence of recombinant EVs, understand their evolutionary relatedness and the possible implication in human disease. We have used metagenomic (untargeted) NGS to generate full-length EV genomes from CSF samples of EV-positive aseptic meningitis cases in Southern Spain between 2015 and 2018. Our analyses reveal the co-circulation of multiple Enterovirus B (EV-B) types (E6, E11, E13 and E30), including a novel E13 recombinant form. We observed a genetic turnover where emergent lineages (C1 for E6 and I [tentatively proposed in this study] for E30) replaced previous lineages circulating in Spain, some concomitant with outbreaks in other parts of Europe. Metagenomic sequencing provides an effective approach for the analysis of EV genomes directly from PCR-positive CSF samples. The detection of a novel, disease-associated, recombinant form emphasizes the importance of genomic surveillance to monitor spread and evolution of EVs. This work was funded by the Junta de Andalucía, Consejería de Salud y Familias (Project number PI-0216-2019) and by the Acción Estratégica en Salud Intramural (Project number PI20CIII/00005). MD Fernandez-Garcia received a Miguel Servet Research Contract (CP18/00067) from the Strategic Action in Health 2018 and funded by National Institute of Health Carlos III (ISCIII). ESL acknowledges funding from the INCEPTION programme (Investissements d’Avenir grant ANR-16-CONV-0005). Sí

Human milk (HM) is considered the most complete food for infants as its nutritional composition is specifically designed to meet infant nutritional requirements during early life. HM also provides numerous biologically active components, such as polyunsaturated fatty acids, milk fat globules, IgA, gangliosides or polyamines, among others; in addition, HM has a "bifidogenic effect", a prebiotic effect, as a result of the low concentration of proteins and phosphates, as well as the presence of lactoferrin, lactose, nucleotides and oligosaccharides. Recently, has been a growing interest in HM as a potential source of probiotics and commensal bacteria to the infant gut, which might, in turn, influence both the gut colonization and maturation of infant immune system. Our review aims to address practical approaches to the detection of microbial communities in human breast milk samples, delving into their origin, composition and functions. Furthermore, we will summarize the current knowledge of how HM microbiota dysbiosis acts as a short- and long-term predictor of maternal and infant health. Finally, we also provide a critical view of the role of breast milk-related bacteria as a novel probiotic strategy in the prevention and treatment of maternal and offspring diseases. Yes

The SARS-CoV-2 pandemic led to lockdowns, which affected the elderly, a high-risk group. Lockdown may lead to weight gain due to increased food intake and reduced physical activity (PA). Our study aimed to analyze the impact of a 12-month lifestyle intervention on a metabolically healthy overweight/obese elderly (MHOe) population and how the lockdown by COVID-19 affected this program. Methods: MHOe participants (65–87 years) were recruited to participate in a lifestyle modification intervention based on the Mediterranean diet (MedDiet) and regular PA. Participants were classified into two groups: young-old (&lt, 75 years) or old-old (≥75 years). Anthropometric and clinical characteristics, energy intake, and energy expenditure were analyzed at baseline and after 12 months of intervention. Results: The final sample included 158 MHOe participants of both sexes (age: 72.21 ± 5.04 years, BMI: 31.56 ± 3.82 kg/m2): 109 young-old (age: 69.26 ± 2.83 years, BMI: 32.0 ± 3.85 kg/m2) and 49 old-old (age: 78.06 ± 2.88 years, BMI: 30.67 ± 3.64 kg/m2). After 12 months of intervention and despite lockdown, the young-old group increased MedDiet adherence (+1 point), but both groups drastically decreased daily PA, especially old-old participants. Fat mass significantly declined in the total population and the young-old. Depression significantly increased (26.9% vs. 21.0%, p &lt, 0.0001), especially in the old-old (36.7% vs. 22.0%, p &lt, 0.0001). No significant changes were found in the glycemic or lipid profile. Conclusions: This study indicates that ongoing MedDiet intake and regular PA can be considered preventative treatment for metabolic diseases in MHOe subjects. However, mental health worsened during the study and should be addressed in elderly individuals.

Head and neck cancer (HNC) is the sixth most common cancer worldwide. Yet, less than 60% of HNC survivors receive adequate therapy for treatment-related sequelae. The objective of this study was to determine the efficacy of myofascial induction therapy (MIT) in improving cervical and shoulder pain and range of motion, maximal mouth opening, and cervical muscle function in HNC survivors. This crossover, blinded, placebo-controlled study involved 22 HNC survivors (average age 56.55 ± 12.71) of which 13 were males (59.1%) who received, in a crossover fashion, both a single 30-min session of MIT in the form of manual unwinding and simulated pulsed shortwave therapy (placebo), with a 4-week washout interval between the two. Cervical and shoulder pain (visual analogue scale) and range of motion (cervical range of motion device and goniometer), maximum mouth opening (digital caliper), and cervical muscle function (deep cervical flexor endurance test) were measured before and after the treatment and placebo sessions. A single session of MIT improved cervical and affected side shoulder pain, cervical range of motion, maximum mouth opening, and cervical muscle function. The associated effect sizes ranged from moderate to large. The present study suggests that MIT, in the form of manual unwinding, improves cervical (−3.91 ± 2.77) and affected-side shoulder (−3.64 ± 3.1) pain, cervical range of motion (flexion: 8.41 ± 8.26 deg, extension: 12.23 ± 6.55, affected-side rotation: 14.27 ± 11.05, unaffected-side rotation: 11.73 ± 8.65, affected-side lateroflexion: 7.95 ± 5.1, unaffected-side lateroflexion: 9.55 ± 6.6), maximum mouth opening (3.36 ± 3.4 mm), and cervical muscle function (8.09 ± 6.96 s) in HNC survivors.

Background: Leisure-time physical activity (LTPA) is not the same as occupational activity. Various factors influence both forms of physical activity, including job stress and job satisfaction, but the associations found are weak, and the need for new studies in large populations is emphasized. The objective was to study the relationship between job stress and job satisfaction, and the relationship between these and occupational and leisure-time physical activity according to the National Survey of Health 2017. Methods: A population-based study of 8716 workers between 18 and 65 years of age. The variables age, sex, leisure, and occupational-time physical activity (OTPA), educational level, type of occupation, job stress level, and job satisfaction were collected. A simple and multiple correspondence analysis was performed between the variables that reached statistical significance. Results: 4621 cases (53.02%) correspond to men with a mean age of 44.83 years (SD 10.22) and 4095 cases to women with a mean age of 44.55 years (SD 10.23). Women had higher percentages of higher education (p &lt, 0.001), intermediate to high occupations and unskilled (p &lt, 0.001), job stress (p &lt, 0.001), covered the most extreme levels of satisfaction (p = 0.003), and do less LTPA (p &lt, 0.001) and OTPA (p &lt, 0.001). Also, in women a relationship was found between job stress and LTPA (p = 0.024), as well as between satisfaction and both forms of physical activity (OTPA p = 0.013 and LTPA p &lt, 0.001). In men, significance was only reached in the relationship between job stress and OTPA (p &lt, 0.001). Conclusions. The higher the job stress, the less the job satisfaction, but the relationship is reversed in the intermediate categories. For both sexes, job stress is related to a sedentary lifestyle and higher employment and education levels. Higher levels of satisfaction correspond to higher levels of occupancy. The relationship between job satisfaction and educational level is direct in women but inverse in men. In women, there is a relationship between sedentary occupations and job satisfaction. In addition, intense physical activity at work is related to higher levels of job stress, lower satisfaction levels, and less physical activity in leisure-time.

The most representative indicator of vitamin D status in clinical practice is 25(OH)D3, but new biomarkers could improve the assessment of vitamin D status and metabolism. The objective of this study is to investigate the association of serum vitamin D metabolites and vitamin D metabolite ratios (VMRs) with potentially influential factors in premenopausal women. This is a cross-sectional study based on 1422 women, aged 39-50, recruited from a Madrid Medical Diagnostic Center. Participants answered an epidemiological and a food frequency questionnaire. Serum vitamin D metabolites were determined using an SPE-LC-MS/MS platform. The association between participant's characteristics, vitamin D metabolites, and VMRs was quantified by multiple linear regression models. Mean 25(OH)D3 concentration was 49.2 + 18.9 nmol/L, with greater deficits among obese, nulliparous, dark-skinned women, and with less sun exposure. A lower R2 ratio (1,25(OH)2D3/25(OH)D3) and a higher R4 (24,25(OH)2D3/1,25(OH)2D3) were observed in nulliparous women, with high sun exposure, and those with low caloric intake or high consumption of calcium, vitamin D supplements, or alcohol. Nulliparous women had lower R1 (25(OH)D3/Vit D3) and R3 (24,25(OH)2D3/25(OH)D3), and older women showed lower R3 and R4. Vitamin D status modified the association of the VMRs with seasons. VMRs can be complementary indicators of vitamin D status and its endogenous metabolism, and reveal the influence of certain individual characteristics on the expression of hydroxylase enzymes. This study was funded by the Spanish Ministry of Health (EC11–273) and by the Carlos III Institute of Health (PI15CIII/0029). The article presents independent research. The views expressed are those of the authors and not necessarily those of the Carlos III Institute of Health. Sí

Gender significantly influences sociodemographic, medical, psychiatric and addiction variables in cocaine outpatients. Educational level may be a protective factor showing less severe addictive disorders, longer abstinence periods, and better cognitive performance. The aim was to estimate gender-based differences and the influence of educational level on the clinical variables associated with cocaine use disorder (CUD). A total of 300 cocaine-consuming patients undergoing treatments were recruited and assessed using the Psychiatric Research Interview for Substance and Mental Diseases according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Women developed CUD later but exhibited more consumption of anxiolytics, prevalence of anxiety disorders, eating disorders, and major depressive disorders. Alcohol and cannabis use disorders were more frequent in men. A predictive model was created and identified three psychiatric variables with good prognosis for distinguishing between women and men. Principal component analysis helped to describe the different profile types of men and women who had sought treatment. Low educational levels seemed to be a risk factor for the onset, development, and duration of CUD in both genders. Women and men exhibited different clinical characteristics that should be taken into account when designing therapeutic policies. The educational level plays a protective/risk role in the onset, development and progression of CUD, thus prolonging the years of compulsory education and implementing cognitive rehabilitation programmes could be useful.

MALF was supported by the Spanish National Health Institute Carlos III (Instituto de Salud Carlos III -ISCIII), Miguel Servet--I Investigator Grant/Award Number CP17/00206--EU--FEDER., Objective We evaluated the temporal trend in gender ratios of first and last authors in the field of oncological research published in major general medical and oncology journals and examined the gender pattern in coauthorship. Design We conducted a retrospective study in PubMed using the R package RISmed. We retrieved original research articles published in four general medical journals and six oncology specialty journals. These journals were selected based on their impact factors and popularity among oncologists. We identified the names of first and last authors from 1 January 2002 to 31 December 2019. The gender of the authors was identified and validated using the Gender API database (https:// gender-​api. com/). Primary and secondary outcome measures The percentages of first and last authors by gender and the gender ratios (male to female) and temporal trends in gender ratios of first and last authors were determined. Results We identified 34 624 research articles, in which 32 452 had the gender of both first and last authors identified. Among these 11 650 (33.6%) had women as the first author and 7908 (22.8%) as the last author, respectively. The proportion of female first and last authors increased from 26.6% and 16.2% in 2002, to 32.9% and 27.5% in 2019, respectively. However, the gender ratio (male to female) of first and last authors decreased by 1.5% and 2.6% per year, respectively, which were statistically significant (first author: incidence rate ratio (IRR) 0.98, 95% CI 0.97 to 1.00; last author: IRR 0.97, 95% CI 0.96 to 0.99). Male first and last authorship was the most common combination. Male–female and female– female pairs increased by 2.0% and 5.0%, respectively (IRR 1.02, 95% CI 1.01 to 1.03 and IRR 1.05, 95% CI 1.04 to 1.06, respectively). Conclusions The continued under-representation of women means that more efforts to address parity for advancement of women in academic oncology are needed., Spanish National Health Institute Carlos III (Instituto de Salud Carlos III -ISCIII) CP17/00206--EU--FEDER

Chromosome 22q11.2 deletion syndrome (22q11DS) is characterized by congenital cardiac abnormalities, hypoplastic thymus, palatal abnormalities, and hypocalcemia, although other clinical features are frequent such as autoimmune and psychiatric disorders. One-third of the patients have psychotic disorders, frequently followed by developmental regression and long-term cognitive disturbances. Despite humoral and cellular immunodeficiency are common in 22q11DS, it is associated with an increased prevalence of autoimmune disorders such as idiopathic thrombocytopenic purpura and juvenile idiopathic arthritis, likely due to immune dysregulations associated with thymic abnormalities, which plays a major role in self-tolerance. We report an unique case of a 14-year-old girl with 22q11DS that presented with subacute psychotic symptoms, intolerance to antipsychotics, CSF pleocytosis, and EEG abnormalities, that was successfully treated with empiric immunotherapy after fulfilling criteria for probable seronegative autoimmune encephalitis and probable autoimmune psychosis. The autoimmune etiology of these clinical features of 22q11DS has never been postulated despite the predisposition of this syndrome to present autoimmune disorders. We suggest the systematic evaluation with serum and CSF neuronal antibodies, MRI, and EEG of patients with 22q11DS that develop subacute psychotic symptoms or rapidly progressive cognitive decline. Early immunomodulatory therapies should be carefully considered if criteria of probable autoimmune psychosis or possible autoimmune encephalitis are fulfilled, as it may prevent long-term disabilities. Further studies are required to assess the autoimmune origin of psychosis and cognitive impairment associated with 22q11DS.

Scholastic factors (academic achievement) are hypothesized to be important determinants of health-related behaviors in adolescents, but there is a lack of knowledge on their influence on physical activity levels (PAL), especially considering the COVID-19 pandemic and the imposed lockdown. This study aimed to investigate the associations between scholastic factors and PAL before and during the pandemic lockdown. The participants were adolescents form Bosnia and Herzegovina (n = 525, 46% females), who were observed prospectively at the baseline (before the pandemic lockdown) and during the lockdown in 2020 (follow-up). The scholastic factors (grade point average, behavioral grade, school absences, unexcused absences) were evidenced at the baseline (predictors). The outcome (PAL) was evaluated using the Physical Activity Questionnaire for Adolescents at the baseline and the follow-up. Gender, age, parental/familial conflict, and sport participation were observed as confounders. No significant influence of the predictors on PAL were evidenced at the baseline or at the follow-up. The scholastic variables were significantly associated with the changes of PAL which occurred due to pandemic lockdown, with a lower risk for negative changes in PAL among adolescents who were better in school (OR = 0.56, 95%CI: 0.34-0.81, and OR = 0.66, 95%CI: 0.34-0.97, for the grade point average and behavioral grade, respectively). Students who do well in school are probably more aware of the health benefits of proper PAL, and therefore are devoted to the maintenance of their PAL even during the home-confinement of lockdown. Public health authorities should focus more on helping adolescents to understand the importance and benefits of proper PAL throughout the school system., \This study received no external funding. The APC was founded by The European University of the Seas (SEA-EU) project (Erasmus+, European Universities; Ref 612468-EPP-1-2019-1-ESEPPKA2-EUR-UNIV).

Recent evidence has revealed anti-inflammatory properties of vitamin D as well as extra-skeletal activity. In this context, vitamin D seems to be involved in infections, autoimmune diseases, cardiometabolic diseases, and cancer development. In recent years, the relationship between vitamin D and insulin resistance has been a topic of growing interest. Low 25-hydroxyvitamin D (25(OH)D) levels appear to be associated with most of the insulin resistance disorders described to date. In fact, vitamin D deficiency may be one of the factors accelerating the development of insulin resistance. Vitamin D deficiency is a common problem in the population and may be associated with the pathogenesis of diseases related to insulin resistance, such as obesity, diabetes, metabolic syndrome (MS) and polycystic ovary syndrome (PCOS). An important question is the identification of 25(OH)D levels capable of generating an effect on insulin resistance, glucose metabolism and to decrease the risk of developing insulin resistance related disorders. The benefits of 25(OH)D supplementation/repletion on bone health are well known, and although there is a biological plausibility linking the status of vitamin D and insulin resistance supported by basic and clinical research findings, well-designed randomized clinical trials as well as basic research are necessary to know the molecular pathways involved in this association. Yes

Viral and host immune kinetics during acute COVID-19 and after remission of acute symptoms need better characterization. SARS-CoV-2 RNA, anti-SARS-CoV-2 IgA, IgM, and IgG antibodies, and proinflammatory cytokines were measured in sequential samples from hospitalized COVID-19 patients during acute infection and six months following diagnosis. Twenty four laboratory confirmed COVID-19 patients with mild/moderate and severe COVID-19 were included. Most were males (83%) with a median age of 61 years. Twenty one percent were admitted to the intensive care unit (ICU) and eight of them (33.3%) met the criteria for severe COVID-19 disease. A delay in SARS-CoV-2 levels’ decline during the first six days of follow up, and viral load persistence until month 3 were related to severe COVID-19, but not viral load levels at the diagnosis. Higher levels of anti-SARS-CoV-2 IgA, IgM, IgG and the cytokines IL-6, IL-8 and MIP-1β at the diagnosis time were related to the severe COVID-19 outcome. Higher levels of MIP-1β, IL-1β, MIP-1α and IFN-γ were observed at month 1 and 3 during mild/moderate disease, compared to severe COVID-19. IgG persisted at low levels after six months of diagnosis. In conclusion, higher concentrations of IgA, IgM, and IgG, and IL-6, IL-8 and MIP-1β are identified as early predictors of COVID-19 severity, whereas no significant association is found between baseline SARS-COV-2 viral load and COVID-19 severity., This work was supported by the Plan Estatal de I+D+I 2013-2016 and 2017–2020 and cofinanced by the Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la investigación del Fondo Europeo de Desarrollo Regional (FEDER), Fondo COVID19 of Instituto de Salud Carlos III (COV20/00698), RETICS, Red de Investigación en SIDA [RD16/0025/0026]; and Fundación Biomédica Galicia Sur. E.R-M. was supported by the Spanish Research Council (CSIC) and by the research grant CV20-85418 from the Consejería de Transformación Económica, Industria, Conocimiento y Universidades (Junta de Andalucía). A.P. was supported by the Instituto de Salud Carlos III, Subprograma Rio Hortega (CM20/00243). A.G.-V. was supported by the Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund (“A way to achieve Europe”), Subprograma Miguel Servet (CP19/00159). E.M.M. was supported by the Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund (“A way to achieve Europe”), Subprogram PFIS (FI19/00304). C.K. was supported by Fondo COVID19 of Instituto de Salud Carlos III (COV20/00823).

Càncer de pulmó; Fumar; Diferències entre sexes Cancer de pulmón; Fumar; Diferencias entre sexos Lung neoplasms; Smoking; Sex Factors Background: Lung cancer causes approximately 25% of all cancer deaths. Despite its relevance, few studies have analyzed differences by sex at the time of diagnosis in terms of symptoms, stage, age or smoking status. We aim to assess if there are differences between men and women on these characteristics at diagnosis. Methods: We analyzed the Thoracic Tumour Registry (TTR), sponsored by the Spanish Lung Cancer Group using a case-series design. This is a nationwide registry of lung cancer cases which started recruitment in 2016. For each case included, clinicians fulfilled an electronic record registering demographic data, symptoms, exposure to lung cancer risk factors, and treatment received in detail. We compared men and women using descriptive statistics. Results: A total of 13,590 participants took part in this study, 25.6% women. Women were 4 years younger than men (64 vs. 69), and men had smoked more frequently. Adenocarcinoma was the most frequent histological type in both sexes. Stage IV at diagnosis was 50.8% in women compared to 43.6% in men. Weight loss/anorexia/asthenia was the most frequent symptom in both sexes and there were no differences in the number of symptoms at diagnosis. There were no relevant differences in the frequency or number of symptoms by sex when non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) were analyzed separately. Smoking status did not appear to cause different lung cancer presentation in men compared to women. Conclusions: There seems to be no differences in lung cancer characteristics by sex at the time at diagnosis on stage, specific symptoms or number of symptoms. This research received funding from the Spanish Lung Cancer Group

Tactile rendering has been implemented in digital musical instruments (DMIs) to offer the musician haptic feedback that enhances his/her music playing experience. Recently, this implementation has expanded to the development of sensory substitution systems known as haptic music players (HMPs) to give the opportunity of experiencing music through touch to the hearing impaired. These devices may also be conceived as vibrotactile music players to enrich music listening activities. In this review, technology and methods to render musical information by means of vibrotactile stimuli are systematically studied. The methodology used to find out relevant literature is first outlined, and a preliminary classification of musical haptics is proposed. A comparison between different technologies and methods for vibrotactile rendering is performed to later organize the information according to the type of HMP. Limitations and advantages are highlighted to find out opportunities for future research. Likewise, methods for music audio-tactile rendering (ATR) are analyzed and, finally, strategies to compose for the sense of touch are summarized. This review is intended for researchers in the fields of haptics, assistive technologies, music, psychology, and human-computer interaction as well as artists that may make use of it as a reference to develop upcoming research on HMPs and ATR. Yes

Background: Identifying those parameters that could potentially predict the deterioration of metabolically healthy phenotype is a matter of debate. In this field, epigenetics, in particular DNA methylation deserves special attention. Results: The aim of the present study was to analyze the long-term evolution of methylation patterns in a subset of metabolically healthy subjects in order to search for epigenetic markers that could predict the progression to an unhealthy state. Twenty-six CpG sites were significantly differentially methylated, both at baseline and 11-year follow-up. These sites were related to 19 genes or pseudogenes, a more in-depth analysis of the methylation sites of these genes showed that CYP2E1 had 50% of the collected CpG sites differently methylated between stable metabolically healthy obesity (MHO) and unstable MHO, followed by HLA-DRB1 (33%), ZBTB45 (16%), HOOK3 (14%), PLCZ1 (14%), SLC1A1 (12%), MUC2 (12%), ZFPM2 (12.5%) and HLA-DQB2 (8%). Pathway analysis of the selected 26 CpG sites showed enrichment in pathways linked to th1 and th2 activation, antigen presentation, allograft rejection signals and metabolic processes. Higher methylation levels in the cg20707527 (ZFPM2) could have a protective effect against the progression to unstable MHO (OR: 0.21, 95%CI (0.067–0.667), p &lt, 0.0001), whilst higher methylation levels in cg11445109 (CYP2E1) would increase the progression to MUO, OR: 2.72, 95%CI (1.094–6.796), p &lt, 0.0014, respectively). Conclusions: DNA methylation status is associated with the stability/worsening of MHO phenotype. Two potential biomarkers of the transition to an unhealthy state were identified and deserve further investigation (cg20707527 and cg11445109). Moreover, the described differences in methylation could alter immune system-related pathways, highlighting these pathways as therapeutic targets to prevent metabolic deterioration in MHO patients.

Objective: The aim of this scoping review was to identify if the phase of the menstrual cycle was considered in observational studies comparing pressure pain sensitivity between women with migraine or tension-type headache (TTH) and headache-free women. Methods: A systematic electronic literature search in PubMed, Medline, Web of Science, Scopus, and CINAHL databases was conducted. Observational studies including one or more groups with TTH and/or migraine comparing pressure pain thresholds (PPTs) were included. The methodological quality (risk of bias) was assessed with the Newcastle-Ottawa Scale. Authors, objectives, inclusion/exclusion criteria, size sample, female sample, tool to assess PPTs, mean age, and the use of any medication were extracted and analyzed independently by two authors. Results: From a total of 1404 and 1832 identified articles for TTH and migraine, 30 and 18 studies satisfied the criteria and were included. Nineteen (63.4%) studies assessing TTH patients and eleven (61.1%) assessing migraine patients showed a high risk of bias. The most common flaws were attributed to improper selection of control and control over other additional factors. Based on the systematic review, just one study including TTH and one including migraine patients considered the menstrual cycle. Conclusion: The results of this scoping review identified that the phase of the menstrual cycle has been rarely considered in studies investigating sensitivity to pressure pain in primary headaches, such as TTH or migraine, although there is evidence showing the relevance of the phase of the menstrual cycle in pain perception. Yes

Background: Intimate partner violence (IPV) affects outcomes of mothers and their offspring. This systematic review collated the worldwide literature on the prevalence rates of different types of IPV in pregnancy. Methods: Two reviewers independently identified cross sectional and cohort studies of IPV prevalence in pregnancy in online databases (PubMed, WOS and Scopus), selected and extracted data [participants' country, study quality, measurement tool (validation and purpose) and rates of IPV in pregnancy]. We considered a high quality study if it had a prospective design, an adequate sampling method, a sample size estimation, a response rate > 90%, a contemporary ascertainment of IPV in the index pregnancy, and a well-developed detailed IPV tool. We performed random effects meta-analysis and explored reasons for heterogeneity of rates. Results: One hundred fifty-five studies were included, of which 44 (28%) met two-thirds of the quality criteria. Worldwide prevalence of physical (126 studies, 220,462 participants), psychological (113 studies, 189,630 participants) and sexual (98 studies, 155,324 participants) IPV in pregnancy was 9.2% (95% CI 7.7-11.1%, I2 95.9%), 18.7% (15.1-22.9%, I2 98.2%), 5.5% (4.0-7.5%, I2 93.4%), respectively. Where several types of IPV were reported combined, the prevalence of any kind of IPV (118 studies, 124,838 participants) was 25.0% (20.3, 30.5%, I2 98.6%). IPV rates varied within and between continents, being the highest in Africa and the lowest in Europe (p < 0.001). Rates also varied according to measurement purpose, being higher for diagnosis than for screening, in physical (p = 0.022) and sexual (p = 0.014) IPV. Conclusions: IPV prevalence in pregnancy varies across countries, with one-quarter of mothers exposed on average globally. Routine systematic antenatal detection should be applied worldwide. Yes

This work was supported by the Ministry of economy and competitiveness and the National Institute of Health: Instituto de Salud Carlos III (ISCIII). Exps: PI14/00067, PI14/01716, PI14/01880, PI14/00556. BA15/00093. FFIS-CC 2016-06 AECC "Junta provincial de Murcia". FEDER and AECC 2015. Dr. J.P. Arrebola is under contract within Ramon y Cajal program (RYC-2016-20155, Ministerio de Economia, Industria y Competitividad, Spain). The EPIC-Spain cohort was supported by the Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology -ICO (Spain)., Background Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). Methods We designed a case-cohort study within the EPIC-Spain cohort. Study population consisted on 4812 participants from 4 EPIC-Spain centers (547 breast cancer cases, 575 prostate cancer cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Borgan II weighted Cox regression was used to estimate hazard ratios. Results Median follow-up time in our study was 16.9 years. BPA geometric mean serum values of cases and sub-cohort were 1.12 ng/ml vs 1.10 ng/ml respectively for breast cancer and 1.33 ng/ml vs 1.29 ng/ml respectively for prostate cancer. When categorizing BPA into tertiles, a 40% increase in risk of prostate cancer for tertile 1 (p = 0.022), 37% increase for tertile 2 (p = 0.034) and 31% increase for tertile 3 (p = 0.072) was observed with respect to values bellow the limit of detection. No significant association was observed between BPA levels and breast cancer risk. Conclusions We found a similar percentage of detection of BPA among cases and sub-cohort from our population, and no association with breast cancer risk was observed. However, we found a higher risk of prostate cancer for the increase in serum BPA levels. Further investigation is needed to understand the influence of BPA in prostate cancer risk., Ministry of economy and competitiveness, National Institute of Health: Instituto de Salud Carlos III (ISCIII), AECC "Junta provincial de Murcia" PI14/00067- PI14/01716- PI14/01880- PI14/00556- BA15/00093- FFIS-CC 2016-06, Spanish Government RYC-2016-20155, Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Catalan Institute of Oncology -ICO (Spain)

The purpose of the present study was to investigate the associations between muscle thickness and echo intensity with cognitive and physical dimensions like functional capacity measured in older people. This cross-sectional study involved 20 older adults (15 women and 5 men, mean age +/- SD: 85 +/- 7 years, body mass index: 25 +/- 3 kg/m(2)) from a geriatric centre in Malaga (Spain). Anthropometric measurements, cognitive assessment with Pfeiffer Short Portable Mental Status Questionnaire and Motor Memory test, Physical Performance with Short Physical Performance Battery, and muscle strength were tested. Additionally, using B-mode ultrasonography, images of wrist flexors, biceps brachii, rectus femoris, vastus lateralis, medial gastrocnemius, and tibialis anterior were captured, and muscle thickness and echo intensity variables were extracted. An association between muscle parameters assessed by ultrasonography and cognitive and physical dimensions were found in older people. Echo intensity was the best predictor in a set of regression models with different muscle parameters and a battery of cognitive and physical tests in older people. Echo intensity adjusted by handgrip strength could be a low cost and ambulatory index and an indirect and reversible indicator of functional capacity., This work was partial financial supported by the Erasmus+ Strategic Partnership for Higher Education Programme (Key Action 203) [Grant number: 2018-1-PL01-KA203-051055].

We assessed the structure–function relationship of the human cholinergic system and hypothesized that structural measures are associated with short-latency sensory afferent inhibition (SAI), an electrophysiological measure of central cholinergic signal transmission. Healthy volunteers (n = 36) and patients with mild cognitive impairment (MCI, n = 20) underwent median nerve SAI and 3T structural MRI to determine the volume of the basal forebrain and the thalamus. Patients with MCI had smaller basal forebrain (p p 10% SAI) had more basal forebrain volume than non-responders (p = 0.004) or patients with MCI (p r = 0.33, p

Abnormal trinucleotide expansions cause rare disorders that compromise quality of life and, in some cases, lifespan. In particular, the expansions of the CGG-repeats stretch at the 5'-UTR of the Fragile X Mental Retardation 1 (FMR1) gene have pleiotropic effects that lead to a variety of Fragile X-associated syndromes: the neurodevelopmental Fragile X syndrome (FXS) in children, the late-onset neurodegenerative disorder Fragile X-associated tremor-ataxia syndrome (FXTAS) that mainly affects adult men, the Fragile X-associated primary ovarian insufficiency (FXPOI) in adult women, and a variety of psychiatric and affective disorders that are under the term of Fragile X-associated neuropsychiatric disorders (FXAND). In this review, we will describe the pathological mechanisms of the adult "gain-of-function" syndromes that are mainly caused by the toxic actions of CGG RNA and FMRpolyG peptide. There have been intensive attempts to identify reliable peripheral biomarkers to assess disease progression and onset of specific pathological traits. Mitochondrial dysfunction, altered miRNA expression, endocrine system failure, and impairment of the GABAergic transmission are some of the affectations that are susceptible to be tracked using peripheral blood for monitoring of the motor, cognitive, psychiatric and reproductive impairment of the CGG-expansion carriers. We provided some illustrative examples from our own cohort. Understanding the association between molecular pathogenesis and biomarkers dynamics will improve effective prognosis and clinical management of CGG-expansion carriers. Yes

BackgroundWhether immunosuppressed (IS) patients have a worse prognosis of COVID-19 compared to non-IS patients is not known. The aim of this study was to evaluate the clinical characteristics and outcome of IS patients hospitalized with COVID-19 compared to non-IS patients.MethodsWe designed a retrospective cohort study. We included all patients hospitalized with laboratory-confirmed COVID-19 from the SEMI-COVID-19 Registry, a large multicentre national cohort in Spain, from March 27thuntil June 19th, 2020. We used multivariable logistic regression to assess the adjusted odds ratios (aOR) of in-hospital death among IS compared to non-IS patients.ResultsAmong 13 206 included patients, 2 111 (16.0%) were IS. A total of 166 (1.3%) patients had solid organ (SO) transplant, 1081 (8.2%) had SO neoplasia, 332 (2.5%) had hematologic neoplasia, and 570 (4.3%), 183 (1.4%) and 394 (3.0%) were receiving systemic steroids, biological treatments, and immunosuppressors, respectively. Compared to non-IS patients, the aOR (95% CI) for in-hospital death was 1.60 (1.43–1.79) for all IS patients, 1.39 (1.18–1.63) for patients with SO cancer, 2.31 (1.76–3.03) for patients with haematological cancer and 3.12 (2.23–4.36) for patients with SO transplant. The aOR (95% CI) for death for patients who were receiving systemic steroids, biological treatments and immunosuppressors compared to non-IS patients were 2.16 (1.80–2.61), 1.97 (1.33–2.91) and 2.06 (1.64–2.60), respectively. IS patients had a higher odds than non-IS patients of in-hospital acute respiratory distress syndrome, heart failure, myocarditis, thromboembolic disease and multiorgan failure.ConclusionsIS patients hospitalized with COVID-19 have a higher odds of in-hospital complications and death compared to non-IS patients.

Resumen: Objetivo principal: Evaluar la respuesta clínica a las 24 semanas de la infiltración, medida como alivio del dolor y recuperación funcional, en el síndrome de hombro doloroso (SHD) en atención primaria (AP). Diseño: Serie de casos longitudinal con tratamiento de inyección en la articulación escapulohumeral; se describen la funcionalidad y la evolución del dolor previa y a las 24 semanas postinfiltración. Emplazamiento: Atención Primaria. Centro de salud no urbano. Participantes: Pacientes con patología osteoarticular de hombro susceptible de infiltración, fracaso de tratamiento farmacológico y calificación en la escala analógica visual (EVA) ≥ 4 o Constant Score (CS) ≤ 70. Intervenciones: Inyección intraarticular corticosteroide y anestésico local en la articulación escapulohumeral, describiendo su evolución a 1, 4, 12 y 24 semanas postinfiltración. Mediciones principales: Respuesta de la infiltración según EVA antes-después, CS antes-después, número de infiltraciones, efectos secundarios, incapacidad laboral transitoria (ILT). Resultados: Se infiltraron 66 pacientes, edad media 51,1 años (DE: 14,7), 57,6% mujeres, 63,3% infiltración hombro derecho. El 22,7% precisaron ILT y cursaron alta con una mediana de 14 días (rango de 7-56 días). Precisaron una infiltración (80,3%) y la patología infiltrada más frecuente fue la tendinitis de los rotadores (90,9%). Sufrieron efectos secundarios leves un 9,4%. Encontramos disminución de dolor de severo a leve y una mejoría funcional de pobre a buena. Las variables: ser jubilado (OR: 37,82, p = 0,001) y tener un puntaje EVA previo a la infiltración > 8 (OR; 15,67, p = 0,055, cuasi significativo) se asociaron a mala respuesta. Conclusiones: La administración intraarticular de corticosteroides en el SHD disminuye el dolor y aporta una mejoría funcional tras la primera semana postinfiltración, manteniéndose a largo plazo. Esto permite una rápida incorporación laboral con una infiltración a las 2 semanas, disminuyendo en un 50% el tiempo de recuperación, con escasos efectos secundarios. Abstract: Main objective: To evaluate the clinical response at 24 weeks after injection, measured as pain relief and functional recovery, in painful shoulder syndrome (PSS) in primary care (PC). Design: Longitudinal case series with injection treatment in the scapulohumeral joint, describing functionality and pain evolution before and at 24 weeks post injection. Location: Non-urban primary care centres. Participants: Patients with osteoarticular shoulder pathology susceptible to injection, failure of pharmacological treatment and rating on the visual analogue scale (VAS) ≥ 4 or constant score (CS) ≤ 70. Interventions: Intra-articular injection of corticosteroid and local anaesthetic into the scapulohumeral joint, describing its evolution at 1, 4, 12 and 24 weeks post injection. Main measurements: Infiltration response according to EVA before and after, CS before and after, number of infiltrations, side effects, temporary inability to work (TIL). Results: Sixty-six patients receiving injection, mean age 51.1 years (SD 14.7), 57.6% were women and 63.3% were injection in the right shoulder. A 22.7% required TIL and were discharged with a median of 14 days (range 7-56 days). They required an injection (80.3%) and the most frequent injection pathology was rotator cuff tendinitis (90.9%). They suffered mild side effects (9.4%). We found a decrease in pain from severe to mild and a functional improvement from poor to good. The variables: being retired (OR: 37.82, P = .001) and having an EVA score prior to injection > 8 (OR: 15.67, P = .055, almost significant) were associated with poor response. Conclusions: Intra-articular administration of corticosteroids in PSS reduces pain and provides functional improvement after the first week after injection, and is maintained in the long term. This allows a quick recovery to work after an injection at two weeks reducing recovery time by 50%, with few side effects.

Background and Objectives To determine the relative importance of global or regional MRI and blood markers of neurodegeneration and neuroaxonal injury in predicting cognitive performance for recently diagnosed patients with multiple sclerosis (MS). Methods Thirty-five newly diagnosed patients with relapsing-remitting MS (RRMS) and 23 healthy controls (HCs) simultaneously completed a full clinical and neuropsychological assessment, structural brain MRI, and serum neurofilament light chain (sNfL) level test. Linear regression analyses were performed to determine which global or regional measures of gray matter (GM) atrophy and cortical thickness (CT), in combination with sNfL levels and clinical scores, are most strongly related to neuropsychological impairment. Results Compared with HCs, patients with MS showed bilateral thalamic GM atrophy (left, p = 0.033; right, p = 0.047) and diminished CT, particularly in the right superior and transverse temporal gyri (p = 0.045; p = 0.037). Regional atrophy failed to add predictive variance, whereas anxiety symptoms, sNfL, and global CT were the best predictors (R-2 = 0.404; p < 0.001) of cognitive outcomes, with temporal thickness accounting for greater variance in cognitive deficits than global CT. Discussion Thalamic GM atrophy and thinning in temporal regions represent a distinctive MRI trait in the early stages of MS. Although sNfL levels alone do not clearly differentiate HCs and patients with RRMS, in combination with global and regional CT, sNfL levels can better explain the presence of underlying cognitive deficits. Hence, cortical thinning and sNfL increases can be considered 2 parallel neurodegenerative markers in the pathogenesis of progression in newly diagnosed patients with MS., This work was supported by the European Regional Development Fund and the Spanish Ministry of Science, Innovation and Universities (grant: RTI2018-096951-A-I00) and the Ministry of Economy and Competitiveness (grant: RYC-2015-18467).

Disease severity, progression and response to therapy might be worse in obese rheumatoid arthritis (RA) patients, but paradoxically, obesity also might protect from radiographic joint damage. Thus, the intricate relationship between obesity and RA needs urgent clarification. The aim of this study was to assess the influence of obesity on the onset and development of RA and to determine whether arthritis could modify the adipose tissue biology and whether conventional Disease Modifying Anti-Rheumatic Drugs (cDMARDs) can modulate these alterations. Two strategies were followed: (1) clinical profiling of two cohorts of RA: non-obese and obese patients; and (2) mechanistic studies carried out in both a collagen-induced arthritis (CIA) in an obese mouse model and 3T3-L1 adipocytes treated with cDMARDs (leflunomide, methotrexate, and hydroxychloroquine). In our cohort of RA patients with low-moderate disease activity, the presence of obesity was not related to a higher activity of the disease; actually, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) was reduced in the obese RA patients. However, the induction of arthritis promoted transcriptomic changes in the adipose tissue under obesity condition in the obese CIA model. Treatment with hydroxychloroquine reduced weight and insulin resistance, accompanied by beneficial metabolic effects in the adipose tissue. These molecular changes in adipose tissue were also observed after methotrexate administration. In sum, arthritis might affect directly the inflammatory burden and metabolic alterations associated with obesity in adipose tissue. Clinicians should be cautious measuring the activity of the disease in obesity and managing the best therapeutic options for the metabolic comorbidities of these patients, where the combination of hydroxychloroquine and methotrexate should be considered to improve adipose tissue dysfunction in obese RA.

The PREDIMED-Plus trial was supported by the European Research Council (Advanced Research grant 2014–2019; agreement #340918; granted to M.Á.M.-G.); the official Spanish institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigación para la Salud (FIS) which is co-funded by the European Regional Development Fund (coordinated FIS projects led by J.S-S. and J.V., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332), and the Especial Action Project “Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus” (J.S.-S.); the Recercaixa (grant number 2013ACUP00194) (J.S.-S.). Moreover, J.S-S. gratefully acknowledges the financial support by ICREA under the ICREA Academia program; the SEMERGEN grant; Department of Health of the Government of Navarra (61/2015), the Fundació La Marató de TV (Ref. 201630.10); the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 (D.R.); grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013; PS0358/2016; PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant; grant of support to research groups 35/2011 (Balearic Islands Government; FEDER funds) (J.A.T.). R.S.-C. acknowledges financial support from the Juan de la Cierva Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-038168- I). N.B.-T. acknowledges financial support from the Juan de la Cierva Formación Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-036016-I). M.R.B.-L. was supported by “Miguel Servet Type I” program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER. S.K.N. acknowledges financial support from the Canadian Institute for Health Research, CIHR Fellowship. J.K. was supported by the ‘FOLIUM’ programme within the FUTURMed project from the Fundación Instituto de Investigación Sanitaria Illes Balears (financed by 2017 annual plan of the sustainable tourism tax and at 50% with charge to the ESF Operational Program 2014–2020 of the Balearic Islands. C.M.-P. was financially supported by a joint grant from the Community of Madrid and the European Social Fund (grant PEJD-2019- POST/SAL-15892). The METHYL-UP project was supported by the Spanish Ministry of Science and Innovation (RTI2018-095569-B-I00, Programa de Proyectos Orientados a los Retos de la Sociedad “Projects Toward Society Challenges Program”)., The association between ultra-processed food (UPF) and risk of cardiometabolic disorders is an ongoing concern. Different food processing-based classification systems have originated discrepancies in the conclusions among studies. To test whether the association between UPF consumption and cardiometabolic markers changes with the classification system, we used baseline data from 5636 participants (48.5% female and 51.5% male, mean age 65.1 4.9) of the PREDIMEDPlus (“PREvention with MEDiterranean DIet”) trial. Subjects presented with overweight or obesity and met at least three metabolic syndrome (MetS) criteria. Food consumption was classified using a 143-item food frequency questionnaire according to four food processing-based classifications: NOVA, International Agency for Research on Cancer (IARC), International Food Information Council (IFIC) and University of North Carolina (UNC). Mean changes in nutritional and cardiometabolic markers were assessed according to quintiles of UPF consumption for each system. The association between UPF consumption and cardiometabolic markers was assessed using linear regression analysis. The concordance of the different classifications was assessed with intra-class correlation coefficients (ICC3, overall = 0.51). The highest UPF consumption was obtained with the IARC classification (45.9%) and the lowest with NOVA (7.9%). Subjects with high UPF consumption showed a poor dietary profile. We detected a direct association between UPF consumption and BMI (p = 0.001) when using the NOVA system, and with systolic (p = 0.018) and diastolic (p = 0.042) blood pressure when using the UNC system. Food classification methodologies markedly influenced the association between UPF consumption and cardiometabolic risk markers., European Research Council (ERC) European Commission #340918, Centro de Investigacion Biomedica en Red-Fisiopatologia de la Obesidad y Nutricion PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441 PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471 PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332

Objectives We evaluated breast cancer (BC) care quality indicators (QIs) in clinical pathways and integrated health care processes. Methods Following protocol registration (Prospero no: CRD42021228867), relevant documents were identified, without language restrictions, through a systematic search of bibliographic databases (EMBASE, Scopus, Web of Science, MEDLINE), health care valuable representatives and the World Wide Web in April 2021. Data concerning QIs, measurement tools and compliance standards were extracted from European and North American sources in duplicate with 98% reviewer agreement. Results There were 89 QIs found from 22 selected documents (QI per document mean 13.5 with standard deviation 11.9). The Belgian (38 QIs) and the EUSOMA (European Society of Breast Cancer Specialists) (34 QIs) documents were the ones that best reported the QIs. No identical QI was identified in all the documents analysed. There were 67/89 QIs covering processes (75.3%) and 11/89 (12.4%) for each structure and outcomes QIs. There were 21/89 QIs for diagnosis (30.3%), 43/89 for treatment (48.3%), and 19/89 for staging, counselling, follow-up and rehabilitation (21.4%). Of 67 process QIs and 11 outcome QIs, 20/78 (26%) did not report a minimum standard of care. Shared decision making was only included as a QI in the Italian document. Conclusion More than half of countries have not established a national clinical pathway or integrated breast cancer care process to achieve the excellence of BC care. There was heterogeneity in QIs for the evaluation of BC care quality. Over two-thirds of the clinical pathways and integrated health care processes did not provide a minimum auditable standard of care for compliance, leaving open the definition of best practice. There is a need for harmonisation of BC care QIs. Yes

Background:The coronavirus disease 2019 pandemic has affected millions of people worldwide, compromising the responsiveness of governments and states and thus generating anxiety and fear at the population level.Objective:To assess the level of anxiety and fear of coronavirus disease 2019 in a Spanish adult population group.Methods:A descriptive cross-sectional study, using the anxiety and fear of COVID-19 assessment scale (AMICO, for its acronym in Spanish). The sample was composed of 1038 subjects. Univariate and bivariate statistical analyses were performed, after analysis of normality in the data distribution. Categorical regression analyses were also executed.Findings:The total sample size was 1036 subjects, 56.3% was made up of females, with a mean age of 48.11 years (SD = 15.13). The mean score obtained on the AMICO scale was 5.54 points (SD = 1.83), with a score range between 1.22 and 10. Bivariate analysis only demonstrated statistically significant differences in the mean score of the scale and the variables: sex, marital status, work area and academic level. The executed categorical regression analysis revealed an R2value of 0.75 and a significance of p = 0.00.Conclusions:The results obtained show that the Spanish population presents moderate anxiety levels to coronavirus disease 2019. Women, married, with primary and/or secondary education level, and working in the public transport, services and/or hospitality sectors are more likely to have high levels of fear and anxiety.Application to Practice:These results could be used for therapeutic and preventive psychological interventions, and also to plan new research under sex perspective and observing the socio-economic environment.

(1) Background: The aim of this study was (i) to analyze problems faced by informal caregivers in three areas of their life: health, work and finances, and family and social relationships, (ii) to investigate the main determinants of these problems, and (iii) to explore differences between men and women. (2) Methods: The study population consisted of people aged ≥18 years living in a family home who were providing unpaid care to a dependent person in the same or another home and who were registered as caregivers with the Primary Health Care District of Granada or the Provincial Council of Gipuzkoa. Several logistic regression models were built to analyze the likelihood of caregivers experiencing health, work-related, or social problems as a result of their caregiving responsibilities. (3) Results: Informal female caregivers were more likely to experience problems attributed to caregiving than their male counterparts, particularly in the areas of health and work. Additional factors associated with an increased likelihood of problems were low perceived social support, performance of ungratifying tasks, and fewer years as a caregiver. (4) Conclusions: Informal caregivers in Spain face significant problems as a result of their caregiving duties, and the impact on men and women is different. Policies and interventions to mitigate the negative effects of unpaid caregiving should incorporate differential strategies to meet the specific needs of male and female caregivers in different caregiving contexts.