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The aim of this study is to evaluate the personal dose equivalent Hp(10) in the most frequent (non-cardiac) paediatric interventional radiology (PIR) procedures: central venous catheters (CVC), hepatic/biliary and sclerotherapy interventions. i2 active solid-state dosemeters placed over the lead apron were used to monitor the exposure of three interventional radiologists over 18 months. A database was created to register all procedures performed by each radiologist (including the type of procedure and the kerma-area product, PKA). The mean Hp(10) per procedure for CVC, sclerotherapy and hepatic/biliary interventions was respectively 0.01 ± 0.01 mSv, 0.18 ± 0.13 mSv and 0.12 ± 0.06 mSv (k = 2). A similar value of Hp(10)/PKA was found despite the type of procedure or the patient weight (~10 μSv/Gy·cm2). There was high variability among individual interventions, probably due to the variable level of complexity, which led to uncertainties in the measurements’ mean higher than those associated with the dosemeter’s angular and energy dependence. i2 therefore proved suitable for monitoring Hp(10) in PIR procedures.

We examined whether excess chronic medical comorbidity mediated excess COVID-19 inpatient mortality among people with mental disorders in the early phase of the pandemic, a question with important implications for public health and clinical decision-making. Using records of 2599 COVID-19 hospitalized patients, we conducted a formal causal mediation analysis to estimate the extent to which chronic comorbidity mediates the association between mental disorders and COVID-19 mortality. The Odds Ratio (95% CI) for Natural Indirect Effect and Controlled Direct Effect were 1.07(1.02, 1.14) and 1.40 (1.00, 1.95), respectively, suggesting that a large proportion of excess COVID-19 mortality among people with mental disorders may be explained by factors other than comorbidity.

Objective This study explores whether social cognition and social functioning improve after a mindfulness-based social cognition training (SocialMIND). Methods Thirty-eight outpatients with psychosis completed an assessment with social cognition (Eyes Test, Ambiguous Intentions and Hostility Questionnaire [AIHQ], and Hinting Task) and social functioning tasks (Personal and Social Performance [PSP] scale) before and after eight SocialMIND weekly sessions. Mean differences between timepoints were standardized and 95% confidence intervals were obtained with a paired samples t-test. Results The scores of the Eyes Test (95% CI [.43, 3.32], d = .48), the Hostility Bias subscale (AIHQ) (95% CI [-.29, -.01], d = .44), and the self-care difficulties subscale (PSP) (95% CI [-.77, -.09], d = .45) improved after the intervention. Conclusions and Implications for practice: The results of SocialMIND-8 are very promising in terms of developing comprehensive rehabilitation programs. Further trials must address its effectiveness against a control group during longer follow-up periods. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background In the last two decades, lower-limb exoskeletons have been developed to assist human standing and locomotion. One of the ongoing challenges is the cooperation between the exoskeleton balance support and the wearer control. Here we present a cooperative ankle-exoskeleton control strategy to assist in balance recovery after unexpected disturbances during walking, which is inspired on human balance responses. Methods We evaluated the novel controller in ten able-bodied participants wearing the ankle modules of the Symbitron exoskeleton. During walking, participants received unexpected forward pushes with different timing and magnitude at the pelvis level, while being supported (Exo-Assistance) or not (Exo-NoAssistance) by the robotic assistance provided by the controller. The effectiveness of the assistive strategy was assessed in terms of (1) controller performance (Detection Delay, Joint Angles, and Exerted Ankle Torques), (2) analysis of effort (integral of normalized Muscle Activity after perturbation onset); and (3) Analysis of center of mass COM kinematics (relative maximum COM Motion, Recovery Time and Margin of Stability) and spatio-temporal parameters (Step Length and Swing Time). Results In general, the results show that when the controller was active, it was able to reduce participants’ effort while keeping similar ability to counteract and withstand the balance disturbances. Significant reductions were found for soleus and gastrocnemius medialis activity of the stance leg when comparing Exo-Assistance and Exo-NoAssistance walking conditions. Conclusions The proposed controller was able to cooperate with the able-bodied participants in counteracting perturbations, contributing to the state-of-the-art of bio-inspired cooperative ankle exoskeleton controllers for supporting dynamic balance. In the future, this control strategy may be used in exoskeletons to support and improve balance control in users with motor disabilities.

Introduction and objectives The NitOcclud Le VSD Coil was specifically designed for transcatheter occlusion of ventricular septal defects (VSD) and became available for this purpose in August 2010. Our objective was to describe the Spanish experience of this technique and analyze its reliability and short- to mid-term efficacy. Methods National multicenter observational study, which retrospectively recruited all patients (of any age) with VSD (of any location or type) who underwent percutaneous NitOcclud occlusion, using an intention-to-treat analysis, until January 2019. Results A total of 117 attempts were made to implant at least 1 NitOcclud in 116 patients in 13 institutions. The median [range] age and weight was 8.6 [0.4-69] years and 27 [5.8-97] kg, respectively. In 99 patients (85%), the VSD was an isolated congenital defect. The location was perimembranous in 95 (81%), and 74 (63%) of them were aneurysmatic. The mean fluoroscopy time was 34 [11.4-124] minutes. Of the 117 attempts, 104 were successful (89%) with a follow-up of 31.4 [0.6-59] months. At the last review, final complete occlusion of the defect without residual shunt or with only a minimal shunt was achieved in 92.3% (no shunt, n = 73; trivial shunt, n = 23). Four patients required a second procedure for residual shunt occlusion. Two devices had to be surgically explanted due to severe hemolysis. There were no deaths or other major complications. Conclusions The NitOcclud device can be used successfully for a wide anatomical spectrum of VSD. The main issue is residual shunt, but its incidence decreases over time. The incidence of hemolysis was very low and no permanent changes were detected in atrioventricular conduction.

The synthesis and characterization of four platinum(II) complexes using azobenzenes conveniently functionalized as ligands has been carried out. The characteristic photochemical behavior of the complexes due to the presence of azobenzene-type ligands and the role of the ligands in the activation of the complexes has been studied. Their promising cytotoxicity observed in HeLa cells prompted us to study the mechanism of action of these complexes as cytostatic agents. The interaction of the compounds with DNA, studied by circular dichroism, revealed a differential activity of the Pt(II) complexes upon irradiation. The intercalation abilities of the complexes as well as their reactivity with common proteins present in the blood stream allows to confirm some of the compounds obtained as good anticancer candidates.

To know the influence of the companion in triadic clinical encounter on the quality of doctor-patient communication and the duration of the interview. Cross-sectional descriptive study. 10 Primary Care Centers. Resident doctors of Family and Community Medicine. Peer review of video recordings of clinical demand consultations. CICAA-2 questionnaire to assess communication skills (improvable, acceptable or adequate); age and sex, reasons for consultation and duration of the interview. Bivariate and multivariate analyses. Ethical authorization, oral informed consent and custody of the video recordings. 73 RD (53.8% women, 32.9±7.7 years) participated with 260 interviews (60.3% women and 2.1±1.0 clinical demands). 27.7% of consultations with a companion (female sex 65.3%). The mean duration of the interviews was 8.5±4.0min. Clinical encounters lasted longer when a companion attended (2.7±0.5min more; p Triadic communications challenge the clinician's communication skills, improving their abilities to identify and understand patient problems, albeit at the cost of a greater investment of time.

The aim of this study was to investigate the role of saliva esterase activity on carboxylic esters typically associated with pleasant and fruity aromas in wine. For this, ex vivo experiments using the same fresh and inactivated (without enzymatic activity) human saliva with a mixture of carboxylic esters with different aliphatic chain length (ethyl butanoate, ethyl pentanoate, ethyl hexanoate, ethyl octanoate, ethyl decanoate, and isoamyl acetate) were prepared. Liquid-liquid extraction with dichloromethane and GC-MS analysis were applied to the saliva systems in order to determine the reduction in ester content and the formation of their corresponding metabolic products (carboxylic acids) in the saliva systems before and after incubation at 37C. In addition, to check if there was a relationship between the susceptibility of esters to saliva hydrolysis and the amount of in-mouth ester release during wine intake, the remaining oral amount of each ester was determined by comparing the intraoral amount immediately after spitting out the wine and 4 min later. Ex vivo experiments showed ester degradation by saliva esterase enzymes mainly acted on long chain esters (ethyl octanoate and ethyl decanoate), which gave rise to the formation of their corresponding carboxylic acids. Nonetheless, in spite of their higher susceptibility to saliva enzymes, in vivo experiments showed that long chain carboxylic esters remained in the oral cavity long after swallowing. This confirmed that ester hydrophobicity is closely related to the in-mouth temporal release of these odorants and, therefore, behind wine aroma persistence. In wines, esters represent a group of aromatic compounds of great interest since they are linked to pleasant fruity aroma nuances. Today wine consumers are demanding fresh and long persistent fruity aromatic wines. The present research contributes to better understanding the relationship between ester content in the wine and oral aroma release experienced during wine tasting, considering the changes in these compounds during oral processing. This is a necessary step when trying to unravel the factors involved in wine aroma perception and in consumer preferences, and it represents a necessary knowledge in promoting winemaking practices (e.g., the use of selected microorganisms) for improving the type and amount of these aroma compounds in the wine., Spanish Ministry of Economy and Competitiveness (MINECO), Grant/Award Number: Project AGL2016‐78936‐R

Human-like balance controllers are desired for wearable exoskeletons in order to enhance human-robot interaction. Momentum-based controllers (MBC) have been successfully applied in bipeds, however, it is unknown to what degree they are able to mimic human balance responses. In this paper, we investigated the ability of an MBC to generate human-like balance recovery strategies during stance, and compared the results to those obtained with a linear full-state feedback (FSF) law. We used experimental data consisting of balance recovery responses of nine healthy subjects to anteroposterior platform translations of three different amplitudes. The MBC was not able to mimic the combination of trunk, thigh and shank angle trajectories that humans generated to recover from a perturbation. Compared to the FSF, the MBC was better at tracking thigh angles and worse at tracking trunk angles, whereas both controllers performed similarly in tracking shank angles. Although the MBC predicted stable balance responses, the human-likeness of the simulated responses generally decreased with an increased perturbation magnitude. Specifically, the shifts from ankle to hip strategy generated by the MBC were not similar to the ones observed in the human data. Although the MBC was not superior to the FSF in predicting human-like balance, we consider the MBC to be more suitable for implementation in exoskeletons, because of its ability to handle constraints (e.g. ankle torque limits). Additionally, more research into the control of angular momentum and the implementation of constraints could eventually result in the generation of more human-like balance recovery strategies by the MBC. ispartof: IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING vol:28 issue:9 pages:2015-2024 ispartof: location:United States status: published

Obesity is characterized by excessive fat accumulation and inflammation. Aging has also been characterized as an inflammatory condition, frequently accompanied by accumulation of visceral fat. Beneficial effects of exercise and n-3 long-chain polyunsaturated fatty acids in metabolic disorders have been described. Glucose transporter 12 (GLUT12) is one of the less investigated members of the GLUT family. Glucose, insulin, and tumor necrosis factor alpha (TNF-α) induce GLUT12 translocation to the membrane in muscle, adipose tissue, and intestine. We aimed to investigate GLUT12 expression in obesity and aging, and under diet supplementation with docosahexaenoic acid (DHA) alone or in combination with physical exercise in mice. Aging increased GLUT12 expression in intestine, kidney, and adipose tissue, whereas obesity reduced it. No changes on the transporter occurred in skeletal muscle. In obese 18-month-old mice, DHA further decreased GLUT12 in the 4 organs. Aerobic exercise alone did not modify GLUT12, but the changes triggered by exercise were able to prevent the DHA-diminishing effect, and almost restored GLUT12 basal levels. In conclusion, the downregulation of metabolism in aging would be a stimulus to upregulate GLUT12 expression. Contrary, obesity, an excessive energy condition, would induce GLUT12 downregulation. The combination of exercise and DHA would contribute to restore basal function of GLUT12. Novelty In small intestine, kidney and adipose tissue aging increases GLUT12 protein expression whereas obesity reduces it. Dietary DHA decreases GLUT12 in small intestine, kidney, adipose tissue and skeletal muscle. Exercise alone does not modify GLUT12 expression, nevertheless exercise prevents the DHA-diminishing effect on GLUT12.

BackgroundHealthcare workers (HCWs) from COVID-19 hotspots worldwide have reported poor mental health outcomes since the pandemic's beginning. The virulence of the initial COVID-19 surge in Spain and the urgency for rapid evidence constrained early studies in their capacity to inform mental health programs accurately. Here, we used a qualitative research design to describe relevant mental health problems among frontline HCWs and explore their association with determinants and consequences and their implications for the design and implementation of mental health programs.Materials and methodsFollowing the Programme Design, Implementation, Monitoring, and Evaluation (DIME) protocol, we used a two-step qualitative research design to interview frontline HCWs, mental health experts, administrators, and service planners in Spain. We used Free List (FL) interviews to identify problems experienced by frontline HCWs and Key informant (KI) interviews to describe them and explore their determinants and consequences, as well as the strategies considered useful to overcome these problems. We used a thematic analysis approach to analyze the interview outputs and framed our results into a five-level social-ecological model (intrapersonal, interpersonal, organizational, community, and public health).ResultsWe recruited 75 FL and 22 KI interviewees, roughly balanced in age and gender. We detected 56 themes during the FL interviews and explored the following themes in the KI interviews: fear of infection, psychological distress, stress, moral distress, and interpersonal conflicts among coworkers. We found that interviewees reported perceived causes and consequences across problems at all levels (intrapersonal to public health). Although several mental health strategies were implemented (especially at an intrapersonal and interpersonal level), most mental health needs remained unmet, especially at the organizational, community, and public policy levels.ConclusionsIn keeping with available quantitative evidence, our findings show that mental health problems are still relevant for frontline HCWs 1 year after the COVID-19 pandemic and that many reported causes of these problems are modifiable. Based on this, we offer specific recommendations to design and implement mental health strategies and recommend using transdiagnostic, low-intensity, scalable psychological interventions contextually adapted and tailored for HCWs.

Survival of patients affected by mucinous appendiceal neoplasms with peritoneal dissemination (PD) is mainly related to histopathological features. However, prognostic stratification is still a concern, as the clinical course of the disease is often unpredictable. The aim of this study is to construct and externally validate a nomogram predicting disease-free survival (DFS) in mucinous appendiceal neoplasms with PD treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).Patients treated in two referral centers were included: Hospital General Universitario Gregorio Marañón, Madrid, Spain (derivation cohort) and Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy (validation cohort). Cox regression analysis identified factors associated with shorter DFS in the derivation cohort. The nomogram performance was externally evaluated in the validation cohort using concordance index and calibration plots. Histology was classified according to the Peritoneal Surface Oncology Group International (PSOGI).The derivation cohort included 95 patients, and the validation cohort 348. Five-year DFS rates were 51.5 and 62%, respectively. Cox regression analysis (derivation cohort) identified PSOGI histology of the peritoneal components, number of preoperative elevated tumor marker, and peritoneal disease extent, as assessed by peritoneal carcinomatosis index, to be predictors of DFS. The model's predictive capacity was higher than that of PSOGI classification alone, with respective concordance indexes of 0.702 ± 0.023 and 0.610 ± 0.018 (validation cohort). The nomogram approximated the perfect model in the calibration plots at 3- and 5-year DFS.An easy-to-use model that provides better prognostic stratification than histopathological features has been constructed. This nomogram may help clinicians in individualized survival predictions and informed clinical decision-making.

The dynamic changes in saliva flow and composition (pH, total protein capacity (TPC), total polyphenol index (TPI) and saliva antioxidant activity (SAOX)) after the exposure of the oral cavity to aromatized wine matrices with different chemical compositions (dealcoholized, alcoholized, and synthetic wines) have been investigated. For this, stimulated saliva from ten volunteers were collected five days per week (from Monday to Friday) during three non-consecutive weeks, before (basal saliva) and after the oral intervention with the wines (5 and 15 minutes later) (

To know the influence of the companion in triadic clinical encounter on the quality of doctor-patient communication and the duration of the interview.Cross-sectional descriptive study.10 Primary Care Centers.Resident doctors of Family and Community Medicine.Peer review of video recordings of clinical demand consultations.CICAA-2 questionnaire to assess communication skills (improvable, acceptable or adequate); age and sex, reasons for consultation and duration of the interview. Bivariate and multivariate analyses. Ethical authorization, oral informed consent and custody of the video recordings.73 RD (53.8% women, 32.9±7.7 years) participated with 260 interviews (60.3% women and 2.1±1.0 clinical demands). 27.7% of consultations with a companion (female sex 65.3%). The mean duration of the interviews was 8.5±4.0min. Clinical encounters lasted longer when a companion attended (2.7±0.5min more; p.001 Student t) and with a greater number of clinical demands (40% with ≥3 reasons, p=0.048 XTriadic communications challenge the clinician's communication skills, improving their abilities to identify and understand patient problems, albeit at the cost of a greater investment of time.

Aims The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF. Methods and results Sex differences in 92 blood biomarkers were measured in 364 patients included in our discovery cohort, the identification of a risk profile to guide atrial fibrillation therapy (AF-RISK) study, assessed by multivariable logistic regression and enrichment pathway analysis. Findings were subsequently confirmed in 213 patients included in our validation cohort, the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study. In the discovery cohort, mean age was 59 ± 12 years, 41% were women. CHA2DS2-VASc-score was 1.6 ± 1.4. A total of 46% had hypertension, 10% diabetes, and 50% had heart failure, predominantly with preserved ejection fraction (47%). In women, activated leucocyte cell adhesion molecule (ALCAM) and fatty acid binding protein-4 (FABP-4) were higher. In men, matrix metalloproteinase-3 (MMP-3), C-C motif chemokine-16 (CCL-16), and myoglobin were higher. In the validation cohort, four out of five biomarkers could be confirmed: levels of ALCAM (P = 1.73 × 10–4) and FABP-4 (P = 2.46 × 10–7) and adhesion biological pathways [false discovery rate (FDR) = 1.23 × 10–8] were higher in women. In men, levels of MMP-3 (P = 4.31 × 10–8) and myoglobin (P = 2.10 × 10–4) and markers for extracellular matrix degradation biological pathways (FDR = 3.59 × 10–9) were higher. Conclusion In women with paroxysmal AF, inflammatory biomarkers were more often higher, while in men with paroxysmal AF, biomarkers for vascular remodelling were higher. Our data support the clinical notion that pathophysiological mechanisms in women and men with AF may differ. Trial registration Clinicaltrials.gov identifier NCT01510210 for AF-RISK; Clinicaltrials.gov NCT02726698 for RACE V.

This study was funded by the Spanish Ministry of Health, the Institute of Health Carlos III (ISCIII), and the European Regional Development Fund (grants PS09/02272, PS09/02147, PS09/01095, PS09/00849, PS09/00461, and PI12-02755); the Andalusian Council of Health (grant PI-0569-2010); the Spanish Network of Primary Care Research, redIAPP (grant RD06/ 0018); the Aragon group (grant RD06/0018/0020); the Bizkaya group (grant RD06/0018/0018); the Castilla-Leon group (grant RD06/0018/0027); the Mental Health Barcelona Group (grant RD06/0018/0017); the Mental Health, Services and Primary Care Malaga group (grant RD06/0018/0039); and the projects "PI18/00238" and "PI18/00467" funded by the Institute of Health Carlos III (Co-funded by European Regional Development Fund/European Social Fund "A way tomake Europe"/"Investing in your future"). This study was performed as part of a PhD thesis conducted within the Official Doctoral Programme in Biomedicine of the University of Granada, Spain. Augusto Anguita-Ruiz was supported by a Ministry of Economy and Competitiveness and Institute of Health Carlos III fellowship (IFI17/00048). Juan Antonio Zarza-Rebollo received financial support from the Spanish Ministry of Economy and Competitiveness (BES-2017-082698). Ana M. Perez-Gutierrez was supported by a grant from the Ministry of Economy and Competitiveness and Institute of Health Carlos III (FI19/00228). Elena Lopez-Isac received financial support from the Spanish Ministry of Science and Innovation Juan de la Cierva Incorporacion Program (IJC2019040080-I), and Margarita Rivera was supported by the Ministry of Economy and Competitiveness Ramon y Cajal Program (RYC-2014-15774). The authors thank the Institute of Health Carlos III (ISCIII), the European Regional Development Fund (FEDER), the Andalusian Council of Health and Andalusian Health Service (SAS), the Primary Care Prevention and Health Promotion Research Network (redIAPP), the Biomedical Research Institute of Malaga (IBIMA), and the Biomedical Research Centre (CIBM) from the University of Granada for their economic and logistic support. The authors thank all the patients and General Practitioners who participated in the trial. Depression is strongly associated with obesity among other chronic physical diseases. The latest mega- and meta-analysis of genome-wide association studies have identified multiple risk loci robustly associated with depression. In this study, we aimed to investigate whether a genetic-risk score (GRS) combining multiple depression risk single nucleotide polymorphisms (SNPs) might have utility in the prediction of this disorder in individuals with obesity. A total of 30 depression-associated SNPs were included in a GRS to predict the risk of depression in a large case-control sample from the Spanish PredictD-CCRT study, a national multicentre, randomized controlled trial, which included 104 cases of depression and 1546 controls. An unweighted GRS was calculated as a summation of the number of risk alleles for depression and incorporated into several logistic regression models with depression status as the main outcome. Constructed models were trained and evaluated in the whole recruited sample. Non-genetic-risk factors were combined with the GRS in several ways across the five predictive models in order to improve predictive ability. An enrichment functional analysis was finally conducted with the aim of providing a general understanding of the biological pathways mapped by analyzed SNPs. We found that an unweighted GRS based on 30 risk loci was significantly associated with a higher risk of depression. Although the GRS itself explained a small amount of variance of depression, we found a significant improvement in the prediction of depression after including some non-genetic-risk factors into the models. The highest predictive ability for depression was achieved when the model included an interaction term between the GRS and the body mass index (BMI), apart from the inclusion of classical demographic information as marginal terms (AUC = 0.71, 95% CI = [0.65, 0.76]). Functional analyses on the 30 SNPs composing the GRS revealed an over-representation of the mapped genes in signaling pathways involved in processes such as extracellular remodeling, proinflammatory regulatory mechanisms, and circadian rhythm alterations. Although the GRS on its own explained a small amount of variance of depression, a significant novel feature of this study is that including non-genetic-risk factors such as BMI together with a GRS came close to the conventional threshold for clinical utility used in ROC analysis and improves the prediction of depression. In this study, the highest predictive ability was achieved by the model combining the GRS and the BMI under an interaction term. Particularly, BMI was identified as a trigger-like risk factor for depression acting in a concerted way with the GRS component. This is an interesting finding since it suggests the existence of a risk overlap between both diseases, and the need for individual depression genetics-risk evaluation in subjects with obesity. This research has therefore potential clinical implications and set the basis for future research directions in exploring the link between depression and obesityassociated disorders. While it is likely that future genome-wide studies with large samples will detect novel genetic variants associated with depression, it seems clear that a combination of genetics and non-genetic information (such is the case of obesity status and other depression comorbidities) will still be needed for the optimization prediction of depression in high-susceptibility individuals. Instituto de Salud Carlos III Spanish Government Institute of Health Carlos III (ISCIII) European Commission PS09/02272 PS09/02147 PS09/01095 PS09/00849 PS09/00461 PI12-02755 Andalusian Council of Health PI-0569-2010 Spanish Network of Primary Care Research, redIAPP RD06/ 0018 Gobierno de Aragon RD06/0018/0020 Bizkaya group RD06/0018/0018 Castilla-Leon group RD06/0018/0027 Mental Health Barcelona Group RD06/0018/0017 Mental Health, Services and Primary Care Malaga group RD06/0018/0039 Instituto de Salud Carlos III PI18/00238 PI18/00467 FI19/00228 European Regional Development Fund/European Social Fund "A way tomake Europe"/"Investing in your future" Ministry of Economy and Competitiveness Institute of Health Carlos III fellowship IFI17/00048 Spanish Government BES-2017-082698 Spanish Ministry of Science and Innovation Juan de la Cierva Incorporacion Program IJC2019040080-I Ministry of Economy and Competitiveness Ramon y Cajal Program RYC-2014-15774 Andalusian Council of Health Andalusian Health Service (SAS) Primary Care Prevention and Health Promotion Research Network (redIAPP) Biomedical Research Institute of Malaga (IBIMA) Biomedical Research Centre (CIBM) from the University of Granada European Commission

The synthesis, full characterization, photochemical properties, and cytotoxic activity toward cisplatin-resistant cancer cell lines of new semisquaraine-type Pt(II) complexes are presented. The synthesis of eight semisquaraine-type ligands has been carried out by means of an innovative, straightforward methodology. A thorough structural NMR and X-ray diffraction analysis of the new ligands and complexes has been done. Density functional theory calculations have allowed to assign the trans configuration of the platinum center. Through the structural modification of the ligands, it has been possible to synthesize some complexes, which have turned out to be photoactive at wavelengths that allow their activation in cell cultures and, importantly, two of them show remarkable solubility in biological media. Photodegradation processes have been studied in depth, including the structural identification of photoproducts, thus justifying the changes observed after irradiation. From biological assessment, complexes C7 and C8 have been demonstrated to behave as promising photoactivatable compounds in the assayed cancer cell lines. Upon photoactivation, both complexes are capable of inducing a higher cytotoxic effect on the tested cells compared with nonphotoactivated compounds. Among the observed results, it is remarkable to note that C7 showed a PI > 50 in HeLa cells, and C8 showed a PI > 40 in A2780 cells, being also effective over cisplatin-resistant A2780cis cells (PI = 7 and PI = 4, respectively). The mechanism of action of these complexes has been studied, revealing that these photoactivated platinum complexes would actually present a combined mode of action, a therapeutically potential advantage., Instituto de Salud Carlos III, Spanish Government RTI2018-098027-B-C22, European Commission BIO2015-67358-C2-2-P CTQ2016-75363-R, Spanish Government Instituto de Salud Carlos III Spanish Government, Generalitat de Catalunya 2017SGR-864

Background The objective of the FeminFER project was to assess the value of ferric carboxymaltose following a multicriteria decision analysis in obstetrics and gynaecology in Spain. Methods Ferric carboxymaltose (FCM) and ferrous sulphate were evaluated using the EVIDEM framework. Ten stakeholders participated to collect different perspectives. The framework was adapted considering evidence retrieved with a PICO-S search strategy and grey literature. Criteria/subcriteria were weighted by level of relevance and an evidence-based decision-making exercise was developed in each criterion; weights and scores were combined to obtain the value of intervention relative to each criterion/subcriterion, that were further combined into the Modulated Relative Benefit-Risk Balance (MRBRB). Results The most important criterion favouring FCM was Compared Efficacy/Effectiveness (0.183 ± 0.07), followed by Patient Preferences (0.059 ± 0.10). Only Direct medical costs criterion favoured FS (-0.003 ± 0.03). MRBRB favoured FCM; 0.45 ± 0.19; in a scale from -1 to + 1. Conclusions In conclusion, considering the several criteria involved in the decision-making process, participants agreed with the use of FCM according to its MRBRB.

Mutations in the adaptor protein PSTPIP1 cause a spectrum of autoinflammatory diseases, including PAPA and PAMI; however, the mechanism underlying these diseases remains unknown. Most of these mutations lie in PSTPIP1 F-BAR domain, which binds to LYP, a protein tyrosine phosphatase associated with arthritis and lupus. To shed light on the mechanism by which these mutations generate autoinflammatory disorders, we solved the structure of the F-BAR domain of PSTPIP1 alone and bound to the C-terminal homology segment of LYP, revealing a novel mechanism of recognition of Pro-rich motifs by proteins in which a single LYP molecule binds to the PSTPIP1 F-BAR dimer. The residues R228, D246, E250, and E257 of PSTPIP1 that are mutated in immunological diseases directly interact with LYP. These findings link the disruption of the PSTPIP1/LYP interaction to these diseases, and support a critical role for LYP phosphatase in their pathogenesis., This work has been funded by Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia co-funded by Junta de Castilla y León and ERDF CLC-2017-01 (JMdeP), Programa Estratégico Instituto de Biología y Genética Molecular (IBGM), Junta de Castilla y León CCVC8485 (AA), Fundación Ramón Areces (AA) and Consejería de Sanidad de la Junta de Castilla y León (AA).

This study focus for the first time, in looking for age-gender effects on in vivo volatile release during wine consumption, also considering oral physiological differences (e.g. saliva composition). To do so, the in-mouth Head Space Sorptive Extraction technique was used, which allowed monitoring the oral release of twenty-four different types of volatile compounds from white and red wines. Thirty-two individuals (n = 32) males and females, belonging to two different age groups: young (18–35 y.o) and senior (>55 y.o.) participated in this analytical in vivo study. Results showed differences in volatile release among age-gender groups, which also depended on the volatile compound and wine type. Senior groups (SM, SF) showed a similar release behaviour among them. Contrarily, young males showed a higher release (between 10 and 29%) of alcohols and esters indistinctly of the wine type, while young females showed the lowest oral volatile release among the four age-gender groups. Gender differences in volatile release were more evident in young than in seniors. A higher release of furanic compounds (furfural and 5-methyl furfural) in seniors was likely related to differences in their saliva composition (total protein content, minerals (Mg, Zn) and α-amylase activity)., This research was funded by the Spanish MINECO and MICINN through the AGL201678936-R and PID2019-111734RB-I00 projects. M.P.-J. and C.M.-G. thank MINECO and CAM for their respective predoctoral and postdoctoral (Atracción de Talento CAM, 2019T1/BIO13748) contracts.

The ability of the human oral microbiota to hydrolyze the glycosidic aroma precursor extract isolated from sour guava (

Sexuality is a complex and multidimensional phenomenon that constitutes a fundamental component in human relationships. Pregnancy is a crucial period in women's life and the physiological changes that happen in this period affect their sexuality.Knowing how pregnancy impacts on sexual behaviors in millenial generation compared to baby boom generation.Descriptive and cross-sectional study, by means of a self-completed, population-based survey, to a sample of pregnant women in the third trimester of gestation who attended Primary Care. A descriptive study of the frequency distribution of all the variables was carried out.In baby boom generation and millennial generation, it is observed that during pregnancy couple's attraction decreases slightly. According to variables desire and frequency of intercourse, results obtained show that as the pregnancy progresses there is a marked decrease in desire and intercourse frequency. Women state that they do not have enough information about sexuality in their current state, despite years having passed.During last 35 years, sexual behaviors have not changed in pregnant women. In both generations, changes in desire and intercourse domains were particularly significant, being in third trimester of pregnancy when frequency of intercourse decline. Pregnant women continue to hold erroneous beliefs about sexuality and request more sexual education.

This study is aimed at investigating the changes in serum CypC levels and their relationship with cardiovascular events at 12 months of follow-up in coronary artery disease (CAD) patients.The study included a total of 125 subjects (40 patients with acute CAD, 40 patients with chronic CAD, and 45 control volunteers) and we analyzed plasma CypC levels from baseline to 6 and 12 months for a better understanding of its behavior in atherosclerosis.Serum CypC levels were shown to be gradually increased in CAD patients (30.63 pg/mL ± 3.77 at baseline, 38.70 pg/mL ± 6.41 at 6 months [p = 0.25], and 47.27 pg/mL ± 5.65 at 12 months [p = 0.007]). In addition, serum CypC levels during the follow-up were a significant predictor of CAD (c-statistic 0.76 at 6 months and 0.89 at 12 months; p0.001). Despite it, there was no significant association between CypC and cardiovascular events, but serum CypC levels tended to be higher in patients suffering cardiovascular events during the follow-up (29.02 pg/mL ± 6.39 vs. 79.96 pg/mL ± 22.18; p = 0.029). In this regard, plasma levels of high-sensitivity C-reactive protein (hsCRP)2.3 mg/L plus NT-proBNP300 pg/mL together were significant predictors of cardiovascular events during the follow-up in CAD patients with CypC levels17.5 pg/mL (p = 0.048).Taken together, our results suggest that serum CypC levels increase during the follow-up in CAD patients and could be a novel biomarker with a possible prognostic value in combination with hsCRP and NT-proBNP.Este estudio tiene como objetivo investigar los cambios en los niveles séricos de CypC y su relación con eventos cardiovasculares a los 12 meses de seguimiento en pacientes con EAC.El estudio incluyó un total de 125 sujetos (40 pacientes con EAC aguda, 40 pacientes con EAC crónica y 45 voluntarios de control) y se analizaron los niveles ­plasmáticos de CypC desde el inicio hasta los 6 y 12 meses para comprender mejor su comportamiento en la aterosclerosis.Se demostró que los niveles séricos de CypC aumentaron gradualmente en pacientes con CAD [(30.63 pg/ml ± 3.77 al inicio del estudio, 38.70 pg/ml ± 6.41 a los 6 meses (p = 0.25) y 47.27 pg/ml ± 5.65 a los 12 meses (p = 0,007)]. Además, los niveles séricos de CypC durante el seguimiento fueron un predictor significativo de EAC (estadístico c 0.76 a los 6 meses y 0.89 a los 12 meses; p0.001). A pesar de ello, no hubo asociación significativa entre CypC y eventos cardiovasculares, pero los niveles séricos de CypC tendieron a ser más altos en los pacientes que sufrieron eventos cardiovasculares durante el seguimiento (29.02 pg/mL ± 6.39 vs. 79.96 pg/mL ± 22.18; p = 0.029). En este sentido, los niveles plasmáticos de hsCRP2.3 mg/L más NT-proBNP300 pg/ml juntos fueron predictores significativos de eventos cardiovasculares durante el seguimiento en pacientes con EAC con niveles de CypC17.5 pg/ml (p = 0.048).Tomados en conjunto, nuestros resultados sugieren que los niveles séricos de CypC aumentan durante el seguimiento en pacientes con EAC y podría ser un nuevo biomarcador con un posible valor pronóstico en combinación con hsCRP y NT-proBNP.

The pathophysiology of Takotsubo Syndrome has not yet been precisely defined. Different hypotheses have been proposed, including cardiotoxicity due to catecholaminergic hormone release, metabolic disorders, coronary microvascular dysfunction and epicardial coronary artery spasm. Invasive coronary physiology is considered the cornerstone to understand physiological assessment of coronary blood flow in this setting. We have reviewed most important studies in coronary invasive physiology in this field to update the state of the art in TakoTsubo Syndrome.

Improved assays are critical to the successful implementation of novel HIV-1 cure strategies, given the limited ability of currently available assays to quantify true effects on the viral reservoir. As interventions based on immune clearance target infected cells producing viral antigens, irrespective of whether the viruses generated are infectious or not, we developed a novel assay to identify viral protein production at the single-cell level. The novel viral protein spot (VIP-SPOT) assay, based on the enzyme-linked ImmunoSpot (ELISpot) approach, quantifies the frequency of CD4

Cells are able to precisely control the amount of iron they acquire in the form of transferrin (TF)-bound iron by modulating the synthesis of transferrin receptor 1 (TfR1). In tumor cells, elevated TfR1 seems to be related to poorer outcome for patients. Thus, the direct measurement of this biomarker in breast cancer tissues and cells might serve as a prognosis biomarker. In this work, we have used Nd-labeled antibodies to tag the TfR1 present on the cell surface of two cell models of breast cancer with different malignancy (MCF7 and MDA-MB 231). For this aim, monoclonal antibody anti-TfR1 is first labeled with a polymeric chelator (MAXPAR) with the subsequent incorporation of several isotopic 143Nd atoms. The characterization of the labeled antibody revealed a stoichiometry of 21 Nd atoms per antibody molecule that can be used for further quantification experiments. This antibody is used for cell tagging followed by single-cell analysis using inductively coupled plasma mass spectrometry (ICP-MS) detection. In this case, cell introduction is conducted using a high-efficiency nebulizer and spray chamber to achieve transport efficiencies of up to 55% for cells. Quantitative results revealed a number of receptors per cell significantly higher in the case of the most malignant phenotype (MDA-MB-231). Absolute and relative TfR1 concentration values are obtained in individual cells for the first time using the proposed system.

Resumen: Objetivo: Conocer la oferta de actividades preventivas propuestas por médicos residentes de medicina familiar en la consulta a demanda de Atención Primaria y su relación con las habilidades comunicacionales. Diseño: Estudio descriptivo multicéntrico mediante videograbación de la consulta médica. Emplazamiento: Ocho centros de salud de Jaén (Andalucía). Participantes: Setenta y tres médicos residentes de cuarto año. Mediciones principales: Se valora la oferta de actividades preventivas (según el Programa español de actividades preventivas y promoción de la salud –PAPPS–) y las características del médico, el paciente y la consulta. Valoración por pares de la comunicación médico-paciente mediante la escala CICAA. Análisis descriptivo, bivariable y de regresión logística. Resultados: Se valoran 260 entrevistas (duración 8,5 ± 4,0 min) de 73 residentes (50,7% mujeres, edad media 32,9 ± 7,7 años, 79% medio urbano). El paciente es más frecuentemente mujer (60%), que acude sola (72%) por procesos agudos (80%) y con 2,1 ± 1,0 motivos de consulta. Se ofertan actividades preventivas en un 47% (duración inferior al minuto) de tipo primario (70%) y secundario (59%) mediante consejo (72%) o cribado (52%), centradas en el área cardiovascular (52%) y estilos de vida (53%). Un 80% se relaciona con el motivo de consulta. Habilidades en comunicación: 41% mejorables, 26% adecuadas, 23% excelentes. La oferta de actividades preventivas se relaciona con la duración de la consulta (OR = 1,1; IC 95% 1,01; 1,16) y la puntuación del CICAA (OR = 1,03; IC 95% 1,01; 1,10). Conclusiones: Se realizan actividades preventivas en casi la mitad de las consultas, aunque centradas en consejo y cribado y ligadas a la demanda del paciente. El tiempo de consulta y las habilidades de comunicación favorecen una mayor oferta preventiva. Abstract: Objective: To determine the offer of preventive activities by resident physicians of family medicine in the Primary Care consultations and the relation with their communication habilities. Design: A descriptive multicentre study assessing medical consultations video recording. Location: Eight Primary Healthcare centres in Jaen (Andalucia). Participants: Seventy-three resident physicians (4 th year) filmed and observed with patients. Principal measurements: Offer of preventive activities (according to the Spanish Program of Preventive Activities and Health Promotion –PAPPS–). Doctor, patient and consultation characteristics. Peer-review of the communication between physicians and patients, using a CICAA scale. A descriptive, bivariate, logistic regression analysis was performed. Results: Two hundred and sixty interviews were evaluated (duration 8.5 ± 4.0 min) of 73 residents (50.7% women, mean age 32.9 ± 7.7 years, 79% urban environment). The patient is more frequently a woman (60%) who comes alone (72%) due to acute processes (80%) and with 2.1 ± 1.0 demands. Preventive activities are offered in 47% (duration less than one minute) of primary (70%) and secondary (59%) prevention, offered through advice (72%) or screening (52%) and focused on the cardiovascular area (52%) and lifestyles (53%). Eighty percent related to the patient's reason for consultation. Communication skills 41% improvable, 26% adequate, 23% excellent. The offer of preventive activities is related to the duration of the consultation (OR = 1.1, 95% CI 1.01; 1.16) and communication skills (OR = 1.03, 95% CI 1.01; 1.10). Conclusions: Preventive activities are carried out in almost half of the consultations, although focused on advice and screening and linked to the patient's demand. Consultation time and communication skills favor a greater preventive offer. Palabras clave: Promoción de la salud, Prevención de enfermedades, Internado y residencia, Atención Primaria de Salud, Comunicación, Relaciones médico-paciente, Keywords: Health promotion, Disease prevention, Internship and residency, Primary healthcare, Communication, Physician-patient relations

An in-mouth headspace sorptive extraction (HSSE) procedure for the in-mouth volatile sampling of wine aroma compounds during wine tasting has been developed. The procedure is based on the application of a PDMS (polydimethylsiloxane) twister contained inside a tailored made glass tube placed into the headspace of the mouth after rinsing and spitting-off the wine, which is then followed by gas chromatography mass spectrometry analysis (GCMS). Various parameters that might affect the performance of the method (extraction time, aroma concentration) were firstly investigated. Despite the short selected in-mouth extraction time (30 s); the application of the in-mouth HSSE procedure using real wines allowed the detection of >30 volatile compounds from different chemical families in the oral cavity in a single run, and which are also present in the wine at very low concentrations. Additionally, the in-mouth HSSE profile allowed us to distinguish between wines types (with different non-volatile and volatile composition) in a similar way to that when using data from the headspace of the wine (wine-HSSE-GCMS). The simplicity, sensitivity, good repeatability and the easy automatization of this procedure, makes this technique a reliable and feasible tool to determine the chemical and biochemical changes of these compounds in the mouth in real physiological conditions providing useful –in vivo analytical data to better correlate with sensory studies., This work was financially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) (project AGL 2016 78936-R).

To develop and validate a scale to stratify risk of 2-day mortality based on data collected during calls to an emergency dispatch center from patients with suspected coronavirus disease 2019 (COVID-19).Retrospective multicenter study of consecutive patients over the age of 18 years with suspected COVID-19 who were transported from home over the course of 3 months after telephone interviews with dispatchers. We analyzed clinical and epidemiologic variables and comorbidities in relation to death within 2 days of the call. Using data from the development cohort, we built a risk model by means of logistic regression analysis of categorical variables that were independently associated with 2-day mortality. The scale was validated first in a validation cohort in the same province and then in a cohort in a different province.A total of 2320 patients were included. The mean age was 79 years, and 49.8% were women. The overall 2-day mortality rate was 22.6% (376 deaths of patients with severe acute respiratory syndrome coronavirus 2 infection). The model included the following factors: age, location (rural location as a protective factor), institutionalization, desaturation, lung sounds (rhonchi), and altered mental status. The area under the receiver operating characteristic curve for death within 2 days was 0.763 (95% CI, 0.725-0.802; P .001). Mortality in patients at high risk (more than 2.4 points on the scale) was 60%.This risk scale derived from information available to an emergency dispatch center is applicable to patients with suspected COVID-19. It can stratify patients by risk of early death (within 2 days), possibly helping with decision making regarding whether to transport from home or what means of transport to use, and destination.Derivar y validar una escala basada en variables recogidas durante la llamada a un centro coordinador de urgencias (CCU) que permita estratificar el riesgo de mortalidad a 2 días en pacientes con sospecha de enfermedad por COVID-19.Estudio multicéntrico retrospectivo que incluyó a los pacientes consecutivos 18 años durante 3 meses, catalogados como caso sospechoso de COVID-19 después de la entrevista telefónica del CCU y que precisaron evacuación. Se analizaron variables clínico-epidemiológicas, comorbilidades y resultado de muerte a los 2 días. Se derivó una escala con las variables categóricas asociadas de forma independiente con la mortalidad a 2 días mediante regresión logística, en la cohorte de derivación. La escala se validó mediante una cohorte de validación y otra de revalidación obtenida en una provincia distinta.Se incluyeron 2.320 pacientes (edad mediana 79 años, 49,8% mujeres). La mortalidad global fue del 22,6% (376 casos en pacientes con SARS-CoV-2). El modelo incluyó edad, localización (zona rural como variable protectora), institucionalización, desaturación, roncus, taquipnea y alteración del nivel de conciencia. El área bajo la curva (ABC) para la mortalidad a 2 días fue de 0,763 (IC 95%: 0,725-0,802; p 0,001). La mortalidad en los pacientes de alto riesgo (2,4 puntos) fue del 60%.La escala, derivada a través de información obtenida con datos del CCU, es aplicable a pacientes con sospecha de infección por COVID-19, estratifica el riesgo de mortalidad precoz (menos de 2 días) y puede ser una herramienta que ayude en la toma de decisiones, referidas a su evacuación, destino o vector de transporte.

Predictive models of tumor response based on heterogeneity metrics in medical images, such as textural features, are highly suggestive. However, the demonstrated sensitivity of these features to noise does affect the model being developed. An in-depth analysis of the noise influence on the extraction of texture features was performed based on the assumption that an improvement in information quality can also enhance the predictive model. A heuristic approach was used that recognizes from the beginning that the noise has its own texture and it was analysed how it affects the quantitative signal data. A simple procedure to obtain noise image estimation is shown; one which makes it possible to extract the noise-texture features at each observation. The distance measured between the textural features in signal and estimated noise images allows us to determine the features affected in each observation by the noise and, for example, to exclude some of them from the model. A demonstration was carried out using synthetic images applying realistic noise models found in medical images. Drawn conclusions were applied to a public cohort of clinical images obtained using FDG-PET to show how the predictive model could be improved. A gain in the area under the receiver operating characteristic curve between 10 and 20% when noise texture information is used was shown. An improvement between 20 and 30% can be appreciated in the estimated model quality.

The human epidermal growth factor receptor 2 (HER2) is a transmembrane protein that has become one of the most specific prognostic and predictive biomarker of breast cancer. Its early detection is key for optimizing the patient clinical outcome. This work is focused on the detection of HER2 in individual cells using an antibody containing lutetium (Lu) as reporter group that is monitored by introducing the individual cells into the inductively coupled plasma mass spectrometer (ICP-MS). This Lu-containing antibody probe is used to label different breast cancer cell lines considered HER2 negative (MDA-MB-231) and positive (SKBR-3 and BT-474). Optimizations regarding the amount of the probe necessary to ensure complete labelling reactions are conducted in the different cell models. Concentrations in the range of 0.006 fg Lu/cell and 0.030 fg Lu/cell could be found in the HER2 negative and HER2 positive cells, respectively. In addition, the selectivity of the labelling reaction is tested by using two different metal-containing antibody probes for HER2 (containing Lu) and for transferrin receptor 1 (containing Nd), respectively, within the same cell population. Finally, the methodology is applied to the targeting of HER2 positive cells in complex cell mixtures containing variable amounts of BT-474 and MDA-MB-231 cells. The obtained results showed the excellent capabilities of the proposed strategy to discriminate among cell populations. This finding could help for scoring HER2 positive tumors improving existing technologies.

Resumen: Objetivos: Conocer si existe relación entre el lugar de fallecimiento y el proveedor de cuidados: equipo de atención primaria (EAP), equipo de soporte atención paliativa domiciliaria (ESAPD) o ambos. Identificar otras variables que pueden influir en el lugar de fallecimiento. Diseño: Estudio descriptivo observacional retrospectivo. Emplazamiento: Tres centros de salud, Dirección Asistencial Sureste, Comunidad de Madrid. Participantes: Pacientes mayores de 18 años con episodio A.99.01 (paciente con necesidad de cuidados paliativos), según la codificación CIAP2, activo en su historia clínica informatizada (AP-Madrid) desde enero de 2016 hasta diciembre de 2018 (n = 499). No cumplieron criterios de inclusión 224 pacientes. Mediciones y resultados principales: Se incluyeron 275 pacientes, la edad media fue de 78 años. El 80,4% (n = 221) tenían enfermedad oncológica. El 67,6% (n = 186) pertenecían al ámbito urbano. Existían diferencias significativas entre el lugar de fallecimiento y el equipo proveedor de cuidados: fallecieron en domicilio el 23,1% (n = 6) en seguimiento por EAP, el 14,5% (n = 10) en seguimiento por ESAPD y el 29,4% (n = 53) con seguimiento conjunto (p

We are grateful for the support received from the Consejeria de Innovacion, Ciencia y Empresa, Andalusian Regional Government (Project P06-CTS-01435), and from the Spanish Ministry of Economy and Competitivity (SAF2011-29648); the CIBERehd is funded by the Instituto de Salud Carlos III., This paper forms part of the Doctoral Program in Nutrition and Food Science of the University of Granada., Diabetes is a disease with an inflammatory component that courses with an anemic state. Vanadium (V) is an antidiabetic agent that acts by stimulating insulin signaling. Hepcidin blocks the intestinal absorption of iron and the release of iron from its deposits. We aim to investigate the effect of V on hepcidin mRNA expression and its consequences on the hematological parameters in streptozotocin-induced diabetic Wistar rats. Control healthy rats, diabetic rats, and diabetic rats treated with 1 mgV/day were examined for five weeks. The mineral levels were measured in diet and serum samples. Hepcidin expression was quantified in liver samples. Inflammatory and hematological parameters were determined in serum or whole blood samples. The inflammatory status was higher in diabetic than in control rats, whereas the hematological parameters were lower in the diabetic rats than in the control rats. Hepcidin mRNA expression was significantly lower in the V-treated diabetic rats than in control and untreated diabetic rats. The inflammatory status remained at a similar level as the untreated diabetic group. However, the hematological profile improved after the V-treatment, reaching similar levels to those found in the control group. Serum iron level was higher in V-treated than in untreated diabetic rats. We conclude that V reduces gene expression of hepcidin in diabetic rats, improving the anemic state caused by diabetes., Consejeria de Innovacion, Ciencia y Empresa, Andalusian Regional Government P06-CTS-01435, Spanish Ministry of Economy and Competitivity SAF2011-29648, Instituto de Salud Carlos III European Commission

La pandemia por el SARS-CoV-2 persiste con toda su virulencia a pesar de haberse administrado 650.382.819 dosis de vacuna anti-COVID a nivel mundial. La prueba de referencia para la identificación de la infección es la reacción en cadena de la polimerasa con transcriptasa inversa (RT-qPCR). La utilidad de esta prueba puede disminuir al simplificar su resultado como positivo o negativo. Determinar el número de ciclos (Ct) en las pruebas RT-qPCR positivas puede ayudar en la toma de decisiones cuando se interpretan en el contexto clínico de los pacientes.

To compare the effect of a mindfulness-based mobile application versus an in-person mindfulness-based training program in terms of reducing anxiety and increasing empathy, self-compassion, and mindfulness in a population of healthcare students.The authors conducted a single-blind, randomised controlled trial with three parallel groups. Participants were allocated to the mobile app, the in-person mindfulness-based program (IMBP), or a control group. Assessments at baseline and postintervention (8 weeks) included measures of anxiety, empathy, self-compassion, and mindfulness.Of 168 students randomised, 84 were analysed on an intention-to-treat basis (app:A mobile app can be as effective as an IMBP in reducing anxiety and increasing self-compassion and mindfulness among healthcare students.

A systematic investigation on the cellular uptake, intracellular dissolution, and in vitro biological effects of ultra-small (

Three novel dinuclear Cu(II) complexes based on a N,N,O-chelating salphen-like ligand scaffold and bearing varying aromatic substituents (−H, −Cl, and −Br) have been synthesized and characterized. The experimental and computational data obtained suggest that all three complexes exist in the dimeric form in the solid state and adopt the same conformation. The mass spectrometry and electron paramagnetic resonance results indicate that the dimeric structure coexists with the monomeric form in solution upon solvent (dimethyl sulfoxide and water) coordination. The three synthesized Cu(II) complexes exhibit high potentiality as ROS generators, with the Cu(II)/Cu(I) redox potential inside the biological redox window, and thus being able to biologically undergo Cu(II)/Cu(I) redox cycling. The formation of ROS is one of the most promising reported cell death mechanisms for metal complexes to offer an inherent selectivity to cancer cells. In vitro cytotoxic studies in two different cancer cell lines (HeLa and MCF7) and in a normal fibroblast cell line show promising selective cytotoxicity for cancer cells (IC50 about 25 μM in HeLa cells, which is in the range of cisplatin and improved with respect to carboplatin), hence placing this N,N,O-chelating salphen-like metallic core as a promising scaffold to be explored in the design of future tailor-made Cu(II) cytotoxic compounds., Three novel dinuclear Cu(II) complexes based on a N,N,O-chelating salphen-like ligand scaffold and bearing varying aromatic substituents (−H, −Cl, and −Br) have been synthesized and characterized. They three exhibit high potentiality as reactive oxygen species (ROS) generators, with the Cu(II)/Cu(I) redox potential inside the biological redox window. In vitro studies in two different cancer cell lines (HeLa and MCF7) and in a normal fibroblast cell line show promising selective cytotoxicity for cancer cells.

B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. As predicted by its prenatal origin, infant B-ALL (iB-ALL) shows an exceptionally silent DNA mutational landscape, suggesting that alternative epigenetic mechanisms may substantially contribute to its leukemogenesis. Here, we have integrated genome-wide DNA methylome and transcriptome data from 69 patients with de novo MLL-rearranged leukemia (MLLr) and non-MLLr iB-ALL leukemia uniformly treated according to the Interfant-99/06 protocol. iB-ALL methylome signatures display a plethora of common and specific alterations associated with chromatin states related to enhancer and transcriptional control in normal hematopoietic cells. DNA methylation, gene expression, and gene coexpression network analyses segregated MLLr away from non-MLLr iB-ALL and identified a coordinated and enriched expression of the AP-1 complex members FOS and JUN and RUNX factors in MLLr iB-ALL, consistent with the significant enrichment of hypomethylated CpGs in these genes. Integrative methylome-transcriptome analysis identified consistent cancer cell vulnerabilities, revealed a robust iB-ALL–specific gene expression–correlating dmCpG signature, and confirmed an epigenetic control of AP-1 and RUNX members in reshaping the molecular network of MLLr iB-ALL. Finally, pharmacological inhibition or functional ablation of AP-1 dramatically impaired MLLr-leukemic growth in vitro and in vivo using MLLr-iB-ALL patient–derived xenografts, providing rationale for new therapeutic avenues in MLLr-iB-ALL., We thank CERCA/Generalitat de Catalunya (SGR180) and Fundació Josep Carreras-Obra Social la Caixa for their institutional support. Financial support for this work was obtained from the European Research Council (CoG-2014-646903 and PoC-2018-811220 to PM), the Spanish Ministry of Economy and Competitiveness (SAF-2019-108160-R and SAF2016-76758-R to PM and IV, respectively), the Spanish Association against cancer (AECC-CI-2015 and PROYE18061FERN to CB and MFF), the Fundación Uno entre Cienmil (to PM), the Health Institute Carlos III (ISCIII/FEDER, PI17/01028, PI15/00892, PI18/01527 to CB and AFF/MFF, respectively). We also acknowledge the Plan de Ciencia, Tecnología e Innovación from the Asturias Government cofunding 2018–2022/FEDER (IDI/2018/146to MFF). MFF also acknowledges funding from Fundación General CSIC (0348_CIE_6_E). PM also acknowledges financial support from Fundación Leo Messi. JRT and MV are supported by Juan de la Cierva fellowships by the Spanish Ministry of Science and Innovation (FJCI-2015-26965, IJC2018-36825-I, IJCI-2017-3317) and IUOPA-ISPA-FINBA (The IUOPA is supported by the Obra Social Cajastur-Liberbank, Spain). RTR is supported by a fellowship from the AECC scientific foundation. RFP and PSO are supported by the Severo Ochoa program (BP17-114 and BP17-165, respectively).

Recent advances in the control of overground exoskeletons are being centered on improving balance support and decreasing the reliance on crutches. However, appropriate methods to quantify the stability of these exoskeletons (and their users) are still under development. A reliable and reproducible balance assessment is critical to enrich exoskeletons’ performance and their interaction with humans. In this work, we present the BenchBalance system, which is a benchmarking solution to conduct reproducible balance assessments of exoskeletons and their users. Integrating two key elements, i.e., a hand-held perturbator and a smart garment, BenchBalance is a portable and low-cost system that provides a quantitative assessment related to the reaction and capacity of wearable exoskeletons and their users to respond to controlled external perturbations. A software interface is used to guide the experimenter throughout a predefined protocol of measurable perturbations, taking into account antero-posterior and mediolateral responses. In total, the protocol is composed of sixteen perturbation conditions, which vary in magnitude and location while still controlling their orientation. The data acquired by the interface are classified and saved for a subsequent analysis based on synthetic metrics. In this paper, we present a proof of principle of the BenchBalance system with a healthy user in two scenarios: subject not wearing and subject wearing the H2 lower-limb exoskeleton. After a brief training period, the experimenter was able to provide the manual perturbations of the protocol in a consistent and reproducible way. The balance metrics defined within the BenchBalance framework were able to detect differences in performance depending on the perturbation magnitude, location, and the presence or not of the exoskeleton. The BenchBalance system will be integrated at EUROBENCH facilities to benchmark the balance capabilities of wearable exoskeletons and their users., This research was funded by the European project EUROBENCH2020 (eurobench2020.eu), grant number n779963, BenchBalance. This work benefited from work/discussions in the COST Action Wearable Robots CA16116, and the project Discover2Walk under Grant PID2019-105110RB-C31 by the Spanish Ministry of Science and Innovation.

In this article, we aim to develop a political economy of mass hysteria. Using the background of COVID-19, we study past mass hysteria. Negative information which is spread through mass media repetitively can affect public health negatively in the form of nocebo effects and mass hysteria. We argue that mass and digital media in connection with the state may have had adverse consequences during the COVID-19 crisis. The resulting collective hysteria may have contributed to policy errors by governments not in line with health recommendations. While mass hysteria can occur in societies with a minimal state, we show that there exist certain self-corrective mechanisms and limits to the harm inflicted, such as sacrosanct private property rights. However, mass hysteria can be exacerbated and self-reinforcing when the negative information comes from an authoritative source, when the media are politicized, and social networks make the negative information omnipresent. We conclude that the negative long-term effects of mass hysteria are exacerbated by the size of the state.

Purpose To assess occupational lens exposure in a mixed interventional radiology department, comparing pediatric and adult procedures. To analyze the correlation between the lens dose and the doses measured at the chest and collar level and the kerma-area product (PKA ). Methods For 17 months, three radiologists performing both pediatric and adult interventions were monitored by means of 14 dosimeters per worker: 12 single-point optically stimulated luminescent (OSL) dosimeters calibrated in terms of Hp (0.07) were placed on the inside and outside of two pairs of lead glasses, one for pediatric procedures and one for adult interventions; another whole-body OSL dosimeter calibrated in terms of Hp (10) was placed over the thyroid shield; finally, an additional active solid-state dosimeter, also calibrated for Hp (10), was worn on the chest, over the apron. Furthermore, a database was created to register the demographic and dosimetric data of the procedures, as well as the name of the radiologist acting as first operator. Results For the three radiologists, who performed 276-338 procedures/year (20% pediatric), cumulative annual doses to the left bare eye exceeded 20 mSv (21-61 mSv). Considering the glasses' protection, annual doses exceeded 6 mSv (13-48 mSv) for both eyes. No important differences were observed in lens dose per procedure between pediatric and adult interventions (0.16 vs. 0.18, 0.12 vs. 0.09, and 0.07 vs. 0.07 mSv), although lens dose per PKA was 4.1-4.5 times higher in pediatrics (5.8 vs. 1.3, 3.3 vs. 0.8, and 2.6 vs 0.6 µSv/Gy·cm2 ) despite a similar use of the ceiling-suspended screen. Lens doses were highly correlated with collar readings (with Pearson coefficients [r] ranging from 0.86 to 0.98) and with chest readings (with r ranging from 0.75 to 0.93). However, slopes of the linear regressions varied greatly among radiologists. Conclusions There is real risk of exceeding the occupational dose limit to the eye lens in mixed interventional radiology rooms if radiation protection tools are not used properly. Regular monitoring of the lens dose is recommended, given lens exposure might easily exceed 6 mSv/year. Using a collar dosimeter for this purpose might be suitable if it is preceded by an individualized regression analysis. The same radiation protection measures should be applied to interventional radiologists regardless of whether they are treating pediatric or adult patients.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disorder that results from the progressive accumulation of genomic alterations in T-cell precursors developing in the thymus. T-ALL is characterized by the infiltration of bone marrow by immature T-cell lymphoblasts, while immature T-cell tumors characterized by a thymic mass and limited bone marrow infiltration are instead diagnosed as T-cell lymphoblastic lymphoma (T-LBL). T-ALL was described as an independent disease in the 1970s, after finding thymus-associated markers expressed on the surface of leukemic cells from pediatric patients [1]. Its incidence is higher in children than in adults (up to 25% and 15% of newly diagnosed ALL cases, respectively) [2], and it is twice as prevalent in males as in females [3]. Patients with T-ALL are frequently classified as high-risk due to the unfavorable features of the disease that include high leukocyte count, hematopoietic failure, and medullar and extramedullar infiltration with high probability of a ectation of the central nervous system (CNS), which represents a frequent site of relapse [4]. In 1995, the European Group for Immunological Characterization of Leukemias (EGIL) established a classification of different clinically relevant T-ALL subtypes based on the expression of cell surface markers corresponding to sequential intrathymic T-cell developmental stages [5]: pro-T, pre-T, cortical and mature T-ALL (Figure 1). However, in recent years, improved genomic and transcriptomic techniques have provided new insights into the characterization of the prevalent genetic lesions involved in T-ALL pathogenesis [6–8], which has proved more valuable for risk-stratification of patients at the time of diagnosis [9–11]. Detection of translocations of enhancers or promoters of T-cell receptor (TCR) genes to other chromosomal regions helped the identification of the first T-ALL oncogenes, Ministerio de Ciencia e Innovación (SAF2016-75442-R) (Agencia Estatal de Investigación/European Regional Development Fund, European Union); Fundación Asociación Española Contra el Cáncer (CICPF18030TORI); Fundación Uno Entre Cien Mil; Fundación Ramón Areces; and Fundación Lair. Institutional grants from the Fundación Ramón Areces and Banco de Santander to the Centro de Biología Molecular Severo Ochoa

The measures to contain the spread of the COVID-19 outbreak have no precedent in the recent history of many countries. Around 2,000 million people in the world are in isolation or quarantine, and gatherings of people have been expressly banned in many countries. In Spain, this prohibition affects workplaces, schools, and the national health system, where most of the healthcare is being provided either on the phone or online.

In primary health care only chronic pain surpass depression and anxiety in loss of quality-adjusted life years. More than 70% of people suffering from common mental disorders consulted their GPs for this reason. However, 'the declining halves rule' is a reality: less than 50% of primary care attendees with common mental disorders were correctly diagnosed, of these less than 50% received adequate treatment (pharmacological or psychological) and of these less than 50% patients were adherent. Collaborative models of common mental disorders care in primary health care have demonstrated their effectiveness through clinical trials; however, its implementation in a more general and real context is difficult and its effectiveness remains unclear. Risk algorithms have been developed and validated in primary health care to predict the onset and prognosis of common mental disorders; which are useful for their treatment and prevention. There is evidence that psychological and psychoeducational interventions (and possibly those of physical exercise) are effective for the primary prevention of common mental disorders, even in primary health care; although their effects are small or moderate. These interventions have a high potential to be scalable in schools, workplace and primary health care; in addition, when they are administered through information and communication technologies (e.g. by App), in self-guided or minimally guided programs, they have demonstrated their effectiveness for the treatment and prevention of common mental disorders. They are also very accessible, have low cost and contribute to the massive implementation of these interventions in different settings.

Resumen La pandemia por COVID-19 ha provocado un desajuste en todos los sistemas de salud. La mayoría de los países habían olvidado cómo comportarse ante una epidemia de estas características sin disponer de los recursos adecuados. Es preciso realizar un balance de todo lo sucedido, instruir a la población y generar un nuevo conocimiento que nos permita afrontar nuevas epidemias.

BACKGROUND/PURPOSE The main indication of covered stents (CS) is coronary artery perforation (CAP), but, they have been increasingly used in other scenarios. Data on the long-term follow-up of CS is limited, and no studies have been conducted specifically using new-generation polyurethane-covered cobalt-chromium Papyrus CS. PURPOSE to evaluate the clinical outcomes after hospital discharge of Papyrus CS and to compare their outcome after implantation in CAP or coronary artery aneurysms (CAA). METHODS/MATERIALS We evaluated the baseline clinical characteristics, lesion subsets, procedural features and the outcomes after initial discharge of Papyrus CS implanted in 17 high-PCI-volume centers. RESULTS 127 Papyrus CS were implanted in 108 patients (68 ± 1 years; 82.8% male) admitted for stable coronary disease (32.3%), NSTEMI (42.4%) or STEMI (25.3%). The number of CS per patient was 1.2 ± 0.6 (diameter: 3.5 ± 1.7 mm; length: 18.5 ± 3.7 mm). Angiographic success rate was 96%. CS diameter was larger in CAA (CAP:3.04 ± 0.5 mm vs CAA:4.1 ± 2.7 mm; p = .022). Intracoronary imaging techniques were used more frequently in CAA (p

Background: Alzheimer&rsquo, s disease (AD) which is the most common type of dementia is characterized by mental or cognitive disorders. People suffering with this condition find it inherently difficult to communicate and describe symptoms. As a consequence, both detection and treatment of comorbidities associated with Alzheimer&rsquo, s disease are substantially impaired. Equally, action protocols in the case of emergencies must be clearly formulated and stated. Methods: We performed a bibliography search followed by an observational and cross-sectional study involving a thorough review of medical records. A group of AD patients was compared with a control group. Each group consisted of 100 people and were all Le&oacute, n residents aged &ge, 65 years. Results: The following comorbidities were found to be associated with AD: cataracts, urinary incontinence, osteoarthritis, hearing loss, osteoporosis, and personality disorders. The most frequent comorbidities in the control group were the following: eye strain, stroke, vertigo, as well as circulatory and respiratory disorders. Comorbidities with a similar incidence in both groups included type 2 diabetes mellitus, glaucoma, depression, obesity, arthritis, and anxiety. We also reviewed emergency procedures employed in the case of an emergency involving an AD patient. Conclusions: Some comorbidities were present in both the AD and control groups, while others were found in the AD group and not in the control group, and vice versa.

Objective: To study DNA methylation patterns of cortical pyramidal layers susceptible to late-onset Alzheimer's disease (LOAD) neurodegeneration. Methods: Laser-assisted microdissection to select pyramidal layers’ cells in frontal cortex of 32 human brains (18 LOAD) and Infinium DNA Methylation 450K analysis were performed to find differential methylated positions and regions, in addition to the corresponding gene set functional enrichment analyses. Results: Differential hypermethylation in several genomic regions and genes mainly in HOXA3, GSTP1, CXXC1-3 and BIN1. The functional enrichment analysis revealed genes significantly related to oxidative-stress and synapsis. Conclusion: The present results indicate the differentially methylated genes related to neural projections, synapsis, oxidative stress and epigenetic regulator genes and represent the first epigenome of cortical pyramidal layers in LOAD.