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Abstract The low resolution of spatial transcriptomics data necessitates additional information for optimal use. We developed scDOT, which combines spatial transcriptomics and single cell RNA sequencing to improve the ability to reconstruct single cell resolved spatial maps and identify senescent cells. scDOT integrates optimal transport and expression deconvolution to learn non-linear couplings between cells and spots and to infer cell placements. Application of scDOT to lung spatial transcriptomics data improves on prior methods and allows the identification of the spatial organization of senescent cells, their neighboring cells and novel genes involved in cell-cell interactions that may be driving senescence.

Introduction: Nonalcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is an escalating health concern linked to obesity and type 2 diabetes. Despite liver biopsy being the gold standard, its invasiveness underscores the need for noninvasive diagnostic methods. Methods: A cross-sectional study was performed to assess MASLD using the noninvasive OWLiver® serum lipidomics test in a cohort of 117 patients with severe obesity undergoing bariatric surgery, comparing outcomes with liver biopsy. Exclusions (n = 24) included insufficient data, liver disease etiology other than MASLD, corticosteroid treatment, excessive alcohol consumption, low glomerular filtration rate, and declination to participate. Comprehensive laboratory tests, demographic assessments, and liver biopsies were performed. Serum metabolites were analyzed using OWLiver®, a serum lipidomic test that discriminates between healthy liver, steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and MASH with fibrosis ≥2 by means of three algorithms run sequentially. Results: Liver biopsy revealed a MASLD prevalence of 95.7%, with MASH present in 28.2% of cases. OWLiver® demonstrated a tendency to diagnose more severe cases. Body mass index (BMI), rather than the presence of type 2 diabetes, emerged as the sole independent factor linked to the probability of concordance. Therefore, the all-population concordance of 63.2% between OWLiver® and liver biopsy notably raised to 77.1% in patients with a BMI

Violence is a public health problem, and when it affects childhood, it can cause illness throughout the individual’s life. Apart from being able to cause damage in the physical, mental and social spheres, it represents a violation of the rights of the affected children, and a high consumption of resources, both economic and social.A multitude of investigations have improved attention to this violence. However, these advances are not consistent with the practical management of victims, both in Primary and Hospital Care. There is a significant area of improvement for paediatric care.Through this article, different professionals from all established paediatric health care facilities develop general lines of knowledge and action regarding violence against children. An overview is taken of the legislation related to childhood, the different types of abuse that exist, their effects, management and prevention. It concludes with an epilogue, through which we aim to move sensibilities.In summary, this work aims to promote the training and awareness of all professionals specialized in children’s health, so that they pursue the goal of achieving their patients’ greatest potential in life, and in this way, to help create a healthier society, with less disease, and more justice. Resumen: La violencia es un problema de salud pública. Esta, cuando afecta a la infancia, puede generar enfermedad a lo largo de toda la vida del individuo. Aparte de poder producir daños en la esfera física, psíquica y social, supone una vulneración de los derechos de los niños afectados y un elevado consumo de recursos tanto económicos como sociales.Multitud de investigaciones han mejorado la atención a esta violencia. Sin embargo, estos avances no son parejos con el manejo práctico que se realiza a las víctimas tanto en la atención primaria como en la hospitalaria. Existe una significativa área de mejora para la atención pediátrica.A través de este artículo, distintos profesionales de todas las áreas sanitarias pediátricas establecidas desarrollan líneas generales de conocimiento y actuación con respecto a la violencia contra la infancia. Se hace un recorrido a través de la legislación relacionada con la infancia, las distintas tipologías de maltrato que existen, sus efectos, manejo y prevención. Concluye con un epílogo, a través del cual pretendemos mover sensibilidades.En resumen, este es un trabajo que pretende fomentar la formación y sensibilización de todos los profesionales especializados en la salud infantil, para que persigan como objetivo el que sus pacientes alcancen su mayor potencial en la vida y, de esa manera, ayudar a crear una sociedad más sana, con menos enfermedad y más justa.

Resumen: La violencia es un problema de salud pública. Esta, cuando afecta a la infancia, puede generar enfermedad a lo largo de toda la vida del individuo. Aparte de poder producir daños en la esfera física, psíquica y social, supone una vulneración de los derechos de los niños afectados y un elevado consumo de recursos tanto económicos como sociales.Multitud de investigaciones han mejorado la atención a esta violencia. Sin embargo, estos avances no son parejos con el manejo práctico que se realiza a las víctimas tanto en la atención primaria como en la hospitalaria. Existe una significativa área de mejora para la atención pediátrica.A través de este artículo, distintos profesionales de todas las áreas sanitarias pediátricas establecidas desarrollan líneas generales de conocimiento y actuación con respecto a la violencia contra la infancia. Se hace un recorrido a través de la legislación relacionada con la infancia, las distintas tipologías de maltrato que existen, sus efectos, manejo y prevención. Concluye con un epílogo, a través del cual pretendemos mover sensibilidades.En resumen, este es un trabajo que pretende fomentar la formación y sensibilización de todos los profesionales especializados en la salud infantil, para que persigan como objetivo el que sus pacientes alcancen su mayor potencial en la vida y, de esa manera, ayudar a crear una sociedad más sana, con menos enfermedad y más justa. Abstract: Violence is a public health problem, and when it affects childhood, it can cause illness throughout the individual's life. Apart from being able to cause damage in the physical, mental and social spheres, it represents a violation of the rights of the affected children, and a high consumption of resources, both economic and social.A multitude of investigations have improved attention to this violence. However, these advances are not consistent with the practical management of victims, both in Primary and Hospital Care. There is a significant area of improvement for paediatric care.Through this article, different professionals from all established paediatric health care facilities develop general lines of knowledge and action regarding violence against children. An overview is taken of the legislation related to childhood, the different types of abuse that exist, their effects, management and prevention. It concludes with an epilogue, through which we aim to move sensibilities.In summary, this work aims to promote the training and awareness of all professionals specialized in children's health, so that they pursue the goal of achieving their patients’ greatest potential in life, and in this way, to help create a healthier society, with less disease, and more justice.

IntroductionNonalcoholic fatty liver disease (NAFLD) affects a quarter of the world’s population and encompasses a spectrum of liver conditions, from non-alcoholic steatohepatitis (NASH) to inflammation and fibrosis. In addition, NAFLD also links to extrahepatic conditions like diabetes or obesity. However, it remains unclear if NAFLD independently correlates with the onset and progression of atherosclerosis.Material and methodsThis cross-sectional study aimed to explore the relationship between NAFLD severity, assessed via liver biopsy, and early atherosclerosis using adventitial vasa vasorum (VV) density. It included 44 patients with obesity (33 with steatosis, 11 with NASH) undergoing bariatric surgery.ResultsResults revealed no significant differences in adventitial VV density between steatosis and NASH groups, neither in the mean values [0.759 ± 0.104 vs. 0.780 ± 0.043, P=0.702] nor left-right sides. Similarly, carotid intima-media thickness (cIMT) did not vary between these groups. Additionally, no linear correlation existed between VV density and cIMT. Only gender showed an association with VV density.ConclusionThese findings suggest that NASH severity doesn’t independently drive early atherosclerosis or affects cIMT. Gender might play a role in early atherosclerotic disease in NAFLD, impacting VV density and cIMT. This highlights the need to consider other risk factors when evaluating cardiovascular risk in NAFLD patients.

Background: Outcomes of bariatric surgery (BS) in patients with schizophrenia are poorly understood. We aimed to analyze the effects of BS in patients with schizophrenia (SZ) or schizoaffective disorder (SZA). Methods: This was a multicenter, retrospective case-control study in patients with SZ or SZA who had undergone BS in seven public referral hospitals in Spain. Controls without psychiatric comorbidity were selected in a 1:4 ratio. Detailed clinical and biochemical data were collected preoperatively and at 12, 24, 36, 48, and 60 months after BS. Results: Twenty patients with SZ (n = 15; 75%) or SZA (n = 5; 25%) and 80 matched controls were studied. There were no differences between patients and controls concerning the evolution of the percentage of total weight loss. The remission rate of the main comorbidities was similar between groups except for hypertension, which was lower in patients with a psychotic disorder from year 3. There were no mortalities within 30 days of surgery in either group. The psychiatric medication burden did not change during follow-up. Conclusions: BS is safe and effective in carefully selected patients with SZ. The course of the psychiatric disease does not seem to be worsened by the procedure.

Type II alveolar epithelial cell (AECII) redox imbalance contributes to the pathogenesis of idiopathic pulmonary fibrosis (IPF), a deadly disease with limited treatment options. Here, we show that expression of membrane-bound cytochrome B5 reductase 3 (CYB5R3), an enzyme critical for maintaining cellular redox homeostasis and soluble guanylate cyclase (sGC) heme iron redox state, is diminished in IPF AECIIs. Deficiency of CYB5R3 in AECIIs led to sustained activation of the pro-fibrotic factor TGF-β1 and increased susceptibility to lung fibrosis. We further show that CYB5R3 is a critical regulator of ERK1/2 phosphorylation and the sGC/cGMP/protein kinase G axis that modulates activation of the TGF-β1 signaling pathway. We demonstrate that sGC agonists (BAY 41-8543 and BAY 54-6544) are effective in reducing the pulmonary fibrotic outcomes of in vivo deficiency of CYB5R3 in AECIIs. Taken together, these results show that CYB5R3 in AECIIs is required to maintain resilience after lung injury and fibrosis and that therapeutic manipulation of the sGC redox state could provide a basis for treating fibrotic conditions in the lung and beyond.

Grape pomace is one of the main by-products in the wine industry and contains some high-added-value compounds, such as polysaccharides. Considering the wide application possibilities of polysaccharides in wine and in the food industry, the revalorization of grape pomace to extract polysaccharides presents itself as an opportunity for by-product management. Therefore, the aim of this study was to characterize polysaccharide extracts obtained from pomace by-products of different white grape varieties. The type and content of polysaccharides, proteins and phenols were analyzed. Statistically significant differences were found between the varietal extracts in the types and concentrations of polysaccharides. The extracts obtained from the Verdejo and Puesta en Cruz varieties showed the highest polysaccharide purity and contents, but the type of polysaccharides was different in each case. The Verdejo provided extracts richer in non-pectic polysaccharides, while the Puesta en Cruz provided extracts richer in pectic polysaccharides. The protein and polyphenol contents were low in all extracts, below 2.5% and 3.7%, respectively. These results open up a new possibility for the revalorization of grape pomace by-products to obtain polysaccharide-rich extracts, although it would be interesting to improve both the yield and the purity of the extracts obtained by studying other extraction techniques or processes.

Abstract The glucagon-like peptide-1 receptor agonist family together with the renal sodium/glucose cotransporter-2 inhibitors have garnered interest as potential therapeutic agents for subjects with type 2 diabetes and obesity. In these patients, bariatric surgery is indicated based in a BMI ≥ 35 kg/m2. A 24-week non-blinded, randomized pilot study to assess the efficacy of subcutaneous exenatide 2.0 mg once weekly plus oral dapagliflozin 10 mg once daily (Group A) compared to a control group (Group B) in 56 patients with type 2 diabetes awaiting bariatric surgery was conducted (EudraCTid.: 2017-001,454-33). Both groups received an energy-deficit low-fat diet. The primary endpoint was the proportion of patients running off the criteria for bariatric surgery at the end of the follow-up period (BMI ≤ 35.0 kg/m2 or a BMI ≤ 40.0 kg/m2 plus an HbA1c ≤ 6.0%). Changes in the BMI were also of interest. The proportion of patients who ran off the criteria for bariatric surgery was larger in Group A than in the control group (45.8% vs. 12.0%, p = 0.010). Participants in Group A exhibited an absolute decrease in body weight and BMI of 8.1 kg (95%IC: − 11.0 to − 5.2) and 3.3 kg/m2 (95%IC: − 4.5 to − 2.2), respectively (p 10% of their initial body weight (20.8 vs 0%) compared to Group B. The combination of exenatide plus dapagliflozin appears as a strategic option to reduce the waiting list for bariatric surgery, especially in those patients with type 2 diabetes.

Bronchiolitis obliterans syndrome (BOS) is the main reason for poor outcomes after lung transplantation (LTx). We and others have recently identified B cells as major contributors to BOS after LTx. The extent of B cell heterogeneity and the relative contributions of B cell subpopulations to BOS, however, remain unclear. Here, we provide a comprehensive analysis of cell population changes and their gene expression patterns during chronic rejection after orthotopic LTx in mice. Of 11 major cell types, Mzb1-expressing plasma cells (PCs) were the most prominently increased population in BOS lungs. These findings were validated in 2 different cohorts of human BOS after LTx. A Bhlhe41, Cxcr3, and Itgb1 triple-positive B cell subset, also expressing classical markers of the innate-like B-1 B cell population, served as the progenitor pool for Mzb1+ PCs. This subset accounted for the increase in IgG2c production within BOS lung grafts. A genetic lack of Igs decreased BOS severity after LTx. In summary, we provide a detailed analysis of cell population changes during BOS. IgG+ PCs and their progenitors — an innate B cell subpopulation — are the major source of local Ab production and a significant contributor to BOS after LTx.

Adipocyte dysfunction is the driver of obesity and correlates with insulin resistance and the onset of type 2 diabetes. Protein kinase N1 (PKN1) is a serine/threonine kinase that has been shown to contribute to Glut4 translocation to the membrane and glucose transport. Here, we evaluated the role of PKN1 in glucose metabolism under insulin-resistant conditions in primary visceral adipose tissue (VAT) from 31 patients with obesity and in murine 3T3-L1 adipocytes. In addition, in vitro studies in human VAT samples and mouse adipocytes were conducted to investigate the role of PKN1 in the adipogenic maturation process and glucose homeostasis control. We show that insulin-resistant adipocytes present a decrease in PKN1 activation levels compared to nondiabetic control counterparts. We further show that PKN1 controls the adipogenesis process and glucose metabolism. PKN1-silenced adipocytes present a decrease in both differentiation process and glucose uptake, with a concomitant decrease in the expression levels of adipogenic markers, such as PPARγ, FABP4, adiponectin and CEBPα. Altogether, these results point to PKN1 as a regulator of key signaling pathways involved in adipocyte differentiation and as an emerging player of adipocyte insulin responsiveness. These findings may provide new therapeutic approaches for the management of insulin resistance in type 2 diabetes.

Resumen: Introducción: SARS-CoV-2, responsable de la enfermedad por coronavirus 2019 (COVID-19), fue detectado por primera vez en España el 31 de enero de 2020. El 14 de marzo fue declarado el estado de alarma con el objetivo de controlar la pandemia. El objetivo de este estudio es analizar las consecuencias de esta crisis sanitaria sobre el patrón de demanda asistencial, así como el manejo y las características de los pacientes con sospecha de COVID-19 en el Servicio de Urgencias Pediátricas. Pacientes y métodos: Estudio retrospectivo observacional en niños y adolescentes menores de 18 años, atendidos en nuestro Servicio de Urgencias Pediátricas durante el periodo comprendido desde el 14 de marzo hasta el 17 de abril de 2020. Resultados: Durante el periodo de estudio se atendieron 1.666 pacientes, un 65,4% menos que en el mismo periodo de 2019. La edad media fue de 5,4 años y el 51,2% eran varones. El 39,9% fueron clasificados con niveles de alta prioridad, un 6,5% más que en 2019. Los principales motivos de consulta fueron fiebre (26,5%), síntomas respiratorios (16,1%) y traumatismos (15,2%). Un total de 218 pacientes (13%) fueron diagnosticados de posible COVID-19, confirmándose la infección en el 18,4%. El 44% (96/218) fueron diagnosticados de infección respiratoria inferior y el 33,9% (74/218), superior. El 23,8% (52/218) fueron hospitalizados. Conclusiones: Durante el brote epidémico SARS-CoV-2 disminuyó la demanda de asistencia pediátrica urgente, aumentando la proporción de casos con niveles de triaje de alta prioridad. La mayoría de los pacientes con sospecha o confirmación microbiológica de COVID-19 cursaron con clínica respiratoria leve. Abstract: Introduction: SARS-CoV-2, coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in Spain on 31 January 2020. On 14 March 2020, a state of emergency was declared in Spain in a bid to control the spread of the COVID-19 pandemic in the country. The aim of our study is to analyse the impact on emergency medicine attendance after the national lockdown, as well as the clinical presentation and the management of patients with suspected COVID-19 in the Paediatric Emergency Department. Patients and methods: This retrospective observational study included children and adolescents under the age of 18, attended in our Paediatric Emergency Department during the period March 14 to April 17, 2020. Results: A total of 1,666 patients were attended during the study period, 65.4% less than in the same period of 2019. Just over half (51.2%) were males, and mean age was 5.4 years. In triage, 39.9% were high priority levels, 6.5% more than 2019. Most frequent reasons for consultation at the Paediatric Emergency Department were fever (26.5%), respiratory symptoms (16.1%), and trauma (15.2%). A total of 218 patients (13%) received a diagnosis of possible COVID-19, with SARS-CoV-2 infection confirmed in 18.4%, and 23.8% (52/218) were hospitalised. At discharge, 44% (96/218) were diagnosed with lower, and 33.9% (74/218) with upper respiratory infection. Conclusions: During the SARS-CoV-2 outbreak, the demand for urgent paediatric care decreased, with the proportion of cases with high priority triage levels increasing. Most of the patients with suspected or microbiological confirmation of COVID-19 had mild respiratory symptoms.

Introduction: SARS-CoV-2, coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in Spain on 31 January 2020. On 14 March 2020, a state of emergency was declared in Spain in a bid to control the spread of the COVID-19 pandemic in the country. The aim of our study is to analyze the impact on emergency medicine attendance after the national lockdown, as well as the clinical presentation and the management of patients with suspected COVID-19 in the Paediatric Emergency Department. Patients and methods: This retrospective observational study included children and adolescents under the age of 18, attended in our Paediatric Emergency Department during the period March 14 to April 17, 2020. Results: A total of 1666 patients were attended during the study period, 65.4% less than in the same period of 2019. Just over half (51.2%) were males, and mean age was 5.4 years. In triage, 39.9% were high priority levels, 6.5% more than 2019. Most frequent reasons for consultation at the Paediatric Emergency Department were fever (26.5%), respiratory symptoms (16.1%), and trauma (15.2%). A total of 218 patients (13%) received a diagnosis of possible COVID-19, with SARS-CoV-2 infection confirmed in 18.4%, and 23.8% (52/218) were hospitalised. At discharge, 44% (96/218) were diagnosed with lower, and 33.9% (74/218) with upper respiratory infection. Conclusions: During the SARS-CoV-2 outbreak, the demand for urgent paediatric care decreased, with the proportion of cases with high priority triage levels increasing. Most of the patients with suspected or microbiological confirmation of COVID-19 had mild respiratory symptoms. Resumen: Introducción: SARS-CoV-2, responsable de la enfermedad por coronavirus 2019 (COVID-19), fue detectado por primera vez en España el 31 de enero de 2020. El 14 de marzo fue declarado el estado de alarma con el objetivo de controlar la pandemia. El objetivo de este estudio es analizar las consecuencias de esta crisis sanitaria sobre el patrón de demanda asistencial, así como el manejo y las características de los pacientes con sospecha de COVID-19 en el Servicio de Urgencias Pediátricas. Pacientes y métodos: Estudio retrospectivo observacional en niños y adolescentes menores de 18 años, atendidos en nuestro Servicio de Urgencias Pediátricas durante el periodo comprendido desde el 14 de marzo hasta el 17 de abril de 2020. Resultados: Durante el periodo de estudio se atendieron 1.666 pacientes, un 65,4% menos que en el mismo periodo de 2019. La edad media fue de 5,4 años y el 51,2% eran varones. El 39,9% fueron clasificados con niveles de alta prioridad, un 6,5% más que en 2019. Los principales motivos de consulta fueron fiebre (26,5%), síntomas respiratorios (16,1%) y traumatismos (15,2%). Un total de 218 pacientes (13%) fueron diagnosticados de posible COVID-19, confirmándose la infección en el 18,4%. El 44% (96/218) fueron diagnosticados de infección respiratoria inferior y el 33,9% (74/218), superior. El 23,8% (52/218) fueron hospitalizados. Conclusiones: Durante el brote epidémico SARS-CoV-2 disminuyó la demanda de asistencia pediátrica urgente, aumentando la proporción de casos con niveles de triaje de alta prioridad. La mayoría de los pacientes con sospecha o confirmación microbiológica de COVID-19 cursaron con clínica respiratoria leve.

Objective: There is a close relationship between excess adiposity and cardiovascular disease. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. Here, our objective was to assess the usefulness of these anthropometric indices to detect subclinical atheromatous disease. Methods: A cross-sectional study with 6,809 middle-aged subjects (mean age, 57 [53–63] years) with low to moderate cardiovascular risk from the ILERVAS project. Measures of total body fat (BMI, Clínica Universidad de Navarra – Body Adiposity Estimator [CUN-BAE], and Deurenberg’s formula) and central adiposity (waist and neck circumferences, conicity index, waist-to-height ratio, Bonora’s equation, the A body adiposity index, and body roundness index) were performed in all participants. Bilateral carotid and femoral ultrasound vascular studies allowed the identification of subjects with plaque. ­Results: All measured indices were significantly higher in males with subclinical carotid or femoral plaques (p ≤ 0.021 for all). Also, a positive and significant correlation between all indices and the number of affected territories was found (p ≤ 0.013 for all). From the ROC analysis, all measurements identified patients with asymptomatic atheromatosis but none of them helped make clinical decisions. Regarding females, the results were less conclusive. Conclusion: Obesity indices are related to subclinical atheromatosis, especially in men, in a large cohort of middle-aged subjects. However, the indices could not detect the presence of arterial plaque, so, when used in isolation, are unlikely to be decisive.

Introduction: Diets are currently unsustainable in many countries as evidenced by the growing burden of malnutrition, degradation of natural resources, contributions to climate change, and unaffordability of healthy diets. Agreement on what constitutes a healthy and sustainable diet has been debated. In 2019, FAO and WHO published the Sustainable Healthy Diets Guiding Principles, defining what qualifies as a sustainable healthy diet. While valuable, these principles require measurable indicators to support their operationalization. Our scoping review aims to describe how sustainable healthy diets have been assessed in the literature since 2010.Methods: A search for English-language articles published in peer-reviewed journals was conducted from January 2010 through February 2020 across three databases. Out of the 504 articles initially identified, 103 articles were included. Metadata were extracted from each article on: publication year, country of study, study aims, methods, main data sources, indicators used to assess sustainable healthy diets, reported indicator strengths or limitations, and main study findings. A qualitative content analysis identified major conceptual themes across indicators and their frequency of use.Findings: From the 103 empirical articles included in our review, 57.3% were published after 2017. Most studies were carried out in high-income countries (74%). Approximately 42% of the articles assessed the sustainability of diets using solely health and environmental indicators;

Background: The significance of national tourism in the global data highlights the importance of studying the characteristics of Spanish tourists that show interest in visiting Valencia (Spain). Personality traits might influence tourism behavior, and their importance has scarcely been addressed in the prior tourism literature. Objectives: We aimed to identify the touristic profiles of national tourists based on their lifestyles and to analyze the influence of personality traits in tourism segmentation. Methodology: 329 individuals participated in this study, they responded questionnaires about sociodemography, personality, lifestyle and a 3-item questionnaire developed by the authors. We performed analysis to obtain profiles by lifestyle, we carried out tests to study differences in personality traits among profiles and we analyzed the effects of the responses to the author-developed questionnaire and the demographic characteristics of the subjects on their cluster membership. Results: The results show that this market can be segmented into four clusters. We found significant statistical differences in personality traits among profiles. In addition, the authors present an author-designed questionnaire that, together with demographic variables, is able to predict participants’ profiles. Conclusion: The results suggest that lifestyle is an appropriate indicator for this market segmentation and the analysis of its relationship with personality provides a deep comprehension of the resulting profiles. In addition, the profile prediction by the responses to the author-developed questionnaire constitutes a new basis for tourism segmentation, as these predictors might be used as “quick touristic classifiers”. Implications or recommendations: The study of decision-making processes in tourism allows researchers and sellers to predict tourist behaviors and adapt offers to tourists’ preferences and interests.

There is an increasing interest in the valorization of wine waste by-products. Grape pomace/marc can be an important source of polyphenols but also of polysaccharides (PSs). Therefore, the aim of this work was to extract PSs from grape pomace and musts and incorporate them into wines to improve their quality and valorize these residues. Two white wines were elaborated and treated with four different PS extracts obtained from white grape pomace, white must, a wine purified extract rich in RG-II, and commercial inactivated yeasts. In general, the use of grape PSs extracted from grape pomace or must improve some characteristics of wine, increasing the polysaccharide and volatile concentrations. These PS extracts can be useful to modulate some taste attributes such as an excess of acidity and bitterness and can also prevent the loss of volatile compounds associated with fruity and floral notes over time. This is the first study that shows the effects of grape polysaccharides on the chemical composition and sensory characteristics of white wines. Considering the obtained results, the grape pomace and surplus of musts can be considered valuable sources to obtain polysaccharide-rich products, opening a new opportunity to take advantage of by-products from the wine industry.

Studies of individuals under conditions of confinement or severe social and physical restrictions have consistently shown deleterious mental health effects but also high levels of adaptability when dealing with such conditions. Considering the role of physical activity and sport in psychological adaptation, this paper describes a longitudinal study to explore to what extent the imposed restrictions due to the outbreak of SARS-CoV-2 may have affected athletes’ mental health outcomes and how far the process of adaptation to confinement conditions is differentially affected depending on whether the sports activity was practiced individually or in a group, and outdoors, indoors, or both. Two hundred and seventy-four athletes were assessed over 7 weeks using the GHQ-28 and an ad hoc survey exploring the practice of physical activity. A mixed-model fixed effects ANCOVA was used to analyze the effects of time, place, and company in which the sport was practiced, with an index of the amount of physical activity expended as a covariate. Results show a significant effect of time in three out of four of the GHQ-28 subscales, in all cases showing a consistent adaptation to conditions over time. Results also show that playing sport indoors, outdoors, or both, and practicing alone vs. with others differentially affect the somatic symptoms exhibited during confinement: Athletes who practiced sport with others showed higher levels of somatic symptoms at the beginning of the set of data but a quicker rate of adaptation. Differences arising from practicing sport alone or with others were more pronounced in the case of indoor sports, which could be related to the fact that physical activity that can be practiced during confinement is more similar to that practiced indoors alone. Implications relating to what sport psychologists and other health professionals may offer to athletes in stressful situations are discussed.

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology. It is characterized by deposition of extracellular matrix proteins, like collagen and fibronectin in the lung interstitium leading to respiratory failure. Our understanding of the pathobiology underlying IPF is still incomplete; however, it is accepted that aging is a major risk factor in the disease while growing evidence suggests that the mitochondria plays an important role in the initiation and progression of pulmonary fibrosis. Mitochondria dysfunction and metabolic reprogramming had been identified in different IPF lung cells (alveolar epithelial cells, fibroblasts, and macrophages) promoting low resilience and increasing susceptibility to activation of profibrotic responses. Here we summarize changes in mitochondrial numbers, biogenesis, turnover and associated metabolic adaptations that promote disrepair and fibrosis in the lung. Finally, we highlight new possible therapeutic approaches focused on ameliorate mitochondrial dysfunction.

Introduction: Paired cohort investigations assessing the evolution of anthropometric indices are scarce. Here we assessed the 10-year evolution of BMI, total body fat, and lean body mass in 50,019 participants aged 18–90 years at the time of first assessment.Material and Methods: A retrospective cohort study using an electronic database that contains anonymized, longitudinal data from Primary Care medical records covering the 2007–2008 and 2017–2018 periods. Total body fat was estimated using the Clínica Universidad de Navarra-Body Adiposity Estimator formula, and the Hume formula was applied to estimate lean body mass.Results: The mean BMI of participants

Aim: The aim of this work was to determine the physico-chemical variables that differentiating red wines from the “Castilla y León” Spanish region by their Protected Designation of Origin (PDO) and wine category ("young", “oak”, “crianza”, or “reserve”). Methods and results: A total of 135 commercial red wines from four Spanish PDOs in the region of Castilla and León were analysed. Forty physico-chemical parameters, related to classical enological parameters, phenolic and polysacharidic composition, and content of higher alcohols were evaluated. Differences in physico-chemical composition were found in red wines from different PDOs and different categories. Stepwise linear discriminant analysis (SLDA) was applied to find a linear combination of the physico-chemical variables that separate and classify the red wines according to the PDO or category. One SLDA model selected 15 physico-chemical variables that allowed for good discrimination and classification of the wines from different PDOs. The SLDA model selected seven variables for wine category differentiation, but only allowed for good discrimination between young wines and aged wines (“crianza” and “reserve”). Conclusions: The variables that contributed most to the separation of Tempranillo red wines were total polyphenols, total tannins, and absorbance values at 230 nm and 280 nm. The polysaccharides with an average molecular weight of 10 kDa, flavanols, stilbenes and 2-methyl-1-butanol were those most associated with the differentiation of the wines elaborated with the Mencía grape variety. The percentage of polymeric anthocyanins and absorbance at 230 nm could be proposed as good indicators for aged wines, and total tannins for young wines. Significance and impact of the study: This study provides improved knowledge of the physico-chemical variables that could be used as markers of the origin of wines and/or the grape variety (Tempranillo and Mencía) and that allow differentiating young wines from those aged for a long time.

Aim: The aim of the work was to determine the physico-chemical variables that allow differentiating the red wines from “Castilla y León” Spanish region by their Protected Designation of Origin (PDO) and wine category (young, “oak”, “crianza”, “reserve”). Methods and results: One hundred and thirty five commercial red wines from four Spanish PDOs sited in the region of Castilla and León were analysed. Forty physico-chemical parameters, related with classical enological parameters, phenolic and polysacharidic composition, and content of higher alcohols were evaluated. Differences in physico-chemical composition were found in red wines from different PDOs and different category. Stepwise linear discriminant analysis (SLDA) was applied to find a linear combination of the physico-chemical variables that separate and classify the red wines according to the PDO or category. One SLDA model selected fifteen physico-chemical variables that allowed a good discrimination and classification of the wines from different PDOs, and the other selected seven variables that discriminate between young wines and aged wines (“crianza” and “reserve”). Conclusions: Total polyphenols, total tannins, and absorbance values at 230 nm and 280 nm were the variables that most contributed to the separation of Tempranillo red wines. Polysaccharides with an average molecular weight of 10 kDa, flavanols, stilbenes and 2-methyl-1-butanol were the most associated with the differentiation of the wines elaborated with Mencía grape variety. The percentage of polymeric anthocyanins and absorbance at 230 nm could be proposed as good indicators for aged wines, and total tannins for young wines. Significance and impact of the study: This study reports a better knowledge of the physico-chemical variables that could be used as markers of the origin of wines and/or the grape variety (Tempranillo and Mencía). This study also reports the physico-chemical variables that allow differentiating young wines from those aged for a long time.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease for which age is the most important risk factor. Different mechanisms associated with aging, including stem cell dysfunction, have been described to participate in the pathophysiology of IPF. We observed an extrapulmonary effect associated with IPF: increase in cell senescence of bone marrow-derived mesenchymal stem cells (B-MSCs). Methods B-MSCs were obtained from vertebral bodies procured from IPF patients and age-matched normal controls. Cell senescence was determined by cell proliferation and expression of markers of cell senescence p16INK4A, p21, and β-galactosidase activity. Mitochondrial function and DNA damage were measured. Paracrine induction of senescence and profibrotic responses were analyzed in vitro using human lung fibroblasts. The reparative capacity of B-MSCs was examined in vivo using the bleomycin-induced lung fibrosis model. Results In our study, we demonstrate for the first time that B-MSCs from IPF patients are senescent with significant differences in mitochondrial function, with accumulation of DNA damage resulting in defects in critical cell functions when compared with age-matched controls. Senescent IPF B-MSCs have the capability of paracrine senescence by inducing senescence in normal-aged fibroblasts, suggesting a possible link between senescent B-MSCs and the late onset of the disease. IPF B-MSCs also showed a diminished capacity to migrate and were less effective in preventing fibrotic changes observed in mice after bleomycin-induced injury, increasing illness severity and proinflammatory responses. Conclusions We describe extrapulmonary alterations in B-MSCs from IPF patients. The consequences of having senescent B-MSCs are not completely understood, but the decrease in their ability to respond to normal activation and the risk of having a negative impact on the local niche by inducing inflammation and senescence in the neighboring cells suggests a new link between B-MSC and the onset of the disease.

Weight loss after bariatric surgery decreases the earlier expansion of the adventitial vasa vasorum (VV), a biomarker of early atheromatous disease. However, no data are available regarding weight loss achieved by very low calorie ketogenic diets (VLCKD) on VV and lipid-based atherogenic indices. A randomized clinical trial was performed to examine changes in adventitial VV density in 20 patients with moderate obesity who underwent a 6-month very low calorie ketogenic diet (VLCKD, 600–800 kcal/day), and 10 participants with hypocaloric diet based on the Mediterranean Diet (MedDiet, estimated reduction of 500 kcal on the usual intake). Contrast-enhanced carotid ultrasound was used to assess the VV. Body composition analysis was also used. The atherogenic index of plasma (log (triglycerides to high-density lipoprotein cholesterol ratio)) and the triglyceride-glucose index were calculated. Serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. The impact of weight on quality of life-lite (IWQOL-Lite) questionnaire was administered. Participants of intervention groups displayed a similar VV values. Significant improvements of BMI (−5.3 [−6.9 to −3.6] kg/m2, p < 0.001), total body fat (−7.0 [−10.7 to −3.3] %, p = 0.003), and IWQOL-Lite score (−41.4 [−75.2 to −7.6], p = 0.027) were observed in VLCKD group in comparison with MedDiet group. Although after a 6-months follow-up period VV density (mean, right and left sides) did not change significantly in any group, participants in the VLCKD exhibited a significantly decrease both in their atherogenic index of plasma and serum concentration of sICAM-1. A 6-month intervention with VLCKD do not impact in the density of the adventitial VV in subjects with moderate obesity, but induces significant changes in markers of endothelial dysfunction and CV risk.

The quality of wines has often been associated with their geographical area of production, as well as the grape variety used in their elaboration. Many research studies have been carried out to characterize and differentiate between red wines labeled with Protected Designation of Origin (PDO) from different geographical areas, but very few have been carried out on white and rosé wines. The objective of this work was to characterize white and rosé PDO wines from different geographical areas of Spain very close to each other elaborated with different grape varieties and select the variables that most contribute to their differentiation. Analysis of variance (ANOVA) and principal component analysis (PCA) were used as statistical methods. The ethanol content was the nonvolatile variable that most contributed to differentiating between some of the white and rosé wines according to their PDO. The white wines from RD (Ribera del Duero) and BI (Bierzo) were characterized by a high terpenic content (floral notes) while the wines from RU (Rueda), TO (Toro) and CI (Cigales)by a high content of ethyl esters and alcohol acetates (fruity aromas). The rosé wines elaborated with the Mencía grape variety from BI were characterized by their highest polysaccharidic content, which could have a positive sensory effect on the mouthfeel. The rosé wines from CI were characterized by their volatile profile complexity, having the highest content of volatile compounds from the oak wood, terpenes and C6 alcohols which provide pleasant woody, floral and herbaceous aromas. On the contrary, the RD wines were richest in alcohol acetates responsible for fruity aromas.

Subjects with sleep apnea-hypopnea syndrome (SAHS) show an increased carotid intima-media thickness. However, no data exist about earlier markers of atheromatous disease, such as the proliferation and expansion of the adventitial vasa vasorum (VV) to the avascular intima in this setting. Our aim was to assess carotid VV density and its relationship with sleep parameters in a cohort of obese patients without prior vascular events. A total of 55 subjects evaluated for bariatric surgery were prospectively recruited. A non-attended respiratory polygraphy was performed. The apnea-hypopnea index (AHI) and the cumulative percentage of time spent with oxygen saturation below 90% (CT90) were assessed. Serum concentrations of soluble intercellular adhesion molecule 1, P-selectin, lipocalin-2 and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. Contrast-enhanced carotid ultrasound was used to assess the VV density. Patients with SAHS (80%) showed a higher adventitial VV density (0.801±0.125 vs. 0.697±0.082, p = 0.005) and higher levels of sVCAM-1 (745.2±137.8 vs. 643.3±122.7 ng/ml, p = 0.035) than subjects with an AHI lower than 10 events/hour. In addition, a positive association exist between mean VV density and AHI (r = 0.445, p = 0.001) and CT90 (r = 0.399, p = 0.005). Finally, in the multiple linear regression analysis, female sex, fasting plasma glucose and AHI (but not CT90) were the only variables independently associated with the mean adventitial VV density (R2 = 0.327). In conclusion, a high VV density is present in obese subjects with SAHS, and chronic intermittent hypoxia is pointed as an independent risk factor for the development of this early step of atheromatous disease.

We have previously shown that endoplasmic reticulum stress (ER stress) represses the PTEN inducible kinase 1 (PINK1) in lung type II alveolar epithelial cells (AECII) reducing mitophagy and increasing the susceptibility to lung fibrosis. Although increased circulating mitochondrial DNA (mtDNA) has been reported in chronic lung diseases, the contribution of mitophagy in the modulation of mitochondrial DAMP release and activation of profibrotic responses is unknown. In this study, we show that ER stress and PINK1 deficiency in AECII led to mitochondrial stress with significant oxidation and damage of mtDNA and subsequent extracellular release. Extracellular mtDNA was recognized by TLR9 in AECII by an endocytic-dependent pathway. PINK1 deficiency-dependent mtDNA release promoted activation of TLR9 and triggered secretion of the profibrotic factor TGF-β which was rescued by PINK1 overexpression. Enhanced mtDNA oxidation and damage were found in aging and IPF human lungs and, in concordance, levels of circulating mtDNA were significantly elevated in plasma and bronchoalveolar lavage (BAL) from patients with IPF. Free mtDNA was found elevated in other ILDs with low expression of PINK1 including hypersensitivity pneumonitis and autoimmune interstitial lung diseases. These results support a role for PINK1 mediated mitophagy in the attenuation of mitochondrial damage associated molecular patterns (DAMP) release and control of TGF-β mediated profibrotic responses.

At present, the etiology of idiopathic pulmonary fibrosis (IPF) remains elusive. Over the past two decades, however, researchers have identified and described the underlying processes that result in metabolic dysregulation, metabolic reprogramming, and mitochondrial dysfunction observed in the cells of IPF lungs. Metabolic changes and mitochondrial dysfunction in IPF include decreased efficiency of electron transport chain function with increasing production of reactive oxygen species, decreased mitochondrial biogenesis, and impaired mitochondrial macroautophagy, a key pathway for the removal of dysfunctional mitochondria. Metabolic changes in IPF have potential impact on lung cell function, differentiation, and activation of fibrotic responses. These alterations result in activation of TGF-β and predispose to the development of pulmonary fibrosis. IPF is a disease of the aged, and many of these same bioenergetic changes are present to a lesser extent with normal aging, raising the possibility that these anticipated alterations in metabolic processes play important roles in creating susceptibility to the development of IPF. This review explores what is known regarding the cellular metabolic and mitochondrial changes that are found in IPF, and examines this body of literature to identify future research direction and potential points of intervention in the pathogenesis of IPF.

Helicobacter pylory (HP) infection has been associated to an increased rate of type 2 diabetes (T2D) and liver disease through its effect on insulin resistance and systemic inflammation. However, results are inconstant and no studies exist in morbidly obese patients, in which both insulin resistance and inflammation coexist.Cross-sectional study to evaluate the relationship between HP infection and alterations in carbohydrate metabolism, lipid profile, inflammation markers, and liver disease in patients awaiting for bariatric surgery. HP infection was histologically assessed in gastric antrum biopsy from 416 subjects. Liver biopsy was also available in 93 subjects.Both impaired fasting glucose and T2D were similar when comparing subjects with and without HP infection (24.2% vs. 22%, p = 0.290 and 29.4% vs. 29.1%, p = 0.916, respectively), with no differences between groups in the HOMA-IR, lipid profile neither inflammatory parameters. However, HP infection was higher among subjects with a BMI ≥ 40.0 kg/m2 in comparison with lower degrees of obesity (71.7% vs. 60.0%, p = 0.041). In addition, subjects without HP infection showed higher degrees of steatosis (44.1±26.4% vs. 32.0±20.7%, p = 0.038), as well as a lower prevalence of non-alcoholic steatohepatitis (9.3% vs. 30.7%, p = 0.023).In patients with morbid obesity, HP infection does not seem to be associated with abnormal carbohydrate metabolism. In addition, less advanced degrees of non-alcoholic fatty disease were observed. We suggest that low-grade inflammation that accompanies obesity mitigates the diabetogenic effect of HP, so the presence of obesity should be considered in studies that evaluate the HP metabolic effects.

Prader-Willi syndrome (PWS) is characterized by severe hyperphagia. Brain-derived neurotrophic factor (BDNF) and leptin are reciprocally involved in energy homeostasis.To analyze the role of BDNF and leptin in satiety in genetic subtypes of PWS.Experimental study.University hospital.90 adults: 30 PWS patients; 30 age-sex-BMI-matched obese controls; and 30 age-sex-matched lean controls.Subjects ingested a liquid meal after fasting ≥10 hours.Leptin and BDNF levels in plasma extracted before ingestion and 30', 60', and 120' after ingestion. Hunger, measured on a 100-point visual analogue scale before ingestion and 60' and 120' after ingestion.Fasting BDNF levels were lower in PWS than in controls (p = 0.05). Postprandially, PWS patients showed only a truncated early peak in BDNF, and their BDNF levels at 60' and 120' were lower compared with lean controls (p

Proteins perform many useful molecular tasks, and their biotechnological use continues to increase. As protein activity requires a stable native conformation, protein stabilisation is a major scientific and practical issue. Towards that end, many successful protein stabilisation strategies have been devised in recent years. In most cases, model proteins with a two-state folding equilibrium have been used to study and demonstrate protein stabilisation. Many proteins, however, display more complex folding equilibria where stable intermediates accumulate. Stabilising these proteins requires specifically stabilising the native state relative to the intermediates, as these are expected to lack activity. Here we discuss how to investigate the ‘relevant’ stability of proteins with equilibrium intermediates and propose a way to dissect the contribution of side chain interactions to the overall stability into the ‘relevant’ and ‘nonrelevant’ terms. Examples of this analysis performed on apoflavodoxin and in a single-chain mini antibody are presented.