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Abstract Background The EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project (IMI2-853966) aimed to develop tools to establish integrated research platforms (IRP) for conducting adaptive-design trials in various diseases, including metabolic-dysfunction associated steatohepatitis (MASH). One essential component of a successful MASH IRP is a robust and reliable Clinical Research Network (CRN). Herein, we outline the required elements and anticipated steps to set-up such a CRN. Methods We identified European clinical research sites that could potentially serve as the foundation for MASH IRP and a CRN. A survey was sent to sites to assess their interest in joining a CRN, their familiarity with platform trials, and their capacity to participate in a future MASH IRP. Results A total of 141 investigators were invited to participate in the survey, and 40% responded. More than half of the answers (52%) identify MASH with advanced fibrosis (F3-4) as the subpopulation with the greatest unmet need. Regarding the difficulty in identifying candidates for trials, 65% find it is moderately difficult and 30% very difficult. Most respondents (94%) believe that a platform trial could offer substantial benefits to patients. Nearly all researchers express interest in participating in a platform trial (78%), with 22% indicating their interest would be contingent on initial industry funding. Conclusion While preliminary, our findings on responding sites are encouraging for the potential establishment of a CRN for a MASH IRP. However, funding schemes and sustainability strategies to provide proof-of-platform in MASH seem key in the short-term scenario.

Background & Aims: Expression of P21, encoded by the CDKN1A gene, has been associated with fibrosis progression in steatotic liver disease (SLD); however, the underlying mechanisms remain unknown. In the present study, we investigated the function of CDKN1A in SLD. Methods: CDKN1A expression levels were evaluated in different patient cohorts with SLD, fibrosis, and advanced chronic liver disease (ACLD). Cdkn1a-/- and Cdkn1a+/+ mice were fed with either a Western diet (WD), a Lieber-DeCarli (LdC) diet plus multiple EtOH (ethanol) binges, or a DuAL diet (metabolic dysfunction-associated fatty liver disease and alcohol-related liver). Primary hepatocytes were isolated and functional assays performed. Results: A significant increase in CDKN1A expression was observed in patients with steatohepatitis and fibrosis (with a positive correlation with both NAFLD Activity Score and fibrosis staging scores), cirrhosis and ACLD. Cdkn1a+/+ mice, fed a DuAL diet exhibited liver injury and cell death increased reactive oxygen species (ROS), and markers of senescence (γH2AX, β-GAL, Cdkn1a/p53) contributing to steatosis and inflammation. In contrast, Cdkn1a-/- mutant mice showed a significant decrease in senescence-associated markers as well as in markers of liver injury, hepatic steatosis and an increase in fatty acid oxidation and reduction in free fatty acid uptake as well as de novo lipogenesis. Mechanistically, activation of the AMPK-SIRT3 was observed in Cdkn1a-deleted animals. Conclusions: Cdkn1a deletion protected against preclinical SLD by promoting fatty acid oxidation and preventing free fatty acid uptake and de novo lipogenesis via the AMPK-SIRT3 axis. CDKN1A expression was found to be directly correlated with increased severity of NAFLD Activity Score and fibrosis in patients with SLD. CDKN1A could be a potential theragnostic target for the treatment of metabolic dysregulation in patients with SLD, with and without alcohol consumption. Impact and implications:: Expression of p21, encoded by the CDKN1A gene, has been associated with fibrosis progression in steatotic liver disease (SLD), but the molecular mechanisms remain elusive. Interestingly, in this study we found that Cdkn1a deletion protected against preclinical SLD by promoting fatty acid oxidation and preventing free fatty acid uptake and de novo lipogenesis, via the AMPK-SIRT3 axis. Translationally, Cdkn1a expression was found to be directly correlated with increased severity of NAFLD Activity Score (NAS) and fibrosis in SLD patients, and therefore, CDKN1A might be used potential theragnostic target for the treatment of metabolically induced SLD, with and without alcohol consumption.

Abstract Progressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS−/−) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl4) intoxication and bile duct ligation (BDL). In wild-type (N-RAS+/+) mice both hepatotoxic procedures augmented N-RAS expression in the liver. Compared to N-RAS+/+ counterparts, N-RAS−/− mice subjected to either CCl4 or BDL showed exacerbated liver injury and fibrosis, which was associated with enhanced hepatic stellate cell (HSC) activation and leukocyte infiltration in the damaged liver. At the molecular level, after CCl4 or BDL, N-RAS−/− livers exhibited augmented expression of necroptotic death markers along with JNK1/2 hyperactivation. In line with this, N-RAS ablation in a human hepatocytic cell line resulted in enhanced activation of JNK and necroptosis mediators in response to cell death stimuli. Of note, loss of hepatic N-RAS expression was characteristic of chronic liver disease patients with fibrosis. Collectively, our study unveils a novel role for N-RAS as a negative controller of the progression of liver injury and fibrogenesis, by critically downregulating signaling pathways leading to hepatocyte necroptosis. Furthermore, it suggests that N-RAS may be of potential clinical value as prognostic biomarker of progressive fibrotic liver damage, or as a novel therapeutic target for the treatment of chronic liver disease.

Objective: To compare, from an empirical point of view, the use of focus group and photovoice as we conducted two studies on food environment in neighbourhoods with different socio-economic profiles. Method: The European project Heart Healthy Hoods studied the association between the physical and social environment of Madrid (Spain) and the cardiovascular health of its residents. Two ancillary studies were developed to further expand the study of urban health inequalities using focus group and photovoice. Both studies, similar in their objectives and study populations, are the basis for comparing both techniques. The comparison considered the following methodological aspects: study design, logistic aspects, commitment and involvement, ethical issues, and data analysis. Results: We identified differences, similarities, potentialities, and limitations of each technique with their corresponding results. We found that depending on the research objectives, one technique was more beneficial than the other. If the objective is producing new knowledge, using focus group would be the most appropriate technique, whereas if the objective includes generating social change, photovoice would be more suitable. We found that photovoice is a powerful technique in public health, especially studying social processes related to population health, requiring extra effort from researchers and a special care with the related ethical considerations. Conclusions: Increasing participants’ awareness, involving decision makers to channel proposals, the atypical role of researchers and ethical implications of photography are aspects to be considered when choosing photovoice instead of focus group. Resumen: Objetivo: Comparar empíricamente el uso del grupo focal y el fotovoz en investigación sobre el entorno alimentario en barrios con diferente perfil socioeconómico. Método: El proyecto europeo Heart Healthy Hoods estudió la asociación entre el entorno físico y social de Madrid y la salud cardiovascular de sus residentes. Dentro de él se desarrollaron dos estudios para analizar las desigualdades en salud utilizando las técnicas del grupo focal y el fotovoz. Ambos estudios, similares en sus objetivos y población diana, fueron la base para comparar las dos técnicas. Consideramos los siguientes aspectos metodológicos: diseño, aspectos logísticos, compromiso e implicación del equipo investigador y de las personas participantes, cuestiones éticas y análisis de los datos. Resultados: Identificamos diferencias, similitudes, potencialidades y limitaciones de cada técnica utilizada con sus correspondientes resultados. Dependiendo de los objetivos, una técnica sería más beneficiosa que la otra. Si el objetivo es producir nuevo conocimiento, el grupo focal sería la técnica más adecuada, mientras que, si el objetivo incluye generar cambio social, el fotovoz sería más apropiado. Consideramos el fotovoz una técnica muy provechosa para la investigación en salud pública, especialmente para estudiar procesos sociales en relación con la salud de la población, aunque requiere un esfuerzo adicional por parte del equipo investigador y de los participantes, y un cuidado especial con las consideraciones éticas. Conclusiones: Aumentar la conciencia de las personas participantes, involucrar a decisores políticos para canalizar las propuestas resultantes, el papel atípico del equipo investigador y las implicaciones éticas de la fotografía son aspectos a considerar si elegimos el fotovoz frente al grupo focal.

La formación del profesorado sobre la especificidad de las escuelas situadas en territorios rurales se torna necesaria y clave para hacer frente a la imagen sesgada, victimizada y desvirtuada que se difunde en los medios de comunicación, en las políticas educativas neoconservadoras y en los manuales didácticos. Parte del cambio está en la inclusión de la realidad de estas escuelas en los planes formativos de los Grados de Educación Infantil y Educación Primaria, con la finalidad de dotar al futuro profesorado de conocimientos, habilidades y actitudes que les permita desarrollar prácticas educativas conectadas y coherentes a la casuística de cada territorio rural. Esto debe ser enfocado desde una triple vertiente: organizativo, didáctico-curricular y sociocultural. La sostenibilidad de los territorios rurales depende en parte del ejercicio profesional del profesorado que puede contribuir al arraigo y a la fijación de la población para prevenir el fenómeno de la España vaciada.

Abstract The present work aims to characterize the ephemeral mineral assemblage related to the fumarolic fields of the Tajogaite volcano, formed in 2021 in La Palma Island (Canary Islands, Spain). A set of 73 samples was obtained after two sampling campaigns in different fumarole sectors of the studied area. Mineralization related to these fumaroles formed efflorescent patches located at variable distance from the main volcanic craters. Distal patches are predominantly whitish, while in the vicinities they typically show yellowish to orange colours. Field observations also revealed that fumaroles usually occur in elevated topographic areas as well as over fractured and porous volcanic pyroclastic materials. The mineralogical and textural characterisation of the Tajogaite fumaroles unfolds a complex mineral assemblage, comprising cryptocrystalline phases related to low (

AbstractAlcohol consumption in unlicensed public places has become a topic of intense debate in Spain due to its negative impact on health and social outcomes, and the inefficiency of current alcohol policies. This research aimed to explore the perceptions of individuals aged 40 and over regarding alcohol consumption in unlicensed public places in socioeconomically diverse neighbourhoods in Madrid. 37 semi-structured interviews and 29 focus groups were conducted in three neighbourhoods with different socioeconomic statuses. The analysis drew on Corbin and Strauss’s grounded theory coding strategies. The findings of the study showed that people aged 40 and over problematised alcohol consumption in unlicensed public places, such as parks and squares. The problematisation followed a two-step process. Initially, non-compliance with current restrictions on alcohol sales during the night-time in convenience stores, including the sale of alcohol to minors, was identified as an issue. This, in turn, led to alcohol consumption in unlicensed public places, which was associated with negative outcomes such as alcohol-related litter, noise nuisance, and violence. These consequences were disproportionally perceived in the least affluent neighbourhood. To address the disproportionate impact of alcohol-related behaviours in the least affluent neighbourhoods, reinforcing existing alcohol sales policies is warranted. This may reduce alcohol consumption in unlicensed public places and its related negative outcomes.

Abstract The natural history of compensated cirrhosis due to nonalcoholic fatty liver disease (NAFLD) has not been completely characterized. The aim of the present study was to assess the incidence and risk factors of acute decompensation of cirrhosis, hepatocellular carcinoma, and extrahepatic cancers. This was a multicenter, retrospective, cohort study including 449 patients with compensated cirrhosis due to NAFLD. We calculated cumulative incidences and used competitive risk analysis to determine the risk factors associated with decompensation and cancer development. Over a median of 39 months of follow‐up, 124 patients (28%) presented acute decompensation. The most frequent decompensation was ascites (21%) followed by hepatic encephalopathy (15%), variceal bleeding (9%), and spontaneous bacterial peritonitis (3%). Acute‐on‐chronic liver failure was diagnosed in 6% of patients during follow‐up. Liver function parameters and specifically an albumin level below 40 g/L were independently associated with an increased risk of decompensation. The presence of ischemic heart disease was independently associated with acute decompensation. Seventy‐eight patients (18%) developed hepatocellular carcinoma or extrahepatic cancers during follow‐up (51 and 27, respectively). Conclusion: Patients with compensated cirrhosis due to NAFLD are at high risk of severe liver complications, such as the development of acute decompensation, in a relative short follow‐up time. This population is at high risk of hepatic and extrahepatic cancers.

Resumen: Objetivo: Investigar la prevalencia de la morbilidad metabólica (MM) en población penitenciaria. Diseño: Estudio observacional, transversal y multicéntrico. Emplazamiento: Los 9 centros penitenciarios de Cataluña. Participantes: Reclusos que no están en «régimen abierto» y, por consiguiente, dependen sanitariamente de los equipos de atención primaria penitenciaria (EAPP). Intervenciones: Se consideraron internos con MM los que presentaban al menos un componente del síndrome metabólico: obesidad, hipertensión arterial, diabetes tipo 2 y/o dislipidemia. Se estudiaron variables antropométricas, antecedentes clínicos y parámetros analíticos asociados a la MM. Fuente de información: Sistema de Información de los Servicios de Atención Primaria de Cataluña (SISAP). Mediciones principales: Cálculo de prevalencia de la MM, total y por categorías. Para estudiar variables asociadas se realizó un análisis de regresión logística multivariante, calculándose la odds ratio ajustada (ORA) con intervalo de confianza del 95%. Resultados: Un total de 4.338 internos estudiados: el 93,9% hombres, edad media 38,4 años, 51,7% de la Unión Europea y 6,7% (8,2% de los analizados) infectados por VIH. Presentaron más MM los de más edad y las personas infectadas por VIH y menos los europeos de países no miembros de la Unión Europea, los del Magreb y los del África subsahariana. Conclusiones: La prevalencia de MM es alta en presos, aun siendo una población joven, especialmente en reclusos de mayor edad y en infectados por VIH. La prevalencia varía mucho según el origen geográfico. Es conveniente que la MM sea detectada precozmente para evitar complicaciones. La prevención, la detección y el manejo terapéutico deben ser actividades prioritarias de la atención primaria penitenciaria. Abstract: Objective: To investigate the prevalence of metabolic morbidity (MM) amongst prison inmates. Design: Multicentric, cross-sectional observational study. Setting: All (nine) prisons in Catalonia. Participants: Convicted inmates that are not in an «open regime», whose healthcare relies on the Prison Primary Care Teams. Interventions: MM was defined as the presence of at least one component of the metabolic syndrome, i.e., obesity, arterial hypertension, type 2 diabetes, and/or dyslipidemia. The variables collected included anthropometric measurements, medical history and laboratory values related to MM. The source of information was the Catalan Primary Healthcare Services Information System (SISAP). Main measurements: The prevalence of MM, overall and by several participant subcategories, was calculated. To investigate the risk factors associated to a higher prevalence of MM, a multivariable logistic regression analysis was carried out and expressed as adjusted odds ratios and 95% confidence intervals. Results: 4338 inmates were studied, of whom 93.9% were male. Mean age was 38.4 years, 51.7% were born in European Union countries, and 6.7% were infected by HIV. The variables associated with a significantly increased risk of presenting MM were older age and HIV infection, whereas certain geographical origins (i.e., non-UE European countries, Maghreb and Sub-Saharan Africa) were associated with lower risk of MM. Conclusions: In spite of being an overall young population, prison inmates present high rates of MM. Older age, HIV infection and geographic origin appear as the most strongly associated factors with MM in the prison population. MM should be detected early in order to prevent complications. Prevention, screening and treatment of MM ought to be considered a priority in the clinical routine of prison healthcare professionals.

Abstract Introduction Non‐alcoholic fatty liver disease (NAFLD) has become a significant concern among people living with HIV (PLHIV), albeit its burden remains unclear. The primary objective of this systematic review (SR) and meta‐analysis (MA) was to estimate the prevalence of NAFLD and significant fibrosis in PLHIV. The secondary objective was to determine the risk factors for NAFLD among PLHIV. Methods We searched MEDLINE and Scopus from inception to 30 December 2022 for peer‐reviewed studies that included PLHIV and reported the prevalence of NAFLD. MA of proportions was used to estimate the pooled prevalence of NAFLD and significant fibrosis. MA of pre‐calculated effect estimates examined risk factors for NAFLD in PLHIV. Results We included 24 articles published between 2009 and 2022, encompassing 6326 PLHIV. The pooled prevalence of NAFLD was 38% (95% CI: 31–45%) with high heterogeneity (I2 = 96.3%). The pooled prevalence of significant fibrosis was 13% (95% CI: 8–18%) with high heterogeneity (I2 = 92.09%). Subgroup analyses showed a NAFLD prevalence of 40% (95% CI: 24–57%) in the United States, 33% (95% CI: 31–36) in Asia, 42% (95% CI: 24–61%) in Europe and 33% (95% CI: 29–37) in South America. When stratifying by income level, NAFLD was 39% (95% CI: 31–48) prevalent in PLHIV from high‐income economies and 34% in both upper‐middle‐income (95% CI: 31–37%) and lower‐middle‐income economies (95% CI: 28–41%). Higher body mass index (BMI) (OR = 1.32, 95% CI: 1.13–1.55; I2 = 89.9%), increasing triglycerides (OR = 1.48, 95% CI: 1.22–2.79; I2 = 27.2%) and dyslipidaemia (OR = 1.89, 95% CI: 1.32–2.71; I2 = 15.5%) were all associated with higher risk‐adjusted odds of NAFLD in PLHIV. Discussion The burden of NAFLD and significant fibrosis in PLHIV is significant. Therefore, targeted efforts to screen and diagnose NAFLD in this population are needed. Health services for PLHIV could include ways to target NAFLD risk factors, screen for liver disease and implement interventions to treat those with significant fibrosis or more advanced stages of liver disease. Taking no action to address NAFLD in PLHIV should not be an option. Conclusions This SR and MA found a 38% NAFLD and 13% significant fibrosis prevalence in PLHIV. Increasing triglyceride levels, higher BMI values and dyslipidaemia were associated with higher risk‐adjusted odds of NAFLD among PLHIV.

Objective: To describe the design and methodology of a qualitative study to explore the main factors influencing dietary inequalities in adolescents in Madrid and Bilbao, Spain. Method: The study area included six neighborhoods (three in each city) of different socioeconomic status (SES): low, medium, and high. We sampled 12 secondary schools (six in each city: two per socioeconomic level). Our methodology comprised: 1) developing an ad hoc index to classify all neighborhoods according to their SES; 2) selecting the study area and sample; 3) conducting semi-structured interviews (n = 36) and focus groups (n = 24). Grounded theory and phenomenological analysis will be employed in data analysis. Initially, we found factors influencing in adolescents’ diet such as gender, family environment, and SES. Conclusions: Systematizing the selection of neighborhoods and secondary schools, along with using appropriate methods, could serve as a foundation for future studies on health inequalities among adolescents. Resumen: Objetivo: Describir el diseño y la metodología de un estudio cualitativo que explora los factores principales que influyen en la desigualdad alimentaria en los adolescentes en Madrid y Bilbao, España. Método: Se seleccionaron seis barrios (tres en cada ciudad) de diferente estatus socioeconómico (ESE): bajo, medio y alto. Obtuvimos una muestra de 12 institutos (seis en cada ciudad y dos por nivel socioeconómico). La metodología consistió en: 1) desarrollo de un índice ad hoc para clasificar los barrios según su ESE; 2) selección de las áreas de estudio y de institutos; 3) realización de entrevistas semiestructuradas (n = 36) y grupos de discusión (n = 24). En el análisis se utilizarán la teoría fundamentada y el análisis fenomenológico. Inicialmente, encontramos factores que influyen en la alimentación de los adolescentes, como el género, el entorno familiar y el ESE. Conclusiones: La sistematización en la selección de barrios e institutos, y la utilización de metodología adecuada, pueden servir como base para futuros estudios sobre las desigualdades de salud en adolescentes.

Background & Aims: The COVID-19 pandemic has had a major negative impact on health systems and many chronic diseases globally. We aimed to evaluate the impact of the first year of the pandemic on the outcomes of people with NAFLD cirrhosis. Methods: We conducted a before-after study in four University hospitals in Catalonia, Spain. Study subperiods were divided into Pre-pandemic (March/2019–February/2020) vs. Pandemic (March/2020–February/2021). The primary outcome was the rate of first liver-related event (LRE). Overall clinical outcomes (LREs plus cardiovascular plus all-cause mortality) were also assessed. Results: A total of 354 patients were included, all of whom were compensated at the beginning of the study period; 83 individuals (23.5%) had a history of prior hepatic decompensation. Mean age was 67.3 years and 48.3% were female. Median BMI was 31.2 kg/m2 and type 2 diabetes was present in 72.8% of patients. The rates of first LRE in the Pre-pandemic and Pandemic periods were 7.4% and 11.3% (p = 0.12), respectively. Whilst the rate of overall events was significantly higher in the Pandemic period (9.9% vs. 17.8%; p = 0.009), this was strongly associated with COVID-19-related deaths. The rate of worsened metabolic status was significantly higher in the Pandemic period (38.4% vs. 46.1%; p = 0.041), yet this was not associated with the risk of first LRE during the Pandemic period, whereas type 2 diabetes (odds ratio [OR] 3.77; 95% CI 1.15–12.32; p = 0.028), albumin 2.67 (OR 15.74; 95% CI 2.01–123.22; p = 0.009) were identified as risk factors in the multivariable analysis. Conclusion: Overall, people with NAFLD cirrhosis did not present poorer liver-related outcomes during the first year of the pandemic. Health system preparedness seems key to ensure that people with NAFLD cirrhosis receive appropriate care during health crises. Lay summary: Mobility restrictions and social stress induced by the COVID-19 pandemic have led to increased alcohol drinking and worsened metabolic control (e.g., weight gain, poor control of diabetes) in a large proportion of the population in many countries. We aimed to analyze whether people with cirrhosis due to non-alcoholic fatty liver disease, who are particularly vulnerable to such lifestyle modifications, were significantly impacted during the first year of the pandemic. We compared the clinical situation of 354 patients one year before the pandemic and one year after. We found that although metabolic control was indeed worse after the first year of the pandemic and patients presented worse clinical outcomes, the latter was mostly due to non-liver causes, namely COVID-19 itself. Moreover, the care provided to these patients did not worsen during the first year of the pandemic.

El dolor crónico no oncológico (DCNO) es un problema de salud bastante extendido que transforma la rutina diaria de quienes lo padecen y de quienes les rodean. Este estudio busca conocer la influencia del padecimiento de DCNO en la calidad de vida del enfermo/a y de su cuidador/a principal en el entorno familiar. Se ha aplicado un diseño metodológico cualitativo a través de entrevistas semiestructuradas a personas que padecen DCNO (n=9) y a cuidadores/as principales del entorno familiar de personas con este problema de salud (n=8). Los resultados han mostrado que la situación de dolor-cuidado influye negativamente en la calidad de vida de las personas que padecen esta condición y de quienes las cuidan. El apoyo del cuidador/a principal es esencial para el afrontamiento de la situación, pero conlleva un impacto negativo en la salud de las personas, en especial en las mujeres, que ejercen las tareas de cuidados.

IntroductionNon-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developed countries, with its incidence growing parallel to the epidemics of obesity and type 2 diabetes mellitus (T2DM). Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are becoming a cornerstone in the management of cardiovascular health and some studies suggest the potential role in NAFLD. However, patients under treatment with SGLT2i are at risk of developing genitourinary fungal infections (GFIs). Moreover, both NAFLD and SGLT2i have a strong influence on the immune system, and therefore the risk of infections other than GFIs could be increased in NAFLD patients treated with SGLT2i. We aimed to examine the possible association of SGLT2i with infections and hepatic outcomes in NAFLD patients.MethodsWe conducted a case-control study including NAFLD patients with T2DM visited at the Liver Unit outpatient clinic from 2016 to 2021 with a minimum follow-up of 6 months by selecting 65 patients receiving SGLT2i and 130 matched patients with other types of antidiabetic treatment.ResultsDuring follow-up, GFIs were significantly higher in the SGLT2i group (15.4% vs. 3.8%; p=0.008), whereas there were no differences in the occurrence of overall infections (41.5% vs. 30%; p=0.1) nor in other types of specific infections. In the multivariable analysis, treatment with SGLT2i was not independently associated with higher odds of overall infection. On the other hand, SGLT2i patients showed a significantly lower incidence of hepatic events (1.5% vs. 10.7%; p=0.02). There were no significant different in all-cause mortality between cases and controls.ConclusionsNAFLD patients with T2DM receiving SGLT2i more frequently presented GFIs, whereas the incidence of other types of infections was not found to be higher than in other patients with NAFLD and T2DM treated with other drugs. Moreover, SGLT2i-treated patients had a lower occurrence of hepatic events. Further studies are warranted to validate our data.

Este trabajo, mediante el uso de técnicas de investigación cualitativas -entrevistas semi-estructuradas a personas dependientes, cuidadores formales e informales y empleados públicos, privados o del tercer sector-, tiene como objetivo analizar las diferencias y similitudes existentes en las posiciones discursivas sobre cómo se efectúa la provisión de cuidados a los mayores dependientes en función de hábitat de residencia. Los resultados muestran que la inexistencia o inadecuación de recursos formales en los municipios rurales origina relatos que resaltan el peso de las atenciones familiares precisadas por los mayores dependientes. A su vez, la tradicional red informal de cuidados se percibe como debilitada en las zonas rurales debido al envejecimiento, los procesos migratorios campo-ciudad y las transformaciones sociales, familiares y culturales acontecidas desde el último tercio del siglo XX.

Background & Aims: Integrin α4β7 mediates lymphocyte trafficking to the gut and gut-associated lymphoid tissues, a process critical for recruitment of effector lymphocytes from the circulation to the gut mucosa in inflammatory bowel disease (IBD) and murine models of intestinal inflammation. Antibody blockade of β7 integrins generally is efficacious in IBD; however, some patients fail to respond, and a few patients can experience exacerbations. This study examined the effects of loss of β7 integrin function in murine models of IBD. Methods: In a mouse IBD model caused by lack of interleukin 10, a cytokine important in CD25hiFoxP3+ regulatory T cell (Treg) function, genetic deletion of β7 integrin or antibody blockade of α4β7–mucosal addressin cell adhesion molecule-1 interaction paradoxically exacerbated colitis. Results: Loss of β7 impaired the capacity of Tregs homing to the gut and therefore suppress intestinal inflammation in an adoptive T-cell transfer model; however, the intrinsic suppressive function of β7-deficient Tregs remained intact, indicating that the β7 deficiency selectively impacts gut homing. Deletion of β7 integrin did not worsen colitis in an acute dextran sodium sulfate model in which Treg number and function were normal. Conclusions: In Integrin subunit beta (Itgb)7-/-Il10-/- mice, loss of β7-dependent Treg homing to gut-associated lymphoid tissues combined with loss of intrinsic Treg function exacerbated intestinal inflammation. These results suggest that IBD patients with reduced CD25hiFoxP3+ Treg numbers or function or lack of interleukin 10 could be at risk for failure of α4β7 blocking therapy. Keywords: Integrin β7 Blockade, Inflammatory Bowel Disease, Regulatory T Cells, Gut-Associated Lymphoid Tissue

Objective: Qualitative methods may help to understand features related to health urban inequalities as a way to include citizens’ perceptions of their neighbourhoods in relation to their health-related behaviours. The aim of this article is to describe the methods and design of a qualitative urban health study. Methods: The Heart Healthy Hoods (HHH) analyses cardiovascular health in an urban environment using mixed methods: electronic health records, quantitative individual questionnaires, physical examination, semi-structured Interviews (SSIs), focus groups (FGs) and participatory technics such as photovoice. This article focuses on the HHH qualitative methods and design. A case study was used to select three neighbourhoods in Madrid with different socioeconomic levels: low, medium, and high. The selection process for these three neighbourhoods was as follows: classification of all Madrid's neighbourhoods (128) according to their socioeconomic level; after ranking this classification, nine neighbourhoods, three by socioeconomic level, were short-listed; different urban sociology criteria and non-participant observation were used for the final selection of three neighbourhoods. After selecting the three neighbourhoods, thirty SSIs were held with residents and six SSIs were held with key informants. Finally, twenty-nine FGs will be conducted over the course of 8 months, between May and December of 2018. Conclusions: Systematization in the selection of neighbourhoods and the use of adequate techniques are essential for the qualitative study of urban health inequalities. Resumen: Objetivo: La metodología cualitativa puede ayudar a entender aspectos relacionados con las desigualdades en salud urbana, incluyendo la percepción de los ciudadanos de su barrio en relación con los comportamientos relacionados con su salud. El objetivo de este artículo es describir los métodos y el diseño de un estudio cualitativo sobre salud urbana. Método: Heart Healthy Hoods (HHH) es un estudio que analiza la salud cardiovascular en un ámbito urbano, utilizando métodos mixtos: registros electrónicos de salud, cuestionarios individuales cuantitativos, exploraciones físicas, entrevistas semiestructuradas (ESE), grupos de discusión (GD) y técnicas participativas como el fotovoz. Este artículo se centra en los métodos y el diseño de la fase cualitativa del HHH. Se aplicó un estudio de caso, seleccionando tres barrios de Madrid con diferente nivel socioeconómico: bajo, medio y alto. El proceso de selección para estos tres barrios fue el siguiente: clasificación de todos los barrios de Madrid (128) según su nivel socioeconómico; tras graduar la clasificación se seleccionaron nueve barrios de Madrid, tres por nivel socioeconómico; se utilizaron diferentes criterios de sociología urbana y observación no participante para la selección final de tres barrios. Tras la elección de los tres barrios, se realizaron 30 ESE a vecinos y 6 ESE a informantes clave. Finalmente, se están organizando 29 GD con vecinos durante 8 meses, entre mayo y diciembre de 2018. Conclusiones: La sistematización en la selección de barrios y la utilización de las técnicas adecuadas son fundamentales para el estudio cualitativo de las desigualdades en el entorno urbano. Keywords: Qualitative method, Urban health, Health inequalities, Neighbourhoods, Palabras clave: Metodología cualitativa, Salud urbana, Desigualdades en salud, Barrios

Abstract Aim To analyse the perception that immigrant women caregivers have of their relationship with the person receiving the care and their family and the possible impact those relationships may have on a caregiver's health. Design A qualitative study was conducted. Methods Thirty‐four semi‐structured interviews were applied in the Spanish city of Salamanca from November 2015–November 2016. The “interpretative hermeneutics” technique was used as the framework for the analysis. Results The discourse studied indicated that the immigrant women's cultural background, as well as their gender's assumed stereotypes, gave rise to an emotional attachment to the person receiving the care, which could generate a burden. Most of the women interviewed reported situations of abuse from the old people under their care. The fact that increasingly more old people are being cared for by immigrant women renders it necessary for social and health policies to consider this collective.

El sistema de frenos de un automóvil debe satisfacer un conjunto complejo de requerimientos importantes, tales como la seguridad vial, la cual se basa en función del arreglo geométrico y el tipo de material. El objetivo de este trabajo es proponer un nuevo arreglo geométrico para la optimización del flujo de aire en un disco de freno automotriz, teniendo en cuenta pilares de ventilación fundamentados en perfiles aerodinámicos tipo NACA 66-209. Para sustentar esta propuesta de diseño, se llevó a cabo la construcción de un prototipo a escala 1:1 por medio de manufactura aditiva y al igual que el diseño de una instalación que permite el montaje del disco para medir el campo de velocidades generado en la zona de succión y descarga mediante el uso de la Velocimetría por Imágenes de Partícula (VIP). La validación del arreglo geométrico se efectuó bajo cinco (5) condiciones de velocidad angular: 541, 641, 741, 841 y 941 rpm. Los resultados obtenidos muestran la optimización de la velocidad del aire en la zona de de carga de 0,1151 y 0,2317 m/s a 35 rpm por evidenciar la importancia de diseños experimentales con los cuales se pueda mejorar la geometría de los frenos de disco, autoventilados y de esta manera garantizar la eficiencia y seguridad del sistema.

Smoke-free legislations aim to protect non-smokers from second-hand smoke (SHS) exposure and improve population health outcomes. The aim of this study was to explore residents’ perceptions to understand how people living in distinctive SES neighborhoods are differently affected by comprehensive smoke-free laws in a large city like Madrid, Spain.We conducted a qualitative project with 37 semi-structured interviews and 29 focus group discussions in three different SES neighborhoods within the city of Madrid. Constructivist grounded theory was used to analyze the transcripts.One core category arose in our analyses: Neighborhood inequalities in second-hand smoke (SHS) exposure in outdoor places. The enactment of the comprehensive smoke-free law resulted in unintended consequences that affected neighborhoods differently: relocation of smokers to outdoor setting, SHS exposure, noise disturbance and cigarette butt littering. Changes in the urban environment in the three neighborhoods resulted in the denormalization of smoking in outdoor public places, which was more clearly perceived in the high SES neighborhood. Changes in the built environment in outdoor areas of hospitality venues were reported to actually facilitate smoking. Comprehensive smoke-free laws resulted in denormalization of smoking, which might be effective in reducing SHS exposure. Extending smoking bans to outdoor areas like bus stops and hospitality venues is warranted and should include a public health inequalities perspective.

The analysis of urban health transformations must include the study of how neighbourhoods are influenced by demographic changes such as immigration. The objective of this study was to analyse how the relationship between native and immigrant residents in neighbourhoods with different socio-economic levels influenced the use of urban health assets, such as public spaces and food stores. Three Madrid neighbourhoods of different socio-economic levels were selected and studied by conducting 37 semi-structured interviews and 29 focus groups. Data analysis was based on qualitative sequential discourse.The main finding was that the presence of immigrants in Madrid neighbourhoods, especially with low and medium socio-economic levels, was perceived negatively, affecting the use of public spaces and food stores. This negative perception unfolded in three dimensions: (1) difficulties for natives and immigrants to live together; (2) limitations on using public spaces caused by a feeling of insecurity; (3) criticism of immigrant food stores, especially Chinese-run food stores. Our findings showed a worrisome lack of social contact between immigrants and native residents, which affected the use of urban health assets, such as public spaces and food stores.

We aimed to propose a reliable and accurate model using non-destructive measurements of leaf length (L) and/or width (W) for estimating leaf area (LA) of three genotypes of purging nut (Jatropha curcas L.), i.e. Astrea and Barranca, both Colombian and a Mexican genotype. For model construction, ~500 healthy leaves were collected from at least 20 healthy plants naturally grown at each locations, and encompassed the full spectrum of measurable leaf sizes. Equations with L and/or W were generated; however, the best fit were made when product between L and W (LW). To validate these models, independent data set of 450 leaves were used. Thus, we developed a single model (Yi = β0 * LWβ1) with high precision and accuracy, random dispersion pattern of residuals and unbiased. In spite of this, a single equation, joining all the studied genotypes, was developed [LA = 0.822 * (LW)0.983; standard errors: β0 = 0.020, β1 = 0.004; R2a = 0.976], which greatly simplifies the process of measuring the leaf area of the genotypes, a fact that should be highlighted.

Dapsone (DDS) is an antibacterial drug with well-known antioxidant properties. However, the antioxidant behavior of its derivatives has not been well explored. In the present work, the antioxidant activity of 10 dapsone derivatives 4-substituted was determined by an evaluation in two in vitro models (DPPH radical scavenging assay and ferric reducing antioxidant power). These imine derivatives 1–10 were obtained through condensation between DDS and the corresponding aromatic aldehydes 4-substuited. Three derivatives presented better results than DDS in the determination of DPPH (2, 9, and 10). Likewise, we have three compounds with better reducing activity than dapsone (4, 9, and 10). In order to be more insight, the redox process, a conceptual DFT analysis was carried out. Molecular descriptors such as electronic distribution, the total charge accepting/donating capacity (I/A), and the partial charge accepting/donating capacity (ω+/ω−) were calculated to analyze the relative donor-acceptor capacity through employing a donor acceptor map (DAM). The DFT calculation allowed us to establish a relationship between GAPHOMO-LUMO and DAM with the observed antioxidant effects. According to the results, we concluded that compounds 2 and 3 have the lowest Ra values, representing a good antioxidant behavior observed experimentally in DPPH radical capturing. On the other hand, derivatives 4, 9, and 10 display the best reducing capacity activity with the highest ω− and Rd values. Consequently, we propose these compounds as the best antireductants in our DDS imine derivative series.

Seamounts constitute an obstacle to the ocean circulation, modifying it. As a result, a variety of hydrodynamical processes and phenomena may take place over seamounts, among others, flow intensification, current deflection, upwelling, Taylor caps, and internal waves. These oceanographic effects may turn seamounts into very productive ecosystems with high species diversity, and in some cases, are densely populated by benthic organisms, such corals, gorgonians, and sponges. In this study, we describe the oceanographic conditions over seamounts and other underwater features in the path of the Mediterranean Outflow Water (MOW), where populations of benthic suspensions feeders have been observed. Using CTD, LADPC and biochemical measurements carried out in the Ormonde and Formigas seamounts and the Gazul mud volcano (Northeast Atlantic), we show that Taylor caps were not observed in any of the sampled features. However, we point out that the relatively high values of the Brunt–Väisälä frequency in the MOW halocline, in conjunction with the slope of the seamount flanks, set up conditions for the breakout of internal waves and amplification of the currents. This may enhance the vertical mixing, resuspending the organic material deposited on the seafloor and, therefore, increasing the food availability for the communities dominated by benthic suspension feeders. Thus, we hypothesize that internal waves could be improving the conditions for benthic suspension feeders to grow on the slope of seamounts.

El artículo presenta los resultados sobre cuidado y maternidad de una investigación que tiene como objetivo explicar los procesos de reconstrucción del sentido en familias con un hijo con una enfermedad degenerativa. La investigación se realiza a través de un proceso cualitativo con enfoque constructivista social. La recolección de datos es a través de método metafórico, entrevista enfocada y observación participante; el análisis se realiza por método metafórico y análisis cualitativo. Se encuentra que el sentido se reconstruye en los diversos discursos socioculturales, puede relacionarse con las creencias religiosas; maternidad y cuidado son procesos corporizados en la mujer.

The inflammatory Bowel diseases (IBDs) are a chronic, relapsing inflammatory diseases of the gastrointestinal tract with heterogeneous behavior and prognosis. The introduction of biological therapies including anti-TNF, anti-IL-12/23, and anti-integrins, has revolutionized the treatment of IBD, but these drugs are not universally effective. Due to the complex molecular structures of biologics, they are uniformly immunogenic. New discoveries concerning the underlying mechanisms involved in the pathogenesis of IBD have allowed for progress in the development of new treatment options. The advantage of small molecules (SMs) over biological therapies includes their lack of immunogenicity, short half-life, oral administration, and low manufacturing cost. Among these, the Janus Kinases (JAKs) inhibition has emerged as a novel strategy to modulate downstream cytokine signaling during immune-mediated diseases. These drugs target various cytokine signaling pathways that participate in the pathogenesis of IBD. Tofacitinib, a JAK inhibitor targeting predominantly JAK1 and JAK3, has been approved for the treatment of ulcerative colitis (UC), and there are other specific JAK inhibitors under development that may be effective in Crohn’s. Similarly, the traffic of lymphocytes can now be targeted by another SM. Sphingosine-1-phosphate receptor (S1PR) agonism is a novel strategy that acts, in part, by interfering with lymphocyte recirculation, through blockade of lymphocyte egress from lymph nodes. S1PR agonists are being studied in IBD and other immune-mediated disorders. This review will focus on SM drugs approved and under development, including JAK inhibitors (tofacitinib, filgotinib, upadacitinib, peficitinib) and S1PR agonists (KRP-203, fingolimod, ozanimod, etrasimod, amiselimod), and their mechanism of action.

En este texto nos proponemos hacer una reflexión sobre la eclosión mediática del fenómeno de la despoblación en el ámbito rural español. Dicho brote ha tenido lugar a través de distintas publicaciones divulgativas, principalmente a modo de ensayos y novelas, de programas de televisión y radio, y de iniciativas políticas. Hemos elegido dos textos, probablemente los que han “encendido la mecha”, la España vacía –Viaje por un país que nunca fue- de Sergio del Molino y Los Últimos –Voces de la Laponia española- de Paco Cerdá- para analizarlos y reflexionar sobre el enfoque que prima en dichos libros. Nuestro objetivo es tratar de entender el fenómeno de la despoblación rural como un elemento más del desarrollo capitalista y post-capitalista, y de la evolución demográfica, enfatizando la lógica racional de esta dinámica pero sin soslayar la probable erosión que se puede producir en nuestro acervo cultural si los procesos, que describen la literatura científica y divulgativa, culminan con la desaparición “real” de muchos de estos pequeños pueblos. Nuestro planteamiento se basa en la discusión de la inevitabilidad de la reducción poblacional de las localidades del ámbito rural y en el abordaje de las posibles consecuencias que este decremento puede tener.

La depresión es una enfermedad que tiene un impacto especialmente preocupante en la vejez por el incremento de factores precipitantes de enfermedades en esta etapa de la vida. En México, aún hay pocos estudios poblacionales que estudien la depresión en la senectud. Los objetivos de nuestro estudio son: 1) estimar la prevalencia de síntomas depresivos en el adulto mayor; 2) analizar la asociación entre síntomas depresivos y diferentes factores favorecedores de la depresión; y 3) reflexionar en qué sentido los resultados de este trabajo pueden contribuir a la mejora de las políticas de salud en México. La investigación es poblacional y transversal y se realizó en Ciudad Victoria, Tamaulipas. Se estudió a 1.126 personas mayores (455 hombres y 671 mujeres), que suponían aproximadamente el 5,1% de toda la población mayor de Ciudad Victoria en el momento de realización del estudio. La depresión fue medida mediante la escala Geriatric Depression Scale. Los resultados indican que: 1) la prevalencia de síntomas depresivos se sitúa en un 29%; y 2) los factores favorecedores de la depresión fueron la dependencia en actividades de la vida diaria, el deterioro cognitivo, la falta de apoyo social, la edad, el sexo, la soledad, la pobreza, los eventos estresantes y la percepción subjetiva de salud. La reducción de la depresión no sólo está vinculada a la mejora de aspectos relacionados con la salud, sino a la mejora de las condiciones de vida de los ancianos.

reseñas, review

Thomas Piketty, en su celebérrima y reciente obra El capital en el siglo XXI, analiza la evolución de la desigualdad de la distribución de la riqueza en el mundo desde finales del siglo XVIII hasta nuestros días. A través de dicho análisis, Piketty trata de demostrar la importancia del capital –bienes de todo tipo, incluido el dinero- en relación a los ingresos obtenidos a través del salario. El peso específico de dicho capital y su distribución no equitativa, incrementados a partir de la década de los años ochenta del pasado siglo, ha producido una amplificación de la desigualdad, llegando a niveles similares que los de finales del siglo XIX.

Introducción: El marco teórico en el que se basa nuestro estudio es el modelo ecológico. Objetivo: Conocer la percepción de los cuidadores de los ancianos con demencia sobre el maltrato y la violencia ejercida sobre las personas ancianas con dicha enfermedad. Métodos: Se realizó un estudio cualitativo basado en la confección de 5 grupos de discusión, que se llevaron a cabo en Segovia, Soria y León. Resultados: Se consideraba al maltrato como un proceso y no como acciones puntuales, que eran justificadas, sobre todo, en la fase de los trastornos conductuales. Se calificaba a la falta de soporte institucional como una forma de maltrato. El abuso estaba determinado por la no aceptación de la enfermedad, por una sobrecarga del cuidado, que en el caso de la mujer es acentuado por su sentimiento de obligatoriedad para atender al enfermo, mediatizado por las identidades de género. Hubo una doble cara en la consideración de los servicios formales institucionales, a los centros de día se les valoraba positivamente y se recelaba de la institucionalización permanente. Conclusiones: El maltrato en la demencia viene principalmente determinado por un mal manejo de los síntomas de la demencia por parte de los cuidadores.

Se describe la anatomía de la madera de Salvia pubescens, S. regla y S. sessei, especies pertenecientes a la sección Erythrostachys, subgénero Calosphace del género Salvia. Para la realización del trabajo se recolectaron dos muestras de la madera del fuste de cada una de las especies para obtener preparaciones permanentes. Los cortes transversal, radial y tangencial fueron utilizados para elaborar la descripción anatómica de cada uno de los taxa. La madera presenta porosidad anular, el diámetro tangencial de los vasos es pequeño (34-85 ?m), los elementos de vaso son cortos (94-257 ?m), con punteaduras areoladas alternas, engrosamientos en espiral y placa de perforación simple. Se presentan traqueidas vasicéntricas. El parénquima axial es paratraqueal escaso, apotraqueal difuso y marginal. Los radios son uniseriados y multiseriados heterogéneos, agregados y no agregados. Las fibras son libriformes con y sin septo. Se presentan gomas, tílides, granos de almidón y cristales prismáticos. Las características observadas coinciden con las reportadas para el género.

Sin resumen

El artículo destaca el dinamismo de la inversión extrajera directa (l. E.D.) a partir de la década de los ochenta, el cual supera no sólo al de la producción mundial sino también a los de comercio y crédito internacionales. Expone siete tesis sobre la economía mundial y la IED: crisis del régimen de acumulación comandado por Estados Unidos, la internalización de costos de transacción como característica de dicho régimen, la globalización como redefinición del estado económico de valorización, la l. E.D. como expresión de la expansión financiera, los Estados Unidos como deudor neto del mundo y receptor de I.E.D., la I.E.D. como internalizadora del mercado mundial y transformadora del espacio económico del capital y las condiciones para la sustitución de los Estados Unidos por Asia, comandada por Japón.