Alcohol consumption patterns and adherence to the Mediterranean diet in the adult population of Spain.

PURPOSE: The objective is to evaluate the association between various indicators of alcohol consumption and the degree of adherence to the Mediterranean diet among the Spanish adult population. METHODS: A cross-sectional study including 44,834 participants ≥ 15 years of age from the 2017 National Health Survey and the 2020 European Health Survey in Spain. Alcohol patterns were defined based on (1) average intake: individuals were classified as low risk (1-20 g/day in men and 1-10 g/day in women) and high risk (> 20 g/day in men or > 10 g/day in women), (2) binge drinking, and (3) alcoholic beverage preference. Non-adherence to the Mediterranean diet was defined as scoring < 7 points on an adapted Mediterranean Diet Adherence Screener index (range 0-10). Odds ratios (OR) were estimated using logistic regression models adjusted for relevant covariates. RESULTS: Compared to non-drinkers, low and high-risk drinkers were more likely to report non-adherence to the Mediterranean diet: ORs 1.35 (95% CI 1.23; 1.49) and 1.54 (95% CI 1.34; 1.76), respectively. Similarly, reports of binge drinking less than once a month was associated with higher likelihood of non-adherence (OR 1.17; 95% CI 1.04; 1.31). Individuals reporting no preference for a specific beverage and those with a preference for beer or for spirits had lower adherence: ORs 1.18 (95% CI 1.05; 1.33), 1.31 (95% CI 1.17; 1.46), and 1.72 (95% CI 1.17; 2.54), respectively, while a preference for wine showed no association (OR 1.01; 95% CI 0.90; 1.13). CONCLUSION: Alcohol consumption, even in low amounts, is associated with lower adherence to the Mediterranean diet. Therefore, alcoholic beverages should not be included in measures that define the Mediterranean diet.

BI-3231, an enzymatic inhibitor of HSD17B13, reduces lipotoxic effects induced by palmitic acid in murine and human hepatocytes.

17-ß-hydroxysteroid dehydrogenase 13 (HSD17B13), a lipid droplet-associated enzyme, is primarily expressed in the liver and plays an important role in lipid metabolism. Targeted inhibition of enzymatic function is a potential therapeutic strategy for treating steatotic liver disease (SLD). The present study is aimed at investigating the effects of the first selective HSD17B13 inhibitor, BI-3231, in a model of hepatocellular lipotoxicity using human cell lines and primary mouse hepatocytes in vitro. Lipotoxicity was induced with palmitic acid in HepG2 cells and freshly isolated mouse hepatocytes and the cells were coincubated with BI-3231 to assess the protective effects. Under lipotoxic stress, triglyceride (TG) accumulation was significantly decreased in the BI-3231-treated cells compared with that of the control untreated human and mouse hepatocytes. In addition, treatment with BI-3231 led to considerable improvement in hepatocyte proliferation, cell differentiation, and lipid homeostasis. Mechanistically, BI-3231 increased the mitochondrial respiratory function without affecting ß-oxidation. BI-3231 inhibited the lipotoxic effects of palmitic acid in hepatocytes, highlighting the potential of targeting HSD17B13 as a specific therapeutic approach in steatotic liver disease.NEW & NOTEWORTHY 17-ß-Hydroxysteroid dehydrogenase 13 (HSD17B13) is a lipid droplet protein primarily expressed in the liver hepatocytes. HSD17B13 is associated with the clinical outcome of chronic liver diseases and is therefore a target for the development of drugs. Here, we demonstrate the promising therapeutic effect of BI-3231 as a potent inhibitor of HSD17B13 based on its ability to inhibit triglyceride accumulation in lipid droplets (LDs), restore lipid metabolism and homeostasis, and increase mitochondrial activity in vitro.

Impact of psychological distress on mortality in Spain. The importance of early detection and treatment of mental disorders.

BACKGROUND: Mental health problems account for 14% of mortality worldwide. The aim of this study was to evaluate the association between psychological distress and mortality in the Spanish adult population. METHODS: Data came from a longitudinal study in population ≥15 years of age (n=21,005) who participated in the 2011-12 Spanish National Health Survey, which was linked to mortality records as of December 2020. Mental health was assessed with the GHQ-12, defining psychological distress as a dichotomous variable using a GHQ-12 score ≥3 as the cutoff point. Using Poisson regression, standardized mortality rate ratios (SRR) were estimated for all-cause, cardiovascular disease, and tumor-related mortality, adjusting for sociodemographic variables, lifestyles, and comorbidities. RESULTS: The standardized overall mortality rate in individuals with and without psychological distress was 14.58 and 10.90 per 1000 person-years, respectively, estimating an SRR of 1.34 (95%CI: 1.19-1.50). The SRR for tumor-related mortality was 1.17 (95%CI: 0.90-1.53), and cardiovascular-related mortality was related to higher distress (GHQ-12 ≥ 4): SRR of 1.22 (95%CI: 0.98-1.51). Among psychological distressed individuals, the overall mortality SRR for those with a previous mental disorder diagnosis was 1.18 (95%CI: 0.91-1.53) versus 1.34 (95%CI: 1.18-1.54) for those without such diagnosis (p for interaction=0.067). Similarly, distressed participants taking prescription drugs for mental disorders had a lower mortality risk than those not taking them (p for interaction=0.016). CONCLUSIONS: Individuals with psychological distress had a higher risk of overall-, cardiovascular disease- and tumor-related mortality. This association was higher among participants not previously diagnosed with a mental disorder and those not taking medication for mental issues.

Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice.

Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the leading causes of liver disease worldwide. To identify disease-specific pathomechanisms, we analyzed the lipidome, metabolome and immune cell recruitment in livers in both diseases. Mice harboring ASH or NASH had comparable disease severities regarding mortality rate, neurological behavior, expression of fibrosis marker and albumin levels. Lipid droplet size was higher in NASH than ASH and qualitative differences in the lipidome were mainly based on incorporation of diet-specific fatty acids into triglycerides, phosphatidylcholines and lysophosphatidylcholines. Metabolomic analysis showed downregulated nucleoside levels in both models. Here, the corresponding uremic metabolites were only upregulated in NASH suggesting stronger cellular senescence, which was supported by lower antioxidant levels in NASH as compared to ASH. While altered urea cycle metabolites suggest increased nitric oxide synthesis in both models, in ASH, this depended on increased L-homoarginine levels indicating a cardiovascular response mechanism. Interestingly, only in NASH were the levels of tryptophan and its anti-inflammatory metabolite kynurenine upregulated. Fittingly, high-content immunohistochemistry showed a decreased macrophage recruitment and an increased polarization towards M2-like macrophages in NASH. In conclusion, with comparable disease severity in both models, higher lipid storage, oxidative stress and tryptophan/kynurenine levels were seen in NASH, leading to distinct immune responses.

Meningitis por Listeria: serie de casos en un hospital de tercer nivel y utilidad de las nuevas técnicas de diagnóstico microbiológico

Introducción: La meningitis por Listeria monocytogenes (MLM) es una entidad grave con complicaciones a corto plazo. La reacción de polimerasa en cadena (RPC) puede ayudar a mejorar su diagnóstico y pronóstico. Objetivos: Conocer las características de los pacientes diagnosticados de meningitis por L. monocytogenes en los últimos años, a través de diferentes métodos microbiológicos. Pacientes y Métodos: Serie de casos de pacientes adultos ingresados con MLM en el Hospital Clínico San Carlos, Madrid, España, durante doce años (2009-2021). Se describieron variables epidemiológicas, clínicas, microbiológicas, radiológicas y terapéuticas. Resultados: Se registraron doce pacientes con MLM (edad media 67,5 años, 75% varones). En ocho se obtuvo un cultivo positivo a L. monocytogenes. La RPC en líquido cefalorraquídeo (LCR) fue positiva en los dos casos en los que se realizó la prueba. El tratamiento dirigido en todos los casos fue ampicilina durante 21 días. Se registraron complicaciones en un cuarto de los casos. Del total de pacientes uno falleció. Conclusiones: La MLM es una enfermedad poco frecuente y de difícil diagnóstico. En nuestra serie de casos los dos pacientes diagnosticados por RPC tuvieron resultado de cultivo de LCR negativo, y presentaron buena evolución. La determinación de RPC podría permitir diagnosticar un mayor número de casos y con mayor precocidad.

Background: Listeria monocytogenes meningitis (LMM) is a serious entity with short-term complications. Polymerase chain reaction (PCR) can help to improve its diagnosis and prognosis. Aim: To know the characteristics of patients diagnosed with meningitis by L. monocytogenes in recent years, through different microbiological methods. Methods: Case series of adult patients admitted with LMM at the Hospital Clínico San Carlos of Madrid, Spain, during twelve years (2009-2021). Epidemiological, clinical, microbiological, radiological and therapeutic variables were described. Results: Twelve patients with LMM were recorded (mean age 67.5 years, 75% male). Eight had a positive culture for L. monocytogenes. cerebrospinal fluid (CSF) PCR was positive in the two cases in which the test was performed. Treatment in all cases was ampicillin for 21 days. Complications were recorded in a quarter of the cases. One patient died. Conclusions: LMM is a rare and difficult to diagnose disease. In our series of cases, the two patients diagnosed by PCR had negative CSF culture results, and presented good evolution. PCR determination could allow a greater number of cases to be diagnosed earlier.

Cambios en el abandono del consumo de tabaco en España, 1987-2020 / Changes in smoking cessation in Spain, 1987-2020

Introducción: El objetivo del estudio fue estimar y describir la evolución del abandono del consumo de tabaco en España desde 1987 hasta 2020, según las principales características sociodemográficas.Material y métodoAnálisis de la serie histórica de la Encuesta Nacional de Salud y la Encuesta Europea de Salud en España. Se definió la proporción de abandono (PA) como el número de exfumadores entre el total de personas que fuman o han fumado alguna vez en su vida. Otras variables de estudio fueron: año de la encuesta, edad, sexo y nivel de estudios. Se elaboraron modelos de regresión de Poisson ajustados simultáneamente por las características sociodemográficas, estimando para cada año la PA estandarizada y sus intervalos de confianza al 95%.ResultadosLa diferencia absoluta de la PA estandarizada aumentó desde 1987 a 2017 un 18,6% (IC95%: 16,8-20,4), siendo moderadamente superior en los hombres (19,2%; IC95%: 17,1-21,4) que en las mujeres (16,5%; IC95%: 13,3-19,7). Se observó un incremento del abandono en todos los grupos etarios, pero de mayor magnitud según aumentaba la edad, estimando una diferencia de PA entre 1987 y 2017 del 22,4% (IC95%: 17,7-27,1) en los ≥65años. Las personas con estudios universitarios mostraron un mayor incremento durante el periodo (32,7%; IC95%: 27,5-38,0), especialmente si se compara con los de menor nivel de estudios (9,0%; IC95%: 4,8-13,2).ConclusiónLa PA se ha incrementado intensamente y de forma sostenida desde 1987, pero se detectan importantes diferencias según la edad y el nivel de estudios, destacando el gran incremento de la inequidad observada en estos 33 años de evolución. (AU)

Introduction: The goal of this study was to estimate and to describe the smoking cessation changes in Spain from 1987 to 2020, according to the main sociodemographic characteristics.Material and methodAnalysis of the historical series of the Spanish National Health Survey and the European Health Survey in Spain. Quit rate (QR) was defined as the number of former smokers among the total number of people who are smokers or have smoked at some time in their life. Other included variables were year of survey, age, gender and educational level. Poisson regression models were simultaneously adjusted for sociodemographic characteristics, estimating QR and its 95% confidence intervals (CIs) for each year.ResultsThe absolute difference in standardized QR increased from 1987 to 2017 by 18.6% (95%CI: 16.8-20.4), being moderately higher in men (19.2%; 95%CI: 17.1-21.4) than in women (16.5%; 95%CI: 13.3-19.7). An increase in QR was observed in all age groups, but its magnitude increased with age, estimating a difference in QR between 1987 and 2017 of 22.4% (95%CI: 17.7-27.1) in those aged over 64. People having university studies showed a higher QR during the period, 32.7% (95%CI: 27.5-38.0), especially when compared to those with a lower level of education (9.0%; 95%CI: 4.8-13.2).ConclusionQR has increased sharply and steadily since 1987, however important differences were detected according to age and educational level, highlighting the large increase in inequity observed in these 33 years of evolution. (AU)

Neprilysin-dependent neuropeptide Y cleavage in the liver promotes fibrosis by blocking NPY-receptor 1.

Development of liver fibrosis is paralleled by contraction of hepatic stellate cells (HSCs), the main profibrotic hepatic cells. Yet, little is known about the interplay of neprilysin (NEP) and its substrate neuropeptide Y (NPY), a potent enhancer of contraction, in liver fibrosis. We demonstrate that HSCs are the source of NEP. Importantly, NPY originates majorly from the splanchnic region and is cleaved by NEP in order to terminate contraction. Interestingly, NEP deficiency (Nep-/-) showed less fibrosis but portal hypertension upon liver injury in two different fibrosis models in mice. We demonstrate the incremental benefit of Nep-/- in addition to AT1R blocker (ARB) or ACE inhibitors for fibrosis and portal hypertension. Finally, oral administration of Entresto, a combination of ARB and NEP inhibitor, decreased hepatic fibrosis and portal pressure in mice. These results provide a mechanistic rationale for translation of NEP-AT1R-blockade in human liver fibrosis and portal hypertension.

The non-selective Rho-kinase inhibitors Y-27632 and Y-33075 decrease contraction but increase migration in murine and human hepatic stellate cells.

BACKGROUND: The Rho-kinase ROCK II plays a major role in the activation of hepatic stellate cells (HSC), which are the key profibrotic and contractile cells contributing to the development of chronic liver disease. Inhibition of ROCK II ultimately blocks the phosphorylation of the myosin light chain (MLC) and thus inhibits stress fibre assembly and cell contraction. We investigated the effects of the ROCK inhibitors Y-33075 as well as Y-27632 in murine and human hepatic stellate cells. METHODS: Primary isolated HSC from FVB/NJ mice and the immortalized human HSC line TWNT-4 were culture-activated and incubated with Y-27632 and Y-33075 (10nM to 10µM) for 24h. Protein expression levels were analyzed by Western Blots and transcriptional levels of pro-fibrotic markers and proliferative markers were evaluated using real-time qPCR. Migration was investigated by wound-healing assay. Proliferation was assessed by BrdU assay. Contraction of HSC was measured using 3D collagen matrices after incubation with Y-27632 or Y-33075 in different doses. RESULTS: Both Rho-kinase inhibitors, Y-27632 and Y-33075, reduced contraction, fibrogenesis and proliferation in activated primary mouse HSC (FVB/NJ) and human HSC line (TWNT-4) significantly. Y-33075 demonstrated a 10-times increased potency compared to Y-27632. Surprisingly, both inhibitors mediated a substantial and unexpected increase in migration of HSC in FVB/NJ. CONCLUSION: ROCK inhibition by the tested compounds decreased contraction but increased migration. Y-33075 proved more potent than Y27632 in the inhibition of contraction of HSCs and should be further evaluated in chronic liver disease.

Light cigarette smoking and all-cause mortality in Spain. A national population-based cohort study.

PURPOSE: Regular light cigarette consumption (light smoking) is increasing in many countries; however, few studies have assessed its impact on mortality. The main aim of this study is to estimate the association between the number of cigarettes consumed and all-cause mortality in Spain while focusing on light smoking. METHODS: Longitudinal study based on data from 42,902 individuals aged ≥15 years included in the 2011-2012 (Spanish) National Health Survey or the 2014 European Health Survey for Spain. Data were linked with the mortality registry up to December 2020. Multivariate Cox regression models were used to estimate hazard ratios (HR) adjusted for sociodemographic variables, lifestyle factors, and health status indicators. RESULTS: Compared to never smokers, the mortality HR for nondaily smokers was 1.30 (95% CI: 0.81-2.09), increasing to 2.23 (95% CI: 1.25-3.96) among those smoking 1-2 cigarettes/d, and to 1.54 (95%CI: 1.14-2.07) for consumers of 3-5 cigarettes/day. When individuals who reported trying to quit during the previous year were excluded, resulting HRs were 1.31 (95% CI: 0.81-2.10), 1.48 (95% CI: 0.69-3.19) and 1.64 (95% CI: 1.16-2.34), respectively. CONCLUSIONS: Compared to never smokers, consumers of small quantities of tobacco, that is, light smoking, had an increased mortality risk. In view of these results, we suggest the need for awareness-raising campaigns regarding how smoking even a small number of cigarettes a day causes serious harm to one´s health.

Janus kinase 2 inhibition by pacritinib as potential therapeutic target for liver fibrosis.

BACKGROUND AND AIMS: Janus kinase 2 (JAK2) signaling is increased in human and experimental liver fibrosis with portal hypertension. JAK2 inhibitors, such as pacritinib, are already in advanced clinical development for other indications and might also be effective in liver fibrosis. Here, we investigated the antifibrotic role of the JAK2 inhibitor pacritinib on activated hepatic stellate cells (HSCs) in vitro and in two animal models of liver fibrosis in vivo . APPROACH AND RESULTS: Transcriptome analyses of JAK2 in human livers and other targets of pacritinib have been shown to correlate with profibrotic factors. Although transcription of JAK2 correlated significantly with type I collagen expression and other profibrotic genes, no correlation was observed for interleukin-1 receptor-associated kinase and colony-stimulating factor 1 receptor. Pacritinib decreased gene expression of fibrosis markers in mouse primary and human-derived HSCs in vitro . Moreover, pacritinib decreased the proliferation, contraction, and migration of HSCs. C 57 BL/6J mice received ethanol in drinking water (16%) or Western diet in combination with carbon tetrachloride intoxication for 7 weeks to induce alcoholic or nonalcoholic fatty liver disease. Pacritinib significantly reduced liver fibrosis assessed by gene expression and Sirius red staining, as well as HSC activation assessed by alpha-smooth muscle actin immunostaining in fibrotic mice. Furthermore, pacritinib decreased the gene expression of hepatic steatosis markers in experimental alcoholic liver disease. Additionally, pacritinib protected against liver injury as assessed by aminotransferase levels. CONCLUSIONS: This study demonstrates that the JAK2 inhibitor pacritinib may be promising for the treatment of alcoholic and nonalcoholic liver fibrosis and may be therefore relevant for human pathology.

Functional Brain Connectivity Prior to the COVID-19 Outbreak Moderates the Effects of Coping and Perceived Stress on Mental Health Changes: A First Year of COVID-19 Pandemic Follow-up Study.

BACKGROUND: The COVID-19 pandemic provides a unique opportunity to investigate the psychological impact of a global major adverse situation. Our aim was to examine, in a longitudinal prospective study, the demographic, psychological, and neurobiological factors associated with interindividual differences in resilience to the mental health impact of the pandemic. METHODS: We included 2023 healthy participants (age: 54.32 ± 7.18 years, 65.69% female) from the Barcelona Brain Health Initiative cohort. A linear mixed model was used to characterize the change in anxiety and depression symptoms based on data collected both pre-pandemic and during the pandemic. During the pandemic, psychological variables assessing individual differences in perceived stress and coping strategies were obtained. In addition, in a subsample (n = 433, age 53.02 ± 7.04 years, 46.88% female) with pre-pandemic resting-state functional magnetic resonance imaging available, the system segregation of networks was calculated. Multivariate linear models were fitted to test associations between COVID-19-related changes in mental health and demographics, psychological features, and brain network status. RESULTS: The whole sample showed a general increase in anxiety and depressive symptoms after the pandemic onset, and both age and sex were independent predictors. Coping strategies attenuated the impact of perceived stress on mental health. The system segregation of the frontoparietal control and default mode networks were found to modulate the impact of perceived stress on mental health. CONCLUSIONS: Preventive strategies targeting the promotion of mental health at the individual level during similar adverse events in the future should consider intervening on sociodemographic and psychological factors as well as their interplay with neurobiological substrates.

[Changes in smoking cessation in Spain, 1987-2020]. / Cambios en el abandono del consumo de tabaco en España, 1987-2020.

INTRODUCTION: The goal of this study was to estimate and to describe the smoking cessation changes in Spain from 1987 to 2020, according to the main sociodemographic characteristics. MATERIAL AND METHOD: Analysis of the historical series of the Spanish National Health Survey and the European Health Survey in Spain. Quit rate (QR) was defined as the number of former smokers among the total number of people who are smokers or have smoked at some time in their life. Other included variables were year of survey, age, gender and educational level. Poisson regression models were simultaneously adjusted for sociodemographic characteristics, estimating QR and its 95% confidence intervals (CIs) for each year. RESULTS: The absolute difference in standardized QR increased from 1987 to 2017 by 18.6% (95%CI: 16.8-20.4), being moderately higher in men (19.2%; 95%CI: 17.1-21.4) than in women (16.5%; 95%CI: 13.3-19.7). An increase in QR was observed in all age groups, but its magnitude increased with age, estimating a difference in QR between 1987 and 2017 of 22.4% (95%CI: 17.7-27.1) in those aged over 64. People having university studies showed a higher QR during the period, 32.7% (95%CI: 27.5-38.0), especially when compared to those with a lower level of education (9.0%; 95%CI: 4.8-13.2). CONCLUSION: QR has increased sharply and steadily since 1987, however important differences were detected according to age and educational level, highlighting the large increase in inequity observed in these 33years of evolution.

Rural-urban gradients and all-cause, cardiovascular and cancer mortality in Spain using individual data.

•The literature reporting on rural-urban health status disparities remains inconclusive.•We analyzed data from a longitudinal population-based study using individual observations.•Our results show that the risks of all-cause and cancer mortality are greater in large cities than in other municipalities, with no clear urban-rural gradient.•Not differences were found among territories in cardiovascular mortality.

Evidence of a population of leaf-eared mice Phyllotis vaccarum above 6,000 m in the Andes and a survey of high-elevation mammals.

Biologists have long pondered the extreme limits of life on Earth, including the maximum elevation at which species can live and reproduce. Here we review evidence of a self-sustaining population of mice at an elevation that exceeds that of all previously reported for mammals. Five expeditions over 10 years to Volcán Llullaillaco on the Argentina/Chile border observed and collected mice at elevations ranging from 5,070 m at the mountain's base to the summit at 6,739 m (22,110 feet). Previously unreported evidence includes observations and photographs of live animals and mummified remains, environmental DNA, and a soil microbial community reflecting animal activity that are evaluated in combination with previously reported video recordings and capture of live mice. All of the evidence identifies the mouse as the leaf-eared mouse Phyllotis vaccarum, and it robustly places the population within a haplotype group containing individuals from the Chilean Atacama Desert and nearby regions of Argentina. A critical review of the literature affirms that this population is not only an elevational record for mammals but for all terrestrial vertebrates to date, and we further find that many extreme elevations previously reported for mammals are based on scant or dubious evidence.

Durante mucho tiempo los biólogos han reflexionado sobre los límites extremos de altura a la que las especies pueden vivir y reproducirse. Aquí presentamos nueva evidencia sobre la existencia de una población de ratones establecida a una elevación que supera todos los reports previos para mamíferos. Durante 10 años fueron realizadas 5 expediciones al Volcán Llullaillaco, ubicado en la frontera entre Argentina y Chile; observando y colectando ratones en elevaciones que van desde los 5,070 m hasta la cima de 6,739 m (22,110 feet). La nueva evidencia incluye fotografías de restos momificados, ADN ambiental y la actividad microbiana del suelo que confirman la presencia del animal, la cual fue analizada junto a videos reportados anteriormente y la captura de ejemplares vivos. Toda esta información indica que dicha población corresponde al ratón orejudo amarillento Phyllotis vaccarum y lo posicionan dentro de un grupo de haplotipos compuesto por individuos del Desierto de Atacama y regiones cercanas en Argentina. La revisión crítica de la literatura demostró que esta población no solo es un récord de elevación para los mamíferos, sino para todos los vertebrados terrestres; igualmente, que los reportes de elevaciones extremas reportados para mamíferos se derivan de evidencias escasas y dudosas.

Predictive capacity of self-rated health on all-cause mortality in Spain: differences across sex, age and educational level.

BACKGROUND: Published evidence on self-rated health's capacity to predict mortality and its variability across subpopulations lacks consistency. Our objective is to evaluate this predictive association and whether/how it varies by sex, age and educational attainment at the population level in Spain. METHODS: Data came from a prospective longitudinal study based on 42 645 individuals aged ≥15 years who participated in the 2011-2012 and 2014 Spanish Health Surveys. Median follow-up time for mortality was 5.4 years. Cox proportional hazards models adjusted for sociodemographic, lifestyle and chronic disease variables were used to estimate the predictive capacity of self-rated health on mortality. RESULTS: Self-rated health was associated with mortality with a dose-response effect (p value for linear trend <0.001). Compared with respondents who rated their health as very good, those rating it as very poor presented an HR of 3.33 (95% CI 2.50 to 4.44). Suboptimal self-rated health was a stronger predictor of mortality among 15-44 year-olds (HR 2.87; 95% CI 1.59 to 5.18), compared with the estimate for 45-64 year-olds (HR 1.86; 95% CI 1.45 to 2.39) (p value for interaction=0.001) and for those 65 and older (HR 1.51; 95% CI 1.36 to 1.68) (p value for interaction <0.001). Regarding educational attainment, the association was stronger for individuals with university studies (HR 2.51; 95% CI 1.67 to 3.76) than for those with only primary or no studies (HR 1.31; 95% CI 1.17 to 1.48) (p value for interaction=0.010). No statistically significant differences were observed between men and women. CONCLUSIONS: Self-rated health may be considered a good predictor of all-cause mortality in the population of Spain, although the magnitude of this predictive association varies by age and educational level.

Dynamic human liver proteome atlas reveals functional insights into disease pathways.

Deeper understanding of liver pathophysiology would benefit from a comprehensive quantitative proteome resource at cell type resolution to predict outcome and design therapy. Here, we quantify more than 150,000 sequence-unique peptides aggregated into 10,000 proteins across total liver, the major liver cell types, time course of primary cell cultures, and liver disease states. Bioinformatic analysis reveals that half of hepatocyte protein mass is comprised of enzymes and 23% of mitochondrial proteins, twice the proportion of other liver cell types. Using primary cell cultures, we capture dynamic proteome remodeling from tissue states to cell line states, providing useful information for biological or pharmaceutical research. Our extensive data serve as spectral library to characterize a human cohort of non-alcoholic steatohepatitis and cirrhosis. Dramatic proteome changes in liver tissue include signatures of hepatic stellate cell activation resembling liver cirrhosis and providing functional insights. We built a web-based dashboard application for the interactive exploration of our resource (www.liverproteome.org).

Physical and social environmental factors related to co-occurrence of unhealthy lifestyle behaviors.

Previous work identifying determinants of co-occurrence of behavioral risk factors have focused on their association with individuals' characteristics with scant attention paid to their relationship to contextual factors. Data came from 21,007 individuals ≥15 years of age who participated in the cross-sectional 2011-2012 Spanish National Health Survey. Two indicators were defined by tobacco consumption, alcohol intake, diet, physical activity, and body mass index. The first indicator, based on dichotomized measures, ranges from 0 to 5. The second one (unhealthy lifestyle index), ranges from 0 to 15, with 0 denoting the healthiest score. Among the determinants, we examined social support, five perceived characteristics of the neighborhood, and the socioeconomic deprivation index of the census tract of residence. Data were analyzed using multilevel linear and logistic regression models adjusted for the main sociodemographic characteristics. Using the dichotomized indicator, the probability of having 3-5 risk factors versus <3 factors was associated with low social support (Odds Ratio [OR] 1.50; 95% Confidence Interval [CI]: 1.25-1.80). Issues surrounding neighborhood cleanliness (OR = 1.18; 95%CI: 1.04-1.33), air pollution (OR = 1.38; 95%CI: 1.16-1.64), and street crime (OR = 1.21; 95%CI: 1.03-1.42) were associated with determinants of co-occurrence. Risk factors co-occurrence increased as deprivation level increased: the OR for the highest deprivation quintile versus the lowest was 1.30 (95%CI: 1.14-1.48). Similar results were observed when using the unhealthy lifestyle index. Poorer physical and social environments are related to greater co-occurrence of risk factors for chronic diseases. Health promotion interventions targeting the prevention of risk factors should consider the contextual characteristics of the neighborhood environment.

Sense of Coherence Mediates the Relationship Between Cognitive Reserve and Cognition in Middle-Aged Adults.

In recent years, supported by new scientific evidence, the conceptualization of cognitive reserve (CR) has been progressively enriched and now encompasses not only cognitive stimulating activities or educational level, but also lifestyle activities, such as leisure physical activity and socialization. In this context, there is increasing interest in understanding the role of psychological factors in brain health and cognitive functioning. In a previous study, we have found that these factors mediated the relationship between CR and self-reported cognitive functioning. In this study, we have confirmed an association between two important constructs included in the psychological wellbeing and salutogenic models, "purpose in life" and "sense of coherence," CR, as assessed using a questionnaire, and cognitive functioning, as evaluated using a comprehensive neuropsychological battery. Results from 888 middle-aged healthy participants from the Barcelona Brain Health Initiative indicate that both sense of coherence (SoC) and CR were positively associated with verbal memory, reasoning and attention, working memory, and global cognition. Moreover, the relation between CR and cognitive functioning in the different domains is partially mediated by SoC. When we controlled for brain integrity, introducing into the model neurofilament light chain measures, the mediator role of SoC was confirmed for reasoning and attention and global cognition. However, purpose in life was not associated with cognitive functioning. These results reveal the central role of the SoC construct, which mediates the association between classic CR estimates and cognitive functions, potentially representing a modifiable target for interventions that aim to promote brain health.

Pandemic parenting: A pilot study of in-person versus internet-DOCS K-5 for caregivers of school-age children with disruptive behaviors.

Behavioral parent training (BPT) programs are needed to address disruptive behavior disorders among school-aged children. Given the prolonged COVID-19 pandemic and associated mental health consequences, adapting BPTs to telehealth modalities is necessary to ensure continued services to children and families. This pilot study evaluated the use of a telehealth vs in-person modality to deliver the Developing Our Children's Skills K-5 (DOCS K-5) BPT. Participants were caregivers of children enrolled in elementary school exhibiting disruptive behaviors who participated in either in-person DOCS K-5 (n = 21) or internet-DOCS K-5 (i-DOCS K-5; n = 34). Pre- and post-intervention outcome measures were collected for child disruptive behavior, parenting stress, and caregiver symptoms of depression while consumer satisfaction was assessed at post-test only. Multiple linear and Poisson regression models were performed to assess the effect of session modality on the outcomes. Child disruptive behavior, parenting stress and depression, and consumer satisfaction scores were not significantly different across groups, even after adjusting for baseline characteristics. The results of this study provide preliminary evidence that the i-DOCS K-5 modality is as effective as the in-person program. Study findings may be beneficial to practitioners treating school-age children and utilizing telehealth interventions during the COVID-19 pandemic and onward.

Clustering of unhealthy lifestyle behaviors, self-rated health and disability.

The main objective was to identify sociodemographic characteristics of the population at risk for a greater clustering of unhealthy behaviors and to evaluate the association of such clustering with self-rated health status and disability. Data come from the 2017 Spanish National Health Survey with a sample of 21,947 participants of 15 years of age or older. Based on tobacco consumption, risk drinking, unbalanced diet, sedentarism, and body mass index <18.5/≥25 we created two indicators of risk factor clustering: 1) Number of unhealthy behaviors (0-5); and 2) Unhealthy lifestyle index (score: 0-15). Self-rated health was dichotomized into "optimal" and "suboptimal," and disability was classified as "no disability," "mild," and "severe" based on the Global Activity Limitation Index (GALI). We estimated prevalence ratios (PR) adjusted for covariates using generalized linear models using the clustering count variable, and dose-response curves using the unhealthy lifestyle index. Most participants (77.4%) reported 2 or more risk factors, with men, middle-age individuals, and those with low socioeconomic status being more likely to do so. Compared to those with 0-1 risk factors, the PR for suboptimal health was 1.26 (95% CI:1.18-1.34) for those reporting 2-3 factors, reaching 1.43 (95% CI:1.31-1.55) for 4-5 factors. The PR for severe activity limitation was 1.66 (95% CI:1.35-2.03) for those reporting 2-3 factors and 2.06 (95% CI:1.59-2.67) for 4-5 factors. The prevalence of both health indicators increased in a non-linear fashion as the unhealthy lifestyle index score increased, increasing rapidly up to 5 points, slowing down between 5 and 10 points, and plateauing afterwards.