Determination and inference of eukaryotic transcription factor sequence specificity.

Transcription factor (TF) DNA sequence preferences direct their regulatory activity, but are currently known for only ∼1% of eukaryotic TFs. Broadly sampling DNA-binding domain (DBD) types from multiple eukaryotic clades, we determined DNA sequence preferences for >1,000 TFs encompassing 54 different DBD classes from 131 diverse eukaryotes. We find that closely related DBDs almost always have very similar DNA sequence preferences, enabling inference of motifs for ∼34% of the ∼170,000 known or predicted eukaryotic TFs. Sequences matching both measured and inferred motifs are enriched in chromatin immunoprecipitation sequencing (ChIP-seq) peaks and upstream of transcription start sites in diverse eukaryotic lineages. SNPs defining expression quantitative trait loci in Arabidopsis promoters are also enriched for predicted TF binding sites. Importantly, our motif "library" can be used to identify specific TFs whose binding may be altered by human disease risk alleles. These data present a powerful resource for mapping transcriptional networks across eukaryotes.

Including microbiome information in a multi-trait genomic evaluation: a case study on longitudinal growth performance in beef cattle.

BACKGROUND: Growth rate is an important component of feed conversion efficiency in cattle and varies across the different stages of the finishing period. The metabolic effect of the rumen microbiome is essential for cattle growth, and investigating the genomic and microbial factors that underlie this temporal variation can help maximize feed conversion efficiency at each growth stage. RESULTS: By analysing longitudinal body weights during the finishing period and genomic and metagenomic data from 359 beef cattle, our study demonstrates that the influence of the host genome on the functional rumen microbiome contributes to the temporal variation in average daily gain (ADG) in different months (ADG1, ADG2, ADG3, ADG4). Five hundred and thirty-three additive log-ratio transformed microbial genes (alr-MG) had non-zero genomic correlations (rg) with at least one ADG-trait (ranging from |0.21| to |0.42|). Only a few alr-MG correlated with more than one ADG-trait, which suggests that a differential host-microbiome determinism underlies ADG at different stages. These alr-MG were involved in ribosomal biosynthesis, energy processes, sulphur and aminoacid metabolism and transport, or lipopolysaccharide signalling, among others. We selected two alternative subsets of 32 alr-MG that had a non-uniform or a uniform rg sign with all the ADG-traits, regardless of the rg magnitude, and used them to develop a microbiome-driven breeding strategy based on alr-MG only, or combined with ADG-traits, which was aimed at shaping the rumen microbiome towards increased ADG at all finishing stages. Combining alr-MG information with ADG records increased prediction accuracy of genomic estimated breeding values (GEBV) by 11 to 22% relative to the direct breeding strategy (using ADG-traits only), whereas using microbiome information, only, achieved lower accuracies (from 7 to 41%). Predicted selection responses varied consistently with accuracies. Restricting alr-MG based on their rg sign (uniform subset) did not yield a gain in the predicted response compared to the non-uniform subset, which is explained by the absence of alr-MG showing non-zero rg at least with more than one of the ADG-traits. CONCLUSIONS: Our work sheds light on the role of the microbial metabolism in the growth trajectory of beef cattle at the genomic level and provides insights into the potential benefits of using microbiome information in future genomic breeding programs to accurately estimate GEBV and increase ADG at each finishing stage in beef cattle.

Increased Deaths From Fungal Infections During the Coronavirus Disease 2019 Pandemic-National Vital Statistics System, United States, January 2020-December 2021.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated fungal infections cause severe illness, but comprehensive data on disease burden are lacking. We analyzed US National Vital Statistics System (NVSS) data to characterize disease burden, temporal trends, and demographic characteristics of persons dying of fungal infections during the COVID-19 pandemic. METHODS: Using NVSS's January 2018-December 2021 Multiple Cause of Death Database, we examined numbers and age-adjusted rates (per 100 000 population) of deaths due to fungal infection by fungal pathogen, COVID-19 association, demographic characteristics, and year. RESULTS: Numbers and age-adjusted rates of deaths due to fungal infection increased from 2019 (n = 4833; rate, 1.2 [95% confidence interval, 1.2-1.3]) to 2021 (n = 7199; rate, 1.8 [1.8-1.8] per 100 000); of 13 121 such deaths during 2020-2021, 2868 (21.9%) were COVID-19 associated. Compared with non-COVID-19-associated deaths (n = 10 253), COVID-19-associated deaths more frequently involved Candida (n = 776 [27.1%] vs n = 2432 [23.7%], respectively) and Aspergillus (n = 668 [23.3%] vs n = 1486 [14.5%]) and less frequently involved other specific fungal pathogens. Rates of death due to fungal infection were generally highest in nonwhite and non-Asian populations. Death rates from Aspergillus infections were approximately 2 times higher in the Pacific US census division compared with most other divisions. CONCLUSIONS: Deaths from fungal infection increased during 2020-2021 compared with previous years, primarily driven by COVID-19-associated deaths, particularly those involving Aspergillus and Candida. Our findings may inform efforts to prevent, identify, and treat severe fungal infections in patients with COVID-19, especially in certain racial/ethnic groups and geographic areas.

Behavioral and Personal Characteristics Associated With Risk of SARS-CoV-2 Infection in a Spanish University Cohort.

The aim of this study was to analyze the life habits and personal factors associated with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) risk in a university environment with in-person lectures during the coronavirus disease 2019 (COVID-19) pandemic. To our knowledge, there are no previous longitudinal studies that have analyzed associations of behavioral and personal factors with the risk of SARS-CoV-2 infection on an entire university population. A cohort study was conducted in the 3 campuses of the University of Navarra between August 24, 2020, and May 30, 2021, including 14,496 students and employees; the final sample included 10,959. Descriptive and multivariate-adjusted models were fitted using Cox regression. A total of 1,032 (9.4%) participants were diagnosed with COVID-19 (879 students and 153 employees), almost 50% living with their families. COVID-19 was associated with living in college or residence (hazard ratio (HR) = 1.96, 95% CI: 1.45, 2.64), motor transportation (HR = 1.35, 95% CI: 1.14, 1.61), South American origin (HR = 1.43, 95% CI: 1.20, 1.72), and belonging to Madrid's campus (HR = 3.11, 95% CI: 2.47, 3.92). International students, especially from Latin America, mostly lived in university apartments or shared flats and cohabited with 4-11 people. Living in a big city (Madrid), was a significant risk factor.

Estimation of fatty liver disease clinical role on glucose metabolic remodelling phenotypes and T2DM onset.

INTRODUCTION: Metabolic syndrome (MetS), prediabetes (PreDM) and Fatty Liver Disease (FLD) share pathophysiological pathways concerning type 2 diabetes mellitus (T2DM) onset. The non-invasive assessment of fatty liver combined with PreDM and MetS features screening might provide further accuracy in predicting hyperglycemic status in the clinical setting with the putative description of singular phenotypes. The objective of the study is to evaluate and describe the links of a widely available FLD surrogate -the non-invasive serological biomarker Hepatic Steatosis Index (HSI)- with previously described T2DM risk predictors, such as preDM and MetS in forecasting T2DM onset. PATIENTS AND METHODS: A retrospective ancillary cohort study was performed on 2799 patients recruited in the Vascular-Metabolic CUN cohort. The main outcome was the incidence of T2DM according to ADA criteria. MetS and PreDM were defined according to ATP III and ADA criteria, respectively. Hepatic steatosis index (HSI) with standardized thresholds was used to discriminate patients with FLD, which was referred as estimated FLD (eFLD). RESULTS: MetS and PreDM were more common in patients with eFLD as compared to those with an HSI < 36 points (35% vs 8% and 34% vs. 18%, respectively). Interestingly, eFLD showed clinical effect modification with MetS and PreDM in the prediction of T2DM [eFLD-MetS interaction HR = 4.48 (3.37-5.97) and eFLD-PreDM interaction HR = 6.34 (4.67-8.62)]. These findings supported the description of 5 different liver status-linked phenotypes with increasing risk of T2DM: Control group (1,5% of T2DM incidence), eFLD patients (4,4% of T2DM incidence), eFLD and MetS patients (10,6% of T2DM incidence), PreDM patients (11,1% of T2DM incidence) and eFLD and PreDM patients (28,2% of T2DM incidence). These phenotypes provided independent capacity of prediction of T2DM incidence after adjustment for age, sex, tobacco and alcohol consumption, obesity and number of SMet features with a c-Harrell=0.84. CONCLUSION: Estimated Fatty Liver Disease using HSI criteria (eFLD) interplay with MetS features and PreDM might help to discriminate patient risk of T2DM in the clinical setting through the description of independent metabolic risk phenotypes. [Correction added on 15 June 2023, after first online publication: The abstract section was updated in this current version.].

Prediction of effective humoral response to SARS-CoV-2 vaccines in healthy subjects by cortical thickness of post-vaccination reactive lymphadenopathy.

PURPOSE: To study the association between ultrasound cortical thickness in reactive post-vaccination lymph nodes and the elicited humoral response and to evaluate the performance of cortical thickness as a predictor of vaccine effectiveness in patients with and without a previous history of COVID-19 infection. METHODS: A total of 156 healthy volunteers were recruited and followed prospectively after receiving two COVID-19 vaccination doses using different protocols. Within a week after receiving the second dose, an axillary ultrasound of the ipsilateral vaccinated arm was performed, and serial post-vaccination serologic tests (PVST) were collected. Maximum cortical thickness was chosen as a nodal feature to analyze association with humoral immunity. Total antibodies quantified during consecutive PVST in previously-infected patients and in coronavirus-naïve volunteers were compared (Mann-Whitney U test). The association between hyperplastic-reactive lymph nodes and effective humoral response was studied (odds ratio). The performance of cortical thickness in detecting vaccination effectiveness was evaluated (area under the ROC curve). RESULTS: Significantly higher values for total antibodies were observed in volunteers with a previous history of COVID-19 infection (p < 0.001). The odds ratio associating immunized coronavirus-naïve volunteers after 90 and 180 days of the second dose with a cortical thickness ≥ 3 mm was statistically significant (95% CI 1.52-6.97 and 95% CI 1.47-7.29, respectively). The best AUC result was obtained comparing antibody secretion of coronavirus-naïve volunteers at 180 days (0.738). CONCLUSIONS: Ultrasound cortical thickness of reactive lymph nodes in coronavirus-naïve patients may reflect antibody production and a long-term effective humoral response elicited by vaccination. CLINICAL RELEVANCE STATEMENT: In coronavirus-naïve patients, ultrasound cortical thickness of post-vaccination reactive lymphadenopathy shows a positive association with protective antibody titers against SARS-CoV-2, especially in the long term, providing new insights into previous publications. KEY POINTS: • Hyperplastic lymphadenopathy was frequently observed after COVID-19 vaccination. • Ultrasound cortical thickness of reactive post-vaccine lymph nodes may reflect a long-term effective humoral response in coronavirus-naïve patients.

The long-term boomerang effect of COVID-19 on admissions for non-COVID diseases: the ECIEN-2022 study.

Since COVID-19 pandemic started, many changes have been seen in the cycling patterns of pediatric pathologies. On year 2020, we described the initial effects of COVID-19, with a significant decrease in emergency visits and admissions, but 2 years later the situation seems to be reversed. Our study bridges a literature gap by exploring the lasting effects of COVID-19 on pediatric non-COVID admissions, particularly the resurgence of respiratory illnesses. ECIEN-2022 is a single-center, retrospective, observational-study conducted 3 years after the pandemic onset, to describe the long-term effects of COVID-19 in pediatric admissions for non-COVID diseases. Admissions during year 2022 were compared with the Pre-Pandemic Period (PPP: 2015-2019). Pediatric Emergency Department (P-ED) visits, hospital, and Intensive Care Unit (P-ICU) admissions were compared across pre- and post-pandemic periods. Monthly distribution and year-waves are presented. P-ED monthly visits (mean and Standard deviation (SD) raised from 3521 (533) in the PPP to 3775 (996) in 2022 (p < 0.001). Monthly hospital admissions in the 3rd quarter of the Pre-Pandemic Period were 111.7/month (SD:29), dropped to 88.5(SD:6.5) in 2020 and raised to 149(SD:38.8) in 2022 (p = 0.036). An increase in respiratory illnesses was observed in 2022 compared to PPP; Bronchiolitis increased 38%, bronchitis 56%, and admissions for Respiratory Syncytial Virus 67%.  Conclusion: COVID-19 pandemic has had a significant impact on the use and nature of pediatric health services. The initial decrease has been followed by a boomerang effect with an increase of cases, mainly due to an increase in respiratory infections when pandemic control measures and social restrictions have been lifted. It is essential to maintain an active surveillance and monitorization of these patterns to ensure appropriate healthcare access and utilization. What is Known: • COVID-19 pandemic initially led to a significant decrease in emergency visits and admissions for non-COVID diseases. What is New: • ECIEN-2022 study investigated the long-term effects of COVID-19 on pediatric admissions for non-COVID diseases, detecting a "boomerang effect" with an increase in pediatric admissions for non-COVID diseases in year 2022. • Pediatric Emergency Department visits and hospital admissions for non-COVID diseases, especially those due to respiratory infections, increased significantly in 2022 when compared to the Pre-Pandemic Period.

The Mediterranean Lifestyle and the Risk of Depression in Middle-Aged Adults.

BACKGROUND: Recent evidence has indicated a greater number of protective factors are associated with a greater decreased risk for depression and depressive symptoms compared with individual factors alone. Moreover, adherence to healthy modifiable lifestyle behaviors may lower the risk of depression regardless of underlying genetic risk. OBJECTIVES: We longitudinally evaluated the association of the Mediterranean lifestyle (MEDLIFE) with the risk of depression. METHODS: We prospectively analyzed data from 15,279 participants (6089 men and 9190 women, mean age 37 y) in the Seguimiento Universidad de Navarra cohort. The MEDLIFE index is composed of 28 items on food consumption, dietary habits, physical activity, rest, social habits, and conviviality, each of which was assigned 0 or 1 point. Final scores ranged from 0 to 28 points and were categorized into quartiles of MEDLIFE adherence. Cox proportional regression models determined the association of total MEDLIFE adherence, each item, and block with incident depression. RESULTS: After a mean follow-up of 11.7 y, 912 (6%) incident cases of depression were reported. The mean ± SD final score for MEDLIFE adherence was 11.9 ± 2.7 points. The multivariable model showed that compared with the first quartile, the second and third quartiles of MEDLIFE adherence were significantly associated with a decreased relative risk for incident depression (HR: 0.82; 95% CI: 0.69, 0.96 and HR: 0.74; 95% CI: 0.61, 0.89, respectively). The fourth quartile did not show a statistically significant association with incident depression (HR: 0.89; 95% CI: 0.73, 1.09). CONCLUSIONS: MEDLIFE adherence may decrease the risk of depression in a Spanish cohort of university graduates. Given no clear association was observed among the highest MEDLIFE adherence, future studies are warranted to better understand the nature of this association. Evidence on MEDLIFE, beyond the Mediterranean diet, may contribute toward more effective prevention strategies for depression.

Control of SARS-CoV-2 Infection Rates at a Spanish University With In-Person Class Attendance.

The "Safe Campus Program," implemented in 2020 through 2021 at the University of Navarra (Spain), aimed to guarantee a safe return to university campus and prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks, avoiding university-wide lockdown. It included COVID-19 education, campus adaptation, and polymerase chain reaction (PCR) testing. We describe the main characteristics of the program and analyze the SARS-CoV-2 cumulative incidence among 14 496 university members. The 14-day cumulative incidence in the university was 415.2 versus 447.7 in the region. The program, sustainable in the long term, achieved low SARS-CoV-2 in-campus rates. (Am J Public Health. 2022;112(4):570-573. https://doi.org/10.2105/AJPH.2021.306682.

Unilateral axillary adenopathy induced by COVID-19 vaccine: US follow-up evaluation.

OBJECTIVES: This study was conducted in order to investigate COVID-19 vaccine influence on unilateral axillary lymph nodes, comparing nodal basal features with their characteristics after the first and second vaccination dose. METHODS: Ninety-one volunteer employees from our center who participated in the BNT162b2 (Pfizer-BioNTech) vaccination campaign were prospectively recruited. A total of three axillary ultrasound evaluations of the ipsilateral vaccinated arm were performed: before vaccination, the week after the first dose and the week after the second dose. The following findings were recorded: the total number of visible nodes, the maximum measurements of the diameter and cortex, Bedi's classification, and color Doppler evaluation. The collected data were compared using paired-sample Student's t-test for quantitative continuous variables and Wilcoxon rank-sum test for ordinal variables. Additional analyses were performed after classifying patients according to the previous history of COVID-19 disease. Differences among both groups were evaluated with the Mann-Whitney U test. Variables with a p value < 0.05 were considered statistically significant. RESULTS: Comparative analyses between the three US examinations showed a statistically significant augmentation of total visible nodes, maximum diameter, cortical thickness, grade of Bedi's classification, and Doppler signal (p < 0.001). Analyses between patients with and without previous COVID-19 infection showed a higher lymph node response in naïve patients compared to those who were previously infected. CONCLUSIONS: According to our results, both doses of COVID-19 vaccine induced an increase of all axillary lymph node parameters with statistically significant differences, especially in coronavirus-naïve patients. KEY POINTS: • Pfizer COVID-19 vaccine induces a high incidence of ipsilateral axillary lymphadenopathy. • US scan identified an increase of all lymph nodes parameters, especially in coronavirus-naïve patients.

Axillary lymph node imaging in mRNA, vector-based, and mix-and-match COVID-19 vaccine recipients: ultrasound features.

OBJECTIVES: To assess ultrasound characteristics of ipsilateral axillary lymph nodes after two doses of four different COVID-19 vaccination protocols, to determine whether these parameters differed with age, and to describe how they changed on follow-up imaging. METHODS: A total of 247 volunteer employees from our center who had received two doses of COVID-19 vaccination were recruited and followed prospectively. Axillary ultrasound of the ipsilateral vaccinated arm was performed the week after receiving the second dose to analyze lymph node features (number, long-axis, cortical thickness, morphology, and vascular imaging). Axillary lymphadenopathy resulting from four vaccination protocols-mRNA (BNT162b2, mRNA-1273), ChAdOx1-S, and mix-and-match-was compared. Analysis was conducted using the Kruskal-Wallis test and post hoc analysis with Bonferroni corrections. Nodal reactogenicity was evaluated for two age groups: young (< 45 years old) and middle-aged ( ≥ 45 years old). All parameters were compared between both groups using an unpaired-sample Student t test. A p value < 0.05 was considered statistically significant. RESULTS: Significantly higher values for total number of visible nodes, cortical thickness, Bedi's classification (p < 0.001), and vascularity (p < 0.05) were observed in mRNA vaccine recipients compared to full ChAdOx1-S protocol recipients. Moreover, mix-and-match protocol recipients showed greater nodal cortical thickness and higher Bedi's classification than full ChAdOx1-S recipients (p < 0.001). Analyses between age groups revealed greater cortical thickness, Bedi's classification, and color Doppler signal in younger patients (p < 0.05). CONCLUSIONS: Nodal parameters of Bedi's classification and cortical thickness were more often increased in mRNA and mix-and-match vaccine recipients when compared to ChAdOx1-S vaccine alone, especially in younger patients. KEY POINTS: • Hyperplastic lymphadenopathy was observed more frequently in mRNA and mix-and-match vaccine protocols compared to full vector-based vaccination. • Higher values for cortical thickness, Bedi's classification, and color Doppler signal parameters were identified in younger patients. • Observed lymph node findings normalized in greater than 80% of patients by the third month following vaccination.

A Systematic Review and Meta-Analysis of Advanced Biomarkers for Predicting Incident Cardiovascular Disease among Asymptomatic Middle-Aged Adults.

Cardiovascular disease (CVD) continues as the most important cause of mortality. Better risk screening and prediction are needed to reduce the cardiovascular disease burden. The aim of the study was to assess the role of serum biomarkers in the prediction of CVD among asymptomatic middle-aged adults with no prior CVD history. A systematic review and meta-analysis were carried out using literature from PubMed and following PRISMA reporting guidelines. Twenty-five studies met our inclusion criteria and were included in the systematic review. The most commonly studied biomarker was high-sensitivity C reactive protein (hs-CRP) (10 studies), which showed that higher hs-CRP levels are associated with an increased risk of subsequent CVD events and mortality. In addition, several less-studied biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), fibrinogen, gamma-glutamyl transferase (GGT), and others) also showed significant associations with greater future risk of CVD. A meta-analysis was possible to perform for hs-CRP and NT-proBNP, which showed statistically significant results for the ability of hs-CRP (hazard ratio (HR) 1.19, (95% CI: 1.09−1.30), p < 0.05) and NT-proBNP (HR 1.22, (1.13−1.32), p < 0.05) to predict incident CVD among middle-aged adults without a prior CVD history or symptoms. Several serum biomarkers, particularly hs-CRP and NT-proBNP, have the potential to improve primary CVD risk prevention among asymptomatic middle-aged adults.

A Mediterranean lifestyle reduces the risk of cardiovascular disease in the "Seguimiento Universidad de Navarra" (SUN) cohort.

BACKGROUND AND AIMS: A healthy lifestyle is essential to prevent cardiovascular disease (CVD). However, beyond dietary habits, there is a scarcity of studies comprehensively assessing the typical traditional Mediterranean lifestyle with a multi-dimensional index. We assessed the association between the Mediterranean lifestyle (measured with the MEDLIFE index including diet, physical activity, and other lifestyle factors) and the incidence of CVD. METHODS AND RESULTS: The "Seguimiento Universidad de Navarra" (SUN) project is a prospective, dynamic and multipurpose cohort of Spanish university graduates. We calculated a MEDLIFE score, composed of 28 items on food consumption, dietary habits, physical activity, rest, social habits, and conviviality, for 18,631 participants by assigning 1 point for each typical Mediterranean lifestyle factor achieved, for a theoretically possible final score ranging from 0 to 28 points. During an average follow-up of 11.5 years, 172 CVD cases (myocardial infarction, stroke or cardiovascular death) were observed. An inverse association between the MEDLIFE score and the risk of primary cardiovascular events was observed, with multivariable-adjusted hazard ratio (HR) = 0.50; (95% confidence interval, 0.31-0.81) for the highest MEDLIFE scores (14-23 points) compared to the lowest scores (0-9 points), p (trend) = 0.004. CONCLUSION: A higher level of adherence to the Mediterranean lifestyle was significantly associated with a lower risk of CVD in a Spanish cohort. Public health strategies should promote the Mediterranean lifestyle to preserve cardiovascular health.

A dimensional reduction approach to modulate the core ruminal microbiome associated with methane emissions via selective breeding.

The rumen is a complex microbial system of substantial importance in terms of greenhouse gas emissions and feed efficiency. This study proposes combining metagenomic and host genomic data for selective breeding of the cow hologenome toward reduced methane emissions. We analyzed nanopore long reads from the rumen metagenome of 437 Holstein cows from 14 commercial herds in 4 northern regions in Spain. After filtering, data were treated as compositional. The large complexity of the rumen microbiota was aggregated, through principal component analysis (PCA), into few principal components (PC) that were used as proxies of the core metagenome. The PCA allowed us to condense the huge and fuzzy taxonomical and functional information from the metagenome into a few PC. Bivariate animal models were applied using these PC and methane production as phenotypes. The variability condensed in these PC is controlled by the cow genome, with heritability estimates for the first PC of ~0.30 at all taxonomic levels, with a large probability (>83%) of the posterior distribution being >0.20 and with the 95% highest posterior density interval (95%HPD) not containing zero. Most genetic correlation estimates between PC1 and methane were large (≥0.70), with most of the posterior distribution (>82%) being >0.50 and with its 95%HPD not containing zero. Enteric methane production was positively associated with relative abundance of eukaryotes (protozoa and fungi) through the first component of the PCA at phylum, class, order, family, and genus. Nanopore long reads allowed the characterization of the core rumen metagenome using whole-metagenome sequencing, and the purposed aggregated variables could be used in animal breeding programs to reduce methane emissions in future generations.

Dimensions of leisure-time physical activity and risk of depression in the "Seguimiento Universidad de Navarra" (SUN) prospective cohort.

BACKGROUND: An inverse association between total leisure-time physical activity (LTPA) and depression has been previously documented in the scientific literature. Our objective was to prospectively assess the association of LTPA with the risk of depression, focusing on several dimensions of LTPA (intensity, duration and type). METHODS: The SUN (Seguimiento Universidad de Navarra) project is a prospective cohort study formed by Spanish university graduates. A total of 15,488 adults (40.2% men, mean age 37 ± 12 years) initially free of depression were assessed. A report of a validated medical diagnosis of depression or the habitual use of antidepressants (any of both) were considered as incident cases of depression. LTPA was estimated through previously validated self-reported questionnaires. Participants were classified following Physical Activity recommendations from the World Health Organization, and according to the intensity, duration and type of LTPA. Cox proportional hazards regression models were run, adjusted for demographic, lifestyle, and dietary factors, to estimate adjusted hazard ratios (HR) of depression and 95% confidence intervals (CI). RESULTS: During 163,059 person-years of follow-up we registered 870 incident cases of depression. Participants with higher total LTPA (METs-h/wk) and higher duration of LTPA (hours/wk) exhibited a lower risk of depression HR = 0.84 (95% CI: 0.72-0.99) and HR = 0.83 (0.70-0.99) respectively, whereas intensity of LTPA (MET) did not show any association with depression. CONCLUSION: Participants with higher LTPA had a lower risk of depression. The inverse association was stronger for total LPTA time than for its intensity. Higher duration of LTPA should be encouraged to prevent depression.

Correction to: Dimensions of leisure-time physical activity and risk of depression in the "Seguimiento Universidad de Navarra" (SUN) prospective cohort.

After publication of our article [1] we have been notified that Table 2 was incorrectly formatted.

Do healthy doctors deliver better messages of health promotion to their patients?: Data from the SUN cohort study.

BACKGROUND: Healthy lifestyle adherence is associated with lower chronic disease morbidity/mortality. The role of doctors, as counselors and role models, is essential. Among physicians participating in a prospective cohort, we investigated the behavioral counseling on diet and lifestyle provided to their patients in association with their own personal behaviors. METHODS: We assessed 890 doctors aged ≤65 years participating in the 'Seguimiento Universidad de Navarra' (SUN) cohort, who replied to an online questionnaire regarding their practices on behavioral counseling and drug prescription to their patients. Data were combined with previous baseline information on their personal healthy habits. RESULTS: Among doctors, 31% reported <10 min per visit; 73% counseled 60-100% of their patients on smoking cessation, 58% on physical activity, 54% on weight control, 51% on healthy nutrition, 44% on alcohol avoidance/reduction and 28% recommended alcohol moderate consumption. The percentage of doctors that counseled 100% of their patients about lifestyle was 43% for smoking cessation, 15% for exercise and 13% for weight control and nutrition. Better doctor's adherence to the Mediterranean dietary pattern was associated with more frequent and longer nutrition counseling. Higher practice of physical activity was associated with longer time on counseling about exercise to their patients. Among doctors both current and former smoking were inversely associated with the frequency and duration of their smoking cessation/avoidance counseling practices. CONCLUSIONS: Personal behavioral changes among doctors and better training of medical doctors on a personal healthy diet and lifestyle are likely to contribute to improve the behavioral counseling given to patients.

Structural equation models to disentangle the biological relationship between microbiota and complex traits: Methane production in dairy cattle as a case of study.

The advent of metagenomics in animal breeding poses the challenge of statistically modelling the relationship between the microbiome, the host genetics and relevant complex traits. A set of structural equation models (SEMs) of a recursive type within a Markov chain Monte Carlo (MCMC) framework was proposed here to jointly analyse the host-metagenome-phenotype relationship. A non-recursive bivariate model was set as benchmark to compare the recursive model. The relative abundance of rumen microbes (RA), methane concentration (CH4 ) and the host genetics was used as a case of study. Data were from 337 Holstein cows from 12 herds in the north and north-west of Spain. Microbial composition from each cow was obtained from whole metagenome sequencing of ruminal content samples using a MinION device from Oxford Nanopore Technologies. Methane concentration was measured with Guardian® NG infrared gas monitor from Edinburgh Sensors during cow's visits to the milking automated system. A quarterly average from the methane eructation peaks for each cow was computed and used as phenotype for CH4 . Heritability of CH4 was estimated at 0.12 ± 0.01 in both the recursive and bivariate models. Likewise, heritability estimates for the relative abundance of the taxa overlapped between models and ranged between 0.08 and 0.48. Genetic correlations between the microbial composition and CH4 ranged from -0.76 to 0.65 in the non-recursive bivariate model and from -0.68 to 0.69 in the recursive model. Regardless of the statistical model used, positive genetic correlations with methane were estimated consistently for the seven genera pertaining to the Ciliophora phylum, as well as for those genera belonging to the Euryarchaeota (Methanobrevibacter sp.), Chytridiomycota (Neocallimastix sp.) and Fibrobacteres (Fibrobacter sp.) phyla. These results suggest that rumen's whole metagenome recursively regulates methane emissions in dairy cows and that both CH4 and the microbiota compositions are partially controlled by the host genotype.

Sarcopenia: Molecular Pathways and Potential Targets for Intervention.

Aging is associated with sarcopenia. The loss of strength results in decreased muscle mass and motor function. This process accelerates the progressive muscle deterioration observed in older adults, favoring the presence of debilitating pathologies. In addition, sarcopenia leads to a decrease in quality of life, significantly affecting self-sufficiency. Altogether, these results in an increase in economic resources from the National Health Systems devoted to mitigating this problem in the elderly, particularly in developed countries. Different etiological determinants are involved in the progression of the disease, including: neurological factors, endocrine alterations, as well as nutritional and lifestyle changes related to the adoption of more sedentary habits. Molecular and cellular mechanisms have not been clearly characterized, resulting in the absence of an effective treatment for sarcopenia. Nevertheless, physical activity seems to be the sole strategy to delay sarcopenia and its symptoms. The present review intends to bring together the data explaining how physical activity modulates at a molecular and cellular level all factors that predispose or favor the progression of this deteriorating pathology.

Biochemical and Muscle Mechanical Postmarathon Changes in Hot and Humid Conditions.

Gutiérrez-Vargas, R, Martín-Rodríguez, S, Sánchez-Ureña, B, Rodríguez-Montero, A, Salas-Cabrera, J, Gutiérrez-Vargas, JC, Simunic, B, and Rojas-Valverde, D. Biochemical and muscle mechanical postmarathon changes in hot and humid conditions. J Strength Cond Res 34(3): 847-856, 2020-The aim of this study was to compare biochemical changes and mechanical changes in the lower-limb muscles before and after a marathon race in hot and humid conditions. Eighteen healthy runners participated in a marathon at between 28 and 34° C and 81% humidity in Costa Rica. Serum magnesium (Mg), creatine phosphokinase (CPK), lactate dehydrogenase, and hematocrit (HCT) were measured before and after the marathon. Tensiomyography measurements from the rectus femoris (RF) and vastus medialis, muscle displacement (Dm), contraction time (Tc), and velocities of contraction to 10 and 90% of Dm (V10 and V90) were obtained before and after the marathon. Postrace measurements showed a 544% increase in CPK (t(17): -6.925, p < 0.01), a 16% increase in HCT (t(17): -7.466, p < 0.01), a 29% decrease in Mg (t(17): 3.91, p = 0.001), a 2% decrease in body mass (t(17): 4.162, p = 0.001), a 4% increase in Tc of the RF (t(17): -2.588, p = 0.019), and a 12% increase in Dm of the RF (t(17): -2.131, p < 0.048) compared with prerace measurements. No significant biochemical or mechanical differences were found between runners in terms of their finish times. These findings showed that completing a marathon in hot and humid conditions induced a significant reduction in lower-limb muscle stiffness, body mass, and Mg, and increased neuromuscular fatigue, CPK, and HCT, because of muscle damage and dehydration. Knowledge of the effects of heat and humidity may be of value for coaches and sports medicine practitioners in developing effective hydration and recovery protocols for marathon runners in these special conditions.