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Background The gut microbiota can impact older adults’ health, especially in patients with frailty syndrome. Understanding the association between the gut microbiota and frailty syndrome will help to explain the etiology of age-related diseases. Low-grade systemic inflammation is a factor leading to geriatric disorders, which is known as “inflammaging”. Intestinal dysbiosis has a direct relationship with low-grade systemic inflammation because when the natural gut barrier is altered by age or other factors, some microorganisms or their metabolites can cross this barrier and reach the systemic circulation. Objectives This review had two general goals: first, to describe the characteristics of the gut microbiota associated with age-related diseases, specifically frailty syndrome. The second aim was to identify potential interventions to improve the composition and function of intestinal microbiota, consequently lessening the burden of patients with frailty syndrome. Methods A search of scientific evidence was performed in PubMed, Science Direct, and Redalyc using keywords such as “frailty”, “elderly”, “nutrient interventions”, “probiotics”, and “prebiotics”. We included studies reporting the effects of nutrient supplementation on frailty syndrome and older adults. These studies were analyzed to identify novel therapeutic alternatives to improve gut microbiota characteristics as well as subclinical signs related to this condition. Results The gut microbiota participates in many metabolic processes that have an impact on the brain, muscles, and other organs. These processes integrate feedback mechanisms, comprising their respective axis with the intestine and the gut microbiota. Alterations in these associations can lead to frailty. We report a few interventions that demonstrate that prebiotics and probiotics could modulate the gut microbiota in humans. Furthermore, other nutritional interventions could be used in patients with frailty syndrome. Conclusion Probiotics and prebiotics may potentially prevent frailty syndrome or improve the quality of life of patients with this disorder. However, there is not enough information about their appropriate doses and periods of administration. Therefore, further investigations are required to determine these factors and improve their efficacy as therapeutic approaches for frailty syndrome.

Treatment of chronic hypercapnic failure in COPD patients with home noninvasive ventilation (HNIV) remains unclear.To create a curated cohort of all COPD patients on HNIV in Catalonia, perform a cluster analysis, and evaluate mortality evolution.This study was a multicenter, observational study including all COPD patients on HNIV on 1st January of 2018. Patients were selected through the Catalan Health Service, and administrative and clinical data were obtained in the previous four years. Principal component analysis of mixed data and hierarchical clustering were performed to identify clusters of patients. Mortality was evaluated from 1 January 2018 until 31 December 2020.A total of 247 patients were enrolled. They were mostly male (78.1%), with a median (SD) age of 70.4 (9.4) years old. In 60%, 55% and 29% of patients, obesity, sleep apnea and heart failure coexisted, respectively. Cluster analysis identified four well-differentiated groups labeled for their clinical characteristics: (1) obese smokers, (2) very severe COPD, (3) sleep apnea and (4) older comorbid males. Patients belonging to Clusters (2) and (4) had a worse prognosis than patients in Clusters (1) and (3).A high heterogeneity in the prescription of HNIV was demonstrated. Cluster analysis identifies four different groups, of which only one had COPD as the main cause of ventilation, while the other three clusters showed a predominance of other comorbidities. This leads to different survival outcomes, including an overlapping phenotype of obesity-related disease and sleep apnea with better survival.

We characterized the polysomnography (PSG) parameters associated with alterations in the circadian blood pressure (BP) pattern aiming to identify the main contributors to explain the nondipper profile in obstructive sleep apnea (OSA). This is an observational prospective-multicenter study that included participants referred to the sleep unit for suspected OSA. Following a PSG study, subjects with an apnea–hypopnea index (AHI) ≥5 events/hr were included. Two groups were established based on the 24-hr ambulatory blood pressure monitoring dipping ratio (DR; night/day BP ratio): dippers (DR ≤ 0.9) and nondippers (DR > 0.9). The cohort consisted of 299 patients: 131 (43.8%) dippers and 168 (56.2%) nondippers. A significant increase in the risk of presenting a nondipper BP pattern was found along with AHI gain [odds ratio (OR) (95% CI) = 1.71 (1.28 to 2.28)]. The best AHI cutoff for predicting nondipper status was 25.2 events/hr, increasing the OR (95% CI) to 3.50 (2.02 to 6.07). The hypopnea index [OR (95% CI) = 1.70 (1.27 to 2.26)], TSat90 [OR (95% CI) = 1.41 (1.06 to 1.87)], and respiratory arousal index [OR (95% CI) = 1.74 (1.30 to 2.34)] were individually associated with the risk of a nondipping pattern. Multivariate variable selection processes identified the respiratory arousal index as the most relevant risk factor for the nondipper profile, beyond classical clinical risk factors and usual PSG metrics.

The CARMENES instrument was conceived to deliver high-accuracy radial velocity (RV) measurements with long-term stability to search for temperate rocky planets around a sample of nearby cool stars. The broad wavelength coverage was designed to provide a range of stellar activity indicators to assess the nature of potential RV signals and to provide valuable spectral information to help characterise the stellar targets. The CARMENES Data Release 1 (DR1) makes public all observations obtained during the CARMENES guaranteed time observations, which ran from 2016 to 2020 and collected 19,633 spectra for a sample of 362 targets. The CARMENES survey target selection was aimed at minimising biases, and about 70% of all known M dwarfs within 10 pc and accessible from Calar Alto were included. The data were pipeline-processed, and high-level data products, including 18,642 precise RVs for 345 targets, were derived. Time series data of spectroscopic activity indicators were also obtained. We discuss the characteristics of the CARMENES data, the statistical properties of the stellar sample, and the spectroscopic measurements. We show examples of the use of CARMENES data and provide a contextual view of the exoplanet population revealed by the survey, including 33 new planets, 17 re-analysed planets, and 26 confirmed planets from transiting candidate follow-up. A subsample of 238 targets was used to derive updated planet occurrence rates, yielding an overall average of 1.44+/-0.20 planets with 1 M_Earth < M sin i < 1000 M_Earth and 1 d < P_orb < 1000 d per star, and indicating that nearly every M dwarf hosts at least one planet. CARMENES data have proven very useful for identifying and measuring planetary companions as well as for additional applications, such as the determination of stellar properties, the characterisation of stellar activity, and the study of exoplanet atmospheres., Published in A&A (https://www.aanda.org/10.1051/0004-6361/202244879), 25 pages, 12 figures, Tables 1 and 2 only available online

A Bayesian Network (BN) is a graphical structure, with associated conditional probability tables. This structure allows us to obtain different knowledge than the one obtained from standard classifiers. With a BN, representing a dataset, we can calculate different probabilities about a set of features with respect to other ones. This inference can be more powerful than the one obtained from classifiers. A BN can be built from data and have analytical and diagnostic capabilities that make it very suitable for credit domains. Credit scoring and risk analysis are fundamental tasks for financial institutions with the aim to avoid important losses. In these tasks and other domains, an excessive number of features can convert a BN into a complex and difficult to interpret model, but a few number of features can represent a loss of information obtained from data. A new method based on imprecise probabilities is presented to select an informative subset of features. Using this new feature selection method, we can build a BN that has an excellent adjustment to the data, considering a reduced number of features. Via a set of experiments, it is shown that the adjustment is better than the ones obtained with no previous variable selection method and with a similar and successful variable subset selection method based on precise probabilities. Finally, a BN is built with two important characteristics: (i) it represents a better adjustment to the data; and (ii) it has a low complexity (better interpretability) due to the small number of important selected features. A practical example about inference on a BN to help on credit risk analysis is also presented.

Background MicroRNAs (miRNAs) are noncoding RNAs involved in post-transcriptional genetic regulation with a proposed role in intercellular communication. miRNAs are considered promising biomarkers in ischemic heart disease. Invasive physiological evaluation allows a precise assessment of each affected coronary compartment. Although some studies have associated the expression of circulating miRNAs with invasive physiological indexes, their global relationship with coronary compartments has not been assessed. Here, we will evaluate circulating miRNAs profiles according to the coronary pattern of the vascular compartment affectation. Study and design This is an investigator-initiated, multicentre, descriptive study to be conducted at three centres in Spain (NCT05374694). The study will include one hundred consecutive patients older than 18 years with chest pain of presumed coronary cause undergoing invasive physiological evaluation, including fractional flow reserve (FFR) and index of microvascular resistance (IMR). Patients will be initially classified into four groups, according to FFR and IMR: macrovascular and microvascular affectation (FFR≤0.80 / IMR≥25), isolated macrovascular affectation (FFR≤0.80 / IMR0.80 / IMR ≥25) and normal coronary indexes (FFR>0.80 / IMR Conclusions The results of this study will identify miRNA profiles associated with patterns of coronary affectation and will contribute to a better understanding of the mechanistic pathways of coronary pathology.

To evaluate the sleep and circadian rest-activity pattern of critical COVID-19 survivors 3 months after hospital discharge.Observational, prospective study.Single-center study.One hundred seventy-two consecutive COVID-19 survivors admitted to the ICU with acute respiratory distress syndrome.Seven days of actigraphy for sleep and circadian rest-activity pattern assessment; validated questionnaires; respiratory tests at the 3-month follow-up.The cohort included 172 patients, mostly males (67.4%) with a median (25th-75th percentile) age of 61.0 years (52.8-67.0 yr). The median number of days at the ICU was 11.0 (6.00-24.0), and 51.7% of the patients received invasive mechanical ventilation (IMV). According to the Pittsburgh Sleep Quality Index (PSQI), 60.5% presented poor sleep quality 3 months after hospital discharge, which was further confirmed by actigraphy. Female sex was associated with an increased score in the PSQI (p0.05) and IMV during ICU stay was able to predict a higher fragmentation of the rest-activity rhythm at the 3-month follow-up (p0.001). Furthermore, compromised mental health measured by the Hospital Anxiety and Depression Scale was associated with poor sleep quality (p0.001).Our findings highlight the importance of considering sleep and circadian health after hospital discharge. Within this context, IMV during the ICU stay could aid in predicting an increased fragmentation of the rest-activity rhythm at the 3-month follow-up. Furthermore, compromised mental health could be a marker for sleep disruption at the post-COVID period.

Background: Up to 80% of patients surviving acute respiratory distress syndrome (ARDS) secondary to SARS-CoV- 2 infection present persistent anomalies in pulmonary function after hospital discharge. There is a limited un-derstanding of the mechanistic pathways linked to post-acute pulmonary sequelae. Aim: To identify the molecular underpinnings associated with severe lung diffusion involvement in survivors of SARS-CoV-2-induced ARDS. Methods: Survivors attended to a complete pulmonary evaluation 3 months after hospital discharge. RNA sequencing (RNA-seq) was performed using Illumina technology in whole-blood samples from 50 patients with moderate to severe diffusion impairment (DLCO

The long-term clinical management and evolution of a cohort of critical COVID-19 survivors have not been described in detail. We report a prospective observational study of COVID-19 patients admitted to the ICU between March and August 2020. The follow-up in a post-COVID consultation comprised symptoms, pulmonary function tests, the 6-minute walking test (6MWT), and chest computed tomography (CT). Additionally, questionnaires to evaluate the prevalence of post-COVID-19 syndrome were administered at 1 year. A total of 181 patients were admitted to the ICU during the study period. They were middle-aged (median [IQR] of 61 [52;67]) and male (66.9%), with a median ICU stay of 9 (5–24.2) days. 20% died in the hospital, and 39 were not able to be included. A cohort of 105 patients initiated the follow-up. At 1 year, 32.2% persisted with respiratory alterations and needed to continue the follow-up. Ten percent still had moderate/severe lung diffusion (DLCO) involvement (

Introduction: Cardiovascular diseases are one of the leading causes of death in Mexico. Although the use of anthropometric indicators facilitates the diagnosis of cardiovascular risk (CVR), their use is limited in rural communities with limited resources. This article evaluated and demonstrated predictive capacity of three anthropometric indexes for CVR in Indigenous women in Mexico from Matlatzinca ethnic group. Methods: A cross-sectional study of 93 Indigenous women was carried out. CVR was calculated with the Framingham risk score and used as the reference method by comparing it with waist circumference (WC), conicity index (CoI) and waist-height index (WHI). Receiver operating characteristic (ROC) curves were used to analyze the area under the curve (AUC), sensitivity and specificity for each anthropometric index. Results: Cut-off points (and AUC) for each anthropometric index were WHI 0.63 (0.763), CoI 1.29 (0.756) and WC 91 (0.663). Conclusion: In this population, WHI presented the greatest discrimination power; it was considered the best predictor of CVR because of its high sensitivity. It was demonstrated that the anthropometric indexes WC, CoI and WHI could be used in clinical practice in rural areas without sufficient resources for serological tests.

Question: We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae. Materials and methods: Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge. Results: We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p25;p75] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29-4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42-4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of - 10.77 (95% CI - 18.40 to - 3.15), with a greater number of affected lobes (+ 1.51 [95% CI 0.89-2.13]) and a greater TSS (+ 4.35 [95% CI 2.41-6.27]) in the chest CT scan. Conclusions: Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up. The study was supported in part by ISCIII (CIBERESUCICOVID, COV20/00110), co‑funded by ERDF, “Una manera de hacer Europa” and Donation pro‑gram "estar preparados". UNESPA. Madrid. Spain David de Gonzalo Calvo acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII); Miguel Servet 2020: CP20/00041), co‑funded by the European Social Fund (ESF), “Investing in your future”. JdB acknowledges receiving financial support from Instituto de Salud Carlos III (Miguel Servet 2019: CP19/00108), co‑funded by European Regional European Social Fund (ESF), “Investing in your future"

Background Chimeric Antigen Receptor (CAR)-T cells directed against CD19 have induced high rates of response in patients with relapsed/refractory (R/R) B-cell malignancies. Two CD19-targeting constructs have been approved by the FDA and EMA (Yescarta ®, Kymriah ®) for B lymphoblastic leukemia (B-ALL) and aggressive lymphoma. Despite deep remissions, there are still major challenges and disparate data are reported about the immunogenicity induced by CART-cell therapy. On May/2017, the Spanish Agency of Medicines approved our first clinical trial (clinicaltrials.gov NCT03144583) with a fully academic CART-19. Materials and Methods Eligibility criteria included R/R B-ALL (adult and pediatric), non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia(CLL) who failed standard therapy. The primary objective of the study was safety and secondary objectives were response rate and its duration. The humoral anti-CART response was assessed by a (cell-based) fluorescence assay to detect human anti-murine antibodies (HAMA) in patients sera. Assessment was conducted at different time points: 1) at baseline (pre-dose), 2) on day 14 after the administration of ARI-0001 cells, 3) on day 28, 4) on day 100, and 5) every 3 months thereafter. Results Forty-seven patients (37 adults/10 pediatrics) received ARI-0001 cells. Thirty-eight patients had a diagnosis of R/R B-ALL (28 adults and 10 children); all but 5 had relapsed after allogeneic hematopoietic stem cell transplant (HCT). Seven patients had a diagnosis of NHL, four of them (57%) had relapsed after HCT, and 2 patients had a diagnosis of CLL (2). Median age was 27 years (3–68). After conditioning with fludarabine (90 mg/m2) and cyclophosphamide (900 mg/m2), a total dose of 0.5–5 x106 ARI-0001 cells/kg was infused. Autologous T-cells from peripheral blood were expanded and transduced with a lentivirus to express a CAR with a single-chain variable fragment (scFv) with anti-CD19 specificity, conjugated with the co-stimulatory regions 4-1BB and CD3z. The scFv was originated from a mouse monoclonal antibody A3B1. Twenty-five per cent of the patients tested positive for the presence of anti-CAR antibodies, all of them post-dose, in contrast to previous data reported on Kymriah® with a significant presence of pre-dose anti-murine CAR19 antibody. Of these 12 patients, 8 patients presented with a weak, and 4 patients with a strong presence of HAMA. The last 4 patients had lost the effectiveness of the CART- therapy at that time point, reflected by simultaneous B-cell recovery in the periphery. Moreover, three of them received a second dose of CART-19, which did not revert the relapse. Conclusions To conclude, these data suggest the importance of the immunogenicity induced by CART-cell therapies. Immune monitoring should include the assessment of humoral response, especially before considering a second dose after relapse. Disclosure Information N. Klein-Gonzalez: None. E.A. Gonzalez-Navarro: None. A. Bartolo-Ibars: None. V. Ortiz-Maldonado: None. M. Torrebadell: None. M. Castella: None. D. Benitez: None. M. Caballero-Banos: None. R. Cabezon: None. M. Espanol: None. T. Baumann: None. E. Gine: None. P. Castro: None. J. Esteve: None. J. Yague: None. S. Rives: None. A. Alvaro Urbano-Ispizua: None. J. Delgado: None. M. Juan: None.

Native maize is the main cereal in the diet in rural communities in México, especially in those with a traditional maize-based food-pattern. Although maize has a high nutritional value, its consumption in rural communities has declined in recent decades. Traditional food replacement by modern and processed foods seems to adversely affect the composition of the diet. The aims of this study were: to evaluate the consumption of maize, its influence on nutrient intake in Matlatzincas women, and to analyze the association between the intake of maize food products with specific nutrients within the context of the most current dietary pattern in this indigenous group from central México. In this longitudinal study, we assessed diet over a one-year period, using eight 24-h dietary recalls and a food frequency questionnaire in a rural representative sample of 92 indigenous women aged 19 to 90 years. We derived dietary patterns using principal component analysis based on the intake of ten predefined food groups according to the Mexican equivalents food system. A specific food group based on maize products (maize-food-group) such as tortilla, sopes, pozole, atole, pinole, tacos, etc., was created to identify separately maize consumption in the habitual diet. The percentage of daily energy intake attributed to maize-food-group as well as the intake of macro and micronutrients were estimated. Based on the nutrimental composition of each food group, we analyzed habitual intakes of energy (kcal/d), carbohydrates, proteins, lipids, fiber, vitamins A, D, C and B12 (mg/d), and micronutrients: phosphorus, calcium, iron and zinc (mg/d). Analysis of variance and Pearsońs correlation test were used to evaluate the association between the tertiles of the consumption of maize-food-group and nutrient intake. Additionally, a diet score was calculated to assess diet quality according to maize-food-group consumption. All dietary data were energy-adjusted for the analysis. The consumption of maize-based-foods corresponded to 23.0% of the total caloric intake. Consumption of maize was higher among older women. Consumption of maize-food-group was positively correlated with the ingest of proteins, lipids, dietary fiber, calcium, phosphorus, iron, B12 vitamin, D vitamin and energy (p < 0.05). Better diet quality was associated with a high consumption of maize-food-group. We conclude that the high consumption of maize food products and its positive correlation with the intake of recommended nutrients for healthy diet in adult women, needs interventions in public health to promote a better diet-quality aimed to increase the intake of maize-based food group.

Ultra-processed food consumption has increased in recent years. The evidence suggests a positive association between consumption of ultra-processed food consumption and low diet-quality and malnutrition, characterized by nutritional deficiencies and high prevalence of obesity and overweight. In México the combined prevalence of overweight and obesity in schoolchildren is 33.2%, and ultra-processed food consumption varies from 40.4% to 81.5% depending on the product. The objective of this study was to describe the association between ultra-processed food consumption, diet-quality and nutritional status in Mexican schoolchildren. We analyzed dietetic and anthropometric data from 364 children (6–12 years) of two communities in the center of México. Four 3d-recalls (three days records followed up for ten months including weekdays and weekends) were used for data collection. Consumed foods were classified according to the level of processing using the NOVA classification. Portions of each food, dietary energy, macro and micronutrients intakes were calculated in accordance with the Mexican equivalent food system, nutrition labelling of each product and software Nutrimind® 15.0. Nutritional status was evaluated according to BMI categories; diet-quality was assessed calculating a dietary score. All data were adjusted by energy. In our study, 32% of foods consumed by schoolchildren were ultra-processed, 49% were minimally processed or unprocessed. 30% of the energy intake derived from ultra-processed foods (95% CI 29.2–33.2%). Major ultra-processed foods in habitual diet were bakery, pastries (23%), sugar-sweetened beverages (dairy and non-dairy) (22%), processed meat (18%), pizzas and pastas (9%), and canned vegetables (4%). Children in the highest quartile of ultra-processed foods consumption, presented lower diet-quality than those in the lowest quartile. In this group of children, 38.0% presented combined overweight or obesity, although there were no statistically significant differences between nutritional status and ultra-processed food consumption. Regular ultra-processed food consumption is associated with a lower diet quality in healthy schoolchildren. It is necessary to implement strategies to reduce intake of these products to avoid possible risks to health in early ages.

Additional file 1: Suppl Table 1. The most stable miRNAs in plasma samples of subjects included in the screening cohort. Suppl Figure 1. TaqMan Low Density Array determinations quality control. Number of determinations/missings. Suppl Figure 2. Ct distribution of miRNAs in TaqMan Low Density Array. Suppl Figure 3. The expression stability of the selected candidates characterized by means of GeNorm and Bestkeeper. Suppl Figure 4. Ct distribution of miRNAs in RT-qPCR cohort. Suppl Figure 5. Spearman’s correlations between the selected miRNAs and age.

Synthetic glucocorticoids (GCs) are widely used to treat inflammatory conditions. However, chronic use of GCs can lead to hypertension. The cause of this undesired side effect remains unclear. Previously, we developed an in vivo rat model to study the mechanisms underlying hypertension induced by the chronic administration of the potent synthetic GC, dexamethasone (DEX) and found that the catecholamine biosynthetic pathway plays an important role. In the current study, we used this model to investigate the role of the adrenal medulla, renal nerves, and other peripheral sympathetic nerves in DEX-induced hypertension. After 5 days of baseline telemetric recording of mean arterial pressure (MAP) and heart rate (HR), rats were subjected to one of the following treatments: renal denervation (RDNX), adrenal medullectomy (ADMX), 6-hydroxydopamine (6-OHDA, 20 mg/kg, i.p.) to induce chemical sympathectomy, or a combination of ADMX and 6-OHDA. On day 11, the animals received vehicle (VEH) or DEX in drinking water for 7 days, with the latter causing an increase in MAP in control animals. ADMX and RDNX by themselves exacerbated the pressor effect of DEX. In the chemical sympathectomy group, DEX still caused a rise in MAP but the response was lower (ΔMAP of 6-OHDA/DEX < VEH/DEX, p = 0.039). However, when ΔMAP was normalized to day 10, 6-OHDA + DEX did not show any difference from VEH + DEX, certainly not an increase as observed in DEX + ADMX or RDNX groups. This indicates that sympathetic nerves do not modulate the pressor effect of DEX. TH mRNA levels increased in the adrenal medulla in both VEH/DEX (p = 0.009) and 6-OHDA/DEX (p = 0.031) groups. In the 6-OHDA group, DEX also increased plasma levels of norepinephrine (NE) (p = 0.016). Our results suggest that the activation of catecholamine synthetic pathway could be involved in the pressor response to DEX in animals even under chemical sympathectomy with 6-OHDA.