Changes In Serum CXCL13 Levels Are Associated With Outcomes of Colorectal Cancer Patients Undergoing First-Line Oxaliplatin-Based Treatment.

Metastatic colorectal cancer (mCRC) currently lacks reliable biomarkers for precision medicine, particularly for chemotherapy-based treatments. This study examines the behavior of 11 CXC chemokines in the blood of 104 mCRC patients undergoing first-line oxaliplatin-based treatment to pinpoint predictive and prognostic markers. Serum samples were collected before treatment, at response evaluation (EVAR), and at disease progression or last follow-up. Chemokines were assessed in all samples using a Luminex® custom panel. CXCL13 levels increased at EVAR in responders, while in non-responders it decreased. Increasing levels of CXCL13 at EVAR, independently correlated with improved progression-free survival (PFS) and overall survival (OS). Nanostring® analysis in primary tumor samples showed CXCL13 gene expression's positive correlation not only with gene profiles related to an immunogenic tumor microenvironment, increased B cells and T cells (mainly CD8+) but also with extended OS. In silico analysis using RNAseq data from liver metastases treated or not with neoadjuvant oxaliplatin-based combinations, and deconvolution analysis using the MCP-counter algorithm, confirmed CXCL13 gene expression's association with increased immune infiltration, improved OS, and Tertiary Lymphoid Structures (TLSs) gene signatures, especially in neoadjuvant-treated patients. CXCL13 analysis in serum from 36 oxaliplatin-treated patients from the METIMMOX study control arm, reported similar findings. In conclusion, the increase of CXCL13 levels in peripheral blood and its association with the formation of TLSs within the metastatic lesions, emerges as a potential biomarker indicative of the therapeutic efficacy in mCRC patients undergoing oxaliplatin-based treatment.

Cardiac index-guided therapy to maintain optimised postinduction cardiac index in high-risk patients having major open abdominal surgery: the multicentre randomised iPEGASUS trial.

BACKGROUND: It is unclear whether optimising intraoperative cardiac index can reduce postoperative complications. We tested the hypothesis that maintaining optimised postinduction cardiac index during and for the first 8 h after surgery reduces the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. METHODS: In three German and two Spanish centres, high-risk patients having elective major open abdominal surgery were randomised to cardiac index-guided therapy to maintain optimised postinduction cardiac index (cardiac index at which pulse pressure variation was <12%) during and for the first 8 h after surgery using intravenous fluids and dobutamine or to routine care. The primary outcome was the incidence of a composite outcome of moderate or severe complications within 28 days after surgery. RESULTS: We analysed 318 of 380 enrolled subjects. The composite primary outcome occurred in 84 of 152 subjects (55%) assigned to cardiac index-guided therapy and in 77 of 166 subjects (46%) assigned to routine care (odds ratio: 1.87, 95% confidence interval: 1.03-3.39, P=0.038). Per-protocol analyses confirmed the results of the primary outcome analysis. CONCLUSIONS: Maintaining optimised postinduction cardiac index during and for the first 8 h after surgery did not reduce, and possibly increased, the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. Clinicians should not strive to maintain optimised postinduction cardiac index during and after surgery in expectation of reducing complications. CLINICAL TRIAL REGISTRATION: NCT03021525.

The Nutri-Score nutrition label: Associations between the underlying nutritional profile of foods and lipoprotein particle subclass profiles in adults.

BACKGROUND AND AIMS: Lipoprotein particle concentrations and size are associated with increased risk for atherosclerosis and premature cardiovascular disease. Certain dietary behaviours may be cardioprotective and public health strategies are needed to guide consumers' dietary choices and help prevent diet-related disease. The Food Standards Agency nutrient profiling system (FSAm-NPS) constitutes the basis of the five-colour front-of-pack Nutri-Score labelling system. No study has examined FSAm-NPS index associations with a wide range of lipoprotein particle subclasses. METHODS: This was a cross-sectional study of 2006 middle-to older-aged men and women randomly selected from a large primary care centre. Individual participant FSAm-NPS dietary scores were derived from validated food frequency questionnaires. Lipoprotein particle subclass concentrations and size were determined using nuclear magnetic resonance spectroscopy. Multivariate-adjusted linear regression analyses were performed to examine FSAm-NPS relationships with lipoprotein particle subclasses. RESULTS: In fully adjusted models which accounted for multiple testing, higher FSAm-NPS scores, indicating poorer dietary quality, were positively associated with intermediate-density lipoprotein (ß = 0.096, p = 0.005) and small high-density lipoprotein (HDL) (ß = 0.492, p = 0.006) concentrations, a lipoprotein insulin resistance score (ß = 0.063, p = 0.02), reflecting greater lipoprotein-related insulin resistance, and inversely associated with HDL size (ß = -0.030, p = 0.045). CONCLUSIONS: A higher FSAm-NPS score is associated with a less favourable lipoprotein particle subclass profile in middle-to older-aged adults which may be a potential mechanism underlying reported health benefits of a healthy diet according to Nutri-Score rating.

Plant-based diet adherence is associated with metabolic health status in adults living with and without obesity.

PURPOSE: Metabolic health phenotypes exist across the body mass index spectrum. Diet may be an important modifiable risk factor, yet limited research exists on dietary patterns in this context. We investigated associations between dietary patterns, reflecting dietary quality, healthfulness and inflammatory potential, and metabolic health phenotypes in adults living with and without obesity. METHODS: This cross-sectional study included 2,040 middle- to older-aged men and women randomly selected from a large primary care centre. The Dietary Approaches to Stop Hypertension score, Healthy Eating Index, Dietary Inflammatory Index, overall, healthful and unhealthful plant-based dietary indices and Nutri-Score were derived from validated food frequency questionnaires. Descriptive and logistic regression analyses were used to examine diet score relationships with metabolic health phenotypes (Metabolically Healthy/Unhealthy Obese (MHO/MUO) and Non-Obese (MHNO/MUNO)), defined using three separate metabolic health definitions, each capturing different aspects of metabolic health. RESULTS: In fully adjusted models, higher unhealthful plant-based dietary scores were associated with a lower likelihood of MHO (OR = 0.96, 95% CI: 0.93-1.00, p = 0.038) and MHNO (OR = 0.97, 95% CI: 0.95-0.99, p = 0.006). Higher Nutri-Score values were associated with an increased likelihood of MHNO (OR = 1.06, 95% CI: 1.01-1.13, p = 0.033). CONCLUSION: These findings provide evidence that more unhealthful plant-based diets may be linked with unfavourable metabolic health status, irrespective of BMI.

Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry.

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed.  A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70-145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient's age, and patients' origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders. What is Known: • Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness. What is New: • Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy. • PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.

Proton-Pump Inhibitors in Eosinophilic Esophagitis: A Review Focused on the Role of Pharmacogenetics.

Proton-pump inhibitors (PPIs) are the most administered first-line treatment for eosinophilic esophagitis (EoE). However, only around half of EoE patients respond histologically to a double dosage of PPI. In addition, 70% of responders maintain EoE in remission after tapering the PPI dose. In order to avoid endoscopy with biopsies-the only accurate method of assessing PPI response-efforts have been made to identify PPI responder patients. The clinical or endoscopic features and biomarkers evaluated so far, however, have not proven to be sufficient in predicting PPI response. Although new approaches based on omics technologies have uncovered promising biomarkers, the specialized and complex procedures required are difficult to implement in clinical settings. Alternatively, PPI pharmacogenetics based on identifying variations in CYP2C19 and STAT6 genes have shown promising results in EoE, and could easily be performed in most laboratories. Other genetic variations have also been associated with PPI response and may explain those cases not related to CYP2C19 or STAT6. Here, we provide an overview of PPI treatment in EoE and evidence of how genetic variations in CYP2C19 and other genes could affect PPI effectiveness, and also discuss studies evaluating the role of pharmacogenetics in predicting PPI response in patients with EoE.

Income insecurity and mental health in pandemic times.

This paper contributes to the literature on the impact of the COVID-19 outbreak on mental health by providing novel evidence of its interaction with labor market conditions and the long-term persistence of these effects. We run four waves of a large-scale representative survey in Spain between April 2020 and April 2022, and benchmark our data against a decade of pre-pandemic information. We document an increase in the share of individuals reporting depressive feelings from 16% prior to the pandemic to 46% in April 2020. We show that this effect is more pronounced for women, younger individuals and those with unstable incomes. We apply machine learning techniques, mediation analysis and event studies to document the role of the labor market as an important driver of these effects. Our results are crucial for the design of targeted policies that proof useful in overcoming the long lasting consequences of the pandemic.

Underneath Images and Robots, Looking Deeper into the Pneumoperitoneum: A Narrative Review.

Laparoscopy offers numerous advantages over open procedures, minimizing trauma, reducing pain, accelerating recovery, and shortening hospital stays. Despite other technical advancements, pneumoperitoneum insufflation has received little attention, barely evolving since its inception. We explore the impact of pneumoperitoneum on patient outcomes and advocate for a minimally invasive approach that prioritizes peritoneal homeostasis. The nonlinear relationship between intra-abdominal pressure (IAP) and intra-abdominal volume (IAV) is discussed, emphasizing IAP titration to balance physiological effects and surgical workspace. Maintaining IAP below 10 mmHg is generally recommended, but factors such as patient positioning and surgical complexity must be considered. The depth of neuromuscular blockade (NMB) is explored as another variable affecting laparoscopic conditions. While deep NMB appears favorable for surgical stillness, achieving a balance between IAP and NMB depth is crucial. Temperature and humidity management during pneumoperitoneum are crucial for patient safety and optical field quality. Despite the debate over the significance of temperature drop, humidification and the warming of insufflated gas offer benefits in peritoneal homeostasis and visual clarity. In conclusion, there is potential for a paradigm shift in pneumoperitoneum management, with dynamic IAP adjustments and careful control of insufflated gas temperature and humidity to preserve peritoneal homeostasis and improve patient outcomes in minimally invasive surgery.

Swallowed topical corticosteroids for eosinophilic esophagitis: Utilization and real-world efficacy from the EoE CONNECT registry.

BACKGROUND: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses. OBJECTIVE: To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice. METHODS: Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations. RESULTS: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness. CONCLUSION: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness.

Fibrous Remodeling in Eosinophilic Esophagitis: Clinical Facts and Pathophysiological Uncertainties.

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease with increasing global prevalence. An eosinophil-predominant inflammation that permeates the epithelium and deeper esophageal layers characterizes the disease. Several cytokines, mainly derived from inflammatory T-helper 2 (Th2) cells and epithelial cells, are involved in perpetuating inflammatory responses by increasing surface permeability and promoting tissue remodeling characterized by epithelial-mesenchymal transition (EMT) and collagen deposition. This leads to esophageal strictures and narrow caliber esophagi, which are proportional a patient's age and untreated disease length. Pathophysiological mechanisms leading to EoE have been described in recent years, and transforming growth factor beta (TGF)-beta have been involved in fibrotic phenomena in EoE. However, evidence on the dependence of these phenomena on TGF-beta is scarce and contradictory. This review provides state-of-the art knowledge on intimate mechanisms of esophageal fibrosis in EoE and its clinical consequences.

Prone Positioning and Molecular Biomarkers in COVID and Non-COVID ARDS: A Narrative Review.

Prone positioning (PP) represents a therapeutic intervention with the proven capacity of ameliorating gas exchanges and ventilatory mechanics indicated in acute respiratory distress syndrome (ARDS). When PP is selectively applied to moderate-severe cases of ARDS, it sensitively affects clinical outcomes, including mortality. After the COVID-19 outbreak, clinical application of PP peaked worldwide and was applied in 60% of treated cases, according to large reports. Research on this topic has revealed many physiological underpinnings of PP, focusing on regional ventilation redistribution and the reduction of parenchymal stress and strain. However, there is a lack of evidence on biomarkers behavior in different phases and phenotypes of ARDS. Patients response to PP are, to date, decided on PaO2/FiO2 ratio improvement, whereas scarce data exist on biomarker tracking during PP. The purpose of this review is to explore current evidence on the clinical relevance of biomarkers in the setting of moderate-severe ARDS of different etiologies (i.e., COVID and non-COVID-related ARDS). Moreover, this review focuses on how PP may modulate biomarkers and which biomarkers may have a role in outcome prediction in ARDS patients.

Systematic Review and Meta-Analysis: Prevalence of Non-Alcoholic Fatty Liver Disease and Liver Fibrosis in Patients with Inflammatory Bowel Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common concomitant condition in patients with inflammatory bowel disease (IBD). We aim to assess the magnitude of this association. METHODS: We searched MEDLINE, EMBASE and Scopus libraries for the period up to February 2023 to identify studies reporting cohorts of IBD patients in which NALFLD was evaluated. RESULTS: Eighty-nine studies were analyzed. The overall prevalence of NAFLD was 24.4% (95%CI, 19.3-29.8) in IBD, 20.2% (18.3-22.3) in Crohn's disease and 18.5% (16.4-20.8) for ulcerative colitis. Higher prevalence was found in male compared to female patients, in full papers compared to abstracts, and in cross-sectional studies compared to prospective and retrospective ones. The prevalence of NAFLD in IBD has increased in studies published from 2015 onwards: 23.2% (21.5-24.9) vs. 17.8% (13.2-22.9). Diagnostic methods for NAFLD determined prevalence figures, being highest in patients assessed by controlled attenuation parameter (38.8%; 33.1-44.7) compared to ultrasonography (28.5%; 23.1-34.2) or other methods. The overall prevalence of fibrosis was 16.7% (12.2-21.7) but varied greatly according to the measurement method. CONCLUSION: One-quarter of patients with IBD might present with NAFLD worldwide. This proportion was higher in recent studies and in those that used current diagnostic methods.

Numerical coupling of 0D and 1D models in networks of vessels including transonic flow conditions. Application to short-term transient and stationary hemodynamic simulation of postural changes.

When modeling complex fluid networks using one-dimensional (1D) approaches, boundary conditions can be imposed using zero-dimensional (0D) models. An application case is the modeling of the entire human circulation using closed-loop models. These models can be considered as a tool to investigate short-term transient and stationary hemodynamic responses to postural changes. The first shortcoming of existing 1D modeling methods in simulating these sudden maneuvers is their inability to deal with rapid variations in flow conditions, as they are limited to the subsonic case. On the other hand, numerical modeling of 0D models representing microvascular beds, venous valves or heart chambers is also currently modeled assuming subsonic flow conditions in 1D connecting vessels, failing when transonic and supersonic flow conditions appear. Therefore, if numerical simulation of sudden maneuvers is a goal in closed-loop models, it is necessary to reformulate the current methodologies used when coupling 0D and 1D models, allowing the correct handling of flow evolution for both subsonic and transonic conditions. This work focuses on the extension of the general methodology for the Junction Riemann Problem (JRP) when coupling 0D and 1D models. As an example of application, the short-term transient response to head-up tilt (HUT) from supine to upright position of a closed-loop model is shown, demonstrating the potential, capability and necessity of the presented numerical models when dealing with sudden maneuvers.

Frequency of symptoms and the associated factors of eating disorders in a group of dental students in Medellín, Colombia.

BACKGROUND: Eating disorders (EDs) are considered a public health problem. Scientific research has focused on teenagers due to their higher prevalence in this population. However, other groups, such as university students, may be exposed to suffering from EDs due to their academic, social and personal characteristics. Identifying the magnitude of EDs and the associated characteristics may impact the generation of prevention strategies. OBJECTIVES: The aim of the present study was to establish the prevalence of the risk of EDs (anorexia nervosa (AN) and bulimia nervosa (BN)) and the associated factors in dental students at the University of Antioquia, Medellín, Colombia.. MATERIAL AND METHODS: A cross-sectional study was conducted on 278 students (76 males, 202 females) with the use of a Google-Forms survey. The validated Spanish version of the Eating Attitudes Test-26 (EAT-26) and the Sick, Control, One Stone, Fat, Food (SCOFF) questionnaire were used. Other recorded variables included sociodemographic data, coronavirus disease 2019 (COVID-19)-related factors, health, and social support (the Duke-11 profile). The bivariate analysis of the risk of EDs was conducted according to different variables (95% confidence interval (CI)), followed by the logistic regression models adjusting for different variables (adjusted prevalence ratio (aPR) and 95% CI). RESULTS: According to EAT-26, the risk of EDs was 27.6% (18.8-38.6) for males and 28.7% (22.9-35.3) for females. However, differences between males and females were higher when the SCOFF questionnaire was applied (males: 6.6% (2.8-14.5); females: 22.3% (17.1-28.5); p < 0.01). According to the SCOFF instrument, after adjusting for sociodemographic and health variables, women were more likely to report the symptoms of EDs (aPR: 2.20; 95% CI: 1.06-4.57). Women receiving information from social networks were more likely to report the symptoms of EDs (aPR: 1.85; 95% CI: 1.19-2.88). Multivariate models showed that women reporting poor self-rated health and some symptoms during the mandatory confinement caused by the COVID-19 pandemic were more likely to report the symptoms of EDs. CONCLUSIONS: A higher risk of EDs was found in dental students. Healthcare, psychological and/or psychiatric interviews, and educational/early prevention strategies are required.

Evaluating employability in contexts of change: validation of a scale.

Introduction: Employability is a crucial factor in managing to emerge and changing job demands. This study validates an expanded version of the Employability Appraisal Scale: EAS-60, as an instrument to identify and improve competencies for employability. Method: The EAS-60 was tested in a cross-sectional study in a Spanish population. An exploratory study was carried out using a sample of 188 workers, and the scale's structure was analyzed and confirmed in two Confirmatory Factor Analyses using a sample of 527 workers. Finally, reliability and validity were evaluated. Results: Exploratory and confirmatory analyses provide evidence supporting the multi-dimensional structure. The scale presents good psychometric properties and criteria for interpreting the scores. Discussion: The EAS-60 is a reliable and valid instrument. It allows Human Resource Managers to offer career plans at work that include specific actions of job socialization, training, improvement of specific skills, etc. Furthermore, employees can increase their employability and develop their professional careers.

Gal-1 Expression Analysis in the GLIOCAT Multicenter Study: Role as a Prognostic Factor and an Immune-Suppressive Biomarker.

Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The ß-galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4 IDH-1 mutant astrocytomas, which have a better prognosis. Our results confirm the role of Gal-1 as a prognostic factor and also suggest its value as an immune-suppressive biomarker in GBM.

Development and validation of the Work Envy Appraisal Scale (WEAS) for Spanish workers.

Envy is an important emotion that affects workers' behavior and performance. Instruments to measure envy are available, but new scales are needed for the analysis of work envy that include appraisals of challenge (benign envy) and threat (malicious envy). Based on Lazarus and Folkman's theory, the objective of this study is to develop and validate the Work Envy Appraisal Scale (WEAS) for Spanish workers. It had been carried out in two studies; in the first study, the scale was constructed and its dimensions were analyzed with a sample of 100 Spanish workers (sample 1). In the second study, the scale was validated and its psychometric properties were analyzed (sample 2, N = 219; sample 3, N = 532). The results of exploratory, confirmatory, and multigroup factor analysis showed good indices of fit for the two-factor structure. Moreover, the results showed adequate convergent and discriminant validity. Furthermore, our findings indicated that the scale is a reliable and valid instrument for measuring envy at work. This way of measuring envy at work (discerning its challenge and threat appraisal) makes it possible to find answers to some recurrent research questions (e.g. social desirability issues, the confusion of envy with other topics, etc.) and can facilitate reliable research on envy at work.

Maternal and Paternal Dietary Quality and Dietary Inflammation Associations with Offspring DNA Methylation and Epigenetic Biomarkers of Aging in the Lifeways Cross-Generation Study.

BACKGROUND: Early-life nutritional exposures may contribute to offspring epigenetic modifications. However, few studies have evaluated parental dietary quality effects on offspring DNA methylation (DNAm). OBJECTIVES: We aim to fill this gap by elucidating the influence of maternal and paternal whole-diet quality and inflammatory potential on offspring DNAm in the Lifeways Cross-generation cohort. METHODS: Families (n = 1124) were recruited around 16 weeks of gestation in the Republic of Ireland between 2001 and 2003. Maternal dietary intake during the first trimester and paternal diet during the 12 previous months were assessed with an FFQ. Parental dietary inflammatory potential and quality were determined using the energy-adjusted Dietary Inflammatory Index (E-DII), the Healthy Eating Index-2015 (HEI-2015), and the maternal DASH score. DNAm in the saliva of 246 children at age nine was measured using the Illumina Infinium HumanMethylationEPIC array. DNAm-derived biomarkers of aging, the Pediatric-Buccal-Epigenetic clock and DNAm estimator of telomere length, were calculated. Parental diet associations with the DNAm concentrations of 850K Cytosine-phosphate-guanine sites (CpG sites) and with DNAm-derived biomarkers of aging were examined using an epigenome-wide association study and linear regressions, respectively. RESULTS: Maternal HEI-2015 scores were inversely associated with DNAm at CpG site (cg21840035) located near the PLEKHM1 gene, whose functions involve regulation of bone development (ß = -0.0036, per 1 point increase in the score; P = 5.6 × 10-8). Higher paternal HEI-2015 score was related to lower methylation at CpG site (cg22431767), located near cell signaling gene LUZP1 (ß = -0.0022, per 1 point increase in the score, P = 4.1 × 10-8). There were no associations with parental E-DII and DASH scores, and no evidence of major effects on biomarkers of aging. CONCLUSIONS: Parental dietary quality in the prenatal period, evaluated by the HEI-2015, may influence offspring DNAm during childhood. Further research to improve our understanding of parental nutritional programming is warranted.

Blood-Based Biomarkers for Eosinophilic Esophagitis and Concomitant Atopic Diseases: A Look into the Potential of Extracellular Vesicles.

Eosinophilic esophagitis (EoE) is a chronic, Th2-inflammatory disease of the esophagus that can severely affect food intake. Currently, diagnosis and assessing response to treatment of EoE is highly invasive and requires endoscopy with esophageal biopsies. Finding non-invasive and accurate biomarkers is important for improving patient well-being. Unfortunately, EoE is usually accompanied by other atopies, which make it difficult to identify specific biomarkers. Providing an update of circulating EoE biomarkers and concomitant atopies is therefore timely. This review summarizes the current knowledge in EoE blood biomarkers and two of its most common comorbidities, bronchial asthma (BA) and atopic dermatitis (AD), focusing on dysregulated proteins, metabolites, and RNAs. It also revises the current knowledge on extracellular vesicles (EVs) as non-invasive biomarkers for BA and AD, and concludes with the potential use of EVs as biomarkers in EoE.