The RNA m6A Reader YTHDF2 Is Essential for the Post-transcriptional Regulation of the Maternal Transcriptome and Oocyte Competence.

YTHDF2 binds and destabilizes N6-methyladenosine (m6A)-modified mRNA. The extent to which this branch of m6A RNA-regulatory pathway functions in vivo and contributes to mammalian development remains unknown. Here we find that YTHDF2 deficiency is partially permissive in mice and results in female-specific infertility. Using conditional mutagenesis, we demonstrate that YTHDF2 is autonomously required within the germline to produce MII oocytes that are competent to sustain early zygotic development. Oocyte maturation is associated with a wave of maternal RNA degradation, and the resulting relative changes to the MII transcriptome are integral to oocyte quality. The loss of YTHDF2 results in the failure to regulate transcript dosage of a cohort of genes during oocyte maturation, with enrichment observed for the YTHDF2-binding consensus and evidence of m6A in these upregulated genes. In summary, the m6A-reader YTHDF2 is an intrinsic determinant of mammalian oocyte competence and early zygotic development.

Development and Validation of a Scoring System to Predict Response to Obeticholic Acid in Primary Biliary Cholangitis.

BACKGROUND & AIMS: Obeticholic acid (OCA) is the only licensed second-line therapy for primary biliary cholangitis (PBC). With novel therapeutics in advanced development, clinical tools are needed to tailor the treatment algorithm. We aimed to derive and externally validate the OCA response score (ORS) for predicting the response probability of individuals with PBC to OCA. METHODS: We used data from the Italian RECAPITULATE (N = 441) and the IBER-PBC (N = 244) OCA real-world prospective cohorts to derive/validate a score including widely available variables obtained either pre-treatment (ORS) or also after 6 months of treatment (ORS+). Multivariable Cox regressions with backward selection were applied to obtain parsimonious predictive models. The predicted outcomes were biochemical response according to POISE (alkaline phosphatase [ALP]/upper limit of normal [ULN]<1.67 with a reduction of at least 15%, and normal bilirubin), or ALP/ULN<1.67, or Normal range criteria (NR: normal ALP, alanine aminotransferase [ALT], and bilirubin) up to 24 months. RESULTS: Depending on the response criteria, ORS included age, pruritus, cirrhosis, ALP/ULN, ALT/ULN, GGT/ULN, and bilirubin. ORS+ also included ALP/ULN and bilirubin after 6 months of OCA therapy. Internally validated c-statistics for ORS were 0.75, 0.78, and 0.72 for POISE, ALP/ULN<1.67, and NR response, which raised to 0.83, 0.88, and 0.81 with ORS+, respectively. The respective performances in validation were 0.70, 0.72, and 0.71 for ORS and 0.80, 0.84, and 0.78 for ORS+. Results were consistent across groups with mild/severe disease. CONCLUSIONS: We developed and externally validated a scoring system capable to predict OCA response according to different criteria. This tool will enhance a stratified second-line therapy model to streamline standard care and trial delivery in PBC.

The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Adherence to Mediterranean Diet and Aromatic Plants Intake are Related with Gustatory Function: A Case-Study from a Portuguese Region.

The Mediterranean Diet has been recognized as one of the healthiest and most sustainable dietary patterns and is flavor rich due to the use of different seasonings, such as aromatic plants, in dish confection. Based on the hypotheses that: 1) gustatory function will affect food choices; 2) seasoning flavors may be differently accepted according to individuals' gustatory functions; the aim of the present study was to assess the association between taste sensitivity and/or preference with Mediterranean Diet adherence and seasoning consumption. A total of 383 adults (18-59 years old; 198 female, 185 male) from southeast of Portugal were enrolled in this study, with 291 (145 female and 146 male) also evaluated for gustatory function. Recognition thresholds were obtained for four tastes (sweet, sour, salty, and bitter) and astringency, as well as preference level for the highest concentration of each stimulus tested. A validated Food Frequency Questionnaire was filled out, and MD adherence was extrapolated from the answers of the Food Frequency Questionnaire according to the Mediterranean Diet Adherence Screener (MEDAS) score. In total, 20.8% of the individuals presented low, 58.2% medium, and 21.0% high adherence. Adherence was higher in women than men and in older individuals than younger adults. Adherence to the Mediterranean Diet was positively correlated with aromatic plants consumption but not spices. Seasonings were associated with gustatory function, and the cluster with higher consumption presented higher preferences for bitter and salty tastes. Total sodium intake was also higher in this cluster, suggesting that these individuals prefer stronger oral sensations. In conclusion, this study shows that MD adherence is not high, even in regions with rural characteristics. The observed association of Mediterranean Diet and seasoning intake with gustatory function do underline the usefulness of this information in strategies aimed at promoting healthy and sustainable eating patterns.

Development and validation of a photograph-based instrument to assess nutrition literacy: The NUTLY project.

Most instruments measuring nutrition literacy evaluate theoretical knowledge, not necessarily reflecting skills relevant to food choices. We aimed to develop and validate a photograph-based instrument to assess nutrition literacy (NUTLY) among adults in Portugal. NUTLY assesses the ability to distinguish foods with different nutritional profiles; from each of several combinations of three photographs (two foods with similar contents and one with higher content) participants are asked to identify the food with the highest energy/sodium content. The NUTLY version with 79 combinations, obtained after experts/lay people evaluations, was applied to a sample representing different age, gender and education groups (n = 329). Dimensionality was evaluated through latent trait models. Combinations with negative or with positive small factor loadings were excluded after critical assessment. Internal consistency was measured using Cronbach's alpha and construct validity by comparing NUTLY scores with those obtained in the Medical Term Recognition Test and the Newest Vital Sign (NVS), and across education and training in nutrition/health groups. The cut-off to distinguish adequate/inadequate nutrition literacy was defined through ROC analysis using the Youden index criterion, after performing a Latent class analysis which identified a two-class model to have the best goodness of fit. Test-retest reliability was assessed after one month (n = 158). The final NUTLY scale was unidimensional and included 48 combinations (energy: 33; sodium: 15; α = 0.74). Mean scores (±standard deviation) were highest among nutritionists (39.9 ± 4.4), followed by health professionals (38.5 ± 4.1) and declined with decreasing education (p < 0.001). Those with adequate nutrition literacy according to NVS showed higher NUTLY scores (37.9 ± 4.3 vs. 33.9 ± 6.9, p < 0.001). Adequate nutrition literacy was defined as a NUTLY score≥35 (sensitivity: 89.3%; specificity: 93.7%). Test-retest reliability was high (ICC = 0.77). NUTLY is a valid and reliable nutrition literacy measurement tool.

Perceived stress modulates the activity between the amygdala and the cortex.

The significant link between stress and psychiatric disorders has prompted research on stress's impact on the brain. Interestingly, previous studies on healthy subjects have demonstrated an association between perceived stress and amygdala volume, although the mechanisms by which perceived stress can affect brain function remain unknown. To better understand what this association entails at a functional level, herein, we explore the association of perceived stress, measured by the PSS10 questionnaire, with disseminated functional connectivity between brain areas. Using resting-state fMRI from 252 healthy subjects spanning a broad age range, we performed both a seed-based amygdala connectivity analysis (static connectivity, with spatial resolution but no temporal definition) and a whole-brain data-driven approach to detect altered patterns of phase interactions between brain areas (dynamic connectivity with spatiotemporal information). Results show that increased perceived stress is directly associated with increased amygdala connectivity with frontal cortical regions, which is driven by a reduced occurrence of an activity pattern where the signals in the amygdala and the hippocampus evolve in opposite directions with respect to the rest of the brain. Overall, these results not only reinforce the pathological effect of in-phase synchronicity between subcortical and cortical brain areas but also demonstrate the protective effect of counterbalanced (i.e., phase-shifted) activity between brain subsystems, which are otherwise missed with correlation-based functional connectivity analysis.

Promoting the use of the PI-QUAL score for prostate MRI quality: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship.

OBJECTIVES: The Prostate Imaging Quality (PI-QUAL) score is a new metric to evaluate the diagnostic quality of multiparametric magnetic resonance imaging (MRI) of the prostate. This study assesses the impact of an intervention, namely a prostate MRI quality training lecture, on the participant's ability to apply PI-QUAL. METHODS: Sixteen participants (radiologists, urologists, physicists, and computer scientists) of varying experience in reviewing diagnostic prostate MRI all assessed the image quality of ten examinations from different vendors and machines. Then, they attended a dedicated lecture followed by a hands-on workshop on MRI quality assessment using the PI-QUAL score. Five scans assessed by the participants were evaluated in the workshop using the PI-QUAL score for teaching purposes. After the course, the same participants evaluated the image quality of a new set of ten scans applying the PI-QUAL score. Results were assessed using receiver operating characteristic analysis. The reference standard was the PI-QUAL score assessed by one of the developers of PI-QUAL. RESULTS: There was a significant improvement in average area under the curve for the evaluation of image quality from baseline (0.59 [95 % confidence intervals: 0.50-0.66]) to post-teaching (0.96 [0.92-0.98]), an improvement of 0.37 [0.21-0.41] (p < 0.001). CONCLUSIONS: A teaching course (dedicated lecture + hands-on workshop) on PI-QUAL significantly improved the application of this scoring system to assess the quality of prostate MRI examinations. KEY POINTS: • A significant improvement in the application of PI-QUAL for the assessment of prostate MR image quality was observed after an educational intervention. • Appropriate training on image quality can be delivered to those involved in the acquisition and interpretation of prostate MRI. • Further investigation will be needed to understand the impact on improving the acquisition of high-quality diagnostic prostate MR examinations.

Nutritional adequacy of commercial food products targeted at 0-36-month-old children: a study in Brazil and Portugal.

In the context of the global childhood obesity, it is essential to monitor the nutrition value of commercial foods. A cross-sectional study (November 2018 to April 2019) aimed to evaluate the nutritional adequacy of processed/ultra-processed food products targeted at 0-36-month-old children in Portugal and in Brazil. The nutrient profiling model developed by the Pan American Health Organization was used. A total of food 171 products were assessed (123 in Portugal and forty eight in Brazil). From the fifteen available meat- or fish-based meals in Brazil, 60 % exceeded the amount of Na and 100 % exceeded the target for total fat. Given the lack of specification of sugars within carbohydrates in the label of the foods in Brazil, it was not possible to calculate free sugars. In Portugal, from the seventeen fruit and vegetable purees and the six juice/smoothie/tea/drinks available, 82 % and 67 %, respectively, surpassed the level of free sugar, while total and saturated fat was excessive in all yogurt and yogurt-related products (n 21), 40 % of biscuit/wafer/crisps (two out of five) and 13 % meat- or fish-based meals (two out of sixteen). These findings demonstrate the relevance of improving the nutritional profile of some food products targeted to young children.

Endoscopic Ultrasound Through-The-Needle Biopsy of Pancreatic Cysts: Toward Procedure Standardization.

BACKGROUND AND AIMS: EUS-guided through-the-needle microforceps biopsy (EUS-TTNB) was introduced as a new diagnostic tool to establish pancreatic cyst histotype and help to better risk stratify the patients. The aim of this study was to describe the technical success, diagnostic yield, and adverse events of through-the-needle biopsy and discuss the technique variations, focusing on future procedure standardization. METHODS: We performed a prospective single-center study including patients with presumed mucinous cysts harboring worrisome features or indeterminate cyst type on imaging, submitted to EUS-TTNB using Moray® microforceps between March 2018 and September 2021. Specimens were processed as a cell-block. RESULTS: We included 40 patients. Technical success was 97.5%. The diagnostic yield was 72.5% for TTNB whereas for cyst fluid cytology/analysis it was 27.5%. Moreover, without TTNB 5 mucinous lesions would not have been diagnosed. TTNB had a sensitivity of 76% and a specificity of 91%, while FNA cytology had a sensitivity and specificity of 35% and 91%, respectively. Moreover for IPMN lesions, subtyping was possible in 63% of cases. TTNB resulted in change in clinical management in 20% of patients. We registered three adverse events: 2 self-limited intracystic bleeding and 1 patient with abdominal pain not associated with pancreatitis. CONCLUSION: TTNB proved superior to cyst fluid analysis and cytology for the definition of cyst histotype and mucinous cyst diagnosis with acceptable risk profile. Further studies should explore the best steps for procedure standardization.

Iodine intake assessment in the staff of a Porto region university (Portugal): the iMC Salt trial.

PURPOSE: Iodine deficiency disorder (IDD) is an ongoing worldwide recognized problem with over two billion individuals having insufficient iodine intake. School-aged children and pregnant women are often target groups for epidemiological studies, but there is a lack of knowledge on the general adult population. The aim of this study was to assess the iodine status among a Portuguese public university staff as a proxy for the adult working population. METHODS: The population study covered 103 adults within the iMC Salt randomized clinical trial, aged 24-69 years. Urinary iodine concentration was measured spectrophotometrically using the Sandell-Kolthoff reaction. Iodine food intake was assessed using a 24-h dietary recall. The contribution of discretionary salt to the iodine daily intake was assessed through 24-h urinary sodium excretion (UIE) and potentiometric iodine determination of household salt. RESULTS: The mean urine volume in 24 h was 1.5 L. The median daily iodine intake estimated from 24-h UIE was 113 µg/day, being lower among women (p < 0.05). Only 22% of participants showed iodine intake above the WHO-recommended cutoff (150 µg/day). The median daily iodine intake estimated from the 24-h dietary recall was 58 µg/day (51 and 68 µg/day in women and men, respectively). Dairy, including yoghurt and milk products, were the primary dietary iodine source (55%). Iodine intake estimated from 24-h UIE and 24-h dietary recall was moderately correlated (Spearman rank correlation coefficient r = 0.34, p < 0.05). The average iodine concentration in household salt was 14 mg I/kg, with 45% of the samples below the minimum threshold preconized by WHO (15 mg I/kg). The contribution of discretionary salt to the daily iodine intake was around 38%. CONCLUSION: This study contributes new knowledge about iodine status in Portuguese working adults. The results revealed moderate iodine deficiency, particularly in women. Public health strategies and monitoring programs are needed to ensure iodine adequacy in all population groups.

mRNA 3' uridylation and poly(A) tail length sculpt the mammalian maternal transcriptome.

A fundamental principle in biology is that the program for early development is established during oogenesis in the form of the maternal transcriptome. How the maternal transcriptome acquires the appropriate content and dosage of transcripts is not fully understood. Here we show that 3' terminal uridylation of mRNA mediated by TUT4 and TUT7 sculpts the mouse maternal transcriptome by eliminating transcripts during oocyte growth. Uridylation mediated by TUT4 and TUT7 is essential for both oocyte maturation and fertility. In comparison to somatic cells, the oocyte transcriptome has a shorter poly(A) tail and a higher relative proportion of terminal oligo-uridylation. Deletion of TUT4 and TUT7 leads to the accumulation of a cohort of transcripts with a high frequency of very short poly(A) tails, and a loss of 3' oligo-uridylation. By contrast, deficiency of TUT4 and TUT7 does not alter gene expression in a variety of somatic cells. In summary, we show that poly(A) tail length and 3' terminal uridylation have essential and specific functions in shaping a functional maternal transcriptome.

Effect of irradiance and exposure time on the adhesive properties of universal adhesives after 2 years of storage.

OBJECTIVE: This study aims to evaluate the effects of exposure time and irradiance on the dentin bonding properties (microtensile bond strength (µTBS) and nanoleakage (NL)) of the Clearfil Universal Bond Quick (CUQ) adhesive and Scotchbond Universal Adhesive (SBU) immediately and after 2 years of water storage. MATERIAL AND METHODS: Hence, 128 human molars were randomly assigned to 16 groups based on adhesive strategy, irradiance/exposure times, and storage time for each universal adhesive tested. The adhesives were applied using the etch-and-rinse and self-etch strategies and were light-cured using four different irradiance/exposure times: 1400 mW/cm2 for 5 s (1400 × 5), 1400 mW/cm2 for 10 s (1400 × 10), 3200 mW/cm2 for 5 s (3200 × 5), and 3200 mW/cm2 for 10 s (3200 × 10). Then, each sample was restored and sectioned into a resin-dentin bonded stick to be tested for µTBS and NL (immediately and after 2 years of water storage). The mean µTBS and NL of all resin-dentin bonded sticks from the same hemi-tooth (factor time) were statistically analyzed using a three-way ANOVA and Tukey's test (a = 0.05). RESULTS: Despite a significant decrease in the µTBS values for all groups after 2 years of water storage, the 3200 × 5 group showed higher µTBS values, whereas the 3200 × 10 group showed lower µTBS values for both universal adhesives tested. Although a significant increase in the NL values was observed for all groups after 2 years of water storage, the 3200 × 10 group showed higher NL values than the other groups (p < 0.001). CONCLUSION: Results indicate that light-curing the adhesive layer with 14-16 J/cm2 led to an improvement in the stability of the resin-dentin adhesive interface. A longer exposure time (10 s) coupled with a higher irradiance (3200 mW/cm2) resulted in a greater degree of degradation of the adhesive interface. CLINICAL SIGNIFICANCE: To guarantee better stability of the adhesive interface, clinicians could be preferred a light-cured universal adhesive layer with 14-16 J/cm2. Higher irradiances should be avoided.

Association of amygdala size with stress perception: Findings of a transversal study across the lifespan.

Daily routines are getting increasingly stressful. Interestingly, associations between stress perception and amygdala volume, a brain region implicated in emotional behaviour, have been observed in both younger and older adults. Life stress, on the other hand, has become pervasive and is no longer restricted to a specific age group or life stage. As a result, it is vital to consider stress as a continuum across the lifespan. In this study, we investigated the relationship between perceived stress and amygdala size in 272 healthy participants with a broad age range. Participants were submitted to a structural magnetic resonance imaging (MRI) to extract amygdala volume, and the Perceived Stress Scale (PSS) scores were used as the independent variable in volumetric regressions. We found that perceived stress is positively associated with the right amygdala volume throughout life.

A novel method for estimating connectivity-based parcellation of the human brain from diffusion MRI: Application to an aging cohort.

Connectivity-based parcellation (CBP) methods are used to define homogenous and biologically meaningful parcels or nodes-the foundations of brain network fingerprinting-by grouping voxels with similar patterns of brain connectivity. However, we still lack a gold standard method and the use of CBPs to study the aging brain remains scarce. Our study proposes a novel CBP method from diffusion MRI data and shows its potential to produce a more accurate characterization of the longitudinal alterations in brain network topology occurring in aging. For this, we constructed whole-brain connectivity maps from diffusion MRI data of two datasets: an aging cohort evaluated at two timepoints (mean interval time: 52.8 ± 7.24 months) and a normative adult cohort-MGH-HCP. State-of-the-art clustering techniques were used to identify the best performing technique. Furthermore, we developed a new metric (connectivity homogeneity fingerprint [CHF]) to evaluate the success of the final CBP in improving regional/global structural connectivity homogeneity. Our results show that our method successfully generates highly homogeneous parcels, as described by the significantly larger CHF score of the resulting parcellation, when compared to the original. Additionally, we demonstrated that the developed parcellation provides a robust anatomical framework to assess longitudinal changes in the aging brain. Our results reveal that aging is characterized by a reorganization of the brain's structural network involving the decrease of intra-hemispheric, increase of inter-hemispheric connectivity, and topological rearrangement. Overall, this study proposes a new methodology to perform accurate and robust evaluations of CBP of the human brain.

Habitual coffee drinkers display a distinct pattern of brain functional connectivity.

Coffee is the most widely consumed source of caffeine worldwide, partly due to the psychoactive effects of this methylxanthine. Interestingly, the effects of its chronic consumption on the brain's intrinsic functional networks are still largely unknown. This study provides the first extended characterization of the effects of chronic coffee consumption on human brain networks. Subjects were recruited and divided into two groups: habitual coffee drinkers (CD) and non-coffee drinkers (NCD). Resting-state functional magnetic resonance imaging (fMRI) was acquired in these volunteers who were also assessed regarding stress, anxiety, and depression scores. In the neuroimaging evaluation, the CD group showed decreased functional connectivity in the somatosensory and limbic networks during resting state as assessed with independent component analysis. The CD group also showed decreased functional connectivity in a network comprising subcortical and posterior brain regions associated with somatosensory, motor, and emotional processing as assessed with network-based statistics; moreover, CD displayed longer lifetime of a functional network involving subcortical regions, the visual network and the cerebellum. Importantly, all these differences were dependent on the frequency of caffeine consumption, and were reproduced after NCD drank coffee. CD showed higher stress levels than NCD, and although no other group effects were observed in this psychological assessment, increased frequency of caffeine consumption was also associated with increased anxiety in males. In conclusion, higher consumption of coffee and caffeinated products has an impact in brain functional connectivity at rest with implications in emotionality, alertness, and readiness to action.

The relationship between height and fruit/vegetable intakes in adults: A nationwide cross-sectional study.

Background: Worldwide, fruit and vegetable intake is below recommendations. There is increasing evidence to suggest an association between height and diet. Aim: to analyse the associations of fruit and vegetable intake with attained height in Portuguese adults. Methods: A representative sample of 17 480 Portuguese adults (56.7% women) participated in this cross-sectional study. The survey comprised sociodemographic characteristics and self-reported height and weight. We performed regression models to assess the associations between height and fruit and vegetable consumption. Results: Compared with no intakes, those men with higher fruit and vegetables intake had 0.54 cm (95% CI 0.04; 1.04) greater height. Also, women with higher intakes of vegetables, fruit and vegetables combined were directly associated with a greater height of 0.29 cm (95% CI 0.03; 0.56 in vegetables) and 0.51 cm (95% CI 0.09; 0.93 in fruit and vegetables combined). Conclusion: Greater consumption of fruit and vegetables was directly associated with higher height in adults. From a health promotion perspective, intervention programmes aiming at improving fruit and vegetable intake should be highlighted so that full height potential is achieved.

Reorganization of brain structural networks in aging: A longitudinal study.

Normal aging is characterized by structural and functional changes in the brain contributing to cognitive decline. Structural connectivity (SC) describes the anatomical backbone linking distinct functional subunits of the brain and disruption of this communication is thought to be one of the potential contributors for the age-related deterioration observed in cognition. Several studies already explored brain network's reorganization during aging, but most focused on average connectivity of the whole-brain or in specific networks, such as the resting-state networks. Here, we aimed to characterize longitudinal changes of white matter (WM) structural brain networks, through the identification of sub-networks with significantly altered connectivity along time. Then, we tested associations between longitudinal changes in network connectivity and cognition. We also assessed longitudinal changes in topological properties of the networks. For this, older adults were evaluated at two timepoints, with a mean interval time of 52.8 months (SD = 7.24). WM structural networks were derived from diffusion magnetic resonance imaging, and cognitive status from neurocognitive testing. Our results show age-related changes in brain SC, characterized by both decreases and increases in connectivity weight. Interestingly, decreases occur in intra-hemispheric connections formed mainly by association fibers, while increases occur mostly in inter-hemispheric connections and involve association, commissural, and projection fibers, supporting the last-in-first-out hypothesis. Regarding topology, two hubs were lost, alongside with a decrease in connector-hub inter-modular connectivity, reflecting reduced integration. Simultaneously, there was an increase in the number of provincial hubs, suggesting increased segregation. Overall, these results confirm that aging triggers a reorganization of the brain structural network.

Exhaled breath condensate pH determinants in school-aged children: A population-based study.

BACKGROUND: Exhaled breath condensate (EBC) pH is a promising biomarker of airway inflammation. Lack of method standardization and interstudy variability precludes its use in clinical practice. While endogenous determinants have been described, underlying mechanisms for variability are mostly unknown. Thus, we aimed to assess the association between asthma and EBC pH in children, while studying potential environmental factors for interstudy variability. METHODS: A cross-sectional analysis of exhaled breath condensates from 613 children, aged 7-12 years, was conducted. Assessments included lung function and airway reversibility, exhaled nitric oxide, allergic sensitization, and body mass index (BMI). Indoor air quality (IAQ) was assessed in children's classrooms during 5 school days. Post-deaeration EBC pH showed a bimodal distribution, and the sample was split into acidic and alkaline groups. Regression models were constructed to assess the effects of asthma and asthma adjusted to IAQ parameters on EBC pH. RESULTS: Following adjustment to gender and BMI, asthma was significantly associated with a lower EBC pH in the acidic group. The effect of asthma on EBC pH was independent of IAQ, in both groups. In the acidic group, EBC pH was significantly affected by temperature [ß = -0.09 (-0.15, -0.02)] and PM 2.5 concentration [ß = -0.16 (-0.32, -0.01)], and in the alkaline group by relative humidity [ß = 0.07 (0.02, 0.13)] and concentration of endotoxins [ß = -0.06 (-0.1, -0.01)]. CONCLUSION: Our study shows that in addition to individual determinants such as asthma, environmental factors may influence and should be taken into consideration when interpreting EBC pH level in children.

Higher diversity of vegetable consumption is associated with less airway inflammation and prevalence of asthma in school-aged children.

BACKGROUND: A diet rich in fruits and vegetables has been suggested to counteract the oxidative stress and inflammation that characterize asthma. We aimed to assess the association between vegetable and fruit diversity consumption and asthma and its related outcomes in school-aged children. METHODS: Participants included 647 children (49% females, aged 7-12 years) recruited from 20 public schools across the city of Porto, in Portugal. Vegetable intake and fruit intake were ascertained using a single self-reported 24-hour recall questionnaire. A diversity score was built taking into account the different number of individual vegetables and fruits consumed and categorized into two groups based on the total reported median consumption, which was rounded to the nearest whole number (≤3 and >3, for vegetables; and ≤1 and >1, for fruits). A questionnaire was used to enquire about self-reported medical diagnosis of asthma and respiratory symptoms. Airway inflammation was assessed measuring exhaled fractional nitric oxide concentration (eNO) and was categorized into two groups (<35 and ≥35 ppb). The association between fruit and vegetable diversity and respiratory outcomes was examined using logistic regression models, adjusting for confounders. RESULTS: A higher vegetable diversity consumption per day was negatively associated with having self-reported asthma (OR = 0.67; 95% CI 0.47, 0.95), while having a vegetable diversity consumption superior to 3 items per day was negatively associated with levels of eNO ≥ 35 ppb (OR = 0.38; 95% CI 0.16, 0.88) and breathing difficulties (OR = 0.39; 95% CI 0.16, 0.97). CONCLUSION: Eating a greater variety of vegetables was associated with a lower chance of airway inflammation and prevalence of self-reported asthma in school children.

Development of an Online App to Predict Post-Endoscopic Retrograde Cholangiopancreatography Adverse Events Using a Single-Center Retrospective Cohort.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding procedure with a high risk for adverse events (AEs). AIM: evaluate patient- and procedure-related risk factors for ERCP-related AEs and develop an online app to estimate risk of AEs. METHODS: retrospective study of 1,491 consecutive patients who underwent 1,991 ERCPs between 2012 and 2017 was conducted. AEs definition and severity were classified according to most recent ESGE guidelines. Each variable was tested for association with occurrence of overall AEs, post-ERCP pancreatitis (PEP) and cholangitis. For each outcome, 2 regression models were built, from which an online Shiny-based app was created. RESULTS: Overall AE rate was 15.3%; in 19 procedures, >1 AE occurred. Main post-ERCP AE was PEP (7.5%), followed by cholangitis (4.9%), bleeding (1.3%), perforation (1%), cardiopulmonary events (0.9%), and cholecystitis (0.3%). Seventy-eight percent of AEs were mild/moderate; of severe (n = 55) and fatal (n = 20) AEs, more than half were related to infection, cardiac/pulmonary AEs, and perforation. AE-related mortality rate was 1%. When testing precannulation, procedural covariates, and ERCP findings, AE occurrence was associated with age (odds ratio [OR] 0.991), previous PEP (OR 2.198), ERCP complexity grade III/IV (OR 1.924), standard bile duct cannulation (OR 0.501), sphincterotomy (OR 1.441), metal biliary stent placement (OR 2.014), periprocedural bleeding (OR 3.024), and biliary duct lithiasis (OR 0.673). CONCLUSION: Our app may allow an optimization of the patients' care, by helping in the process of decision-making, not only regarding patient or endoscopist's selection but also definition of an adequate and tailored surveillance plan after the procedure.