Predictability of B cell clonal persistence and immunosurveillance in breast cancer.

B cells and T cells are important components of the adaptive immune system and mediate anticancer immunity. The T cell landscape in cancer is well characterized, but the contribution of B cells to anticancer immunosurveillance is less well explored. Here we show an integrative analysis of the B cell and T cell receptor repertoire from individuals with metastatic breast cancer and individuals with early breast cancer during neoadjuvant therapy. Using immune receptor, RNA and whole-exome sequencing, we show that both B cell and T cell responses seem to coevolve with the metastatic cancer genomes and mirror tumor mutational and neoantigen architecture. B cell clones associated with metastatic immunosurveillance and temporal persistence were more expanded and distinct from site-specific clones. B cell clonal immunosurveillance and temporal persistence are predictable from the clonal structure, with higher-centrality B cell antigen receptors more likely to be detected across multiple metastases or across time. This predictability was generalizable across other immune-mediated disorders. This work lays a foundation for prioritizing antibody sequences for therapeutic targeting in cancer.

Dietary Protein Quality Affects the Interplay between Gut Microbiota and Host Performance in Nile Tilapia.

Dietary protein quality plays a key role in maintaining intestinal mucosal integrity, but also modulates the growth of luminal microorganisms. This work assessed the effect of dietary protein sources on the performance, gut morphology, and microbiome in Nile tilapia. Four isonitrogenous and isolipidic diets comprising equivalent amounts of the protein supply derived from either PLANT, ANIMAL, INSECT, or BACTERIAL (bacterial biomass) sources were fed to triplicate groups of fish (IBW: 12 g) for 46 days. Fish fed the ANIMAL and BACTERIAL diets showed significantly higher weight gains than those fed the PLANT and INSECT diets (p < 0.05). Relative abundance at the phylum level showed that Bacteroidetes, Fusobacteria, and Proteobacteria were the more abundant phyla in tilapia's intestine, while Cetobacterium was the most representative genus in all treatments. Interesting patterns were observed in the correlation between amino acid intake and genus and species abundance. Metabolism prediction analysis showed that BACTERIAL amine and polyamine degradation pathways are modulated depending on diets. In conclusion, different protein sources modulate the relationship between bacteria functional pathways and amino acid intake.

Salicornia ramosissima Biomass as a Partial Replacement of Wheat Meal in Diets for Juvenile European Seabass (Dicentrarchus labrax).

The green tips of Salicornia ramosissima are used for human consumption, while, in a production scenario, the rest of the plant is considered a residue. This study evaluated the potential of incorporating salicornia by-products in diets for juvenile European seabass, partially replacing wheat meal, aspiring to contribute to their valorization. A standard diet and three experimental diets including salicornia in 2.5%, 5% and 10% inclusion levels were tested in triplicate. After 62 days of feeding, no significant differences between treatments were observed in fish growth performances, feeding efficiency and economic conversation ratio. Nutrient digestibility of the experimental diets was unaffected by the inclusion of salicornia when compared to a standard diet. Additionally, salicornia had significant modulatory effects on the fish muscle biochemical profiles, namely by significantly decreasing lactic acid and increasing succinic acid levels, which can potentially signal health-promoting effects for the fish. Increases in DHA levels in fish fed a diet containing 10% salicornia were also shown. Therefore, the results suggest that salicornia by-products are a viable alternative to partially replace wheat meal in diets for juvenile European seabass, contributing to the valorization of a residue and the implementation of a circular economy paradigm in halophyte farming and aquaculture.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Neural Graph Refinement for Robust Recognition of Nuclei Communities in Histopathological Landscape.

Accurate classification of nuclei communities is an important step towards timely treating the cancer spread. Graph theory provides an elegant way to represent and analyze nuclei communities within the histopathological landscape in order to perform tissue phenotyping and tumor profiling tasks. Many researchers have worked on recognizing nuclei regions within the histology images in order to grade cancerous progression. However, due to the high structural similarities between nuclei communities, defining a model that can accurately differentiate between nuclei pathological patterns still needs to be solved. To surmount this challenge, we present a novel approach, dubbed neural graph refinement, that enhances the capabilities of existing models to perform nuclei recognition tasks by employing graph representational learning and broadcasting processes. Based on the physical interaction of the nuclei, we first construct a fully connected graph in which nodes represent nuclei and adjacent nodes are connected to each other via an undirected edge. For each edge and node pair, appearance and geometric features are computed and are then utilized for generating the neural graph embeddings. These embeddings are used for diffusing contextual information to the neighboring nodes, all along a path traversing the whole graph to infer global information over an entire nuclei network and predict pathologically meaningful communities. Through rigorous evaluation of the proposed scheme across four public datasets, we showcase that learning such communities through neural graph refinement produces better results that outperform state-of-the-art methods.

Center-Focused Affinity Loss for Class Imbalance Histology Image Classification.

Early-stage cancer diagnosis potentially improves the chances of survival for many cancer patients worldwide. Manual examination of Whole Slide Images (WSIs) is a time-consuming task for analyzing tumor-microenvironment. To overcome this limitation, the conjunction of deep learning with computational pathology has been proposed to assist pathologists in efficiently prognosing the cancerous spread. Nevertheless, the existing deep learning methods are ill-equipped to handle fine-grained histopathology datasets. This is because these models are constrained via conventional softmax loss function, which cannot expose them to learn distinct representational embeddings of the similarly textured WSIs containing an imbalanced data distribution. To address this problem, we propose a novel center-focused affinity loss (CFAL) function that exhibits 1) constructing uniformly distributed class prototypes in the feature space, 2) penalizing difficult samples, 3) minimizing intra-class variations, and 4) placing greater emphasis on learning minority class features. We evaluated the performance of the proposed CFAL loss function on two publicly available breast and colon cancer datasets having varying levels of imbalanced classes. The proposed CFAL function shows better discrimination abilities as compared to the popular loss functions such as ArcFace, CosFace, and Focal loss. Moreover, it outperforms several SOTA methods for histology image classification across both datasets.

Predictors of prostate cancer detection in MRI PI-RADS 3 lesions - Reality of a tertiary center.

INTRODUCTION AND OBJECTIVES: The Prostate Imaging Reporting and Data System (PI-RADS) score reports the likelihood of a clinically significant prostate cancer (CsPCa) based on various multiparametric prostate magnetic resonance imaging (mpMRI) characteristics. The PI-RADS category 3 is an intermediate status, with an equivocal risk of malignancy. The PSA density (PSAD) has been proposed as a tool to facilitate biopsy decisions on PI-RADS category 3 lesions. The objective of this study is to determine the frequency of CsPCa, assess the diagnostic value of targeted biopsy and identify clinical predictors to improve the CsPCa detection rate in PI-RADS category 3 lesions. METHODS: Between 1st January 2017 and 31st December 2022, a total of 1661 men underwent a prostate biopsy at our institution. Clinical and mpMRI data of men with PI-RADS 3 lesions was reviewed. The study population was divided into two groups: target group, including those submitted to systematic plus targeted biopsy versus non-target group when only systematic or saturation biopsy were performed. Patients with PI-RADS 3 lesions were divided into three categories based on pathological biopsy results: benign, clinically insignificant disease (score Gleason = 6 or International Society of Urologic Pathologic (ISUP) 1) and clinically significant cancer (score Gleason ≥ 7 (3+4) or ISUP ≥ 2) according to target and non-target group. Univariate and multivariate analyses were performed to identify clinical predictors to improve the CsPCa detection rate in PI-RADS category 3 lesions. RESULTS: A total of 130 men with PIRADS 3 index lesions were identified. Pathologic results were benign in 77 lesions (59.2%), 19 (14.6%) were clinically insignificant (Gleason score 6) and 34 (26.2%) were clinically significant (Gleason score 7 or higher). Eighty-seven of the patients were included in the target group (66.9%) and 43 in the non-target group (33.1%). The CsPCa detection was higher in the non-target group (32.6%, n = 14 vs 23.0%, n = 20 respectively). When systematic and target biopsies were jointly performed, if the results of systematic biopsies are not considered and only the results of target biopsies are taken into account, a CsPCa diagnosis would be missed on 9 patients. The differences of insignificant cancer and CsPCa rates among the target or non-target group were not statistically significant (p = 0.50 and p = 0.24, respectively). on multivariate analysis, the abnormal DRE and lesions localized in Peripheral zone (PZ) were significantly associated with a presence of CsPCa in PI-RADS 3 lesions (oR = 3.61, 95% CI [1.22,10.72], p = 0.02 and oR = 3.31, 95% CI [1.35, 8.11], p = 0.01, respectively). A higher median PSAD significantly predisposed for CsPCa on univariate analyses (p = 0.05), however, was not significant in the multivariate analysis (p = 0.76). In our population, using 0.10 ng/ml/ml as a cut-off to perform biopsy, 41 patients would have avoided biopsy (31.5%), but 5 cases of CsPCa would not have been detected (3.4%). We could not identify any statistical significance between other clinical and imagiological variables and CsPCa detection. CONCLUSIONS: PI-RADS 3 lesions were associated with a low likelihood of CsPCa detection. A systematic biopsy associated or not with target biopsy is essential in PI-RADS 3 lesions, and targeted biopsy did not demonstrate to be superior in the detection of CsPCa. The presence of abnormal DRE and lesions localized in PZ potentially predict the presence of CsPCa in biopsied PI-RADS 3 lesions.

Multicentre Study Into the Use of Polyethylene Glycol With Electrolytes Over at Least 6 Months to Treat Constipation in Paediatric Populations.

Background: Constipation is a common clinical problem in children, for which the first-line therapeutic options are osmotic laxatives, mainly polyethylene glycol (PEG). These treatments are often prescribed for short or limited periods, with progressive treatment withdrawal often resulting in relapses. However, there are a few studies into the long-term use (≥6 months) of PEG 3350 with electrolytes (PEG+E) in terms of the patients' clinical evolution. Objectives: To assess bowel movement and other relevant symptoms in children with constipation receiving PEG+E (≥6 months), as well as parent/caregiver satisfaction with this treatment. Methods: A retrospective, observational, descriptive, longitudinal, and multicentre study was carried out on 74 children diagnosed with functional constipation (ROME IV criteria) who had received PEG+E (≥6 months). Bowel control was assessed using the Bristol stool scale, and the parent's/caregiver's perception of the treatment was also evaluated employing a nonvalidated questionnaire. Results: Children with an average duration of constipation >1 year experienced a significant improvement in bowel movements and stool consistency when using PEG+E. The mean duration of use was 18.6 (±13.4) months, without the need to adjust the dose for weight. All clinical symptoms improved significantly except bloating, and all the parents/caregivers confirmed these clinical improvements. Conclusions: Children treated with PEG+E (≥6 months) normalised their bowel movements, improving the clinical symptoms related to constipation in the absence of serious advert events or the need for dosage adjustments due to weight gain. Parents/caregivers reported good satisfaction with PEG+E treatment.

Microbial oil, alone or paired with ß-glucans, can control hypercholesterolemia in a zebrafish model.

Dyslipidemia is often associated with unhealthy dietary habits, and many mammalian studies have explored the mode of action of certain bioactive compounds such as ß-glucans and n-3 PUFAs to understand their potential to normalize the lipid metabolism. There are only a few investigations that adopted omic approaches to unveil their combined effect on hypercholesterolemia. Zebrafish (Danio rerio) was used as a model organism to reveal the efficacy of Schizochytrium oil and ß-glucans (from Euglena gracilis and Phaeodactylum tricornutum) against cholesterol-rich diet induced dyslipidemia. One of the folowing four diets was fed to a particular group of fish: a control high-cholesterol diet, a Schizochytrium oil diet or one of the two diets containing the oil and ß-glucan. The plasma HDL, expression of hepatic genes linked to, among others, ferric ion binding and plasma phosphatidylcholines were higher and plasma cholesterol esters and triacylglycerols were lower in the microbial oil-fed fish compared to the fish fed high cholesterol diet. While the fish fed a mix of microbial oil and Euglena ß-glucan had lower plasma triacylglycerols and expression of hepatic genes linked to PPAR signaling pathway and enriched biosynthesis of plasma unsaturated fatty acids, the fish fed microbial oil-Phaeodactylum ß-glucan combination had lower abundance of triacylglycerols rich in saturated and mono-unsaturated fatty acids and cholesterol esters in the plasma.

Effect of Dietary Incorporation of Yellow Mealworm as a Partial Fishmeal Replacer on Growth, Metabolism, and Intestinal Histomorphology in Juvenile Meagre (Argyrosomus regius).

Efforts have been made to find alternatives to fish meal (FM), as the sustainability of aquaculture depends on it. Insect meal (IM) is a potential candidate to partially replace FM, being more sustainable and economically viable. In this experimental trial, three diets were tested with different yellow mealworm incorporation: a control diet with no IM, a diet with an inclusion of 10% IM (Ins10), and a diet with an incorporation of 20% IM (Ins20). The diets were tested on 10.5 g meagre for 47 days. The results showed that an IM inclusion higher than 10% affected both growth (2.6 vs. 2.2) and FCR (1.5 vs. 1.9) of meagre juveniles. However, this reduction in growth did not result from lower protein retention or changes in muscle fibre area or density. Little differences were observed in the activity of pancreatic and intestinal enzymes except for aminopeptidase total activity which was higher in the control and Ins10 compared to Ins20 (3847 vs. 3540 mU/mg protein), suggesting no limitations in protein synthesis. Also, the alkaline phosphatase intestinal maturation index was higher in the control group compared to the IM groups (437 vs. 296). On the contrary, several differences were also found in the proteolytic activity in the hepatic and muscle tissues of meagre juveniles fed the Ins10 diet. The inclusion of IM had no impact on intestine histomorphology but changes were detected in the enterocytes of fish from control and Ins10 which showed hypervacuolization and nucleus misplacement compared to the Ins20 treatment. Nevertheless, a higher percentage of Vibrionaceae was recorded for meagre fed on the Ins20 diet. Since no signs of inflammation were observed in the distal intestine, this suggests IM incorporation could have had an important impact on intestinal health due to its antimicrobial properties. This is supported by an increase in the haematocrit in the treatments where IM was added (20 to 25%). In conclusion, incorporations of IM at percentages up to 10% do not seem to have a negative impact on meagre performance at this age but can enhance the fish immune system and protection against intestinal inflammation.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic Gastrointestinal Disorders beyond Eosinophilic Esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Protective mechanisms of a microbial oil against hypercholesterolemia: evidence from a zebrafish model.

A Western diet elevates the circulating lipoprotein and triglyceride levels which are the major risk factors in cardiovascular disease (CVD) development. Consumption of long-chain omega-3 fatty acids can stall the disease progression. Although these fatty acids can significantly impact the intestine under a hypercholesterolemic condition, the associated changes have not been studied in detail. Therefore, we investigated the alterations in the intestinal transcriptome along with the deviations in the plasma lipids and liver histomorphology of zebrafish offered DHA- and EPA-rich oil. Fish were allocated to 4 dietary treatments: a control group, a high cholesterol group and microbial oil groups with low (3.3%) and high (6.6%) inclusion levels. We quantified the total cholesterol, lipoprotein and triglyceride levels in the plasma. In addition, we assessed the liver histology, intestinal transcriptome and plasma lipidomic profiles of the study groups. The results suggested that higher levels of dietary microbial oil could control the CVD risk factor indices in zebrafish plasma. Furthermore, microbial oil-fed fish had fewer liver vacuoles and higher mRNA levels of genes involved in ß-oxidation and HDL maturation. Analyses of the intestine transcriptome revealed that microbial oil supplementation could influence the expression of genes altered by a hypercholesterolemic diet. The plasma lipidomic profiles revealed that the higher level of microbial oil tested could elevate the long-chain poly-unsaturated fatty acid content of triglyceride species and lower the concentration of several lysophosphatidylcholine and diacylglycerol molecules. Our study provides insights into the effectiveness of microbial oil against dyslipidemia in zebrafish.

Specific Blood Plasma Circulating miRs Are Associated with the Physiological Impact of Total Fish Meal Replacement with Soybean Meal in Diets for Rainbow Trout (Oncorhynchus mykiss).

High dietary SBM content is known to induce important physiological alterations, hampering its use as a major FM alternative. Rainbow trout (Oncorhynchus mykiss) juveniles were fed two experimental diets during 9 weeks: (i) a FM diet containing 12% FM; and (ii) a vegetable meal (VM) diet totally devoid of FM and based on SBM (26%). Fish fed the VM diet did not show reduced growth performance when compared with fish fed the FM diet. Nevertheless, fish fed the VM diet had an increased viscerosomatic index, lower apparent fat digestibility, higher aminopeptidase enzyme activity and number of villi fusions, and lower α-amylase enzyme activity and brush border integrity. Small RNA-Seq analysis identified six miRs (omy-miR-730a-5p, omy-miR-135c-5p, omy-miR-93a-3p, omy-miR-152-5p, omy-miR-133a-5p, and omy-miR-196a-3p) with higher expression in blood plasma from fish fed the VM diet. Bioinformatic prediction of target mRNAs identified several overrepresented biological processes known to be associated with high dietary SBM content (e.g., lipid metabolism, epithelial integrity disruption, and bile acid status). The present research work increases our understanding of how SBM dietary content has a physiological impact in farmed fish and suggests circulating miRs might be suitable, integrative, and less invasive biomarkers in fish.

Calanus finmarchicus hydrolysate improves growth performance in feeding trial with European sea bass juveniles and increases skeletal muscle growth in cell studies.

The world will be dependent on the development of novel feed ingredients from renewable sources to ensure sustainable growth of the aquaculture industry. Zooplankton like Calanus finmarchicus are viable new raw material candidates, as they have optimal nutrient profiles for aquatic animals and may be sustainably harvested in large volumes. In this study, the aim was to investigate if a protein hydrolysate of C. finmarchicus was able to influence the growth performance of fish. The effect of dietary inclusion of hydrolysates was tested in a feeding trial with European sea bass (Dicentrarchus labrax) juveniles, benchmarking calanus hydrolysate (CH) against commercially available hydrolysates. The diet with CH inclusion yielded increased growth, with significantly higher body weight than hydrolysates of sardine and tuna fish at the end of the trial. The observed growth-promoting effects were further examined using an in vitro model with skeletal muscle cells from Atlantic salmon. Through bioactivity experiments with muscle cells grown in media containing CH, low-molecular fractions were found to have the greatest positive effect on proliferation, viability, and expression of muscle-specific genes. Characterization of the most potent fraction revealed an abundance of small peptides, along with amino acids and marine metabolites associated with increased muscle growth.

Potential of algae-derived alginate oligosaccharides and ß-glucan to counter inflammation in adult zebrafish intestine.

Alginate oligosaccharides (AOS) are natural bioactive compounds with anti-inflammatory properties. We performed a feeding trial employing a zebrafish (Danio rerio) model of soybean-induced intestinal inflammation. Five groups of fish were fed different diets: a control (CT) diet, a soybean meal (SBM) diet, a soybean meal+ß-glucan (BG) diet and 2 soybean meal+AOS diets (alginate products differing in the content of low molecular weight fractions - AL, with 31% < 3kDa and AH, with 3% < 3kDa). We analyzed the intestinal transcriptomic and plasma metabolomic profiles of the study groups. In addition, we assessed the expression of inflammatory marker genes and histological alterations in the intestine. Dietary algal ß-(1, 3)-glucan and AOS were able to bring the expression of certain inflammatory genes altered by dietary SBM to a level similar to that in the control group. Intestinal transcriptomic analysis indicated that dietary SBM changed the expression of genes linked to inflammation, endoplasmic reticulum, reproduction and cell motility. The AL diet suppressed the expression of genes related to complement activation, inflammatory and humoral response, which can likely have an inflammation alleviation effect. On the other hand, the AH diet reduced the expression of genes, causing an enrichment of negative regulation of immune system process. The BG diet suppressed several immune genes linked to the endopeptidase activity and proteolysis. The plasma metabolomic profile further revealed that dietary SBM can alter inflammation-linked metabolites such as itaconic acid, taurochenodeoxycholic acid and enriched the arginine biosynthesis pathway. The diet AL helped in elevating one of the short chain fatty acids, namely 2-hydroxybutyric acid while the BG diet increased the abundance of a vitamin, pantothenic acid. Histological evaluation revealed the advantage of the AL diet: it increased the goblet cell number and length of villi of the intestinal mucosa. Overall, our results indicate that dietary AOS with an appropriate amount of < 3kDa can stall the inflammatory responses in zebrafish.

Taurine Supplementation to Plant-Based Diets Improves Lipid Metabolism in Senegalese Sole.

Taurine is a sulphur-containing amino acid with important physiological roles and a key compound for the synthesis of bile salts, which are essential for the emulsion and absorption of dietary lipids. This study aimed to evaluate the effects of taurine supplementation to low-fishmeal diets on the metabolism of taurine, bile acids, and lipids of Senegalese sole. A fishmeal (FM) and a plant-protein-based (PP0) diet were formulated, and the latter was supplemented with taurine at 0.5 and 1.5% (diets PP0.5 and PP1.5). Diets were assigned to triplicate tanks containing 35 fish (initial weight ~14 g) for 6 weeks. Fish from the PP0 treatment presented lower taurine and bile-acid concentrations compared with the FM treatment, and a downregulation of cyp7a1 and abcb11 was observed. Triolein catabolism decreased in PP0-fed fish, resulting in increased hepatic fat content and plasma triglycerides, while no effects on plasma cholesterol were observed. Taurine supplementation to plant-based diets resulted in a higher taurine accumulation in fish tissues, increased bile-acid concentration, and upregulation of cyp7a1 and abcb11. Hepatic fat content and plasma triglycerides decreased with increasing dietary taurine supplementation. Taurine supplementation mitigated part of the negative effects of plant-based diets, leading to better lipid utilisation.

Digitally measuring solar ultraviolet radiation in outdoor workers: A study protocol for establishing the use of electronic personal dosimeters in Portugal.

Introduction: The rising incidence of skin cancer over the years has made it a significant public and occupational health issue. However, skin cancer is highly preventable, mainly through reduced exposure to solar ultraviolet radiation (UVR), which can be achieved by a variety of individual and collective protective measures and interventions. The relative risk associated with different patterns of exposure to solar UVR differs for the subtypes of keratinocyte cancers (KC). Specifically, whether the exposure is intermittent or continuous, and occurs in an occupational or leisure/recreational setting. The main aim of the study using this protocol is to contribute to raising public and policy awareness on solar UVR-inflicted occupational skin cancers in Lisbon. This will be achieved by performing direct measurements of the solar UVR dose received by outdoor workers using a digital platform. Results will likely contribute to further understanding the risk estimates for keratinocyte cancer estimations in this population. Methods: A prospective observational study will be conducted in Lisbon, Portugal. Personal electronic dosimeters (GENESIS-UV system) integrated with a digital platform will be used to assess occupational solar UVR doses of gardeners, masons, and gravediggers of the municipality of Lisbon. Two hundred and ten outdoor workers will be selected to wear the dosimeter for 1 month each, between April and October during their daily working hours. A digital web-based platform that offers private access to information through dashboard visualization will provide information for the outdoor workers and facilitate communication with the participants. Discussion: The expected results of the overall proposal comprise the occupational solar UVR doses, expressed in standard erythemal dose (SEDs) per day of outdoor work for 7 months. Study data will provide outdoor workers with information on their personal solar UVR exposure during their working hours and an estimate of their risk of developing skin cancer. It is expected that the occupational solar UVR doses of the outdoor workers in Portugal will be above the threshold of 1 to 1.33 SED/day, due to the latitude of Lisbon and the nature of the occupations. The results prospectively should flow into the design of adequate prevention campaigns for skin cancer in outdoor workers.

The use of amino acid formulas in pediatric patients with allergy to cow's milk proteins: Recommendations from a group of experts.

One of the most common food allergies in children is cow's milk allergy (CMA). In breast-fed infants with CMA, the mother is encouraged to avoid dairy products. If this is not possible, or in formula fed infants, use of hypoallergenic replacement formulas such as extensively hydrolyzed formulas (EHF) is recommended. However, in ∼5% of patients EHFs are not tolerated and/or allergy symptoms can persist. When EHFs are ineffective and in severe forms of CMA, amino acid-based formulas (AAF) should be considered. Six pediatric gastroenterologists with extensive experience in food allergy management reviewed scientific publications and international clinical practice guidelines to provide practical recommendations on AAF. The guidelines reviewed had discrepancies and ambiguities around the specific indications for using formulas as a milk substitute. The panel recommends AAFs as the first therapeutic option in anaphylaxis due to CMA, in acute and chronic severe food protein-induced enterocolitis syndrome, in CMA associated with multiple food allergy, and in cases of eosinophilic esophagitis not responding to an extended exclusion diet or not eating solids. The main benefit of AAF is its absence of residual allergenicity, making it a safe treatment option in severe CMA patients who do not tolerate or respond to an EHF.

Approach to Endoscopic Balloon Dilatation in Pediatric Stricturing Crohn Disease: A Position Paper of the Endoscopy Special Interest Group of ESPGHAN.

Crohn disease (CD) is often complicated by bowel strictures that can lead to obstructive symptoms, resistant inflammation, and penetrating complications. Endoscopic balloon dilatation of CD strictures has emerged as a safe and effective technique for relieving these strictures, which may obviate the need for surgical intervention in the short and medium term. This technique appears to be underutilized in pediatric CD. This position paper of the Endoscopy Special Interest Group of European Society for Pediatric Gastroenterology, Hepatology and Nutrition describes the potential applications, appropriate evaluation, practical technique, and management of complications of this important procedure. The aim being to better integrate this therapeutic strategy in pediatric CD management.

DL-methionyl-DL-methionine as an efficient methionine source for promoting zootechnical performance and methionine-related pathways in the whiteleg shrimp (Penaeus vannamei).

Methionine (MET) supplementation is a current strategy to achieve shrimp requirement. Notwithstanding, the efficiency of the precisely formulated feeds can be diminished since shrimps are slow eaters and masticate feed externally that results in nutrient leaching. In this regard, a methionine dipeptide (DL-methionyl DL-methionine) benefits the feed industry by reducing MET water solubility while increasing its bioavailability. Therefore, the effects of feeding whiteleg shrimp (Penaeus vannamei) with increasing levels of methionine dipeptide were evaluated on zootechnical performance and methionine-, immune- and antioxidant-related pathways. A 74 d growth trial was conducted by feeding a control diet and four diets supplemented with AQUAVI® Met-Met at 0·08, 0·12, 0·24 and 0·32% of DM. Diet digestibility, body amino acids (AA) composition and nitrogen metabolites, metabolic enzymes, oxidative status and gene expression were evaluated. It can be concluded that graded dietary increase of methionine dipeptide up to 0·24 % for 74 d translated in significant gains on the growth performance, feed efficiency, nutrient and nitrogen gain and shrimp survival. Moreover, it was showed that Met-Met dietary spare leads to an improvement of free-AA pool and nitrogen metabolites concentration and reduces the signs of oxidative stress. Finally, in a closer look to the MET-related pathways passive to be altered by Met-Met spare, a clear modulation of the described antioxidant and cell proliferation routes was detected.