Real-life Data on First- and Second-Line Treatment of Metastatic Castration-Resistant Prostate Cancer With Abiraterone, Enzalutamide and Cabazitaxel - A multicentric Study From Portugal.

INTRODUCTION AND OBJECTIVES: New drugs for metastatic castrate resistant prostate cancer (mCRPC) were approved, first in the pos-docetaxel and then in the pre-docetaxel setting. We aim to assess the real daily practice benefit of abiraterone (Abi), enzalutamide (Enz) and cabazitaxel (Cab) in patients with mCRPC, compare it with RCT results and compare Abi vs Enz. MATERIALS AND METHODS: We retrospectively collected the data of all consecutive mCRPC patients treated with Abi, Enz or Cab in the six major oncological hospitals in the north of Portugal until December 2020. RESULTS: A total of 470 treatments pre-docetaxel (163 Abi and 307 Enz) and 373 pos-docetaxel (160 Abi, 148 Enz and 59 Cab) were included, with median follow-up time of 35 months. Mean age was 73.1, 84.4% had ECOG status < 2, ISUP grade was ≥ 4 in 59% and 28.0% had oligometastatic disease. In first line, for Abi and for Enz respectively, the proportion of patients with PSA reduction > 50% was 64.4% and 80.4% (P < .001), the mean duration of treatment (DT) was 10 and 14 months (P = .037) and the median overall survival (OS) was 25 months and 30 months (P = .17). In second line the results for Abi, Enz and Cab were respectively: proportion of patients with PSA reduction > 50% was 40.4%, 57.4% and 24.6% (p for Abi vs Enz=0.004); DT was 7, 8, and 3 months (p for Abi vs Enz = 0.27); OS was 17, 22 and 10 months (p for Abi vs. Enz = 0,07). CONCLUSION: These drugs have good efficacy in real-world evidence, similar to those reported in randomized clinical trials, with the expected exception of lower OS due to the inclusion of a broader sample of patients. Our results add to the evidence that Enz might have better efficacy in this setting compared with Abi.

Sustainable Fish Meal-Free Diets for Gilthead Sea Bream (Sparus aurata): Integrated Biomarker Response to Assess the Effects on Growth Performance, Lipid Metabolism, Antioxidant Defense and Immunological Status.

The growth of the aquaculture industry requires more sustainable and circular economy-driven aquafeed formulas. Thus, the goal of the present study was to assess in farmed gilthead sea bream (Sparus aurata L.) how different combinations of novel and conventional fish feed ingredients supported proper animal performance in terms of growth and physiological biomarkers of blood/liver/head kidney. A 77-day feeding trial was conducted with three experimental diets (PAP, with terrestrial processed animal protein from animal by-products; NOPAP, without processed animal protein from terrestrial animal by-products; MIX, a combination of alternative ingredients of PAP and NOPAP diets) and a commercial-type formulation (CTRL), and their effects on growth performance and markers of endocrine growth regulation, lipid metabolism, antioxidant defense and inflammatory condition were assessed at circulatory and tissue level (liver, head kidney). Growth performance was similar among all dietary treatments. However, fish fed the PAP diet displayed a lower feed conversion and protein efficiency, with intermediate values in MIX-fed fish. Such gradual variation in growth performance was supported by different biomarker signatures that delineated a lower risk of oxidation and inflammatory condition in NOPAP fish, in concurrence with an enhanced hepatic lipogenesis that did not represent a risk of lipoid liver degeneration.

Asparagopsis taxiformis as a Novel Antioxidant Ingredient for Climate-Smart Aquaculture: Antioxidant, Metabolic and Digestive Modulation in Juvenile White Seabream (Diplodus sargus) Exposed to a Marine Heatwave.

The increasing frequency and duration of marine heatwaves (MHWs) due to climate change pose severe threats to aquaculture, causing drastic physiological and growth impairments in farmed fish, undermining their resilience against additional environmental pressures. To ensure sustainable production that meets the global seafood demand and animal welfare standards, cost-effective and eco-friendly strategies are urgently needed. This study explored the efficacy of the red macroalga Asparagopsis taxiformis on juvenile white seabream Diplodus sargus reared under optimal conditions and upon exposure to a MHW. Fish were fed with four experimental diets (0%, 1.5%, 3% or 6% of dried powdered A. taxiformis) for a prophylactic period of 30 days (T30) and subsequently exposed to a Mediterranean category II MHW for 15 days (T53). Biometric data and samples were collected at T30, T53 and T61 (8 days post-MHW recovery), to assess performance indicators, biomarker responses and histopathological alterations. Results showed that A. taxiformis supplementation improved catalase and glutathione S-transferase activities and reduced lipid peroxidation promoted by the MHW, particularly in fish biofortified with 1.5% inclusion level. No histopathological alterations were observed after 30 days. Additionally, fish biofortified with 1.5% A. taxiformis exhibited increased citrate synthase activity and fish supplemented with 1.5% and 3% showed improved digestive enzyme activities (e.g., pepsin and trypsin activities). Overall, the present findings pointed to 1.5% inclusion as the optimal dosage for aquafeeds biofortification with A. taxiformis, and confirmed that this seaweed species is a promising cost-effective ingredient with functional properties and great potential for usage in a climate-smart context.

Nile tilapia and gilthead seabream dietary self-selection of alternative feeds.

Classical assessments of new fish feeds are anthropocentric, focusing mainly on growth. Although this methodology is accurate, it does not consider the fish' perspective. This study aimed to investigate the behavioural responses and feed preferences of Nile tilapia (Oreochromis niloticus) and gilthead seabream (Sparus aurata) through a self-selection trial using self-feeders. Both species were offered three feeds: a control (PD) commercial-like feed and two diets (ORG1 and ORG2) formulated with different inclusions of alternative ingredients to address some of the current environmental concerns and/or ethical issues often associated with commercial formulations. Three groups of tilapia with an average weight of 163.0 g ± 4.3 g (mean ± SD) and four groups of seabreams with 174.7 g ± 27.0 g were tested. Tilapia exhibited a preference for ORG2 (46.5%), influenced by the sensory properties of the feed and post-ingestion signals. Seabream did not show a preference for any feed. These findings highlight the effectiveness of self-selection experiments in allowing fish to express their feeding behaviour and preferences. Therefore, this approach should be considered in the initial screening and design of new aquaculture feeds and ingredients.

Self-Test of Air-Coupled Probe for Sensitivity Map Production Using Parabolic Reflector.

The spatial distribution of a transduction efficiency over the air-coupled probe surface was proposed as a convenient tool for the probe integrity inspection. In this research, a parabolic reflector is used for passive focusing of the acoustic wave on the surface of inspected probe. Therefore, no additional transducer is required for inspection: probe is used for self-inspection. This approach allows to avoid the expensive focused transducer and replaces it by the same-type air-coupled transducers as probe under test. Moreover, the use of the parabolic mirror for focusing is frequency-independent; therefore, such approach allows to inspect a wide range of the probes. Spread spectrum signals were used for excitation to improve the SNR and bandwidth coverage. The results of the experimental measurements of air-coupled transducer sensitivity map with natural and artificial defects implemented have been presented. Comparison with previously proposed techniques is given. It was found that defects presence distorts the focused beam, creating large sidelobes. Therefore, sensitivity map obtained with the proposed technique is lower quality than with previously proposed techniques. Beam profile measurements using a miniature microphone have been presented. Aperture-limiting mask has been proposed to reduce the sidelobes arising due to defects presence and resulting measurements quality has been improved.

Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and histologically by predominantly eosinophilic infiltration of the squamous epithelium. European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published a guideline in 2014; however, the rapid evolution of knowledge about pathophysiology, diagnostic criteria, and therapeutic options have made an update necessary. METHODS: A consensus group of pediatric gastroenterologists from the ESPGHAN Working Group on Eosinophilic Gastrointestinal Diseases (ESPGHAN EGID WG) reviewed the recent literature and proposed statements and recommendations on 28 relevant questions about EoE. A comprehensive electronic literature search was performed in MEDLINE, EMBASE, and Cochrane databases from 2014 to 2022. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence and formulate recommendations. RESULTS: A total of 52 statements based on the available evidence and 44 consensus-based recommendations are available. A revision of the diagnostic protocol, options for initial drug treatment, and the new concept of simplified empiric elimination diets are now available. Biologics are becoming a part of the potential armamentarium for refractory EoE, and systemic steroids may be considered as the initial treatment for esophageal strictures before esophageal dilation. The importance and assessment of quality of life and a planned transition to adult medical care are new areas addressed in this guideline. CONCLUSION: Research in recent years has led to a better understanding of childhood EoE. This guideline incorporates the new findings and provides a practical guide for clinicians treating children diagnosed with EoE.

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.

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.

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.

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.

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.

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.