Insect meal in aquafeeds: A sustainable path to enhanced mucosal immunity in fish.

The mucosal surfaces of fish, including their intestines, gills, and skin, are constantly exposed to various environmental threats, such as water quality fluctuations, pollutants, and pathogens. However, various cells and microbiota closely associated with these surfaces work in tandem to create a functional protective barrier against these conditions. Recent research has shown that incorporating specific feed ingredients into fish diets can significantly boost their mucosal and general immune response. Among the various ingredients being investigated, insect meal has emerged as one of the most promising options, owing to its high protein content and immunomodulatory properties. By positively influencing the structure and function of mucosal surfaces, insect meal (IM) has the potential to enhance the overall immune status of fish. This review provides a comprehensive overview of the potential benefits of incorporating IM into aquafeed as a feed ingredient for augmenting the mucosal immune response of fish.

Disentangling hydroxynitrile glucoside biosynthesis in a barley (Hordeum vulgare) metabolon provides access to elite malting barleys for ethyl carbamate-free whisky production.

Barley produces several specialized metabolites, including five α-, ß-, and γ-hydroxynitrile glucosides (HNGs). In malting barley, presence of the α-HNG epiheterodendrin gives rise to undesired formation of ethyl carbamate in the beverage production, especially after distilling. Metabolite-GWAS identified QTLs and underlying gene candidates possibly involved in the control of the relative and absolute content of HNGs, including an undescribed MATE transporter. By screening 325 genetically diverse barley accessions, we discovered three H. vulgare ssp. spontaneum (wild barley) lines with drastic changes in the relative ratios of the five HNGs. Knock-out (KO)-lines, isolated from the barley FIND-IT resource and each lacking one of the functional HNG biosynthetic genes (CYP79A12, CYP71C103, CYP71C113, CYP71U5, UGT85F22 and UGT85F23) showed unprecedented changes in HNG ratios enabling assignment of specific and mutually dependent catalytic functions to the biosynthetic enzymes involved. The highly similar relative ratios between the five HNGs found across wild and domesticated barley accessions indicate assembly of the HNG biosynthetic enzymes in a metabolon, the functional output of which was reconfigured in the absence of a single protein component. The absence or altered ratios of the five HNGs in the KO-lines did not change susceptibility to the fungal phytopathogen Pyrenophora teres causing net blotch. The study provides a deeper understanding of the organization of HNG biosynthesis in barley and identifies a novel, single gene HNG-0 line in an elite spring barley background for direct use in breeding of malting barley, eliminating HNGs as a source of ethyl carbamate formation in whisky production.

Mucosal barrier status in Atlantic salmon fed rapeseed oil and Schizochytrium oil partly or fully replacing fish oil through winter depression.

The study was designed to investigate the effects of replacing fish oil by algal oil and rapeseed oil on histomorphology indices of the intestine, skin and gill, mucosal barrier status and immune-related genes of mucin and antimicrobial peptide (AMP) genes in Atlantic salmon (Salmo salar). For these purposes, Atlantic salmon smolts were fed three different diets. The first was a control diet containing fish oil but no Schizochytrium oil. In the second diet, almost 50 % of the fish oil was replaced with algal oil, and in the third diet, fish oil was replaced entirely with algal oil. The algal oil contained mostly docosahexaenoic acid (DHA) and some eicosapentaenoic acid (EPA). The study lasted for 49 days in freshwater (FW), after which some fish from each diet group were transferred to seawater (SW) for a 48-h challenge test at 33 ppt to test their ability to tolerate high salinity. Samples of skin, gills, and mid intestine [both distal (DI) and anterior (AI) portions of the mid intestine] were collected after the feeding trial in FW and after the SW-challenge test to assess the effects of the diets on the structure and immune functions of the mucosal surfaces. The results showed that the 50 % VMO (Veramaris® algal oil) dietary group had improved intestinal, skin, and gill structures. Principal component analysis (PCA) of the histomorphological parameters demonstrated a significant effect of the algal oil on the intestine, skin, and gills. In particular, the mucosal barrier function of the intestine, skin, and gills was enhanced in the VMO 50 % dietary group after the SW challenge, as evidenced by increased mucous cell density. Immunolabelling of heat shock protein 70 (HSP70) in the intestine (both DI and AI) revealed downregulation of the protein expression in the 50 % VMO group and a corresponding upregulation in the 100 % VMO group compared to 0 % VMO. The reactivity of HSP70 in the epithelial cells was higher after the SW challenge compared to the FW phase. Immune-related genes related to mucosal defense, such as mucin genes [muc2, muc5ac1 (DI), muc5ac1 (AI), muc5ac2, muc5b (skin), and muc5ac1 (gills)], and antimicrobial peptide genes [def3 (DI), def3 (AI), and cath1 (skin)] were significantly upregulated in the 50 % VMO group. PCA of gene expression demonstrated the positive influences on gene regulation in the 50 % VMO dietary group. In conclusion, this study demonstrated the positive effect of substituting 50 % of fish oil with algal oil in the diets of Atlantic salmon. The findings of histomorphometry, mucosal mapping, immunohistochemistry, and immune-related genes connected to mucosal responses all support this conclusion.

Transportation Noise Pollution and Cardiovascular Health.

Epidemiological studies have found that transportation noise increases the risk for cardiovascular morbidity and mortality, with solid evidence for ischemic heart disease, heart failure, and stroke. According to the World Health Organization, at least 1.6 million healthy life years are lost annually from traffic-related noise in Western Europe. Traffic noise at night causes fragmentation and shortening of sleep, elevation of stress hormone levels, and increased oxidative stress in the vasculature and the brain. These factors can promote vascular (endothelial) dysfunction, inflammation, and arterial hypertension, thus elevating cardiovascular risk. The present review focusses on the indirect, nonauditory cardiovascular health effects of noise. We provide an updated overview of epidemiological research on the effects of transportation noise on cardiovascular risk factors and disease, and mechanistic insights based on the latest clinical and experimental studies and propose new risk markers to address noise-induced cardiovascular effects in the general population. We will discuss the potential effects of noise on vascular dysfunction, oxidative stress, and inflammation in humans and animals. We will elaborately explain the underlying pathomechanisms by alterations of gene networks, epigenetic pathways, circadian rhythm, signal transduction along the neuronal-cardiovascular axis, and metabolism. We will describe current and future noise mitigation strategies. Finally, we will conduct an overall evaluation of the status of the current evidence of noise as a significant cardiovascular risk factor.

Xylooligosaccharides from lignocellulosic biomass and their applications as nutraceuticals: a review on their production, purification, and characterization.

Xylooligosaccharides (XOS) are considered a potent source of prebiotics for humans. The global prebiotic market is expanding in size, was valued at USD 6.05 billion in 2021, and is expected to grow at a 14.9% compound annual growth rate between 2022 and 2030, indicating a huge demand. These XOS are non-digestible pentose sugar oligomers comprising mainly xylose. Xylose is naturally present in the lignocellulosic biomass (LCB), fruits and vegetables. Apart from the prebiotic effect, these XOS have been reported to reduce blood cholesterol, possess antioxidant effects, increase calcium absorption, reduce colon cancer risk, and benefit diabetic patients. The primary use of XOS is reported in the feed industry followed by health, medical use, food and drinks. LCB mainly contains glucan, xylan and lignin. After glucan, xylan is the second-highest available sugar on the globe composed of xylose. Therefore, the xylan fraction of LCB has great significance in producing food, feed and energy. Glucan has been exploited for the commercial production of ethanol, xylitol, furfural, hydroxymethyl furfural and glucose. As of now, xylan has limited applications. Therefore, xylan can be exploited to convert to XOS. The production of XOS from LCB fraction not only helps to produce these at a very low price, but also helps in the reduction of greenhouse gases. Its use in food and drinks is increasing as it can be derived from the abundantly and cheaply available LCB. The article provides a review on the production, purification and characterization of XOS in view of their use as nutraceuticals. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Long-lasting dissociative amnesia.

This case report describes a 29-year-old man, who was admitted to a psychiatric hospital due to a severe depressive episode without psychotic symptoms. After two weeks he developed acute retrograde autobiographical amnesia. No organic cause was identified, and the patient was therefore diagnosed with dissociative amnesia. The depressive symptoms ceased as the amnesia developed. After five months of follow-up in the outpatient clinic, his amnesia for the time preceding its outbreak remained unchanged. He patient managed to resume a functional daily life.

Randomized Phase I Trial of the α-Synuclein Antibody Lu AF82422.

BACKGROUND: Immunotherapy targeting pathological α-synuclein (α-syn) species is a promising strategy for slowing disease progression in neurodegenerative synucleinopathies, including Parkinson's disease (PD). OBJECTIVE: The aim was to evaluate the safety, tolerability, pharmacokinetics, and target engagement of ascending doses of Lu AF82422. METHODS: In this first-in-human study (NCT03611569), healthy participants (18-55 years, cohort A) and patients with PD (40-80 years, Hoehn and Yahr stage ≤3, cohort B) were enrolled in ascending-dose cohorts and randomly assigned to receive single intravenous infusions of Lu AF82422 (cohorts A1-A6: 75, 225, 750, 2250 4500, and 9000 mg, respectively; cohorts B1 and B2: 2250 and 9000 mg, respectively) or placebo. Participants were monitored during a 12-week observational period. RESULTS: Overall, single intravenous infusions of Lu AF82422 were safe and well tolerated, and no serious adverse events (AE) were observed; the most common AEs were related to the study on lumbar punctures, headache, and common infections. Lu AF82422 concentrations (in plasma and cerebrospinal fluid [CSF]) increased in a dose-proportional manner with no observable differences between cohorts; mean plasma half-life was 700 h. Plasma concentrations of Lu AF82422 had an immediate, concentration-dependent lowering effect on the plasma concentration of free α-syn and on the ratio of free to total α-syn in all cohorts and lowered the free-to-total α-syn ratio in CSF in the high-dose PD cohort. CONCLUSIONS: The safety and pharmacokinetic profile of Lu AF82422 were appropriate for further clinical development, and results indicated peripheral target engagement. The central target engagement observed in participants with PD indicates that the doses of Lu AF82422 tested may provide CSF concentrations sufficient to target aggregated forms of α-syn. © 2024 H. Lundbeck A/S. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Video consultation and treatment in the community smoking cessation therapy success rates in patients with mental illness: a randomized controlled trial.

PURPOSE: Smoking is the single factor with the highest impact on reducing life expectancy of patients with mental illness. Patients experience difficulty in participating in smoking cessation programs but are concerned about the impact of tobacco on their health and finances. Smoking cessation advice via videoconferencing might be an alternative to an ordinary in-person consultation. MATERIAL AND METHOD: Randomized controlled trial with follow-up at 6 months. We included patients with diagnoses of schizophrenia and affective disorder from psychiatric outpatient clinics. Intervention 1 involved daily video consultations; intervention 2 was treatment as usual. RESULTS: Seventy patients were included. For both/all groups/interventions, rates of smoking cessation were 45% and predictors for a 50% reduction in smoking were antipsychotic medication load [odds ratio (OR) 0.54; p = 0.045] and number of nicotine patches (OR 1.02; p = 0.06). Predictors for a reduction in the number of cigarettes to < 10 were antipsychotic medication load (OR 0.52; p = 0.04), number of nicotine patches (OR 1.01; p = 0.02) and number of cigarettes at baseline [OR 0.95 (p = 0.09); adjusted OR 0.94 (p = 0.02)]. Patients prevented weight gain during the cessation period. CONCLUSION: The smoking cessation rate was high. One of the reasons for the high cessation rate was that the intervention was carried out by highly experienced and professionally qualified staff. In addition, we used free nicotine patches to increase the patients' motivation to quit smoking. It is very important that we introduce these results into our clinical work with the patients.

Recurrence and Survival Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Synchronous and Metachronous Peritoneal Metastases of Colorectal Origin.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the 5-year survival for colorectal cancer (CRC) patients with peritoneal metastases (PM). Little is known about recurrence patterns and recurrence rates between synchronous (S) and metachronous (M) PM following CRS+HIPEC. We aimed to describe the recurrence patterns, overall survival (OS) and disease-free survival (DFS) in S-PM and M-PM patients after complete CRS+HIPEC. From June 2006 to December 2020, a prospective cohort study included 310 CRC patients, where 181 patients had S-PM (58.4%) and 129 patients had M-PM (41.6%). After a median 10.3-month follow-up, 247/310 (79.7%) patients experienced recurrence, and recurrence sites included isolated peritoneal (32.4%), multifocal (peritoneal and liver and/or lung(s)) (22.7%), isolated liver (17.8%), isolated lung (10.5%) and other (16.6%) sites. Recurrence patterns did not differ between S-PM and M-PM. M-PM patients had an impaired DFS compared to S-PM patients (9.4 months (95% CI: 7.3-12.1) vs. 12.5 months (95% CI: 11.2-13.9), p = 0.01). The median OS was similar for S-PM and M-PM (38.4 months (95% CI: 31.2-46.8) vs. 40.8 months (95% CI: 28.8-46.8), p = 0.86). Despite frequent recurrence at extraperitoneal locations, long-term survival was achievable after CRS+HIPEC in CRC patients with PM. The recurrence patterns and OS did not differ between groups, yet M-PM patients had a shorter DFS.

Hearing Loss, Hearing Aid Use, and Risk of Dementia in Older Adults.

Importance: Hearing loss has been suggested as a risk factor for dementia, but there is still a need for high-quality research to better understand the association between these 2 conditions and the underlying causal mechanisms and treatment benefits using larger cohorts and detailed data. Objective: To investigate the association between hearing loss and incident dementia, as well as how hearing aid use contributes to this association. Design, Setting, and Participants: This population-based cohort study was conducted in Southern Denmark between January 2003 and December 2017 and included all residents 50 years and older. We excluded all persons with dementia before baseline as well as those who did not live in the region 5 years before baseline, with incomplete address history, or who had missing covariate information. Exposures: Individual hearing status based on the Hearing Examinations in Southern Denmark database, which contains data on all pure-tone audiometry examinations performed at public hearing rehabilitation clinics in Southern Denmark. Main Outcomes and Measures: Incident cases of dementia and Alzheimer disease as identified from national registries. Results: The study population comprised 573 088 persons (298 006 women [52%]; mean [SD] age, 60.8 [11.3] years) with 23 023 cases of dementia and mean (SD) follow-up of 8.6 (4.3) years. Having a hearing loss was associated with an increased risk of dementia, with an adjusted hazard ratio (HR) of 1.07 (95% CI, 1.04-1.11) compared with having no hearing loss. Severe hearing loss in the better and worse ear was associated with a higher dementia risk, with an HR of 1.20 (95% CI, 1.09-1.32) and 1.13 (95% CI, 1.06-1.20), respectively, compared with having no hearing loss in the corresponding ear. Compared with people without hearing loss, the risk of dementia was higher among people with hearing loss who were not using hearing aids than those who had hearing loss and were using hearing aids, with HRs of 1.20 (95% CI, 1.13-1.27) and 1.06 (95% CI, 1.01-1.10), respectively. Conclusions and Relevance: The results of this cohort study suggest that hearing loss was associated with increased dementia risk, especially among people not using hearing aids, suggesting that hearing aids might prevent or delay the onset and progression of dementia. The risk estimates were lower than in previous studies, highlighting the need for more high-quality longitudinal studies.

Long-term exposure to ambient air pollution and risk of leukemia and lymphoma in a pooled European cohort.

Leukemia and lymphoma are the two most common forms of hematologic malignancy, and their etiology is largely unknown. Pathophysiological mechanisms suggest a possible association with air pollution, but little empirical evidence is available. We aimed to investigate the association between long-term residential exposure to outdoor air pollution and risk of leukemia and lymphoma. We pooled data from four cohorts from three European countries as part of the "Effects of Low-level Air Pollution: a Study in Europe" (ELAPSE) collaboration. We used Europe-wide land use regression models to assess annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) at residences. We also estimated concentrations of PM2.5 elemental components: copper (Cu), iron (Fe), zinc (Zn); sulfur (S); nickel (Ni), vanadium (V), silicon (Si) and potassium (K). We applied Cox proportional hazards models to investigate the associations. Among the study population of 247,436 individuals, 760 leukemia and 1122 lymphoma cases were diagnosed during 4,656,140 person-years of follow-up. The results showed a leukemia hazard ratio (HR) of 1.13 (95% confidence intervals [CI]: 1.01-1.26) per 10 µg/m3 NO2, which was robust in two-pollutant models and consistent across the four cohorts and according to smoking status. Sex-specific analyses suggested that this association was confined to the male population. Further, the results showed increased lymphoma HRs for PM2.5 (HR = 1.16; 95% CI: 1.02-1.34) and potassium content of PM2.5, which were consistent in two-pollutant models and according to sex. Our results suggest that air pollution at the residence may be associated with adult leukemia and lymphoma.

Concomitant exposure to air pollution, green space and noise, and risk of myocardial infarction: a cohort study from Denmark.

AIMS: The three correlated environmental exposures (air pollution, road traffic noise, and green space) have all been associated with the risk of myocardial infarction (MI). The present study aimed to analyse their independent and cumulative association with MI. METHODS AND RESULTS: In a cohort of all Danes aged 50 or older in the period 2005-17, 5-year time-weighted average exposure to fine particles (PM2.5), ultrafine particles, elemental carbon, nitrogen dioxide (NO2), and road traffic noise at the most and least exposed façades of residence was estimated. Green space around residences was estimated from land use maps. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI), and cumulative risk indices (CRIs) were calculated. All expressed per interquartile range. Models were adjusted for both individual and neighbourhood-level socio-demographic covariates. The cohort included 1 964 702 persons. During follow-up, 71 285 developed MI. In single-exposure models, all exposures were associated with an increased risk of MI. In multi-pollutant analyses, an independent association with risk of MI was observed for PM2.5 (HR: 1.026; 95% CI: 1.002-1.050), noise at most exposed façade (HR: 1.024; 95% CI: 1.012-1.035), and lack of green space within 150 m of residence (HR: 1.018; 95% CI: 1.010-1.027). All three factors contributed significantly to the CRI (1.089; 95% CI: 1.076-1.101). CONCLUSION: In a nationwide cohort study, air pollution, noise, and lack of green space were all independently associated with an increased risk of MI. The air pollutant PM2.5 was closest associated with MI risk.

The present study aimed to analyse their independent and cumulative association of the three correlated environmental exposures: air pollution, road traffic noise, and green space with MI. Air pollution, noise, and lack of green space were all independently associated with MI.Risk estimates for air pollution, noise, and lack of green space were similar, indicating that all may be equally relevant targets for regulatory measures.

Health position paper and redox perspectives - Disease burden by transportation noise.

Transportation noise is a ubiquitous urban exposure. In 2018, the World Health Organization concluded that chronic exposure to road traffic noise is a risk factor for ischemic heart disease. In contrast, they concluded that the quality of evidence for a link to other diseases was very low to moderate. Since then, several studies on the impact of noise on various diseases have been published. Also, studies investigating the mechanistic pathways underlying noise-induced health effects are emerging. We review the current evidence regarding effects of noise on health and the related disease-mechanisms. Several high-quality cohort studies consistently found road traffic noise to be associated with a higher risk of ischemic heart disease, heart failure, diabetes, and all-cause mortality. Furthermore, recent studies have indicated that road traffic and railway noise may increase the risk of diseases not commonly investigated in an environmental noise context, including breast cancer, dementia, and tinnitus. The harmful effects of noise are related to activation of a physiological stress response and nighttime sleep disturbance. Oxidative stress and inflammation downstream of stress hormone signaling and dysregulated circadian rhythms are identified as major disease-relevant pathomechanistic drivers. We discuss the role of reactive oxygen species and present results from antioxidant interventions. Lastly, we provide an overview of oxidative stress markers and adverse redox processes reported for noise-exposed animals and humans. This position paper summarizes all available epidemiological, clinical, and preclinical evidence of transportation noise as an important environmental risk factor for public health and discusses its implications on the population level.

Outcomes after curatively intended treatment of limited peritoneal metastases and thermal ablation for liver metastases from colorectal cancer.

Objectives: Peritoneal metastases (PM) and liver metastases (LM) are present simultaneously in up to 2 % of patients at the time of their colorectal cancer (CRC) diagnosis. Curatively intended treatment includes cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with LM resection. A less invasive treatment for LM is ablation. We aimed to estimate overall survival (OS), disease-free survival (DFS) and postoperative data in patients managed simultaneously with CRS, HIPEC and radiofrequency ablation (RFA) as first choice. Methods: This was a retrospective national cohort study. All patients were treated at Aarhus University Hospital; the only CRS+HIPEC centre in Denmark. We included CRC patients managed with curative intent for simultaneously diagnosed PM and LM in the period January 2016 - December 2021. LM was treated with RFA as first choice, if possible. Survival was calculated by the Kaplan-Meier method. Results: A total of 25 patients were included, the median age was 60 years (range 43-75 years) and 15 (60 %) were females. The median peritoneal cancer index was 7 (range 0-12), the median number of LM was 1 (range 1-3). Ablation was performed as the only treatment for LM in 18 (72 %) patients. After a median follow-up time of 17.1 months (range 4-36 months), the median OS was 28.6 months (95 % confidence interval (Cl) 15.8;36.1), 1-year OS was 84.0 % (95 % Cl 62.8;93.7). Median DFS was 6.1 months (95 % Cl 4.0;10.3). Median LOS was ten days (range 5-26 days). Both 30-day and 90-day mortality were 0 %. Conclusions: The selected treatment modality (RFA) for CRC patients with both LM and PM was safe. However, DFS was low. Further research is warranted to investigate if RFA is as effective as LM resection.

Outpatients with psychotic disorders need physical health-promoting treatment: A cross-sectional multisite study.

Introduction: Impaired quality of life (QoL) and premature death in patients with primary non-affective psychotic disorders is related to lifestyle-induced comorbidities. Current municipal health-promoting treatment and care do not embrace the challenges of living with psychotic disorders. Aim: This cross-sectional study aimed to identify the proportion of outpatients diagnosed with primary psychotic disorders who need health-promoting treatment and care, and who receive municipal health-promoting interventions. Methods: Of 206 eligible invited outpatients from three psychiatric services clinics in Southern Denmark, 165 participated. Demographic and health characteristics, and use of alcohol, cannabis, drugs, and cigarettes were identified via a screening tool. Blood test information, body measurements, and medication status were extracted from the outpatients' medical records. The need for health promotion was assessed based on body mass index (BMI), and use of alcohol, cannabis, drugs, and cigarettes. Results: Seventy-three percent of outpatients needed health promotion, of whom 61 % were not offered municipal health-promoting treatment and care. Thirty-six percent had one or more somatic comorbidities, including diabetes mellitus (15 %) and cardiovascular disease (10 %); 41 % smoked a mean (SD) of 19 (10) cigarettes daily. Mean (SD) BMI was 34 (8) kg/m2 for women and 29 (7) kg/m2 for men. Conclusion: The majority of outpatients with non-affective psychotic disorders need health-promoting interventions, but only about 40 % of these patients receive such municipal health-promoting treatment and care. Future studies should clarify the impact of these interventions on the health status, QoL, and life expectancy of these patients.

Risk factors and outcome following salvage surgery for squamous cell carcinoma of the anus.

BACKGROUND: Chemoradiotherapy is the primary treatment for anal cancer. 15-33% of patients will have persistent or recurrent disease after treatment requiring salvage surgery. Relapse after surgery, postoperative complications, and mortality as well as possible risk factors are not fully understood due to the rareness of the disease. The aim of the study was to report outcomes after salvage surgery as well as evaluate risk factors for postoperative complications, cancer relapse and survival. METHODS: Data were retrospectively collected from electronical patients charts and pathology reports from all patients undergoing salvage surgery from July 1st, 2011 to July 1st, 2021 at the Department of Surgery, Aarhus University Hospital, Denmark. RESULTS: A total of 98 patients were included in the study. The 5-year overall survival was 61.8%. Relapse after surgery occurred in 36.7% of patients and was significantly associated with R1-resection (HR = 4.4) and preoperative nodal metastases (HR = 4.5). Negative prognostic factors for survival were found to be R1-resection (HR = 3.2), preoperative nodal metastases (HR = 2.9), and male gender (HR = 0.5). There was no association found between complications and survival (HR 1.2). None of the possible risk factors were associated with major postoperative complications. CONCLUSIONS: An acceptable overall survival after surgery was found. Survival and relapse-free survival was negatively associated with R1 resections and positive preoperative lymph nodes. Complications did not influence long-term survival.

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.

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.

Exposure to long-term source-specific transportation noise and incident breast cancer: A pooled study of eight Nordic cohorts.

BACKGROUND: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence. METHODS: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution. RESULTS: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th-95th percentile) 5-year residential road traffic noise was 54.8 (40.0-67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2-65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99-1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96-1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using <60 dB as a cutoff, we found HRs of 1.08 (0.99-1.18) for road traffic and 1.19 (0.95-1.49) for railway noise. CONCLUSIONS: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway and aircraft noise before conclusions regarding noise as a risk factor for breast cancer can be made.

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.