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Alzheimer’s Disease (AD) is the leading cause of dementia. Epidemiological studies suggest that AD is linked with poor status of nutrients including DHA, B-vitamins and the vitamins E and C. Ongoing neurodegeneration, particularly synaptic loss, leads to the classical clinical features of AD namely, memory impairment, language deterioration, and executive and visuospatial dysfunction. The main constituents of neural and synaptic membranes are phospholipids. Supplemenation of animals with three dietary precursors of phospholipids namely, DHA, uridine monophosphate and choline, results in increased levels of brain phospholipids, synaptic proteins, neurite outgrowth, dendritic spines formation (i.e. the anatomical precursors of new synapses) and an improvement in learning and memory. Other nutrients act as co-factors in the synthesis pathway of neuronal membranes. For example B-vitamins are involved in methylation processes, thereby enhancing the availability of choline as a synaptic membrane precursor. A multi-nutrient concept that includes these nutrients may improve membrane integrity, thereby influencing membrane-dependent processes such as receptor function and amyloid precursor protein (APP) processing, as shown by reduced amyloid production and amyloid β plaque burden, as well as toxicity. Together, these insights provided the basis for the development of a medical food for patients with AD, Souvenaid®, containing a specific combination of nutrients (Fortasyn™ Connect) and designed to enhance synapse formation in AD. The effect of Souvenaid on memory and cognitive performance was recently assessed in a proof-of-concept study, SOUVENIR I, with 212 drug-naïve mild AD patients (MMSE 20-26). This proof-of-concept study demonstrated that oral nutritional supplementation with Souvenaid® for 12 weeks improves memory in patients with mild AD. To confirm and extend these findings, we have designed and initiated three additional studies. Two of these studies will be completed in 2011; Souvenir II, a 24-week European study, with 259 drug-naïve mild AD patients (MMSE≥20) and S-Connect, another 24-week study, with 527 mild-tomoderate AD patients (MMSE 14-24) using AD medication conducted in the US. The third is the EU-funded LipiDiDiet study, a 24-month study, which will enrol 300 people with prodromal AD to assess the effect on memory performance.

Abstract Background Folate, vitamin B-12, and vitamin B-6 are essential nutritional components in one-carbon metabolism and are required for methylation capacity. The availability of these vitamins may therefore modify methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) by PE-N-methyltransferase (PEMT) in the liver. It has been suggested that PC synthesis by PEMT plays an important role in the transport of polyunsaturated fatty acids (PUFAs) like docosahexaenoic acid (DHA) from the liver to plasma and possibly other tissues. We hypothesized that if B-vitamin supplementation enhances PEMT activity, then supplementation could also increase the concentration of plasma levels of PUFAs such as DHA. To test this hypothesis, we determined the effect of varying the combined dietary intake of these three B-vitamins on plasma DHA concentration in rats. Methods In a first experiment, plasma DHA and plasma homocysteine concentrations were measured in rats that had consumed a B-vitamin-poor diet for 4 weeks after which they were either continued on the B-vitamin-poor diet or switched to a B-vitamin-enriched diet for another 4 weeks. In a second experiment, plasma DHA and plasma homocysteine concentrations were measured in rats after feeding them one of four diets with varying levels of B-vitamins for 4 weeks. The diets provided 0% (poor), 100% (normal), 400% (enriched), and 1600% (high) of the laboratory rodent requirements for each of the three B-vitamins. Results Plasma DHA concentration was higher in rats fed the B-vitamin-enriched diet than in rats that were continued on the B-vitamin-poor diet (P = 0.005; experiment A). Varying dietary B-vitamin intake from deficient to supra-physiologic resulted in a non-linear dose-dependent trend for increasing plasma DHA (P = 0.027; experiment B). Plasma DHA was lowest in rats consuming the B-vitamin-poor diet (P > 0.05 vs. normal, P . enriched and high) and highest in rats consuming the B-vitamin-high diet (P . poor and normal, P > 0.05 vs. enriched). B-vitamin deficiency significantly increased plasma total homocysteine but increasing intake above normal did not significantly reduce it. Nevertheless, in both experiments plasma DHA was inversely correlated with plasma total homocysteine. Conclusion These data demonstrate that dietary folate, vitamin B-12, and vitamin B-6 intake can influence plasma concentration of DHA.

Background: Modifying public awareness of oesophageal cancer symptoms might help to decrease late-stage diagnosis and, in turn, improve cancer outcomes. This study aimed to explore oesophageal cancer symptom awareness and determinants of lower awareness and anticipated time to help-seeking., Methods: We invited 18,156 individuals aged 18 to 75 years using random sampling of the nationwide Dutch population registry. A cross-sectional web-based survey containing items adapted from the Awareness and Beliefs about Cancer measure (i.e., cancer symptom awareness, anticipated time to presentation with dysphagia, health beliefs, and sociodemographic variables) was filled out by 3106 participants (response rate: 17%). Descriptive statistics were calculated and logistic regression analyses were performed to explore determinants of awareness and anticipated presentation (dichotomised as <1 month or ≥1 month)., Results: The number of participants that recognised dysphagia as a potential symptom of cancer was low (47%) compared with symptoms of other cancer types (change in bowel habits: 77%; change of a mole: 93%; breast lump: 93%). In multivariable analyses, non-recognition of dysphagia was associated with male gender (OR 0.50, 95% CI 0.43-0.58), lower education (OR 0.44, 0.35-0.54), and non-western migration background (OR 0.43, 0.28-0.67). Anticipated delayed help-seeking for dysphagia was associated with not recognising it as possible cancer symptom (OR 1.58, 1.27-1.97), perceived high risk of oesophageal cancer (OR 2.20, 1.39-3.47), and negative beliefs about oesophageal cancer (OR 1.86, 1.20-2.87)., Conclusion: Our findings demonstrate a disconcertingly low public awareness of oesophageal cancer symptoms. Educational interventions targeting groups with decreased awareness and addressing negative cancer beliefs may lead to faster help-seeking behaviour, although additional studies are needed to determine the effect on clinical cancer outcomes., (© 2024. The Author(s).)

Background: Novel, less-invasive technologies to screen for Barrett's esophagus (BE) may enable a paradigm shift in early detection strategies for esophageal adenocarcinoma (EAC). Understanding professionals' perspectives on screening is important to determine how to proceed. We aimed to explore and compare professionals' perceptions of screening for BE and EAC screening in three countries., Methods: In this study, 29 Dutch, 20 British and 18 American health care professionals (clinicians, researchers and policy makers) participated in concept mapping: a mixed-methods consensus building methodology. Statements on perceived barriers, facilitators, advantages, disadvantages, implications or worries associated with screening for BE and EAC were collected in asynchronous digital brainstorm sessions. Subsequently, participants sorted the statements into groups according to thematic similarity and assessed the relevance of each statement in evaluating the acceptability of BE and EAC screening. Multidimensional scaling and cluster analysis were used to map the associations between generated statements., Results: Professionals across three countries identified eight consistent themes that relate to their perceptions of screening for BE and EAC: (1) Benefits, (2) Harms, (3) Clinical effectiveness concerns, (4) Screening population, (5) Screening modality, (6) Resources, (7) Ownership, and (8) Public communication. Dutch and American professionals prioritized the potential health benefits of screening but also questioned clinical impact. In contrast, British participants prioritized identification of the screening population and suitable test., Conclusions: Most professionals see potential in less-invasive screening tests for BE and EAC but underline the need to define the target screening population and determine benefits and harms before widely employing them. Successful implementation will require thoughtful consideration of the involvement of general practitioners, readiness of endoscopy and pathology services, balanced public communication, and country-specific regulations., (© 2023. The Author(s).)

Background: Compared to the previous cytology-based program, the introduction of primary high-risk human papillomavirus (hrHPV) based screening in 2017 has led to an increased number of referrals. To counter this, triage of hrHPV-positive women in cervical cancer screening can potentially be optimized by taking sociodemographic and lifestyle risk factors for cervical abnormalities into account. Therefore, it is essential to gain knowledge of the views of women (30-60 years) eligible for cervical cancer screening., Objective: The main goal of this qualitative study was to gain insight in the aspects that influence acceptability of risk-based triage in cervical cancer screening., Design: A focus group study in which participants were recruited via four general medical practices, and purposive sampling was used to maximize heterogeneity with regards to age, education level, and cervical cancer screening experiences., Approach: The focus group discussions were transcribed verbatim and analyzed using reflexive thematic analysis., Participants: A total of 28 women (average age: 45.2 years) eligible for cervical cancer screening in The Netherlands participated in seven online focus group discussions. Half of the participants was higher educated, and the participants differed in previous cervical cancer screening participation and screening result., Key Results: In total, 5 main themes and 17 subthemes were identified that determine the acceptability of risk-stratified triage. The main themes are: 1) adequacy of the screening program: an evidence-based program that is able to minimize cancer incidence and reduce unnecessary referrals; 2) personal information (e.g., sensitive topics and stigma); 3) emotional impact: fear and reassurance; 4) communication (e.g., transparency); and 5) autonomy (e.g., prevention)., Conclusion: The current study highlights several challenges regarding the development and implementation of risk-based triage that need attention in order to be accepted by the target group. These challenges include dealing with sensitive topics and a transparent communication strategy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Screening for early esophageal adenocarcinoma (EAC), including screening for its precursor Barrett's esophagus (BE), has the potential to reduce EAC-related mortality and morbidity. This literature review aimed to explore professionals' views on the justification for EAC screening. A systematic search of Ovid Medline, EMBASE, and PsycInfo, from January 1, 2000 to September 22, 2022, identified 5 original studies and 63 expert opinion articles reporting professionals' perspectives on EAC screening. Included articles were qualitatively analyzed using the framework method, which was deductively led by modernized screening principles. The analyses showed that many professionals are optimistic about technological advancements in BE detection and treatment. However, views on whether the societal burden of EAC merits screening were contradictory. In addition, knowledge of the long-term benefits and risks of EAC screening is still considered insufficient. There is no consensus on who to screen, how often to screen, which screening test to use, and how to manage non-dysplastic BE. Professionals further point out the need to develop technology that facilitates automated test sample processing and public education strategies that avoid causing disproportionately high cancer worry and social stigma. In conclusion, modernized screening principles are currently insufficiently fulfilled to justify widespread screening for EAC. Results from future clinical screening trials and risk prediction modeling studies may shift professionals' thoughts regarding justification for EAC screening., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JS, YP, LR, MG, and MB have no conflicts of interest or financial ties related to this work to disclose. PS is receiving unrestricted research grants from Pentax (Japan), Norgine (UK), Motus GI (USA), MicroTech (China) and The eNose Company (Netherlands) and is in the advisory board of Motus GI (US) and Boston Scientific (US)., (© 2023 The Author(s).)

Objective: Screening for early oesophageal adenocarcinoma (OAC), including its precursor Barrett's oesophagus (BO), can potentially reduce OAC-related morbidity and mortality. This study explores Dutch at-risk individuals' views of screening an at-risk population for BO/OAC., Design: We invited 372 individuals with risk factors for OAC from primary care practices, 73 individuals with surveillance experience, and 221 participants of previous studies (BO/OAC screening trial or survey) to participate in focus groups. Transcripts were inductively and thematically analysed by two independent researchers., Results: A total of 50 individuals (42% with gastro-oesophageal reflux symptoms) of 50-75 years participated. Themes that were raised included: theme 1 'screening intentions' describing participants' motivation to be screened (eg, early diagnosis, potential reassurance, physician recommendation, and knowing someone with cancer) or decline screening (eg, anticipated discomfort or suboptimal accuracy of the test); theme 2 'risk-based eligibility' describing the tension between effectiveness (eg, targeting high-risk individuals) and inclusivity (eg, making screening available for everyone); theme 3 'distributive justice', in which the pressure of a potential new screening programme on healthcare resources was discussed; and theme 4 'information needs' describing the perceived lack of information access and individuals' preference to discuss screening with their general practitioner., Conclusion: Individuals not only expressed high willingness to be screened but also voiced the concern that a new screening programme may pressure limited healthcare resources. If implemented, it is crucial to develop educational materials that meet the public's information needs and explain the test procedures and eligibility criteria while avoiding stigmatising language., Competing Interests: Competing interests: PS is receiving unrestricted grants from Pentax (Japan), Norgine (UK), Motus GI (USA), MicroTech (China), and The eNose Company (Netherlands) and is in the advisory board of Motus GI (USA) and Boston Scientific (USA)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Oesophageal adenocarcinoma (OAC) is increasingly diagnosed and often fatal, thus representing a growing global health concern. Screening for its precursor, Barrett's oesophagus (BO), combined with endoscopic surveillance and treatment of dysplasia might prevent OAC. This review aimed to systematically explore the public's acceptance and uptake of novel screening strategies for OAC. We systematically searched three electronic databases (Ovid Medline/PubMed, Ovid EMBASE and PsycINFO) from date of inception to July 2, 2021 and hand-searched references to identify original studies published in English on acceptability and uptake of OAC screening. Two reviewers independently reviewed and appraised retrieved records and two reviewers extracted data (verified by one other reviewer). Of the 3674 unique records, 19 studies with 15 249 participants were included in the review. Thematic analysis of findings showed that acceptability of OAC screening is related to disease awareness, fear, belief in benefit, practicalities and physical discomfort. The findings were mapped on the Integrated Screening Action Model. Minimally invasive screening tests are generally well-tolerated: patient-reported outcomes were reported for sedated upper endoscopy (tolerability ++), transnasal endoscopy (tolerability +), tethered capsule endomicroscopy (tolerability +/-), and the Cytosponge-TFF3 test (acceptability ++). In discrete choice experiments, individuals mainly valued screening test accuracy. OAC screening has been performed in trials using conventional upper endoscopy ( n  = 231 individuals), transnasal endoscopy ( n  = 966), capsule endoscopy ( n  = 657) and the Cytosponge-TFF3 test ( n  = 9679), with uptake ranging from 14·5% to 48·1%. Intended participation in OAC screening in questionnaire-based studies ranged from 62·8% to 71·4%. We conclude that the general public seems to have interest in OAC screening. The findings will provide input for the design of a screening strategy that incorporates the public's values and preferences to improve informed participation. Identification of a screening strategy effective in reducing OAC mortality and morbidity remains a crucial prerequisite., Funding: This study was funded by the Netherlands Organization for Health Research and Development (ZonMw) under grant 555,004,206., Competing Interests: PS is receiving unrestricted grants from Pentax (Japan), Norgine (UK), Motus GI (USA), MicroTech (China) and The eNose Company (Netherlands) and is in the advisory board of Motus GI (USA) and Boston Scientific (USA). All other authors declare no competing interests., (© 2022 The Author(s).)

The objective of the present study was to evaluate the effect of a paediatric tube feed supplemented with a multifibre mixture on the gut microbiota and nutritional and micronutrient status of children on long-term enteral nutrition (EN). A randomised, controlled, double-blind, cross-over trial (2 × 3 months) with a washout period of 1 month was carried out. Twenty-seven children (80% neurologically impaired) aged 11.9 (SD 3.9) years, on long-term EN (4.8 (SD 3.9) years) were recruited. The analyses of the children's faecal pH, microbiota along with anthropometric measures, bowel movements and markers of blood micronutrient status were made. Twenty children completed the study. A significant increase in the proportion of stool bifidobacteria (+16.6%, P < 0.05) was observed during the multifibre period than during the fibre-free period, together with a significant reduction in stool pH (P < 0.001). Stool frequency and consistency as well as growth did not differ between the two periods. There was a significant increase (P < 0.05) in plasma ferritin at the end of the fibre-free period, but plasma ferritin levels remained within normal ranges during both periods. No diet effects on other blood parameters were observed. In conclusion, addition of a multifibre mixture with prebiotic components to paediatric EN is well tolerated, promotes bifidobacteria and reduces stool pH, indicating an improved gut health.

Effects of dietary polyunsaturated fatty acids (PUFA) on immune responses in poultry have been reported. However, effects on the underlying mechanisms, such as the role of cytokines, have not been documented because the necessary tools were lacking. Recently, primer sets for chicken interleukin (IL)-1beta, IL-2, interferon-gamma (IFN-gamma), myelomonocytic growth factor (MGF), and transforming growth factor (TGF)-beta2 have become available. Therefore, in the present study we first examined the in vivo effects of an inflammatory challenge with Salmonella typhimurium lipopolysaccharide (LPS) on cytokine profiles in growing laying-type chicks. Second, we examined whether dietary fat sources affected the observed cytokine profiles. Two hundred forty chicks were assigned in a 2 x 4 factorial design of treatments, with injection with LPS or saline and dietary fat source as factors. Factors were i.v. injection with S. typhimurium LPS or saline (control) and four dietary fat sources: corn oil, linseed oil, menhaden oil, and tallow. Two hours after injection, birds were killed, and their spleens were removed for RNA extraction. Reverse transcription polymerase chain reactions with primer sets for chicken IL-1beta, IL-2, IFN-gamma, MGF, TGF-beta2, and beta-actin were performed with RNA samples pooled by pen. The expression of cytokine mRNA was expressed relative to the level of beta-actin mRNA. Interleukin-1 (P < 0.001), MGF (P < 0.0001), IL-2 (P < 0.001), and IFN-gamma (P < 0.001) mRNA expressions were enhanced by challenge with LPS. Immunization treatment had no effect on TGF-beta2 or beta-actin expression. Dietary treatment did not affect mRNA expression of IL-1, MGF, IFN-gamma, TGF-beta2, or beta-actin. Interleukin-2 expression in LPS-injected birds that were fed the fish-oil-enriched diet was enhanced (P = 0.05). The present study indicates that in vivo effects of immune challenge on cytokine mRNA expression can be measured in poultry. The observation that mRNA level of IL-2, but not the mRNA levels of IFN-gamma or MGF, is enhanced by dietary fish oil at 2 h suggests that dietary PUFA at this moment initially affected naïve T lymphocytes.

Effects of four levels of dietary linoleic acid (LA), an n-6 fatty acid, and four levels of alpha-linolenic acid (LNA), an n-3 fatty acid, and their interactions on immune responses in growing layer hens were studied. Immune responses were induced by injection with keyhole limpet hemocyanin (KLH) or Mycobacterium butyricum particles at 35 d of age. Antibody (Ab) responses were measured until 21 d after immunization. In addition, delayed-type hypersensitivity, lymphocyte proliferation, weekly feed intake, and BW gain were studied. At Day 7 after immunization, anti-M. butyricum titers in the M. butyricum-immunized hens were decreased by the increase of dietary LA (P < 0.05). In the period from 10 to 14 d after immunization, anti-KLH Ab titers in KLH-immunized animals were affected by the interaction of dietary LA with LNA (P < 0.01). High dietary levels of LA or LNA increased the anti-KLH Ab response. However, at high levels of dietary LA and LNA, anti-KLH Ab titers were not increased. In the same period, anti-M. butyricum Ab titers of M. butyricum-immunized hens were affected by the interaction of dietary LA with LNA (P < 0.05). At low levels of LA and LNA, increased LA levels decreased the Ab response, whereas increased LNA levels at low LA levels hardly affected the anti-M. butyricum response. At a high level of LA, increased dietary LNA increased the anti-M. butyricum response. In vitro proliferation of peripheral blood leukocytes after stimulation with concanavalin A (ConA) was higher in chickens with a high level of dietary LNA. Feed intake decreased when the dietary levels of LA or LNA increased. However, BW gain was not affected by dietary treatments. Feed conversion was more efficient in birds fed high levels of LA and LNA. The present study indicates that various factors affect the Ab responses. First, the interaction of n-6 and n-3 polyunsaturated fatty acids (PUFA) is more important than the separate effects of n-3 or n-6. Second, the actions of dietary PUFA were different between antigens of a different nature. Third was the nature of the antigen affects when dietary PUFA exert their actions and the persistence of these effects. The presence of these multiple factors affecting immune responses should be considered when comparing effects of dietary PUFA on immune responses.

The effects of linoleic (LA)- and linolenic acid (LNA)-enriched diets on humoral and in vivo cellular immune responses to keyhole limpet hemocyanin (KLH)-dinitrophenyl (DNP) and Mycobacterium butyricum were studied in growing layer hens. Pullets were fed one of three diets: a control, LA enriched, or LNA enriched. Pullets were assigned to one of three immunization treatments: KLH-DNP, M. butyricum, or PBS. The LA-enriched diet enhanced the antibody response to KLH in pullets immunized with KLH-DNP. On the other hand, the antibody response to M. butyricum in M. butyricum-immunized birds was decreased by feeding an LA-enriched diet. In vitro lymphocyte proliferation in the presence of Concanavalin A was affected by the interaction between diet and immunization. Neither cutaneous hypersensitivity to KLH nor to M. butyricum was affected by the diet. The BW gain before immunization was not affected by the diet, but after immunization, the LA-enriched diet enhanced growth in birds immunized with M. butyricum. Diets had various effects on organ weights. We concluded that dietary linoleic acid enrichment of the diet has an antigen-dependent divergent effect on the antibody response. The dietary LNA effect on the antibody response is less pronounced and is opposite to that of the LA effect.

Effects of prostaglandin E2 (PGE2) and indomethacin, an inhibitor of PGE2 oxygenase, on primary and secondary antibody (Ab) responses to Mycobacterium butyricum protein or keyhole limpet hemocyanin (KLH) were studied in growing layer hens. Immunizations at 35 and 70 d of age were accompanied by immunomodulating treatments with PGE2, indomethacin, or PBS. In addition, we studied effects of various doses of indomethacin and PGE2 on mitogen-induced T-cell proliferation in vitro. Secondary Ab responses to KLH were enhanced by administration of indomethacin at secondary immunization and, to a lesser extent, by PGE2 administration at secondary immunization. Primary Ab responses to M. butyricum tended to decrease by administration of either PGE2 or indomethacin. Secondary Ab responses to M. butyricum were affected by administration of both PGE2 and indomethacin at primary immunization. Prostaglandin E2 increased phytohemagglutinin (PHA)-induced lymphocyte proliferation. Indomethacin decreased Concanavalin A (ConA)- and PHA-induced lymphocyte proliferation. The net effect of indomethacin on the Ab response could not be explained by inhibition of PGE2 oxygenase only. Our data rather suggest an inhibition by indomethacin of other immunosuppressing factors derived from arachidonic acid. We concluded that polyunsaturated fatty acid-derived products might especially affect secondary antibody responsiveness. This finding may depend on inhibition or enhancement of T-cell responsiveness. Consequently, immunomodulation by dietary polyunsaturated fatty acids may have profound effects at secondary rather than at primary exposure to pathogens.