Erythrocyte Phospholipid Molecular Species and Fatty Acids of Down Syndrome Children Compared with Non-affected Siblings

The majority of children with Down syndrome (DS) develop Alzheimer's disease (AD) at an early age. Although long-chain n-3 fatty acids (FA) are protective of neurodegeneration, little is known about the FA status in DS. In the present study, we aimed to investigate whether children with DS presented altered plasma and erythrocyte membrane phospholipids (PL) FA composition, when compared with their non-affected siblings. Venous blood samples were analysed for plasma and erythrocyte membrane FA composition by TLC followed by GC techniques. Lipid molecular species were determined by electrospray ionisation/tandem MS (ESI-MS/MS). FA analysis measured by standard GC showed an increased concentration of MUFA and a decreased concentration of plasmalogens in major PL fractions, but there were no differences in the concentrations of arachidonic acid or DHA. However, as identified by ESI-MS/MS, children with DS had increased levels of the following erythrocyte PL molecular species: 16 : 0–16 : 0, 16 : 0–18 : 1 and 16 : 0–18 : 2n-6, with reduced levels of 16 : 0–20 : 4n-6 species. Children with DS presented significantly higher levels of MUFA in both plasma and erythrocyte membrane, as well as higher levels of saturated and monounsaturated molecular species. Of interest was the almost double proportion of 16 : 0–18 : 2n-6 and nearly half the proportion of 16 : 0–20 : 4n-6 of choline phosphoacylglycerol species in children with DS compared with their non-affected siblings. These significant differences were only revealed by ESI-MS/MS and were not observed in the GC analysis. Further investigations are needed to explore molecular mechanisms and to test the association between the pathophysiology of DS and the risk of AD

A universal approximate cross-validation criterion and its asymptotic distribution

A general framework is that the estimators of a distribution are obtained by minimizing a function (the estimating function) and they are assessed through another function (the assessment function). The estimating and assessment functions generally estimate risks. A classical case is that both functions estimate an information risk (specifically cross entropy); in that case Akaike information criterion (AIC) is relevant. In more general cases, the assessment risk can be estimated by leave-one-out crossvalidation. Since leave-one-out crossvalidation is computationally very demanding, an approximation formula can be very useful. A universal approximate crossvalidation criterion (UACV) for the leave-one-out crossvalidation is given. This criterion can be adapted to different types of estimators, including penalized likelihood and maximum a posteriori estimators, and of assessment risk functions, including information risk functions and continuous rank probability score (CRPS). This formula reduces to Takeuchi information criterion (TIC) when cross entropy is the risk for both estimation and assessment. The asymptotic distribution of UACV and of a difference of UACV is given. UACV can be used for comparing estimators of the distributions of ordered categorical data derived from threshold models and models based on continuous approximations. A simulation study and an analysis of real psychometric data are presented.Comment: 23 pages, 2 figure

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

IMPORTANCE: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD. DATA SOURCES: A global consortium of 19 studies identified by November 2014. STUDY SELECTION: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS: Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS: The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE: On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.ARIC was carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. CHS was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant U01HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health The Costa-Rican adult study was supported by grant R01HL081549 from the National Institutes of Health. EURAMIC was supported by the Commission of the European Communities, as a Concerted Action within Directorate General-XII, with additional support from Directorate General-V Europe against Cancer. The national studies were financed by the Dutch Ministry of Health. Ulster Cancer Foundation and Milk Intervention Board. Grant AKT76 from Cancer Research Switzerland. Swiss National Science Foundation Grant 32-9257-87. Spanish FIS and Ministry of Science and Education, and German Federal Health Office EPIC-Norfolk was funded by grants from Medical Research Council and Cancer Research UK. Dr. Imamura also received support from the Medical Research Council Epidemiology Unit Core Support (MC_UU_12015/5). HPFS was supported by the NIH grants UM1 CA167552, R01 HL35464, AA11181, HL35464, CA55075, HL60712 and P30 DK46200 The InChianti study was supported as a ‘targeted project’ (ICS 110.1\RS97.71) by the Italian Ministry of Health and in part by the Intramural Research Program of the NIH (Contracts N01-AG-916413 and N01-AG-821336 and Contracts 263 MD 9164 13 and 263 MD 821336) KIND (Kuopio Ischaemic Heart Disease Risk Factor Study) was supported by grants from the Academy of Finland, Helsinki, Finland (grants 41471, 1041086) MCCS (Melbourne Collaborative Cohort Study) recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-MEHC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-001079, and UL1-TR-000040. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affymetric Genome-Wide Human SNP Array 6.0. NSHDS I & II (The Northern Sweden Health & Disease Study I & II) was supported by the Swedish Cancer Society and the Swedish Research Council NHS (Nurses’ Health Study) was supported by research grants UM1 CA186107, R01 CA49449, R01 HL034594, P01CA87969, R01HL034594, and R01HL088521 of the National Institutes of Health The PHS (Physician’s Health Study) was supported by grant R21 HL088081, CA-34944 and CA-40360, and CA-097193 from the National Cancer Institute and grants HL-26490 and HL-34595from the National Heart, Lung, and Blood Institute, Bethesda, MD. The 3C (Three-City) study was conducted under a partnership agreement between the Institut National de la Santé et de la Recherche Médicale (INSERM), the University Bordeaux 2 Victor Segalen and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The Three-City study was also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Conseils Régionaux d’Aquitaine et Bourgogne, Fondation de France, Ministry of Research-INSERM Programme “Cohortes et collections de données biologiques”, Agence Nationale de la Recherche (grant number COGINUT ANR-06-PNRA-005), the Fondation Plan Alzheimer (grant number FCS 2009-2012), and the Caisse Nationale pour la Solidarité et l’Autonomie (CNSA) . Dr Samieri was on a grant from the “Fondation Plan Alzheimer” SHHEC (Scottish Heart Health Extended Cohort) study was funded by the Scottish Health Department Chief Scientist Organization; British Heart Foundation; FP Fleming Trust. The authors would like to acknowledge Dr. Roger Tavendale for his work with the Scottish Heart Health Study. SCHS (Singapore Chinese Health Study) was supported by the Singapore National Medical Research Council (grant number: NMRC 1270/2010) and the U.S. NIH (grant numbers: R01CA 144034 and UM1 CA182876) ULSAM 50 and 70 were funded by the Swedish Research Council for Health, Working Life and Welfare (FORTE) Uppsala City Council (ALF) and Swedish Research CouncilThis is the final version of the article. It first appeared from American Medical Association via http://dx.doi.org/10.1001/jamainternmed.2016.292

Toward a New Philosophy of Preventive Nutrition: From a Reductionist to a Holistic Paradigm to Improve Nutritional Recommendations

The reductionist approach has been predominant to date in human nutrition research and has unraveled some of the fundamental mechanisms at the basis of food nutrients (e.g., those that involve deficiency diseases). In Western countries, along with progress in medicine and pharmacology, the reductionist approach helped to increase life expectancy. However, despite 40 y of research in nutrition, epidemics of obesity and diabetes are growing each year worldwide, both in developed and developing countries, leading to a decrease in healthy life years. Yet, interactions between nutrition-health relations cannot be modeled on the basis of a linear cause-effect relation between 1 food compound and 1 physiologic effect but rather from multicausal nonlinear relations. In other words, explaining the whole from the specific by a bottom-up reductionist approach has its limits. A top-down approach becomes necessary to investigate complex issues through a holistic view before addressing any specific question to explain the whole. However, it appears that both approaches are necessary and mutually reinforcing. In this review, Eastern and Western research perspectives are first presented, laying out bases for what could be the consequences of applying a reductionist versus holistic approach to research in nutrition vis-a-vis public health, environmental sustainability, breeding, biodiversity, food science and processing, and physiology for improving nutritional recommendations. Therefore, research that replaces reductionism with a more holistic approach will reveal global and efficient solutions to the problems encountered from the field to the plate. Preventive human nutrition can no longer be considered as "pharmacology" or foods as "drugs.

Yearb Med Inform

OBJECTIVES: The objective of this review was to identify and analyze the most recent research and prevailing trends in the field of Public Health and Epidemiology Informatics (PHEI). METHODS: We adopted a methodical search approach that was similar to the one used in the previous edition of the PHEI section's synopsis. We conducted a thorough search on PubMed using an extensive range of keywords that cover topics related to public health, epidemiological surveillance, and medical informatics. As a result, there were 840 publications found on PHEI. The three section editors carefully examined the references. Afterwards, nine articles were selected as potential contenders for the "best paper" awards. The candidates underwent a thorough peer-review process that included six external reviewers, as well as the section editors and the two chief editors of the IMIA Yearbook of Medical Informatics. Every paper was subjected to a total of five reviews. RESULTS: The search yielded 840 references, and after review of the nine "best paper" candidates, only two papers emerged as strong contenders for the "best paper" award. The first candidate paper, which received a broader consensus, explored the integration of clinical language models in medicine. This model envisioned working alongside physicians, providing real-time guidance at the point of care. The second candidate fo-cused on developing personalized digital interventions to effectively increase short-term physical activity. CONCLUSION: The recent PHEI section review has identified a significant rise in the quantity of pertinent stud-ies in comparison to the previous edition. The search strategy for this year incorporated precision medicine-related keywords for the first time, which may have led to an increased number of retrieved publications specifically related to PHEI

Yearb Med Inform

OBJECTIVES: The objective of this study is to highlight innovative research and contemporary trends in the area of Public Health and Epidemiology Informatics (PHEI). METHODS: Following a similar approach to last year's edition, a meticulous search was conducted on PubMed (with keywords including topics related to Public Health, Epidemiological Surveillance and Medical Informatics), examining a total of 2,022 scientific publications on Public Health and Epidemiology Informatics (PHEI). The resulting references were thoroughly examined by the three section editors. Subsequently, 10 papers were chosen as potential candidates for the best paper award. These selected papers were then subjected to peer-review by six external reviewers, in addition to the section editors and two chief editors of the IMIA yearbook of medical informatics. Each paper underwent a total of five reviews. RESULTS: Out of the 539 references retrieved from PubMed, only two were deemed worthy of the best paper award, although four papers had the potential to qualify in total. The first best paper by pertains to a study about the need for a new annotation framework due to inadequacies in existing methods and resources. The second paper elucidates the use of Weibo data to monitor the health of Chinese urbanites. The correlation between air pollution and health sensing was measured via generalized additive models. CONCLUSIONS: One of the primary findings of this edition is the dearth of studies identified for the PHEI section, which represents a significant decline compared to the previous edition. This is particularly surprising given that the post-COVID period should have led to an increased use of information and communication technology for public health issues

Behavioural Risk Factors in Mid-Life Associated with Successful Ageing, Disability, Dementia and Frailty in Later Life: A Rapid Systematic Review.

BACKGROUND: Smoking, alcohol consumption, poor diet and low levels of physical activity significantly contribute to the burden of illness in developed countries. Whilst the links between specific and multiple risk behaviours and individual chronic conditions are well documented, the impact of these behaviours in mid-life across a range of later life outcomes has yet to be comprehensively assessed. This review aimed to provide an overview of behavioural risk factors in mid-life that are associated with successful ageing and the primary prevention or delay of disability, dementia, frailty and non-communicable chronic conditions. METHODS: A literature search was conducted to identify cohort studies published in English since 2000 up to Dec 2014. Multivariate analyses and a minimum follow-up of five years were required for inclusion. Two reviewers screened titles, abstracts and papers independently. Studies were assessed for quality. Evidence was synthesised by mid-life behavioural risk for a range of late life outcomes. FINDINGS: This search located 10,338 individual references, of which 164 are included in this review. Follow-up data ranged from five years to 36 years. Outcomes include dementia, frailty, disability and cardiovascular disease. There is consistent evidence of beneficial associations between mid-life physical activity, healthy ageing and disease outcomes. Across all populations studied there is consistent evidence that mid-life smoking has a detrimental effect on health. Evidence specific to alcohol consumption was mixed. Limited, but supportive, evidence was available relating specifically to mid-life diet, leisure and social activities or health inequalities. CONCLUSIONS: There is consistent evidence of associations between mid-life behaviours and a range of late life outcomes. The promotion of physical activity, healthy diet and smoking cessation in all mid-life populations should be encouraged for successful ageing and the prevention of disability and chronic disease.This work was funded by the National Institute for Health and Care Excellence (NICE), invitation to tender reference DDER 42013, and supported by the National Institute for Health Research School for Public Health Research. The scope of the work was defined by NICE and the protocol was agreed with NICE prior to the start of work. The funders had no role in data analysis, preparation of the manuscript or decision to publish.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.014440

Nutrients

Few data are available regarding dietary habits of the elderly, especially about dairy products (DPs) (total DP and milk, fresh DP, and cheese), whereas these are part of healthy habits. The aim was to describe the socio-demographic characteristics, food, and nutritional intakes of elderly DP consumers. The sample consisted of 1584 participants from the Three-City-Bordeaux cohort (France), who answered a food frequency questionnaire and a 24-h dietary recall. Socio-demographic characteristics, practice of physical activity, Body Mass Index, and polymedication were registered. The sample was 76.2 years (SD 5.0 years) on average, 35% were in line with the French dietary guidelines for DP (3 or 4 servings of DP/day), while 49% were below, and 16% above. Women were significantly more likely to declare the highest total DP (≥4 times/day), milk (>1 time/day), and fresh DP (>1.5 times/day) frequency consumption. The highest cheese frequency consumers (>1.5 times/day) were more likely men, married, and ex-smokers. The highest frequency of fresh DP intake was significantly associated with the lowest energy and lipid intakes, and that of cheese with the highest consumption of charcuteries, meat, and alcohol. This cross-sectional analysis confirmed that the socio-demographics and dietary characteristics varied across DP sub-types consumed, which encourages individual consideration of these confounders in further analyses

Int J Public Health

Letter to the editor. This article mentions parts of: Mental Multimorbidity Among General-Population Adults: Sex-Specific Sociodemographic Profiles of Anxiety, Insomnia, and Eating DisordersInternational audienc

Fish Intake and MRI Burden of Cerebrovascular Disease in Older Adults

BACKGROUND AND OBJECTIVE: Fish intake may prevent cerebrovascular disease (CVD), yet the mechanisms are unclear, especially regarding its impact on subclinical damage. Assuming that fish may have pleiotropic effect on cerebrovascular health, we investigated the association of fish intake with global CVD burden based on brain MRI markers. METHODS: This cross-sectional analysis included participants from the Three-City Dijon population-based cohort (aged >/=65 years) without dementia, stroke, or history of hospitalized cardiovascular disease, who underwent brain MRI with automated assessment of white matter hyperintensities, visual detection of covert infarcts, and grading of dilated perivascular spaces. Fish intake was assessed through a frequency questionnaire and the primary outcome measure was defined as the first component of a factor analysis of mixed data applied to MRI markers. The association of fish intake with the CVD burden indicator was studied using linear regressions. RESULTS: In total, 1,623 participants (mean age, 72.3 years; 63% women) were included. The first component of factor analysis (32.4% of explained variance) was associated with higher levels of all three MRI markers. Higher fish intake was associated with lower CVD burden. In a model adjusted for total intracranial volume, compared to participants consuming fish /=4 times per week had a beta = -0.19 (95% CI, -0.37; -0.01) and beta = -0.30 (-0.57; -0.03) lower indicator of CVD burden, respectively (P trend /=75 years. For comparison, in the younger age group, consuming fish 2-3 times a week was roughly equivalent (in opposite direction) to the effect of hypertension. DISCUSSION: In this large population-based study, higher frequency of fish intake was associated with lower CVD burden, especially among participants younger than 75 years, suggesting a beneficial effect on brain vascular health before manifestation of overt brain disease. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in individuals without stroke or dementia, higher fish intake is associated with lower subclinical CVD at MRI