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Effect of storage time, temperature, antioxidant and thawing on fatty acid composition of plasma, serum and red blood cells - A pilot biobank study.

Sun, 10/22/2017 - 13:12
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Effect of storage time, temperature, antioxidant and thawing on fatty acid composition of plasma, serum and red blood cells - A pilot biobank study.

Clin Biochem. 2017 Oct 17;:

Authors: Araujo P, Bjørkkjær T, Frøyland L, Waagbø R

Abstract
BACKGROUND: It studies on the factors that affect the stability of fatty acid profiles from human blood specimens are generally performed by evaluating the effect of a single factor on an individual fatty acid and excluding a considerable amount of data from the total fatty acid profiles.
METHODS: The stability of fatty acids from plasma, serum and red blood cells (RBC) was evaluated in terms of time, temperature, antioxidant and thawing. The fatty acids were methylated and analyzed by gas chromatography. The large volume of data is evaluated simultaneously and automatically by observing an Excel-based colour scale that indicates whether the fatty acid profiles have changed significantly as a result of the storage time (0-52weeks), temperature (-20°C/-80°C), butylated hydroxytoluene (BHT) antioxidant (presence/absence) or thawing (single/multiple).
RESULTS: Fatty acids from plasma were stable at both temperatures (-20°C/-80°C) regardless of BHT. Fatty acids from serum without BHT degrades faster at -80°C than -20°C and fatty acids from RBC without BHT degrades faster at -20°C than -80°C. Addition of BHT inhibits this effect in serum and RBC. Multiple thawing of RBC without BHT demonstrated that polyunsaturated fatty acids were generally more susceptible for changes at -80°C than at -20°C while BHT prevents partially this effect.
CONCLUSIONS: This study draws attention to the importance of pre-analytical considerations when storing blood samples in biobanks and the need of careful judgments when analyzing fatty acids profiles.

PMID: 29054439 [PubMed - as supplied by publisher]

Absolute lymphocyte counts at end of induction correlate with distinct immune cell compartments in pediatric B cell precursor acute lymphoblastic leukemia.

Sat, 10/21/2017 - 14:17
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Absolute lymphocyte counts at end of induction correlate with distinct immune cell compartments in pediatric B cell precursor acute lymphoblastic leukemia.

Cancer Immunol Immunother. 2017 Oct 20;:

Authors: Rolf N, Smolen KK, Kariminia A, Velenosi A, Fidanza M, Strahlendorf C, Seif AE, Reid GSD

Abstract
Several retrospective studies in children with B cell precursor (BCP) acute lymphoblastic leukemia (ALL) provided clinical evidence that higher absolute lymphocyte counts (ALC) early into treatment significantly correlated with improved relapse-free and overall survival. It still remains unknown, however, whether the predictive role of higher ALCs reflects general bone marrow recovery or a more specific attribute of immune function. To investigate this question, we implemented a prospective observational cohort study in 20 children with BCP ALL on day 29 (D29) of induction chemotherapy and immunophenotyped their lymphoid (T, B and natural killer cells) and myeloid (neutrophils, monocytes, dendritic cells) compartments. In a first evaluation of a cohort treated with Children's Oncology Group-based induction chemotherapy, the immune cell compartments were differentially depleted at D29. Neither gender, risk status, minimal residual disease, nor bone marrow recovery markers correlated with D29 ALC. In contrast, both CD3(+) T cell and dendritic cell compartments, which did not correlate with age, significantly correlated with D29 ALC (p < 0.0001). In addition, subset complexity of cellular immune compartments was preserved at D29. This study reveals that D29 ALC significantly correlates with distinct immune cell compartments but not with bone marrow recovery markers, suggesting that higher D29 ALCs may contribute to leukemia control by inducing specific host immune activity.

PMID: 29052781 [PubMed - as supplied by publisher]

Transforming growth factor-β signaling pathway-associated genes SMAD2 and TGFBR2 are implicated in metabolic syndrome in a Taiwanese population.

Sat, 10/21/2017 - 14:17
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Transforming growth factor-β signaling pathway-associated genes SMAD2 and TGFBR2 are implicated in metabolic syndrome in a Taiwanese population.

Sci Rep. 2017 Oct 19;7(1):13589

Authors: Lin E, Kuo PH, Liu YL, Yang AC, Tsai SJ

Abstract
The transforming growth factor-β (TGF-β) signaling pathway and its relevant genes have been correlated with an increased risk of developing various hallmarks of metabolic syndrome (MetS). In this study, we assessed whether the TGF-β signaling pathway-associated genes of SMAD family member 2 (SMAD2), SMAD3, SMAD4, transforming growth factor beta 1 (TGFB1), TGFB2, TGFB3, transforming growth factor beta receptor 1 (TGFBR1), and TGFBR2 are associated with MetS and its individual components independently, through complex interactions, or both in a Taiwanese population. A total of 3,000 Taiwanese subjects from the Taiwan Biobank were assessed. Metabolic traits such as waist circumference, triglyceride, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and fasting glucose were measured. Our results showed a significant association of MetS with the two single nucleotide polymorphisms (SNPs) of SMAD2 rs11082639 and TGFBR2 rs3773651. The association of MetS with these SNPs remained significant after performing Bonferroni correction. Moreover, we identified the effect of SMAD2 rs11082639 on high waist circumference. We also found that an interaction between the SMAD2 rs11082639 and TGFBR2 rs3773651 SNPs influenced MetS. Our findings indicated that the TGF-β signaling pathway-associated genes of SMAD2 and TGFBR2 may contribute to the risk of MetS independently and through gene-gene interactions.

PMID: 29051557 [PubMed - in process]

Improved Efficiency of Ibuprofen by Cationic Carbosilane Dendritic Conjugates.

Sat, 10/21/2017 - 14:17
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Improved Efficiency of Ibuprofen by Cationic Carbosilane Dendritic Conjugates.

Mol Pharm. 2016 Oct 03;13(10):3427-3438

Authors: Perisé-Barrios AJ, Fuentes-Paniagua E, Sánchez-Nieves J, Serramía MJ, Alonso E, Reguera RM, Gómez R, de la Mata FJ, Muñoz-Fernández MÁ

Abstract
In order to improve the efficiency of the anti-inflammatory drug ibuprofen, cationic carbosilane dendrimers and dendrons with ibuprofen at their periphery or at their focal point, respectively, have been synthesized, and the release of the drug was studied using HPLC. Macrophages were used to evaluate the anti-inflammatory effect of the ibuprofen-conjugated dendritic systems and compared with mixtures of non-ibuprofen dendritic systems in the presence of the drug. The cationic ibuprofen-conjugated dendron was the compound that showed higher anti-inflammatory properties. It reduces the LPS-induced COX-2 expression and decreases the release of several inflammatory cytokines such as TNFα, IL-1β, IL-6, and CCL3. These results open new perspectives in the use of these compounds as drug carriers.

PMID: 27533491 [PubMed - indexed for MEDLINE]

Gastric cancer: immunohistochemical classification of molecular subtypes and their association with clinicopathological characteristics.

Fri, 10/20/2017 - 13:03
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Gastric cancer: immunohistochemical classification of molecular subtypes and their association with clinicopathological characteristics.

Virchows Arch. 2017 Oct 19;:

Authors: Birkman EM, Mansuri N, Kurki S, Ålgars A, Lintunen M, Ristamäki R, Sundström J, Carpén O

Abstract
Gastric cancer is traditionally divided into intestinal and diffuse histological subtypes, but recent molecular analyses have led to novel classification proposals based on genomic alterations. While the intestinal- and diffuse-type tumours are distinguishable from each other at the molecular level, intestinal-type tumours have more diverse molecular profile. The technology required for comprehensive molecular analysis is expensive and not applicable for routine clinical diagnostics. In this study, we have used immunohistochemistry and in situ hybridisation in molecular classification of gastric adenocarcinomas with an emphasis on the intestinal subtype. A tissue microarray consisting of 244 gastric adenocarcinomas was constructed, and the tumours were divided into four subgroups based on the presence of Epstein-Barr virus, TP53 aberrations and microsatellite instability. The intestinal- and diffuse-type tumours were separately examined. The distribution of EGFR and HER2 gene amplifications was studied in the intestinal-type tumours. Epstein-Barr virus positive intestinal-type tumours were more common in male patients (p = 0.035) and most often found in the gastric corpus (p = 0.011). The majority of the intestinal-type tumours with TP53 aberrations were proximally located (p = 0.010). All tumours with microsatellite instability showed intestinal-type histology (p = 0.017) and were associated with increased overall survival both in the univariate (p = 0.040) and multivariate analysis (p = 0.015). In conclusion, this study shows that gastric adenocarcinomas can be classified into biologically and clinically different subgroups by using a simple method also applicable for clinical diagnostics.

PMID: 29046940 [PubMed - as supplied by publisher]

Gray matter networks and clinical progression in subjects with predementia Alzheimer's disease.

Thu, 10/19/2017 - 14:43
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Gray matter networks and clinical progression in subjects with predementia Alzheimer's disease.

Neurobiol Aging. 2017 Sep 20;61:75-81

Authors: Tijms BM, Ten Kate M, Gouw AA, Borta A, Verfaillie S, Teunissen CE, Scheltens P, Barkhof F, van der Flier WM

Abstract
We studied whether gray matter network parameters are associated with rate of clinical progression in nondemented subjects who have abnormal amyloid markers in the cerebrospinal fluid (CSF), that is, predementia Alzheimer's disease. Nondemented subjects (62 with subjective cognitive decline; 160 with mild cognitive impairment (MCI); age = 68 ± 8 years; Mini-Mental State Examination (MMSE) = 28 ± 2.4) were selected from the Amsterdam Dementia Cohort when they had abnormal amyloid in CSF (<640 pg/mL). Networks were extracted from gray matter structural magnetic resonance imaging (MRI), and 9 parameters were calculated. Cox proportional hazards models were used to test associations between each connectivity predictor and rate of progression to MCI or dementia. After a median time of 2.2 years, 122 (55%) subjects showed clinical progression. Lower network parameter values were associated with increased risk for progression, with the strongest hazard ratio of 0.29 for clustering (95% confidence interval = 0.12-0.70; p < 0.01). Results remained after correcting for tau, hippocampal volume, and MMSE scores. Our results suggest that at predementia stages, gray matter network parameters may have use to identify subjects who will show fast clinical progression.

PMID: 29040871 [PubMed - as supplied by publisher]

Tobacco exposure and sleep disturbance in 498 208 UK Biobank participants.

Thu, 10/19/2017 - 14:43
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Tobacco exposure and sleep disturbance in 498 208 UK Biobank participants.

J Public Health (Oxf). 2017 Aug 30;:1-10

Authors: Boakye D, Wyse CA, Morales-Celis CA, Biello SM, Bailey MES, Dare S, Ward J, Gill JMR, Pell JP, Mackay DF

Abstract
Background: The prevalence of sleep disturbance is high and increasing. The study investigated whether active, former and passive smoking were associated with sleep disturbance.
Methods: This cross-sectional study used data from the UK Biobank: a cohort study of 502 655 participants, of whom 498 208 provided self-reported data on smoking and sleep characteristics. Multivariable multinomial and logistic regression models were used to examine the associations between smoking and sleep disturbance.
Results: Long-sleep duration (>9 h) was more common among current smokers [odds ratio (OR): 1.47; 95% confidence interval (CI): 1.17-1.85; probability value (P) = 0.001] than never smokers, especially heavy (>20/day) smokers (OR: 2.85; 95% CI: 1.66-4.89; P < 0.001). Former heavy (>20/day) smokers were also more likely to report short (<6 h) sleep duration (OR: 1.41; 95% CI: 1.25-1.60; P < 0.001), long-sleep duration (OR: 1.99; 95% CI: 1.47-2.71; P < 0.001) and sleeplessness (OR: 1.47; 95% CI: 1.38-1.57; P < 0.001) than never smokers. Among never smokers, those who lived with more than one smoker had higher odds of long-sleep duration than those not cohabitating with a smoker (OR: 2.71; 95% CI: 1.26-5.82; P = 0.011).
Conclusions: Active and passive exposure to high levels of tobacco smoke are associated with sleep disturbance. Existing global tobacco control interventions need to be enforced.

PMID: 29040744 [PubMed - as supplied by publisher]

The biological impact of blood pressure associated genetic variants in the natriuretic peptide receptor C gene on human vascular smooth muscle.

Thu, 10/19/2017 - 14:43
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The biological impact of blood pressure associated genetic variants in the natriuretic peptide receptor C gene on human vascular smooth muscle.

Hum Mol Genet. 2017 Oct 10;:

Authors: Ren M, Ng FL, Warren H, Witkowska K, Baron M, Jia Z, Cabrera C, Zhang R, Mifsud B, Munroe PB, Xiao Q, Townsend-Nicholson A, Hobbs A, Ye S, Caulfield M

Abstract
Elevated blood pressure (BP) is a major global risk factor for cardiovascular disease. Genome-wide association studies have identified several genetic variants at the NPR3 locus associated with BP, but the functional impact of these variants remains to be determined. Here we confirmed, by a genome-wide association study within UK Biobank, the existence of two independent BP-related signals within NPR3 locus. Using human primary vascular smooth muscle cells and endothelial cells from different individuals, we found that the BP-elevating alleles within one linkage disequilibrium block identified by the sentinel variant rs1173771 was associated with lower endogenous NPR3 mRNA and protein levels in vascular smooth muscle cells, together with reduced levels in open chromatin and nuclear protein binding. The BP-elevating alleles also increased vascular smooth muscle cell proliferation, angiotensin II-induced calcium flux, and cell contraction. However, an analogous genotype-dependent association was not observed in vascular endothelial cells. Our study identifies novel, putative mechanisms for BP-associated variants at the NPR3 locus to elevate BP, further strengthening the case for targeting NPR-C as a therapeutic approach for hypertension and cardiovascular disease prevention.

PMID: 29040610 [PubMed - as supplied by publisher]

Software Application Profile: PHESANT: a tool for performing automated phenome scans in UK Biobank.

Thu, 10/19/2017 - 14:43
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Software Application Profile: PHESANT: a tool for performing automated phenome scans in UK Biobank.

Int J Epidemiol. 2017 Oct 05;:

Authors: Millard LAC, Davies NM, Gaunt TR, Davey Smith G, Tilling K

Abstract
Motivation: Epidemiological cohorts typically contain a diverse set of phenotypes such that automation of phenome scans is non-trivial, because they require highly heterogeneous models. For this reason, phenome scans have to date tended to use a smaller homogeneous set of phenotypes that can be analysed in a consistent fashion. We present PHESANT (PHEnome Scan ANalysis Tool), a software package for performing comprehensive phenome scans in UK Biobank.
General features: PHESANT tests the association of a specified trait with all continuous, integer and categorical variables in UK Biobank, or a specified subset. PHESANT uses a novel rule-based algorithm to determine how to appropriately test each trait, then performs the analyses and produces plots and summary tables.
Implementation: The PHESANT phenome scan is implemented in R. PHESANT includes a novel Javascript D3.js visualization and accompanying Java code that converts the phenome scan results to the required JavaScript Object Notation (JSON) format.
Availability: PHESANT is available on GitHub at [https://github.com/MRCIEU/PHESANT]. Git tag v0.5 corresponds to the version presented here.

PMID: 29040602 [PubMed - as supplied by publisher]

Collider scope: when selection bias can substantially influence observed associations.

Thu, 10/19/2017 - 14:43
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Collider scope: when selection bias can substantially influence observed associations.

Int J Epidemiol. 2017 Sep 27;:

Authors: Munafò MR, Tilling K, Taylor AE, Evans DM, Davey Smith G

Abstract
Large-scale cross-sectional and cohort studies have transformed our understanding of the genetic and environmental determinants of health outcomes. However, the representativeness of these samples may be limited-either through selection into studies, or by attrition from studies over time. Here we explore the potential impact of this selection bias on results obtained from these studies, from the perspective that this amounts to conditioning on a collider (i.e. a form of collider bias). Whereas it is acknowledged that selection bias will have a strong effect on representativeness and prevalence estimates, it is often assumed that it should not have a strong impact on estimates of associations. We argue that because selection can induce collider bias (which occurs when two variables independently influence a third variable, and that third variable is conditioned upon), selection can lead to substantially biased estimates of associations. In particular, selection related to phenotypes can bias associations with genetic variants associated with those phenotypes. In simulations, we show that even modest influences on selection into, or attrition from, a study can generate biased and potentially misleading estimates of both phenotypic and genotypic associations. Our results highlight the value of knowing which population your study sample is representative of. If the factors influencing selection and attrition are known, they can be adjusted for. For example, having DNA available on most participants in a birth cohort study offers the possibility of investigating the extent to which polygenic scores predict subsequent participation, which in turn would enable sensitivity analyses of the extent to which bias might distort estimates.

PMID: 29040562 [PubMed - as supplied by publisher]

Cohort Profile: The Oxford Biobank.

Thu, 10/19/2017 - 14:43
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Cohort Profile: The Oxford Biobank.

Int J Epidemiol. 2017 Jul 31;:

Authors: Karpe F, Vasan SK, Humphreys SM, Miller J, Cheeseman J, Louise Dennis A, Neville MJ

PMID: 29040543 [PubMed - as supplied by publisher]

Strong impact on plasma protein profiles by precentrifugation delay but not by repeated freeze-thaw cycles, as analyzed using multiplex proximity extension assays.

Thu, 10/19/2017 - 14:43
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Strong impact on plasma protein profiles by precentrifugation delay but not by repeated freeze-thaw cycles, as analyzed using multiplex proximity extension assays.

Clin Chem Lab Med. 2017 Oct 17;:

Authors: Shen Q, Björkesten J, Galli J, Ekman D, Broberg J, Nordberg N, Tillander A, Kamali-Moghaddam M, Tybring G, Landegren U

Abstract
Background A number of factors regarding blood collection, handling and storage may affect sample quality. The purpose of this study was to assess the impact on plasma protein profiles by delayed centrifugation and plasma separation and multiple freeze-thaw cycles. Methods Blood samples drawn from 16 healthy individuals were collected into ethylenediaminetetraacetic acid tubes and kept either at 4 °C or 22 °C for 1-36 h prior to centrifugation. Plasma samples prepared 1 h after venipuncture were also subjected to two to eight cycles of freezing at -80 °C and thawing at 22 °C. Multiplex proximity extension assay, an antibody-based protein assay, was used to investigate the influence on plasma proteins. Results Up to 36 h delay before blood centrifugation resulted in significant increases of 16 and 40 out of 139 detectable proteins in samples kept at 4 °C or 22 °C, respectively. Some increases became noticeable after 8 h delay at 4 °C but already after 1 h at 22 °C. For samples stored at 4 °C, epidermal growth factor (EGF), NF-kappa-B essential modulator, SRC, interleukin 16 and CD6 increased the most, whereas the five most significantly increased proteins after storage at 22 °C were CD40 antigen ligand (CD40-L), EGF, platelet-derived growth factor subunit B, C-X-C motif chemokine ligand 5 and matrix metallopeptidase 1 (MMP1). Only matrix metallopeptidase 7 (MMP7) decreased significantly over time and only after storage at 22 °C. No protein levels were found to be significantly affected by up to eight freeze-thaw cycles. Conclusions Plasma should be prepared from blood after a limited precentrifugation delay at a refrigerated temperature. By contrast, the influence by several freeze-thaw cycles on detectable protein levels in plasma was negligible.

PMID: 29040064 [PubMed - as supplied by publisher]

Heritability of Addison's disease and prevalence of associated autoimmunity in a cohort of 112,100 Swedish twins.

Thu, 10/19/2017 - 14:43
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Heritability of Addison's disease and prevalence of associated autoimmunity in a cohort of 112,100 Swedish twins.

Endocrine. 2017 Oct 16;:

Authors: Skov J, Höijer J, Magnusson PKE, Ludvigsson JF, Kämpe O, Bensing S

Abstract
PURPOSE: The pathophysiology behind autoimmune Addison's disease (AAD) is poorly understood, and the relative influence of genetic and environmental factors remains unclear. In this study, we examined the heritability of AAD and explored disease-associated autoimmune comorbidity among Swedish twins.
METHODS: A population-based longitudinal cohort of 112,100 Swedish twins was used to calculate the heritability of AAD, and to explore co-occurrence of 10 organ-specific autoimmune disorders in twin pairs with AAD. Diagnoses were collected 1964-2012 through linkage to the Swedish National Patient Register. The Swedish Prescribed Drug Register was used for additional diagnostic precision. When available, biobank serum samples were used to ascertain the AAD diagnosis through identification of 21-hydroxylase autoantibodies.
RESULTS: We identified 29 twins with AAD. Five out of nine (5/9) monozygotic pairs and zero out of fifteen (0/15) dizygotic pairs were concordant for AAD. The probandwise concordance for monozygotic twins was 0.71 (95% CI 0.40-0.90) and the heritability 0.97 (95% CI 0.88-99). Autoimmune disease patterns of monozygotic twin pairs affected by AAD displayed a higher degree of similarity than those of dizygotic twins, with an incidence rate ratio of 15 (95% CI 1.8-116) on the number of shared autoimmune diagnoses within pairs.
CONCLUSIONS: The heritability of AAD appears to be very high, emphasizing the need for further research on the genetic etiology of the disease. Monozygotic twin concordance for multiple autoimmune manifestations suggests strong genetic influence on disease specificity in organ-specific autoimmunity.

PMID: 29039147 [PubMed - as supplied by publisher]

Standard Versus Simplified Consent Materials for Biobank Participation: Differences in Patient Knowledge and Trial Accrual.

Thu, 10/19/2017 - 14:43
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Standard Versus Simplified Consent Materials for Biobank Participation: Differences in Patient Knowledge and Trial Accrual.

J Empir Res Hum Res Ethics. 2017 Oct 01;:1556264617731869

Authors: Garrett SB, Murphy M, Wiley J, Dohan D

Abstract
Replacing standard consent materials with simplified materials is a promising intervention to improve patient comprehension, but there is little evidence on its real-world implementation. We employed a sequential two-arm design to compare the effect of standard versus simplified consent materials on potential donors' understanding of biobank processes and their accrual to an active biobanking program. Participants were female patients of a California breast health clinic. Subjects from the simplified arm answered more items correctly ( p = .064), reported "don't know" for fewer items ( p = .077), and consented to donate to the biobank at higher rates ( p = .025) than those from the standard arm. Replacing an extant consent form with a simplified version is feasible and may benefit patient comprehension and study accrual.

PMID: 29037106 [PubMed - as supplied by publisher]

Longitudinal 10-year changes in dietary intake and associations with cardio-metabolic risk factors in the Northern Sweden Health and Disease Study.

Thu, 10/19/2017 - 14:43
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Longitudinal 10-year changes in dietary intake and associations with cardio-metabolic risk factors in the Northern Sweden Health and Disease Study.

Nutr J. 2017 Mar 28;16(1):20

Authors: Winkvist A, Klingberg S, Nilsson LM, Wennberg M, Renström F, Hallmans G, Boman K, Johansson I

Abstract
BACKGROUND: Dietary risks today constitute the largest proportion of disability-adjusted life years (DALYs) globally and in Sweden. An increasing number of people today consume highly processed foods high in saturated fat, refined sugar and salt and low in dietary fiber, vitamins and minerals. It is important that dietary trends over time are monitored to predict changes in disease risk.
METHODS: In total, 15,995 individuals with two visits 10 (±1) years apart in the population-based Västerbotten Intervention Programme 1996-2014 were included. Dietary intake was captured with a 64-item food frequency questionnaire. Percent changes in intake of dietary components, Healthy Diet Score and Dietary Inflammatory Index were calculated and related to body mass index (BMI), serum cholesterol and triglyceride levels and blood pressure at the second visit in multivariable regression analyses.
RESULTS: For both sexes, on group level, proportion of energy intake (E%) from carbohydrates and sucrose decreased (largest carbohydrate decrease among 40 year-olds) and E% protein and total fat as well as saturated and poly-unsaturated fatty acids (PUFA) increased (highest protein increase among 30 year-olds and highest fat increase among 60 year-olds) over the 10-year period. Also, E% trans-fatty acids decreased. On individual basis, for both sexes decreases in intake of cholesterol and trans-fatty acids were associated with lower BMI and serum cholesterol at second visit (all P < 0.05). For men, increases in intake of whole grain and Healthy Diet Score were associated with lower BMI and serum cholesterol at second visit (all P < 0.05). Also for men, decreases in intake of trans-fatty acids and increases in Healthy Diet Score were associated with lower systolic blood pressure at second visit (P = 0.002 and P < 0.000). For women, increases in intake of PUFA and Healthy Diet Score were associated with lower BMI at second visit (P = 0.01 and P < 0.05). Surprisingly, increases in intake of sucrose among women were associated with lower BMI at second visit (P = 0.02).
CONCLUSIONS: In this large population-based sample, dietary changes over 10 years towards less carbohydrates and more protein and fat were noted. Individual changes towards the Nordic dietary recommendations were associated with healthier cardio-metabolic risk factor profile at second visit.

PMID: 28351404 [PubMed - indexed for MEDLINE]

Unbiased estimates of cerebrospinal fluid β-amyloid 1-42 cutoffs in a large memory clinic population.

Thu, 10/19/2017 - 14:43
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Unbiased estimates of cerebrospinal fluid β-amyloid 1-42 cutoffs in a large memory clinic population.

Alzheimers Res Ther. 2017 Feb 14;9(1):8

Authors: Bertens D, Tijms BM, Scheltens P, Teunissen CE, Visser PJ

Abstract
BACKGROUND: We sought to define a cutoff for β-amyloid 1-42 in cerebrospinal fluid (CSF), a key marker for Alzheimer's disease (AD), with data-driven Gaussian mixture modeling in a memory clinic population.
METHODS: We performed a combined cross-sectional and prospective cohort study. We selected 2462 subjects with subjective cognitive decline, mild cognitive impairment, AD-type dementia, and dementia other than AD from the Amsterdam Dementia Cohort. We defined CSF β-amyloid 1-42 cutoffs by data-driven Gaussian mixture modeling in the total population and in subgroups based on clinical diagnosis, age, and apolipoprotein E (APOE) genotype. We investigated whether abnormal β-amyloid 1-42 as defined by the data-driven cutoff could better predict progression to AD-type dementia than abnormal β-amyloid 1-42 defined by a clinical diagnosis-based cutoff using Cox proportional hazards regression.
RESULTS: In the total group of patients, we found a cutoff for abnormal CSF β-amyloid 1-42 of 680 pg/ml (95% CI 660-705 pg/ml). Similar cutoffs were found within diagnostic and APOE genotype subgroups. The cutoff was higher in elderly subjects than in younger subjects. The data-driven cutoff was higher than our clinical diagnosis-based cutoff and had a better predictive accuracy for progression to AD-type dementia in nondemented subjects (HR 7.6 versus 5.2, p < 0.01).
CONCLUSIONS: Mixture modeling is a robust method to determine cutoffs for CSF β-amyloid 1-42. It might better capture biological changes that are related to AD than cutoffs based on clinical diagnosis.

PMID: 28193256 [PubMed - indexed for MEDLINE]

Global DNA methylation analysis reveals miR-214-3p contributes to cisplatin resistance in pediatric intracranial nongerminomatous malignant germ cell tumors.

Tue, 10/17/2017 - 14:39

Global DNA methylation analysis reveals miR-214-3p contributes to cisplatin resistance in pediatric intracranial nongerminomatous malignant germ cell tumors.

Neuro Oncol. 2017 Oct 03;:

Authors: Hsieh TH, Liu YR, Chang TY, Liang ML, Chen HH, Wang HW, Yen Y, Wong TT

Abstract
Background: Pediatric central nervous system germ cell tumors (CNSGCTs) are rare and heterogeneous neoplasms, and they can be divided into germinomas and nongerminomatous GCTs (NGGCTs). NGGCTs are further subdivided into mature teratomas and nongerminomatous malignant GCTs (NGMGCTs). Clinical outcomes suggest that NGMGCTs have poor prognosis and survival, and that they require more extensive radiotherapy and adjuvant chemotherapy. However, the mechanisms underlying this difference are still unclear. DNA methylation alteration is generally acknowledged to cause therapeutic resistance in cancers. We hypothesized that the pediatric NGMGCTs exhibit different genome-wide DNA methylation pattern which is involved in the mechanism of its therapeutic resistance.
Methods: We performed methylation and hydroxymethylation DNA immunoprecipitation sequencing (MeDIP-seq and hMeDIP-seq), mRNA expression microarray and small RNA sequencing (smRNA-seq) to determine methylation-regulated genes, including miRNAs.
Results: The expression levels of 97 genes and 8 miRNAs were correlated with the promoter DNA methylation and hydroxymethylation status, such as the miR-199/-214 cluster, and treatment with DNA demethylating agent 5-Aza-2'-deoxycytidine elevated its expression level. Furthermore, smRNA-seq analysis showed 27 novel miRNA candidates with differential expression between germinomas and NGMGCTs. Overexpresssion of miR-214-3p in NCCIT cells leads to reduced expression of the pro-apoptotic protein BCL2L11 (BIM) and induces cisplatin resistance.
Conclusion: We interrogated the differential DNA methylation patterns between germinomas and NGMGCTs and proposed a mechanism for chemoresistance in NGMGCTs. In addition, our sequencing data provide a roadmap for further pediatric CNSGCT research and potential targets for the development of new therapeutic strategies.

PMID: 29036598 [PubMed - as supplied by publisher]

BiobankUniverse: automatic matchmaking between datasets for biobank data discovery and integration.

Tue, 10/17/2017 - 14:39

BiobankUniverse: automatic matchmaking between datasets for biobank data discovery and integration.

Bioinformatics. 2017 Aug 02;:

Authors: Pang C, Kelpin F, van Enckevort D, Eklund N, Silander K, Hendriksen D, de Haan M, Jetten J, de Boer T, Charbon B, Holub P, Hillege H, Swertz MA

Abstract
Motivation: Biobanks are indispensable for large-scale genetic/epidemiological studies, yet it remains difficult for researchers to determine which biobanks contain data matching their research questions.
Results: To overcome this, we developed a new matching algorithm that identifies pairs of related data elements between biobanks and research variables with high precision and recall. It integrates lexical comparison, Unified Medical Language System ontology tagging and semantic query expansion. The result is BiobankUniverse, a fast matchmaking service for biobanks and researchers. Biobankers upload their data elements and researchers their desired study variables, BiobankUniverse automatically shortlists matching attributes between them. Users can quickly explore matching potential and search for biobanks/data elements matching their research. They can also curate matches and define personalized data-universes.
Availability and implementation: BiobankUniverse is available at http://biobankuniverse.com or can be downloaded as part of the open source MOLGENIS suite at http://github.com/molgenis/molgenis .
Contact: m.a.swertz@rug.nl.
Supplementary information: Supplementary data are available at Bioinformatics online.

PMID: 29036577 [PubMed - as supplied by publisher]

Maternal Social Disadvantage and Newborn Telomere Length in Archived Dried Blood Spots from the Michigan Neonatal Biobank.

Tue, 10/17/2017 - 14:39

Maternal Social Disadvantage and Newborn Telomere Length in Archived Dried Blood Spots from the Michigan Neonatal Biobank.

Biodemography Soc Biol. 2017;63(3):221-235

Authors: Needham BL, Hicken MT, Govia IO, Mitchell C, Abdou CM

Abstract
Telomeres are the protective caps at the ends of eukaryotic chromosomes. Short telomere length is associated with morbidity and mortality among adults and may mark the biological impact of social experiences. Using archived dried blood spots from the Michigan Neonatal Biobank, this study examined markers of maternal social disadvantage (educational attainment, receipt of public assistance, marital status, and race/ethnicity) from linked birth certificates as predictors of telomere length at birth in a sample of 192 singleton neonates born to non-Hispanic black, non-Hispanic white, and Latina mothers aged 20-35 years. Consistent with two recent studies in newborns, but counter to the idea that maternal social disadvantage is associated with shorter offspring telomere length, we found that infants born to black mothers had longer telomeres than those born to white mothers (b = 0.12, SE = 0.06, p = .05). However, black/white differences in newborn telomere length varied by receipt of public assistance. Among newborns whose mothers received WIC and/or Medicaid, there were no significant black/white differences in telomere length (b = 0.09, SE = 0.08, p = .25). In contrast, among those whose mothers did not receive public assistance-just 6 out of 69 infants born to black mothers versus 41 out of 69 infants born to white mothers-we found that babies born to black mothers had longer telomere length than babies born to white mothers (b = 0.37, SE = 0.16, p = .03). The interaction between black race/ethnicity and receipt of public assistance did not reach the conventional threshold for statistical significance (b = -0.22, SE = 0.15, p = .13), suggesting that this finding may be due to chance. No other markers of maternal social disadvantage were related to infant telomere length. Although replication of these results in a larger sample with more infants born to black mothers with relatively high socioeconomic status is needed, this study offers preliminary support for the hypothesis that race/ethnic differences in newborn telomere length depend on social context.

PMID: 29035107 [PubMed - in process]

miR-1 suppresses the proliferation and promotes the apoptosis of esophageal carcinoma cells by targeting Src.

Tue, 10/17/2017 - 14:39

miR-1 suppresses the proliferation and promotes the apoptosis of esophageal carcinoma cells by targeting Src.

Cancer Med. 2017 Oct 16;:

Authors: Liao Z, Wang X, Liang H, Yu A, Ur Rehman U, Fan Q, Hu Y, Wang C, Zhou Z, Wang T

Abstract
Nonreceptor tyrosine kinase c-Src, also known as Src, is a potent oncogene involved in a series of biological processes including cell growth, differentiation, and apoptosis; however, its expression pattern and function in esophageal cancer is poorly addressed. In this study, abnormal overexpression of Src protein was observed in esophageal cancer tissues, which fuelled the speculation that microRNA-mediated posttranscriptional regulatory mechanism might be involved. Bioinformatic analyses were applied to identify miRNAs that could potentially target Src. miR-1 was predicted and further validated as a direct repressor of Src. Moreover, we manipulated knockdown and overexpression experiment on TE-1 and TE-10 cells to demonstrate miR-1 suppressed proliferation and promoted apoptosis in esophageal cancer cells by inhibiting Src. Taken together, this study underlines a negative regulatory mechanism in which miR-1 serves as a suppressor of Src in esophageal cancer cells and may provide insights into novel therapeutic approaches for esophageal cancer.

PMID: 29034995 [PubMed - as supplied by publisher]