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Title:
Role of metabolomics in identification of biomarkers related to food intake
Authors:
Collins, Cassandra; McNamara, Aoife E.; Brennan, Lorraine
Abstract:
Dietary assessment methods including FFQ and food diaries are associated with many measurement errors including energy under-reporting and incorrect estimation of portion sizes. Such errors can lead to inconsistent results especially when investigating the relationship between food intake and disease causation. To improve the classification of a person's dietary intake and therefore clarify proposed links between diet and disease, reliable and accurate dietary assessment methods are essential. Dietary biomarkers have emerged as a complementary approach to the traditional methods, and in recent years, metabolomics has developed as a key technology for the identification of new dietary biomarkers. The objective of this review is to give an overview of the approaches used for the identification of biomarkers and potential use of the biomarkers. Over the years, a number of strategies have emerged for the discovery of dietary biomarkers including acute and medium term interventions and cross-sectional/cohort study approaches. Examples of the different approaches will be presented. Concomitant with the focus on single biomarkers of specific foods, there is an interest in the development of biomarker signatures for the identification of dietary patterns. In the present review, we present an overview of the techniques used in food intake biomarker discover, including the experimental approaches used and challenges faced in the field. While significant progress has been achieved in the field of dietary biomarkers in recent years, a number of challenges remain. Addressing these challenges will be key to ensure success in implementing use of dietary biomarkers.
Published:
2019
Title:
Role of nitric oxide in pathogenesis of tumor growth and its possible application in cancer treatment
Authors:
SHEI “Ivano-Frankivsk National Medical University”, Ivano-Frankivsk 76018, Ukraine; Holotiuk*, V.V; Kryzhanivska, A.Y.; SHEI “Ivano-Frankivsk National Medical University”, Ivano-Frankivsk 76018, Ukraine; Churpiy, I.K.; SHEI “Ivano-Frankivsk National Medical University”, Ivano-Frankivsk 76018, Ukraine; Tataryn, B.B.; SHEI “Ivano-Frankivsk National Medical University”, Ivano-Frankivsk 76018, Ukraine; Ivasiutyn, D.Ya.; SHEI “Ivano-Frankivsk National Medical University”, Ivano-Frankivsk 76018, Ukraine
Abstract:
In this review, the role of nitric oxide (NO) in the pathogenesis of the tumor growth and possibilities of its application in the treatment of cancer patients are analyzed. NO is one of the most important mediators of physiological processes being involved in the regulation of practically all body functions in health and disease. The role of NO in the development of many pathological conditions has been extensively studied and debated in recent years. Today it is clear that NO in relation to malignant tumors may exhibit a dual activity — can stimulate tumor growth and cause an opposite antitumor effect. Effects of NO are mostly dependent on its concentration. At low concentrations, NO could inhibit apoptosis and cause mutations that potentially lead to the formation of malignant growth loci. However, a high concentration of NO appears to be detrimental to malignant cells, in particular under conditions of simultaneous exposure to ionizing radiation. In humans, the inducible NO synthase (iNOS, type II) is the most powerful form of NO synthases (NOS) and has the ability to synthesize large amounts of NO for a long time and exert a protective function. iNOS is expressed in macrophages, monocytes, neutrophils, fibroblasts, hepatocytes, and other cell types. In tissue of malignant tumors, the macrophagal iNOS is the main form. Experimental data provide an evidence that activated macrophages and leukocytes, which are the part of peritumorous inflammatory infiltrate, can provide radiosensitization of tumors by direct synthesis of NO and indirectly — through the secretion of cytokines stimulating iNOS activity in cancer cells. Such approach could be useful for the development of new schemes and methods of anticancer therapy based on the activation of endogenous NO biosynthesis pathways.
Published:
2019
Title:
Sitagliptin ameliorates advanced glycation end-product (AGE)-induced degradation of extracellular matrix in human primary chondrocytes
Authors:
Zhu, S.; Gu, Y.; Wang, W.; Bai, J.; Ge, G.; Zhang, W.; Wang, Q.; Guo, X.; Xiao, L.; Tao, Y.; Niu, F.; Nie, Z.; Geng, D.; Wang, Z.
Abstract:
Accumulation of advanced glycation end-products (AGEs) increases inflammation and triggers processes involved in the pathogenesis of osteoarthritis (OA). As a major debilitating age-related disease, it is imperative that novel therapies for OA be sought. In the present study, we investigated the effects of the selective dipeptidyl peptidase IV (DPP-4) inhibitor sitagliptin in human primary chondrocytes exposed to insult by AGEs to elucidate the potential role of sitagliptin in the treatment of OA. Our findings show that inhibition of DPP-4 by sitagliptin could reduce oxidative stress, increase cell viability and prevent degradation of type II collagen and aggrecan by matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) induced by AGEs in human primary chondrocytes. Mechanistically, we found that sitagliptin inhibited AGEs-induced nuclear translocation of p65 protein and drastically decreased the luciferase activity of NF-κB. These findings indicate that sitagliptin may have potential as a novel therapeutic option for the treatment and prevention of OA. © 2019, E-Century Publishing Corporation. All rights reserved.
Published:
2019
Title:
Study protocol: Optimized complementary feeding study (OTIS): A randomized controlled trial of the impact of a protein-reduced complementary diet based on Nordic foods
Authors:
Lind, T.; Johansson, U.; Öhlund, I.; Lindberg, L.; Lönnerdal, B.; Tennefors, C.; Hernell, O.
Abstract:
Background: What we eat as infants and children carries long-term consequences. Apart from breastfeeding, the composition of the complementary diet, i.e. the foods given to the infant during the transition from breast milk/infant formula to regular family foods affects the child's future health. A high intake of protein, a low intake of fruits, vegetables and fish and an unfavorable distribution between polyunsaturated and saturated fats are considered to be associate with health risks, e.g. obesity, type 2 diabetes and dyslipidemia later in life. Methods: In a randomized, controlled study from 6 to 18 months of age we will compare the currently recommended, Swedish complementary diet to one based on Nordic foods, i.e. an increased intake of fruits, berries, vegetables, tubers, whole-grain and game, and a lower intake of sweets, dairy, meat and poultry, with lower protein content (30% decrease), a higher intake of vegetable fats and fish and a systematic introduction of fruits and greens. The main outcomes are body composition (fat and fat-free mass measured with deuterium), metabolic and inflammatory biomarkers (associated with the amount of body fat) in blood and urine, gut microbiota (thought to be the link between early diet, metabolism and diseases such as obesity and insulin resistance) and blood pressure. We will also measure the participants' energy and nutrient intake, eating behavior and temperament through validated questionnaires, acceptance of new and unfamiliar foods through video-taped test meals and assessment of cognitive development, which we believe can be influenced through an increased intake of fish and milk fats, notably milk fat globule membranes (MFGM). Discussion: If the results are what we expect, i.e. improved body composition and a less obesogenic, diabetogenic and inflammatory metabolism and gut microbiota composition, a more sustainable nutrient intake for future health and an increased acceptance of healthy foods, they will have a profound impact on the dietary recommendations to infants in Sweden and elsewhere, their eating habits later in life and subsequently their long-term health. Trial registration: NCT02634749. Registration date 18 December 2015. © 2019 The Author(s).
Published:
2019
Title:
Systematic review: cost-effective strategies of optimizing anti-tumor necrosis and immunomodulators in inflammatory bowel disease
Authors:
Vasudevan, Abhinav; Gibson, Peter R.; Van Langenberg, Daniel R.
Abstract:
Published:
2019
Title:
Targeted next generation sequencing screening of Lynch syndrome in Tunisian population
Authors:
Ben Sghaier, Rihab; Jansen, Anne Maria Lucia; Bdioui, Ahlem; Van Wezel, Tom; Ksiaa, Mehdi; Elgolli, Lamia; Ben Fatma, Leila; Ben Ahmed, Slim; Azzouz, Mohamed Msaddak; Hellara, Olfa; Elghali, Amine; Darbel, Fathi; Skandrani, Karim; Mokkni, Moncef; Gdissa, Ameni; Ltaief, Rached; Saad, Ali; Hmila, Fahmi; Gribaa, Moez; Morreau, Hans
Abstract:
A high colorectal cancer (CRC) incidence is observed in Tunisia, with a relatively high proportion of patients developing CRC before the age of 40. While this suggests a genetic susceptibility, only a few Tunisian Lynch Syndrome families have been described. In this study we aimed to identify the underlying genetic cause in 32 patients with early onset CRC and/or a positive family history. Of twenty-four patients' tumor or biopsies could be analyzed with immunohistochemical staining to detect loss of expression of one of the MMR proteins. Ten tumors showed loss of expression, of which one tumor was from a patient where a germline pathogenic MSH2 variant was detected previously with Sanger sequencing. Next generation sequencing of the MMR, POLE and POLD1 genes was performed in leukocyte and tumor DNA of the remaining nine patients, as well as in two patients with MMR-proficient tumors, but with severe family history. In six of 11 patients a germline variant was detected in MLH1 (n = 5) or MSH2 (n = 1). Two of six patients were from the same family and both were found to carry a novel in-frame MLH1 deletion, predicted to affect MLH1 function. All MLH1 variant carriers had loss of heterozygosity with retention of the variant in the tumors, while a somatic pathogenic variant was detected in the patient with the germline MSH2 variant.
Published:
2019
Title:
The 1 H NMR serum metabolomics response to a two meal challenge: A cross-over dietary intervention study in healthy human volunteers
Authors:
Rådjursöga, M.; Lindqvist, H.M.; Pedersen, A.; Karlsson, G.B.; Malmodin, D.; Brunius, C.; Ellegård, L.; Winkvist, A.
Abstract:
Background: Metabolomics represents a powerful tool for exploring modulation of the human metabolome in response to food intake. However, the choice of multivariate statistical approach is not always evident, especially for complex experimental designs with repeated measurements per individual. Here we have investigated the serum metabolic responses to two breakfast meals: an egg and ham based breakfast and a cereal based breakfast using three different multivariate approaches based on the Projections to Latent Structures framework. Methods: In a cross over design, 24 healthy volunteers ate the egg and ham breakfast and cereal breakfast on four occasions each. Postprandial serum samples were subjected to metabolite profiling using 1 H nuclear magnetic resonance spectroscopy and metabolites were identified using 2D nuclear magnetic resonance spectroscopy. Metabolic profiles were analyzed using Orthogonal Projections to Latent Structures with Discriminant Analysis and Effect Projections and ANOVA-decomposed Projections to Latent Structures. Results: The Orthogonal Projections to Latent Structures with Discriminant Analysis model correctly classified 92 and 90% of the samples from the cereal breakfast and egg and ham breakfast, respectively, but confounded dietary effects with inter-personal variability. Orthogonal Projections to Latent Structures with Effect Projections removed inter-personal variability and performed perfect classification between breakfasts, however at the expense of comparing means of respective breakfasts instead of all samples. ANOVA-decomposed Projections to Latent Structures managed to remove inter-personal variability and predicted 99% of all individual samples correctly. Proline, tyrosine, and N-acetylated amino acids were found in higher concentration after consumption of the cereal breakfast while creatine, methanol, and isoleucine were found in higher concentration after the egg and ham breakfast. Conclusions: Our results demonstrate that the choice of statistical method will influence the results and adequate methods need to be employed to manage sample dependency and repeated measurements in cross-over studies. In addition, 1 H nuclear magnetic resonance serum metabolomics could reproducibly characterize postprandial metabolic profiles and identify discriminatory metabolites largely reflecting dietary composition. Trial registration: Registered with ClinicalTrials.gov, identifier: NCT02039596. Date of registration: January 17, 2014. © 2019 The Author(s).
Published:
2019
Title:
The Effect of Lean-Seafood and Non-Seafood Diets on Fecal Metabolites and Gut Microbiome: Results from a Randomized Crossover Intervention Study
Authors:
Schmedes, Mette; Brejnrod, Asker Daniel; Aadland, Eli Kristin; Kiilerich, Pia; Kristiansen, Karsten; Jacques, Hélène; Lavigne, Charles; Graff, Ingvild Eide; Eng, Øyvin; Holthe, Asle; Mellgren, Gunnar; Young, Jette Feveile; Sundekilde, Ulrik Kraemer; Liaset, Bjørn; Bertram, Hanne Christine
Abstract:
SCOPE: The impact of dietary protein types on the gut microbiome is scarcely studied. The aim of the present study is therefore to examine the effects of lean-seafood and non-seafood proteins on the gut microbiome composition and activity and elucidate potential associations to cardiovascular disease (CVD) risk factors. METHODS: A crossover intervention study in which 20 healthy subjects consumed two diets that varied in protein source was conducted. 1 H NMR spectroscopy and 16S rDNA sequencing analyses were applied to characterize fecal metabolites and gut microbiota composition, respectively. RESULTS: A twofold increase in fecal trimethylamine excretion was observed after the lean-seafood diet period. Circulating TAG and the total to high-density lipoprotein (HDL) cholesterol ratio as well as circulating TMAO levels were each associated with specific gut bacteria. Following the non-seafood diet period, a decreased relative abundance of Clostridium cluster IV and a tendency toward an increased Firmicutes/Bacteroidetes ratio were found. CONCLUSIONS: Lean-seafood and non-seafood diets differentially modulate the gut microbiome composition and activity. Furthermore, the gut microbiota composition seems to affect circulating TMAO levels and CVD risk factors.
Published:
2019
Title:
The Immigrant Health Differential in the Context of Racial and Ethnic Disparities: The Case of Diabetes
Authors:
Engelman, Michal; Ye, Leafia Zi
Abstract:
Purpose: Social and economic disparities between racial/ethnic groups are a feature of the American context into which immigrants are incorporated, and a key determinant of population health. We ask whether racial/ethnic disparities in diabetes vary by nativity and whether native-immigrant disparities in diabetes vary by race and over time in the United States. Methods: Using the 2000–2015 National Health Interview Survey, we estimate logistic regressions to examine the interaction of race/ethnicity, nativity, and duration in the U.S. in shaping diabetes patterns. Results: Relative to their native-born co-ethnics, foreign-born Asian adults experience a significant diabetes disadvantage, while foreign-born Hispanic, Black, and White adults experience a significant advantage. Adjusting for obesity, education, and other covariates eliminates the foreign-born advantage for Black and White adults, but it persists for Hispanic adults. The same adjustment accentuates the disadvantage for foreign-born Asian adults. For Black and Hispanic adults, the protective foreign-born effect erodes as duration in the U.S. increases. For foreign-born Asian adults, the immigrant disadvantage appears to grow with duration in the U.S. Relative to native-born White adults, all non-white groups regardless of nativity see a diabetes disadvantage because the racial/ethnic disadvantage either countervails a foreign-born advantage or amplifies a foreign-born disadvantage. Discussion: Racial/ethnic differentials in diabetes are considerable, and are influenced by each group’s nativity composition. Obesity and (for the foreign-born) time in the U.S. influence these disparities, but do not explain them. These findings underscore the importance of unmeasured, systemic determinants of health in America’s race-conscious society.
Published:
2019
Title:
The Ketogenic and Modified Atkins Diet Therapy for Children With Refractory Epilepsy of Genetic Etiology
Authors:
Jagadish, Spoorthi; Payne, Eric T.; Wong-Kisiel, Lily; Nickels, Katherine C.; Eckert, Susan; Wirrell, Elaine C.
Abstract:
BACKGROUND: The ketogenic diet is an accepted treatment modality in refractory childhood epilepsy. In this study, we analyzed the efficacy and tolerability of the ketogenic and modified Atkins diets in children with refractory epilepsy of genetic etiology and studied the effect of the diet on seizure frequency. METHODS: The records of children with a genetic etiology for refractory epilepsy treated with ketogenic and modified Atkins diet between September 2005 and July 2016 were reviewed. We documented age of seizure and diet onset, seizure characteristics, and specific genetic etiology. The proportion of children remaining on the diet and responder rates (greater than 50% seizure reduction) were noted at one, three, six, 12, and 24 months after diet initiation. Tolerability and safety profile were also recorded. RESULTS: Fifty-nine children with a genetic etiology (63% females, median age at diet onset 2.2 years) were initiated on the diet at our center. Fifty-three (90%) were started on a traditional ketogenic diet, whereas six started a modified Atkins diet. The adverse events at the initiation of diet were vomiting (24%), hypoglycemia (15%), and refusal to feed (11%). Three children stopped the diet before discharge because of poor compliance, severe reflux, and ketoacidosis (n = 1 each). The proportion of children remaining on the diet at one, three, six, 12, and 24 months was 95%, 86%, 69%, 64%, and 47%. The responder rates were 63%, 61%, 54%, 53%, and 41% at one, three, six, 12, and 24 months, respectively. CONCLUSIONS: The ketogenic diet is an effective treatment modality in children with refractory epilepsy of genetic etiology.
Published:
2019
Title:
The effect of camelina sativa oil and fish intakes on fatty acid compositions of blood lipid fractions
Authors:
Manninen, S.; Lankinen, M.; de Mello, V.; Ågren, J.; Laaksonen, D.; Schwab, U.; Erkkilä, A.
Abstract:
BACKGROUND AND AIMS: Blood lipid fractions serve as objective biomarkers of dietary fat intake. It is unclear which fatty acid pool most accurately reflects the dietary intakes of different n-3 PUFAs. We aimed to investigate the effect of fish and camelina sativa oil (CSO) intakes on fatty acid composition of erythrocyte membranes (EM), plasma phospholipids (PL), cholesteryl esters (CE) and triglycerides (TG). We also aimed to identify the most appropriate blood lipid fraction for assessing n-3 PUFA intake. METHODS AND RESULTS: Altogether 79 volunteers with impaired glucose metabolism were randomly assigned either to CSO, fatty fish, lean fish or control groups for 12 weeks. Fatty acid compositions of lipid pools were measured by gas chromatography. The proportion of alpha-linolenic acid (ALA) increased in all lipid pools in the CSO group (false discovery rate (FDR) p < 0.001 for all). Similarly, the proportions of EPA and DHA increased in all lipid fractions in the fatty fish group (FDR p < 0.001 for EM, PL and CE; FDR p = 0.005 for TG; FDR p < 0.001 for EM, PL, CE; FDR p < 0.007 for TG, respectively). Changes in the dietary intakes of ALA, EPA and DHA correlated with the changes in their proportions in all lipid pools (r = 0.3-0.5, p
Published:
2019
Title:
The effects of a randomized trial of brief forms of stress management on RAGE-associated S100A8/A9 in patients with breast cancer undergoing primary treatment
Authors:
Taub, Chloe J.; Lippman, Marc E.; Hudson, Barry I.; Blomberg, Bonnie B.; Diaz, Alain; Fisher, Hannah M.; Nahin, Erica R.; Lechner, Suzanne C.; Kwak, Taekyoung; Hwang, Gyong Ha; Antoni, Michael H.
Abstract:
Background Women with breast cancer (BCa) experience heightened distress, which is related to greater inflammation and poorer outcomes. The s100 protein family facilitates the inflammatory response by regulating myeloid cell function through the binding of Toll-like receptor 4 and the receptor for advanced glycation end products (RAGE). The heterodimer s100A8/A9 RAGE ligand is associated with hastened tumor development and metastasis. Previously, a 10-week stress-management intervention using cognitive behavioral therapy (CBT) and relaxation training (RT) was associated with less leukocyte inflammatory gene expression in patients with BCa; however, its impact on s100A8/A9 was not examined. Because a 10-week intervention may be impractical during primary treatment for BCa, the authors developed briefer forms of CBT and RT and demonstrated their efficacy in reducing distress over 12 months of primary treatment. Here, the effects of these briefer interventions were tested effects on s100A8/A9 levels over the initial 12 months of BCa treatment. Methods Postsurgical patients with BCa (stage 0-IIIB) were randomized to a 5-week, group-based condition: CBT, RT, or health education control (HE). At baseline and at 12 months, women provided sera from which s100A8/A9 levels were determined using any enzyme-linked immunosorbent assay. Results Participants (mean age ± standard deviation, 54.81 ± 9.63 years) who were assigned to either CBT (n = 41) or RT (n = 38) had significant s100A8/A9 decreases over 12 months compared with those who were assigned to HE (n = 44; F[1,114] = 4.500; P = .036) controlling for age, stage, time since surgery, and receipt of chemotherapy or radiation. Greater increases in stress-management skills from preintervention to postintervention predicted greater reductions in s100A8/A9 levels over 12 months (β = −0.379; t[101] = −4.056; P
Published:
2019
Title:
The impact of flake tool attributes and butcher experience on carcass processing time and efficiency during experimental butchery trials
Authors:
Merritt, Stephen R.; Peters, Kara D.
Abstract:
Butchery involves using tools to process animal carcasses during consumption of tissue packages, and this technological adaptation has a deep connection with evolving human dietary ecology. Studying butchery informs archaeological inferences about lithic artefact function and site formation and describes skeletal traces of carcass consumption, which may corroborate the butchery function of certain tools. Diverse methodologies including subjective personal observations and well-controlled experiments that investigate abstracted slicing mechanics or realistic butchery scenarios provide mixed conclusions about which kinds of tools are more efficient for butchery and whether their archaeological traces can be discriminated. Much less analytical attention is devoted to investigating whether a butcher's experience using stone tools to process carcasses impacts their performance, which may confound experimental assessment of how tool attributes are related to butchery efficiency. These experiments examine butchery performance in two novices over 40 goat forelimb and hindlimb trials where a single flake was used to deflesh and disarticulate a limb. By measuring butchery performance as defleshing efficiency (the amount of meat removed per second) and the time necessary to disarticulate limb elements, we demonstrate that in general, both butchers performed similarly when butchering forelimbs and hindlimbs and did not exhibit a strong learning curve of performance improvement. As well, flake weight, size, and cutting edge length were positively related to defleshing efficiency and negatively related to disarticulation time, suggesting that larger flakes are better butchery tools. Our results suggest that anatomical differences between forelimbs and hindlimbs did not impact butchery timing or efficiency and butchery performance is similar across novices. To maximize comparability of experimental butchery results, we encourage future research to examine butchery performance with respect to animal or tissue package size and investigate how butcher experience impacts performance.
Published:
2019
Title:
The impact of keto-adaptation on exercise performance and the role of metabolic-regulating cytokines
Authors:
Sherrier, Matthew; Li, Hongshuai
Abstract:
\textlessp\textgreaterThe ketogenic diet (KD) is a normocaloric diet composed of high-fat, low-carbohydrate, and adequate protein that induces fasting-like effects and results in the production of ketone bodies. Initially used widely for children with refractory epilepsy, the KD gained popularity due to its beneficial effects on weight loss, diabetes, and cancer. In recent years, there has been a resurgence in interest surrounding the KD and exercise performance. This review provides new insights into the adaptation period necessary for enhancement in skeletal muscle fat and ketone oxidation after sustained nutritional ketosis. In addition, this review highlights metabolically active growth factors and cytokines, which may function as important regulators of keto-adaptation in the setting of exercise and the KD.\textless/p\textgreater
Published:
2019
Title:
The microbial metabolite trimethylamine n-oxide links vascular dysfunctions and the autoimmune disease rheumatoid arthritis
Authors:
Chan, M.M.; Yang, X.; Wang, H.; Saaoud, F.; Sun, Y.; Fong, D.
Abstract:
Diet and microbiota each have a direct impact on many chronic, inflammatory, and metabolic diseases. As the field develops, a new perspective is emerging. The effects of diet may depend on the microbiota composition of the intestine. A diet that is rich in choline, red meat, dairy, or egg may promote the growth, or change the composition, of microbial species. The microbiota, in turn, may produce metabolites that increase the risk of cardiovascular disease. This article reviews our current understanding of the effects of the molecule trimethylamine-N-oxide (TMAO) obtained from food or produced by the microbiota. We review the mechanisms of actions of TMAO, and studies that associate it with cardiovascular and chronic kidney diseases. We introduce a novel concept: TMAO is one among a group of selective uremic toxins that may rise to high levels in the circulation or accumulate in various organs. Based on this information, we evaluate how TMAO may harm, by exacerbating inflammation, or may protect, by attenuating amyloid formation, in autoimmune diseases such as rheumatoid arthritis. © 2019 by the authors. Licensee MDPI, Basel, Switzerland. T.
Published:
2019
Title:
The prevalence of estrogen receptor-1 mutation in advanced breast cancer: The estrogen receptor one study (EROS1)
Authors:
Najim, Omar; Huizing, Manon; Papadimitriou, Konstantinos; Trinh, Xuan Bich; Pauwels, Patrick; Goethals, Sofie; Zwaenepoel, Karen; Peterson, Kevin; Weyler, Joost; Altintas, Sevilay; van Dam, Peter; Tjalma, Wiebren
Abstract:
BACKGROUND: Breast cancer has, due its high incidence, the highest mortality of cancer in women. The most common molecular variety of breast cancer is luminal subtype that expresses estrogen and progesterone receptors. Estrogen receptor alpha (ERα), encoded by the estrogen receptor1 (ESR1) gene, is expressed in approximately 70% of all breast cancers, and hormonal therapy represents a major treatment modality in all stages of ER positive breast cancers. Acquired mutations in the ligand-binding domain (LBD) of ERα, referred as ESR1 mutation, result in resistance to different endocrine therapies leading to disease progression or recurrence. Recent studies reviled that these ESR1 mutations lead to constitutive activity of the estrogen receptor ER, meaning that the receptor is active in absence of its ligand conferring resistance against endocrine therapy and tumor growth. Published studies have not yet been able to determine the exact prevalence rate of ESR1 mutations, but set the outer boundaries between 11-55%. PURPOSE: The goal of the present study is to determine the frequency rate of ESR1 mutations in ER positive recurrent breast cancer by using digital droplet PCR (ddPCR) technique. MATERIALS AND METHODS: This retrospective study was conducted in the Multidisciplinary Breast Clinic of Antwerp University Hospital. The seven most common ESR1mutations (c.1138G>C (p. (E380Q)), c.1610A>G (p.(Y537C)), c.1613A>G (p.(p.D538G)), c.1607T>G (p.(L536R)), c.1387T>C (p.S463R)), c.16410A>C (p.(Y537S)), c.609T>A (p.(Y537N)) were assessed in available baseline plasma samples of 21 patients with ER positive recurrent breast cancer. Inclusion criteria for study participation were: female, age above 18 years, ER positive breast cancer, 5years adjuvant hormonal therapy of primary disease, and disease recurrence or metastasis during or after stop of endocrine therapy. ESR1 mutations were analyzed in cell-free DNA (cfDNA) by using digital droplet PCR (ddPCR). RESULTS: cfDNA was obtained from 21 patients with recurrent breast cancer. ESR1 mutations were found in 4/21 (19%; 95% CI, 5%-42%). The test sensitivity was lower than the targeted value 0.05). Adjuvant endocrine therapy for primary disease was Tamoxifen (TAM) for 57% of patients (12 of 21) of whom 8 patients had received aromatase inhibitor (AI) after two years, while 43% of patients (9 of 21) had received AI as first line adjuvant hormonal therapy. All the patients had received aromatase inhibitor AI therapy in first or second line therapy with initially a variable period of good response. CONCLUSION: ESR1 mutation analysis could be determined in archived plasma samples using simple non-invasive methods. In the future, screening for mutation status could improve the therapeutic strategies in controlling ER signaling before the occurrence of wide spread disease metastasis.
Published:
2019
Title:
The role of damage-associated molecular pattern for pathogenesis and biomarkers in adult-onset Still's disease
Authors:
Jung, J.-Y.; Suh, C.-H.; Kim, H.-A.
Abstract:
Introduction: Adult-onset Still's disease (AOSD) is a systemic inflammatory disease, which presents itself as an adult form of systemic juvenile idiopathic arthritis. Innate immune activation driven by a combination of genetic and environmental factors is the primary mechanism underlying disease pathogenesis in AOSD patients. Few biomarkers have been identified for AOSD diagnosis or for the assessment of disease activity or prediction of clinical outcomes. Damage-associated molecular patterns (DAMPs) can activate innate immunity, resulting in tissue damage. Changes in several DAMPs are associated with disease pathogenesis in AOSD patients. Areas covered: This review describes the role of DAMPs in AOSD pathogenesis and discusses their potential for use as disease biomarkers. Together with overall pathogenesis of AOSD, high-mobility group box-1, advanced glycation end products, S100 proteins, and neutrophil extracellular traps are introduced and discussed in detail. Expert opinion: The activation of macrophages and neutrophils is associated with several DAMPs, causing high concentrations of proinflammatory cytokines in AOSD patients. Involvement of certain DAMPs in AOSD patients is well documented due to the presence of sterile inflammation; however, direct evidence for some DAMPs is lacking. Further research into the role of DAMP molecules in AOSD patients may reveal new biomarkers and provide targets for disease intervention.
Published:
2019
Title:
Therapeutic potential of exogenous ketone supplement induced ketosis in the treatment of psychiatric disorders: Review of current literature
Authors:
Kovács, Zsolt; D'Agostino, Dominic P.; Diamond, David; Kindy, Mark S.; Rogers, Christopher; Ari, Csilla
Abstract:
Globally, psychiatric disorders, such as anxiety disorder, bipolar disorder, schizophrenia, depression, autism spectrum disorder and attention-deficit/hyperactivity disorder (ADHD) are becoming more prevalent. Although the exact pathological alterations are not yet clear, recent studies have demonstrated that widespread changes of very complex metabolic pathways may partially underlie the pathophysiology of many psychiatric diseases. Thus, more attention should be directed to metabolic-based therapeutic interventions in the treatment of psychiatric disorders. Emerging evidence from numerous studies suggests that administration of exogenous ketone supplements, such as ketone salts or ketone esters, generates rapid and sustained nutritional ketosis and metabolic changes, which may evoke potential therapeutic effects in cases of central nervous system (CNS) disorders, including psychiatric diseases. Therefore, the aim of this review is to summarize the current information on ketone supplementation as a potential therapeutic tool for psychiatric disorders. Ketone supplementation elevates blood levels of the ketone bodies: D-β-hydroxybutyrate (βHB), acetoacetate (AcAc), and acetone. These compounds, either directly or indirectly, beneficially affect the mitochondria, glycolysis, neurotransmitter levels, activity of free fatty acid receptor 3 (FFAR3), hydroxycarboxylic acid receptor 2 (HCAR2) and histone deacetylase, as well as functioning of NOD-like receptor pyrin domain 3 (NLRP3) inflammasome, and mitochondrial uncoupling protein (UCP) expression. The result of downstream cellular and molecular changes is a reduction in the pathophysiology associated with various psychiatric disorders. We conclude that supplement-induced nutritional ketosis leads to metabolic changes and improvements, for example, in mitochondrial function and inflammatory processes, and suggest that development of specific adjunctive ketogenic protocols for psychiatric diseases should be actively pursued.
Published:
2019
Title:
To flourish or perish: evolutionary TRiPs into the sensory biology of plant-herbivore interactions
Authors:
Startek, Justyna B.; Voets, Thomas; Talavera, Karel
Abstract:
The interactions between plants and their herbivores are highly complex systems generating on one side an extraordinary diversity of plant protection mechanisms and on the other side sophisticated consumer feeding strategies. Herbivores have evolved complex, integrative sensory systems that allow them to distinguish between food sources having mere bad flavors from the actually toxic ones. These systems are based on the senses of taste, olfaction and somatosensation in the oral and nasal cavities, and on post-ingestive chemosensory mechanisms. The potential ability of plant defensive chemical traits to induce tissue damage in foragers is mainly encoded in the latter through chemesthetic sensations such as burning, pain, itch, irritation, tingling, and numbness, all of which induce innate aversive behavioral responses. Here, we discuss the involvement of transient receptor potential (TRP) channels in the chemosensory mechanisms that are at the core of complex and fascinating plant-herbivore ecological networks. We review how "sensory" TRPs are activated by a myriad of plant-derived compounds, leading to cation influx, membrane depolarization, and excitation of sensory nerve fibers of the oronasal cavities in mammals and bitter-sensing cells in insects. We also illustrate how TRP channel expression patterns and functionalities vary between species, leading to intriguing evolutionary adaptations to the specific habitats and life cycles of individual organisms.
Published:
2019
Title:
Unprocessed red meat intakes are associated with increased inflammation, triglycerides and HDL cholesterol in past smokers
Authors:
Wu, T.; Sonoda, S.; Liu, H.
Abstract:
Aim: To determine the associations of unprocessed red meat with serum C-reactive protein and traditional lipid biomarkers among adults with different smoking status. Methods: Using a cross-sectional design, we analysed data collected from 5011 adults (men and women) who had provided information on dietary intakes and the proposed biomarkers for the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Results: We found positive associations between unprocessed red meat and serum C-reactive protein and triglycerides and an inverse association between unprocessed red meat and high-density lipoprotein (HDL) cholesterol in past smokers, but no associations in never smokers and current smokers. Among past smokers, the percent difference of biomarkers between participants with the highest and the lowest quintiles for the intakes of unprocessed red meat was 42% (P = 0.03) for CRP, 32% for triglycerides and −11% (P = 0.02) for HDL cholesterol. No association was found between unprocessed red meat and other lipid biomarkers. Conclusions: Providing individualised nutritional guidelines according to smoking status is important. Our study provided evidence for developing specific guidelines on red meat for past smokers. © 2019 Dietitians Association of Australia
Published:
2019
Title:
Uric acid enhances longevity and endurance and protects the brain against ischemia
Authors:
Cutler, Roy G.; Camandola, Simonetta; Feldman, Neil H.; Yoon, Jeong Seon; Haran, James B.; Arguelles, Sandro; Mattson, Mark P.
Abstract:
Among mammals, there is a positive correlation between serum uric acid (UA) levels and life span. Humans have high levels of UA because they lack a functional urate oxidase (UOX) enzyme that is present in shorter lived mammals. Here, we show that male and female mice with UOX haploinsufficiency exhibit an age-related elevation of UA levels, and that the life span of female but not male UOX+/- mice is significantly increased compared to wild-type mice. Serum UA levels are elevated in response to treadmill exercise in UOX+/- mice, but not wild-type mice, and the endurance of the UOX+/- mice is significantly greater than wild-type mice. UOX+/- mice exhibit elevated levels of brain-derived neurotrophic factor, reduced brain damage and improved functional outcome in a model of focal ischemic stroke. Levels of oxidative protein nitration and lipid peroxidation are reduced in muscle and brain tissues of UOX+/- mice under conditions of metabolic and oxidative stress (running in the case of muscle and ischemia in the case of the brain), consistent with prior evidence that UA can scavenge peroxynitrite and hydroxyl radical. Our findings reveal roles for UA in life span determination, endurance and adaptive responses to brain injury, and suggest novel approaches for protecting cells against injury and for optimizing physical performance.
Published:
2019
Title:
Urinary Metabolomics Profiles Associated to Bovine Meat Ingestion in Humans
Authors:
Khodorova, N.V.; Rutledge, D.N.; Oberli, M.; Mathiron, D.; Marcelo, P.; Benamouzig, R.; Tomé, D.; Gaudichon, C.; Pilard, S.
Abstract:
Scope: The impact of meat consumption on human health is widely examined in nutritional epidemiological studies, especially due to the connection between the consumption of red and processed meat and the risk of colon cancer. Food questionnaires do not assess the exposure to different methods of meat cooking. This study aimed to identify biomarkers of the acute ingestion of bovine meat cooked with two different processes. Methods and results: Non-targeted UPLC-MS metabolite profiling was done on urine samples obtained from 24 healthy volunteers before and 8 h after the ingestion of a single meal composed of intrinsically 15N labelled bovine meat, either cooked at 55 °C for 5 min or at 90 °C for 30 min. A discriminant analysis extension of independent components analysis was applied to the mass spectral data. After meat ingestion, the urinary excretion of 1-methylhistidine, phenylacetylglutamine, and short- and medium-chained acylcarnitines was observed. 15N labelling was detected in these metabolites, thus confirming their origin from ingested meat. However, no difference was observed in urinary metabolomic profiles according to the meat cooking process used. Conclusion: Meat ingestion led to the excretion of several nitrogen-containing compounds, but although a metabolic signature was detected for meat ingestion, the impact of the cooking process was not detectable at the level of urinary metabolic signature in our experimental conditions. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Published:
2019
Title:
Urinary levels of trimethylamine-N-oxide and incident coronary heart disease: A prospective investigation among urban Chinese adults
Authors:
Yu, D.; Shu, X.-O.; Rivera, E.S.; Zhang, X.; Cai, Q.; Calcutt, M.W.; Xiang, Y.-B.; Li, H.; Gao, Y.-T.; Wang, T.J.; Zheng, W.
Abstract:
Background-—Trimethylamine-N-oxide (TMAO), a diet-derived, gut microbial–host cometabolite, has been associated with adverse cardiovascular outcomes in patient populations; however, evidence is lacking from prospective studies conducted in general populations and non-Western populations. Methods and Results-—We evaluated urinary levels of TMAO and its precursor metabolites (ie, choline, betaine, and carnitine) in relation to risk of coronary heart disease (CHD) among Chinese adults in a nested case–control study, including 275 participants with incident CHD and 275 individually matched controls. We found that urinary TMAO, but not its precursors, was associated with risk of CHD. The odds ratio for the highest versus lowest quartiles of TMAO was 1.91 (95% CI, 1.08–3.35; P trend =0.008) after adjusting for CHD risk factors including obesity, diet, lifestyle, and metabolic diseases and 1.75 (95% CI, 0.96–3.18; P trend =0.03) after further adjusting for potential confounders or mediators including central obesity, dyslipidemia, inflammation, and intake of seafood and deep-fried meat or fish, which were associated with TMAO level in this study. The odds ratio per standard deviation increase in log-TMAO was 1.30 (95% CI, 1.03–1.63) in the fully adjusted model. A history of diabetes mellitus modified the TMAO– CHD association. A high TMAO level (greater than or equal to versus lower than the median) was associated with odds ratios of 6.21 (95% CI, 1.64–23.6) and 1.56 (95% CI, 1.00–2.43), respectively, among diabetic and nondiabetic participants (P interaction =0.02). Diabetes mellitus status also modified the associations of choline, betaine, and carnitine with risk of CHD; significant positive associations were found among diabetic participants, but null associations were noted among total and nondiabetic participants. Conclusions-—Our study suggests that TMAO may accelerate the development of CHD, highlighting the importance of diet–gut microbiota–host interplay in cardiometabolic health. © 2019 The Authors.
Published:
2019
Title:
Yield of laboratory testing in pediatric ketogenic diet patients: Critical assessment of abnormal results and impact on clinical care
Authors:
Joshi, Charuta; Stillman, Chelsey; Criteser, Stephanie; Oliver, Jennifer; Conley, Alison; Sillau, Stefan; Zupec-Kania, Beth
Abstract:
OBJECTIVES: To retrospectively assess the incidence of high beta hydroxybutyrate, low bicarbonate (BIC), high acyl carnitine, low selenium, low magnesium, low zinc, low phosphorus, in a cohort of supplemented patients treated with the ketogenic diet (KD) for medically intractable epilepsy. To analyze effect of age, duration of exposure to KD, type of KD, and route of KD intake on lab abnormalities. To analyze the incidence of clinically actionable results, resulting in medical interventions based on abnormal results and to analyze costs of testing. METHODS: Retrospective chart review and statistical analysis. Association between abnormal values (binary) and categorical variables was tested with Chi-square/Fisher's exact test. Associations between abnormal values (binary) and continuous variables were analyzed with logistic regression. Statistical analyses were performed in SAS 9.4. RESULTS: We included 91 patients with average duration on diet of 46.73 months (IQR 18.8-75.5 months). Most patients were on the classic KD (81 KD- 59% on 4:1 ratio, 10 modified Atkins diet). 74% were orally fed and 70% completed lab visits to the 12-month mark. There was no significant association between abnormal laboratory parameters and duration of exposure, type of diet, route of administration. Younger children were more likely to have low BIC, high acyl carnitine. Older children were more likely to have low phosphorus. Less than 15% of patients reported clinical changes to suggest dietary deficiency in vitamins/ minerals and in
Published:
2019
Title:
Zafirlukast attenuates advanced glycation end-products (AGEs)-induced degradation of articular extracellular matrix (ECM)
Authors:
Lei, C.; Wu, S.; Wen, C.; Li, Y.; Liu, N.; Huang, J.; Li, L.; Fu, M.; Liu, J.
Abstract:
Zafirlukast, a leukotriene receptor antagonist, has been shown to exert a wide range of effects including anti-asthmatic, anti-inflammatory and oral anti-bacterial. Osteoarthritis is one of the most prevalent age-related public health burdens in the modern world. In the present study, we applied zafirlukast in the treatment of human primary chondrocytes and found that it exerts potent anti-osteoarthritic effects. Zafirlukast inhibited AGEs-induced degradation of the articular extracellular matrix by suppressing expression of MMPs, ADAMTS, NOX-4, generation of ROS, and activation of NF-κB via the IκBα/JNK/AP-1 pathway through targeted inhibition of CysLTR1. These findings suggest that zafirlukast possesses a protective effect against AGEs- induced damage and dysfunction in human chondrocytes. © 2019 Elsevier B.V.
Published:
2019
Title:
[Serious neurological compromise due to vitamin B12 deficiency in infants of vegan and vegetarian mothers]
Authors:
Aguirre, Juan A.; Donato, María L.; Buscio, Mariela; Ceballos, Verónica; Armeno, Marisa; Aizpurúa, Luciana; Arpí, Lucrecia
Abstract:
Vitamin B12 deficiency is one of the most serious complications of vegetarianism and its variants. Infants born to vegan mothers are at greater risk of serious deficiency, being more vulnerable to their effects. B12 deficiency is not usually suspected by the pediatrician in healthy infants with neurological symptoms. The manifestations are nonspecific: apathy, rejection of food and loss of maturational patterns. A nutritional history of the mother, mainly if she is vegetarian, to estimate her reserves is fundamental to detect risk of deficiency of this vitamin in the small child. The objective of this work is to describe a group of infants, children of vegan mothers, with B12 deficiency and serious neurological compromise: central apneas, seizures, hypotonia, loss of connection with the environment and maturational patterns. Our purpose is to alert about the importance of supplying vegan mothers with B12 before conception until the end of breastfeeding.
Published:
2019
Title:
猪肠道微生物及其营养调控
Authors:
罗, 玉衡; 余, 冰; 何, 军; 毛, 湘冰; 车, 炼强; 陈, 代文
Abstract:
传统动物营养学主要关注营养物质在肠道中被直接消化、吸收和利用的部分,但忽视了肠道微生物的作用。近年来,四川农业大学动物营养研究所猪营养团队在此领域做了系统研究,文章将对此作一综述,以期为健康、高效、安全的动物生产提供新思路。
Published:
2019
Title:
10 patients, 10 years – Long term follow-up of cardiovascular risk factors in Glut1 deficiency treated with ketogenic diet therapies: A prospective, multicenter case series
Authors:
Heussinger, Nicole; Della Marina, Adela; Beyerlein, Andreas; Leiendecker, Baerbel; Hermann-Alves, Sofia; Dalla Pozza, Robert; Klepper, Joerg
Abstract:
Published:
2018-12
Title:
Depression Predicts Delirium After Coronary Artery Bypass Graft Surgery Independent of Cognitive Impairment and Cerebrovascular Disease: An Analysis of the Neuropsychiatric Outcomes After Heart Surgery Study
Authors:
Oldham, Mark A.; Hawkins, Keith A.; Lin, I-Hsin; Deng, Yanhong; Hao, Qing; Scoutt, Leslie M.; Yuh, David D.; Lee, Hochang B.
Abstract:
Published:
2018-12
Title:
Diagnosis and Management of Neuropsychiatric Symptoms in Alzheimer’s Disease
Authors:
Wolinsky, David; Drake, Karina; Bostwick, Jolene
Abstract:
Purpose of Review To explore the most recent developments in the effective diagnosis and treatment of neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD). Recent Findings The clinical diagnosis of NPS in AD is facilitated by the use of the Neuropsychiatric Inventory (NPI). CT and MRI scans can be useful for detecting structural changes indicating AD. Other promising diagnostic methodologies that are less frequently used in the clinical setting include positron emission tomography (PET) scans for detecting amyloid and blood tests for detecting serum biomarkers. Numerous pharmaceutical agents have been studied for their use in managing NPS, with antipsychotics being popular for managing agitation but also having significant side effects. Non-pharmacological interventions, such as reminiscence therapy and the Describe, Investigate, Create, Evaluate (DICE) approach may be able to provide treatment without such adverse effects.
Published:
2018-12
Title:
Dietary approaches to treat MS-related fatigue: comparing the modified Paleolithic (Wahls Elimination) and low saturated fat (Swank) diets on perceived fatigue in persons with relapsing-remitting multiple sclerosis: study protocol for a randomized controlled trial
Authors:
Wahls, Terry; Scott, Maria O.; Alshare, Zaidoon; Rubenstein, Linda; Darling, Warren; Carr, Lucas; Smith, Karen; Chenard, Catherine A.; LaRocca, Nicholas; Snetselaar, Linda
Abstract:
Fatigue is one of the most disabling symptoms of multiple sclerosis (MS) and contributes to diminishing quality of life. Although currently available interventions have had limited success in relieving MS-related fatigue, clinically significant reductions in perceived fatigue severity have been reported in a multimodal intervention pilot study that included a Paleolithic diet in addition to stress reduction, exercise, and electrical muscle stimulation. An optimal dietary approach to reducing MS-related fatigue has not been identified. To establish the specific effects of diet on MS symptoms, this study focuses on diet only instead of the previously tested multimodal intervention by comparing the effectiveness of two dietary patterns for the treatment of MS-related fatigue. The purpose of this study is to determine the impact of a modified Paleolithic and low saturated fat diet on perceived fatigue (primary outcome), cognitive and motor symptoms, and quality of life in persons with relapsing-remitting multiple sclerosis (RRMS). This 36-week randomized clinical trial consists of three 12-week periods during which assessments of perceived fatigue, quality of life, motor and cognitive function, physical activity and sleep, diet quality, and social support for eating will be collected. The three 12-week periods will consist of the following: Because fatigue is one of the most common and disabling symptoms of MS, effective management and reduction of MS-related fatigue has the potential to increase quality of life in this population. The results of this study will add to the evidence base for providing dietary recommendations to treat MS-related fatigue and other symptoms associated with this disease. ClinicalTrials.gov, NCT02914964 . Registered on 24 August 2016.
Published:
2018-12
Title:
Early adipose deposits in sheep: comparative analysis of the perirenal fat transcriptome of Assaf and Churra suckling lambs
Authors:
Suarez-Vega, A.; Arranz, J. J.; Perez, V.; de la Fuente, L. F.; Mateo, J.; Gutierrez-Gil, B.
Abstract:
Adipose deposits influence the quality of ruminant carcasses, and in suckling lambs, internal types of adipose deposits represent a notable proportion of total fat. The aim of this study was to perform a comparative analysis of the perirenal fat transcriptomes of suckling lambs from two breeds with different growth and carcass characteristics. The perirenal fat tissue from 14 suckling lambs (Assaf, n = 8; Churra, n = 6) was used for the RNA-seq analysis. The functional enrichment analysis of the 670 highly expressed genes (>150 fragments per kilobase of exon per million fragments mapped) in the perirenal fat transcriptome of both breeds revealed that the majority of these genes were involved in energy processes. The expression of the UCP1 gene, a classical biomarker of brown fat, and the presence of multilocular adipocytes in the two breeds supported the presence of brown fat at the transition stage towards white fat tissue. The differential expression analysis performed identified 373 differentially expressed genes (DEGs) between the two compared breeds. Brown/white fat gene biomarkers were not included in the list of DEGs. In Assaf lambs, DEGs were enriched in Gene Ontology (GO) biological processes related to fatty-acid oxidation, whereas in Churra lambs, the majority of the significantly enriched GO terms were related to cholesterol synthesis, which suggests that upregulated DEGs in Assaf lambs are implicated in fat burning, whereas the Churra upregulated DEGs are linked to fat accumulation. These results can help to increase knowledge of the genes controlling early fat deposition in ruminants and shed light on fundamental aspects of adipose tissue growth. Copyright © 2018 Stichting International Foundation for Animal Genetics.
Published:
2018-12
Title:
Efficacy of ketogenic diet on body composition during resistance training in trained men: a randomized controlled trial
Authors:
Vargas, Salvador; Romance, Ramón; Petro, Jorge L.; Bonilla, Diego A.; Galancho, Ismael; Espinar, Sergio; Kreider, Richard B.; Benítez-Porres, Javier
Abstract:
Published:
2018-12
Title:
FADS1 and the Timing of Human Adaptation to Agriculture
Authors:
Mathieson, Sara; Mathieson, Iain
Abstract:
Variation at the FADS1/FADS2 gene cluster is functionally associated with differences in lipid metabolism and is often hypothesized to reflect adaptation to an agricultural diet. Here, we test the evidence for this relationship using both modern and ancient DNA data. We show that almost all the inhabitants of Europe carried the ancestral allele until the derived allele was introduced ∼8,500 years ago by Early Neolithic farming populations. However, we also show that it was not under strong selection in these populations. We find that this allele, and other proposed agricultural adaptations at LCT/MCM6 and SLC22A4, were not strongly selected until much later, perhaps as late as the Bronze Age. Similarly, increased copy number variation at the salivary amylase gene AMY1 is not linked to the development of agriculture although, in this case, the putative adaptation precedes the agricultural transition. Our analysis shows that selection at the FADS locus was not tightly linked to the initial introduction of agriculture and the Neolithic transition. Further, it suggests that the strongest signals of recent human adaptation in Europe did not coincide with the Neolithic transition but with more recent changes in environment, diet, or efficiency of selection due to increases in effective population size.
Published:
2018-12
Title:
Hypocholesterolemia is an independent risk factor for depression disorder and suicide attempt in Northern Mexican population
Authors:
Segoviano-Mendoza, Marcela; Cárdenas-de la Cruz, Manuel; Salas-Pacheco, José; Vázquez-Alaniz, Fernando; La Llave-León, Osmel; Castellanos-Juárez, Francisco; Méndez-Hernández, Jazmín; Barraza-Salas, Marcelo; Miranda-Morales, Ernesto; Arias-Carrión, Oscar; Méndez-Hernández, Edna
Abstract:
Published:
2018-12
Title:
Inborn coagulation factors are more important cardiovascular risk factors than high LDL-cholesterol in familial hypercholesterolemia
Authors:
Ravnskov, Uffe; de Lorgeril, Michel; Kendrick, Malcolm; Diamond, David M.
Abstract:
High low-density-lipoprotein cholesterol (LDL-C) is routinely described as the main cause of cardiovascular disease (CVD) in familial hypercholesterolemia (FH). However, numerous observations are in conflict with Bradford Hill's criteria for causality: a) degree of atherosclerosis is not associated with LDL-C; b) on average the life span of people with FH is about the same as for other people; c) LDL-C of people with FH without CVD is almost as high as in FH patients of the same age with CVD; and d) questionable benefit or none at all have been achieved in the controlled, randomized cholesterol-lowering trials that have included FH individuals only. Obviously, those individuals with FH who suffer from CVD may have inherited other and more important risk factors of CVD than high LDL-C. In accordance, several studies of FH individuals have shown that various coagulation factors may cause CVD. Equally, some non-FH members of an FH kindred with early CVD, have been found to suffer from early CVD as well. Cholesterol-lowering has only been successful in an animal experiment by using probucol, which has anticoagulant effects as well. We conclude that systematic studies of all kinds of risk factors among FH individuals are urgently required, because today millions of people with FH are treated with statins, the benefit of which in FH is unproven, and which have many serious side effects. We predict that treatment of FH individuals with elevated coagulation factors with anticoagulative drugs is more effective than statin treatment alone.
Published:
2018-12
Title:
Interaction of long-chain non-coding RNAs and important signaling pathways on human cancers (Review)
Authors:
Sun, Wei; Shi, Ying; Wang, Zhifei; Zhang, Jiye; Cai, Hanhui; Zhang, Jungang; Huang, Dongsheng
Abstract:
Long non-coding RNAs (lncRNAs) usually refer to non-coding RNA transcripts >200 nucleotides in length. In terms of the full genomic transcript, the proportion of lncRNAs far exceeds that of coding RNA. Initially, lncRNAs were considered to be the transcriptional noise of genes, but it has since been demonstrated that lncRNAs serve an important role in the regulation of cellular activities through interaction with DNA, RNA and protein. Numerous studies have demonstrated that various intricate signaling pathways are closely related to lncRNAs. Here, we focus on a large number of studies regarding the interaction of lncRNAs with important signaling pathways. It is comprehensively illustrated that lncRNAs regulate key metabolic components and regulatory factors of signaling pathways to affect the biological activities of tumor cells. Evidence suggests that the abnormal expression or mutation of lncRNAs in human tumor cells, and their interaction with signaling pathways, may provide a basis and potential target for the diagnosis and treatment of human cancers.
Published:
2018-12
Title:
Intracellular cholesterol accumulation and coenzyme Q10 deficiency in Familial Hypercholesterolemia
Authors:
Suárez-Rivero, Juan M.; de la Mata, Mario; Pavón, Ana Delgado; Villanueva-Paz, Marina; Povea-Cabello, Suleva; Cotán, David; Álvarez-Córdoba, Mónica; Villalón-García, Irene; Ybot-González, Patricia; Salas, Joaquín J.; Muñiz, Ovidio; Cordero, Mario D.; Sánchez-Alcázar, José A.
Abstract:
Published:
2018-12
Title:
Is fasting safe? A chart review of adverse events during medically supervised, water-only fasting
Authors:
Finnell, John S.; Saul, Bradley C.; Goldhamer, Alan C.; Myers, Toshia R.
Abstract:
Background: Evidence suggests that fasting, during which only water is consumed, results in potentially health promoting physiological effects. However, peer-reviewed research assessing the safety of water-only fasting is lacking. To address this, we conducted a chart review to describe adverse events (AEs) that occurred during medically supervised, water-only fasting. Methods: Electronic charts from patient visits to a residential medical facility from 2006 to 2011 were reviewed. Patients who were at least 21 years of age and water-only fasted for ≥2 consecutive days with a refeeding period equal to half of the fast length were included. Out of 2539 charts, 768 visits met our inclusion and exclusion criteria. AEs were abstracted from chart notes and classified according to CTCAE (v4.03) and MedDRA (v12.1) terminology. Descriptive analysis of AEs is reported. Results: During the protocol period, the highest grade AE (HGAE) in 555 visits was a grade 2 event or lower, in 212 visits it was a grade 3 event, in 1 visit it was a grade 4 event, and there were no grade 5 events. There were 2 (0.002%) visits with a serious adverse event (SAE). The majority of AEs identified were mild (n = 4490, 75%) in nature and known reactions to fasting. Conclusions: To our knowledge, this is the most comprehensive analysis of AEs experienced during medically supervised, water-only fasting conducted to date. Overall, our data indicate that the majority of AEs experienced were mild to moderate and known reactions to fasting. This suggests that the protocol used in this study can be safely implemented in a medical setting with minimal risk of a SAE.
Published:
2018-12
Title:
Larger Food Portion Sizes Are Associated with Both Positive and Negative Markers of Dietary Quality in Irish Adults
Authors:
Lyons, Jacqueline; Walton, Janette; Flynn, Albert
Abstract:
Reduction in portion size, particularly for energy-dense foods, is increasingly addressed in healthy eating guidelines in a bid to tackle the obesity epidemic. The effect of portion size on other aspects of dietary quality, such as nutrient intakes, is less studied. The aim of the current work was to investigate associations between food portion sizes and key indicators of dietary quality, namely energy-adjusted intakes of saturated fat, dietary fibre, sodium, calcium, iron, folate and vitamin D, and dietary energy density (DED), in Irish adults on the days the foods were consumed. Data from the Irish National Adult Nutrition Survey (2008–2010) (n = 1274, 18–64 years, 4-day semi-weighed record) were used for the analysis. DED was lower on the days larger portions of boiled potatoes, fruit, vegetables and baked beans were consumed, and higher on the days larger portions of white bread, ready-to-eat breakfast cereals (RTEBCs), frying meats, cheese, butter, biscuits, chocolate and sugar-sweetened beverages were consumed. Micronutrient intakes were higher on the days larger portions of brown bread, RTEBCs, vegetables and low-fat spreads were consumed, and lower on the days larger portions of white bread, butter, biscuits, chocolate, sugar-sweetened beverages and beer/cider were consumed, with the exception of folate. The study identifies foods for which larger portion sizes may be associated with positive dietary attributes, as well as the opposite. It provides an important evidence base from which more specific dietary guidance on food portion sizes might be developed for Irish adults.
Published:
2018-12
Title:
Mitochondrial dysfunction and damage associated molecular patterns (DAMPs) in chronic inflammatory diseases
Authors:
Dela Cruz, Charles S.; Kang, Min Jong
Abstract:
Inflammation represents a comprehensive host response to external stimuli for the purpose of eliminating the offending agent, minimizing injury to host tissues and fostering repair of damaged tissues back to homeostatic levels. In normal physiologic context, inflammatory response culminates with the resolution of infection and tissue damage response. However, in a pathologic context, persistent or inappropriately regulated inflammation occurs that can lead to chronic inflammatory diseases. Recent scientific advances have integrated the role of innate immune response to be an important arm of the inflammatory process. Accordingly, the dysregulation of innate immunity has been increasingly recognized as a driving force of chronic inflammatory diseases. Mitochondria have recently emerged as organelles which govern fundamental cellular functions including cell proliferation or differentiation, cell death, metabolism and cellular signaling that are important in innate immunity and inflammation-mediated diseases. As a natural consequence, mitochondrial dysfunction has been highlighted in a myriad of chronic inflammatory diseases. Moreover, the similarities between mitochondrial and bacterial constituents highlight the intrinsic links in the innate immune mechanisms that control chronic inflammation in diseases where mitochondrial damage associated molecular patterns (DAMPs) have been involved. Here in this review, the role of mitochondria in innate immune responses is discussed and how it pertains to the mitochondrial dysfunction or DAMPs seen in chronic inflammatory diseases is reviewed.
Published:
2018-12
Title:
Serum Nitrogen and Carbon Stable Isotope Ratios Meet Biomarker Criteria for Fish and Animal Protein Intake in a Controlled Feeding Study of a Women's Health Initiative Cohort
Authors:
Yun, Hee Young; Niles, Kristine R; O'Brien, Diane M; Lampe, Johanna W; Neuhouser, Marian L; Beresford, Shirley A A; Prentice, Ross L; Tinker, Lesley F; Mossavar-Rahmani, Yasmin; Snetselaar, Linda G; Horn, Linda Van; Van Horn, Linda
Abstract:
Background: Natural abundance stable isotope ratios are candidate biomarkers of dietary intake that have not been evaluated in a controlled feeding study in a US population.Objectives: Our goals were to evaluate dietary associations with serum carbon (CIR), nitrogen (NIR), and sulfur (SIR) isotope ratios in postmenopausal women, and to evaluate whether statistical models of dietary intake that include multiple isotopes and participant characteristics meet criteria for biomarker evaluation.Methods: Postmenopausal women from the Women's Health Initiative (n = 153) were provided a 2-wk controlled diet that approximated each individual's habitual food intake. Dietary intakes of animal protein, fish/seafood, red meat, poultry, egg, dairy, total sugars, added sugars, sugar-sweetened beverages (SSBs), and corn products were characterized during the feeding period with the use of the Nutrition Data System for Research (NDS-R). The CIR, NIR, and SIR were measured in sera collected from fasting women at the beginning and the end of the feeding period. Linear models based on stable isotope ratios and participant characteristics predicted dietary intake. The criterion used for biomarker evaluation was R2 ≥ 0.36, based on the study's power to detect true associations with R2 ≥ 0.50.Results: The NIR was associated with fish/seafood intake and met the criterion for biomarker evaluation (R2 = 0.40). The CIR was moderately associated with intakes of red meat and eggs, but not to the criterion for biomarker evaluation, and was not associated with intake of sugars (total, added, or SSB). A model of animal protein intake based on the NIR, CIR, and participant characteristics met the criterion for biomarker evaluation (R2 = 0.40). Otherwise, multiple isotopes did not improve models of intake, and improvements from including participant characteristics were modest.Conclusion: Serum stable isotope ratios can, with participant characteristics, meet biomarker criteria as measures of fish/seafood and animal protein intake in a sample of postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00000611.
Published:
2018-12
Title:
The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study
Authors:
Bauersfeld, Stephan P.; Kessler, Christian S.; Wischnewsky, Manfred; Jaensch, Annette; Steckhan, Nico; Stange, Rainer; Kunz, Barbara; Brückner, Barbara; Sehouli, Jalid; Michalsen, Andreas
Abstract:
Background: This pilot trial aimed to study the feasibility and effects on quality of life (QOL) and well-being of short-term fasting (STF) during chemotherapy in patients with gynecological cancer. Methods: In an individually-randomized cross-over trial patients with gynecological cancer, 4 to 6 planned chemotherapy cycles were included. Thirty-four patients were randomized to STF in the first half of chemotherapies followed by normocaloric diet (group A;n = 18) or vice versa (group B;n = 16). Fasting started 36 h before and ended 24 h after chemotherapy (60 h-fasting period). QOL was assessed by the FACIT-measurement system. Results: The chemotherapy-induced reduction of QOL was less than the Minimally Important Difference (MID; FACT-G = 5) with STF but greater than the MID for non-fasted periods. The mean chemotherapy-induced deterioration of total FACIT-F was 10.4 ± 5.3 for fasted and 27.0 ± 6.3 for non-fasted cycles in group A and 14.1 ± 5.6 for non-fasted and 11.0 ± 5.6 for fasted cycles in group B. There were no serious adverse effects. Conclusion: STF during chemotherapy is well tolerated and appears to improve QOL and fatigue during chemotherapy. Larger studies should prove the effect of STF as an adjunct to chemotherapy. Trial registration: This trial was registered at clinicaltrials.gov: NCT01954836.
Published:
2018-12
Title:
The synergism of high-intensity intermittent exercise and every-other-day intermittent fasting regimen on energy metabolism adaptations includes hexokinase activity and mitochondrial efficiency
Authors:
Real-Hohn, Antonio; Navegantes, Clarice; Ramos, Katia; Ramos-Filho, Dionisio; Cahuê, Fábio; Galina, Antonio; Salerno, Verônica P.
Abstract:
Visceral lipid accumulation, organ hypertrophy and a reduction in skeletal muscle strength are all signs associated with the severity of obesity-related disease. Intermittent fasting (IF) and high-intensity intermittent exercise (HIIE) are natural strategies that, individually, can prevent and help treat obesity along with metabolic syndrome and its associated diseases. However, the combinatorial effect of IF and HIIE on energetic metabolism is currently not well understood. We hypothesized that their combination could have a potential for more than strictly additive benefits. Here, we show that two months of every-other-day intermittent fasting regimen combined with a high-intensity intermittent exercise protocol (IF/HIIE) produced a synergistic effect, enhancing physical endurance (vs. control, HIIE and IF) and optimizing metabolic pathways of energy production in male Wistar rats. The IF/HIIE group presented enhanced glucose tolerance (vs. control, HIIE and IF), lower levels of plasma insulin (vs. control and HIIE), and a global activation of low Km hexokinases in liver (vs. control, HIIE and IF), heart (vs. control and HIIE) and skeletal muscle (vs. control, HIIE and IF). The IF/HIIE synergism, rather than a simply additive effect, is evidenced by increase in muscle mass and cross-section area, activation of the FoF1 ATP synthase, and the gain of characteristics suggestive of augmented mitochondrial mass and efficiency observed in this group. Finally, important reductions in plasma oxidative stress markers were present preferentially in IF/HIIE group. These findings provide new insights for the implementation of non-pharmaceutical strategies to prevent/treat metabolic syndrome and associated diseases.
Published:
2018-12
Title:
Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages
Authors:
Bohn, Toszka; Rapp, Steffen; Luther, Natascha; Klein, Matthias; Bruehl, Till-Julius; Kojima, Nobuhiko; Lopez, Pamela Aranda; Hahlbrock, Jennifer; Muth, Sabine; Endo, Shogo; Pektor, Stefanie; Brand, Almut; Renner, Kathrin; Popp, Vanessa; Gerlach, Katharina; Vogel, Dennis; Lueckel, Christina; Arnold-Schild, Danielle; Pouyssegur, Jacques; Kreutz, Marina; Huber, Magdalena; Koenig, Jochem; Weigmann, Benno; Probst, Hans-Christian; Stebut, Esther von; Becker, Christian; Schild, Hansjoerg; Schmitt, Edgar; Bopp, Tobias
Abstract:
Tumors can vary in both their control by immunosurveillance and their glycolytic activity. Bopp and colleagues demonstrate that highly glycolytic tumors acidify their microenvironment and use this to initiate a mechanism of localized immunosuppression.
Published:
2018-12
Title:
Clinical effectiveness of golimumab in Crohn's disease: an observational study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)
Authors:
Rundquist, Sara; Eriksson, Carl; Nilsson, Linda; Angelison, Leif; Jäghult, Susanna; Björk, Jan; Grip, Olof; Hjortswang, Henrik; Strid, Hans; Karlén, Per; Montgomery, Scott; Halfvarson, Jonas
Abstract:
OBJECTIVE: The effectiveness of golimumab in Crohn's disease (CD) is largely unknown as it is not approved for the treatment of the disease. We aimed to identify the population of CD patients treated with golimumab in Sweden, to assess the effectiveness of golimumab (defined as the drug retention rate), and to identify predictors of drug discontinuation. METHODS: Patients with CD who received at least one injection of golimumab were identified through the Swedish National Quality Registry for Inflammatory Bowel Disease, which includes prospectively collected clinical information. Cox regression models were used to identify predictors of golimumab discontinuation. RESULTS: The study cohort involved 94 patients of whom the majority (96.8%) had previously discontinued at least one anti-tumour necrosis factor (anti-TNF) agent. The drug retention rate at 12 weeks was 85.1%. Predictors of golimumab discontinuation at 12 weeks were previous surgery (adjusted HR = 7.52, 95% CI: 1.12-50.36), concomitant corticosteroid use at baseline (adjusted HR = 5.70, 95% CI: 1.13-28.68) and female sex (adjusted HR = 6.59; 95% CI: 1.04-41.62). The median duration of follow-up was 89 (IQR: 32-158) weeks. The drug retention at the most recent follow-up was 35.1%. Predictors of golimumab discontinuation at the most recent follow-up were corticosteroid use at baseline (adjusted HR = 2.60, 95% CI: 1.17-5.79) and female sex (adjusted HR = 2.24; 95% CI: 1.19-4.23). CONCLUSION: Patients with CD treated with golimumab were a treatment-refractory group. Despite this, more than one-third of the patients appeared to have had clinical benefit after a median follow-up of more than 1.5 years.
Published:
2018-11
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