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Title:

Evolution of Digestive Enzymes and RNASE1 Provides Insights into Dietary Switch of Cetaceans

Authors:

Wang, Zhengfei; Xu, Shixia; Du, Kexing; Huang, Fang; Chen, Zhuo; Zhou, Kaiya; Ren, Wenhua; Yang, Guang

Abstract:

Although cetaceans (whales, porpoises, and dolphins) have multi-chambered stomachs, feeding habits of modern cetaceans have dramatically changed from herbivorous to carnivorous. However, the genetic basis underlying this dietary switch remains unexplored. Here, we present the first systematic investigation of 10 digestive enzymes genes (i.e., CYP7A1, CTRC, LIPC, LIPF, PNLIP, PGC, PRSS1, SI, SLC5A1, and TMPRSS15) of representative cetaceans, and the evolutionary trajectory of RNASE1 in cetartiodactylans. Positive selections were detected with proteinases (i.e., CTRC, PRSS1, and TMPRSS15) and lipases (i.e., CYP7A1, LIPF, and PNLIP) suggesting that cetaceans have evolved an enhanced digestion capacity for proteins and lipids, the major nutritional components of their prey (fishes and invertebrates). In addition, it was found that RNASE1 gene duplicated after the cetartiodactylan speciation and two independent gene duplication events took place in Camelidae and Ruminantia. Positive selection was detected with RNASE1 of Camelidae and Bovidae, suggesting enhanced digestive efficiency in the ruminants. Remarkably, even though the ancestors of cetaceans were terrestrial artiodactyls that are herbivorous, modern cetaceans lost the pancreatic RNASE1 copy with digestive function, which is in accordance with the dietary change from herbivorous to carnivorous. In sum, this is the first study that provides new insights into the evolutionary mechanism of dietary switch in cetaceans.

Published:

2016

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Title:

Evolving Concepts of Myocardial Energy Metabolism: More Than Just Fats and Carbohydrates

Authors:

Lopaschuk, Gary D.; Ussher, John R.

Abstract:

Although mitochondrial fatty acid and carbohydrate oxidation are the major source of ATP production in the heart, it is becoming increasingly clear that oxidation of other energy substrates, such as ketones and branched chain amino acids (BCAAs), can also contribute to energy production. Of importance is that alterations in cardiac ketone and branched chain amino acids metabolism may also impact the severity of heart failure through alterations in cellular signaling, despite these fuels providing a lower contribution to overall energy production. Dating back to the first studies investigating glucose uptake in the isolated rabbit heart by Locke and Rosenheim in 1907 to the first studies in humans in the late 1940s by Richard Bing and colleagues assessing cardiac substrate extraction via measurement of arterial coronary sinus differences, cardiac energy metabolism has been a topic of interest for cardiologists and scientists alike. The importance of energy metabolism in the heart has become widely appreciated, as has the dynamic nature of the heart's ability to metabolize a wide range of energy substrates to meet its energy requirements. Fatty acids are recognized as a key source of energy for the heart, as well as carbohydrates, such as glucose and lactate (Figure).1 In 1961, Shipp et al2 were the first to demonstrate that increasing fatty acid availability to the heart results in a marked inhibition of glucose oxidation, though credit for the reciprocal relationship between fatty acids and glucose metabolism (glucose/fatty acid cycle) is attributed to the work of Randle et al.3 Confirmation of Randle's glucose/fatty acid cycle in the rodent heart has since been demonstrated in the human heart.1 Figure. Interaction of energy substrates for oxidative energy production and branched chain amino acid (BCAA)/ketone body regulation of cellular signaling in the heart .The figure depicts how energy substrates compete \ldots

Published:

2016

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Title:

Exercise raises high-density lipoprotein cholesterol in men after consumption of ground beef with a high but not low monounsaturated fatty acid-saturated fatty acid ratio

Authors:

Crouse, Stephen F.; Green, John S.; Meade, Thomas H.; Smith, Dana R.; Smith, Stephen B.

Abstract:

Exercise and diets with higher monounsaturated fatty acid (MUFA):saturated fatty acid (SFA) ratios are independently linked to improved blood lipid profiles, yet interactive effects in men have not been studied. We hypothesized that dietary ground beef with a high MUFA:SFA ratio (HR = 1.1) would augment the beneficial changes in the lipid profile induced by exercise compared to dietary ground beef with a lower MUFA:SFA ratio (LR = 0.71). Untrained men (n = 13, age = 35 +/- 12 y, weight = 91.4 +/- 14.2 kg, body mass index = 27.8 +/- 3.3kg/m(2)) consumed 5 HR or LR 114 g ground beef patties weekly for 5 weeks (random order) interspersed with a 4-week self-selected (SS) washout diet. One session of exercise (70% VO2max, 1675 kJ) was completed at the end of HR and LR diets, and again after a 5-week SS diet. Diets and physical activity were otherwise not controlled. Fasting blood samples for lipid and lipoprotein analyses were obtained 30 min before and 24 h after exercise. Subjects reported no other changes in diets or physical activity patterns, and body weight and body mass index did not change over the study duration. Diet (3) x Exercise Time (2) repeated measures analysis of variance (alpha = .05) and follow-up analyses revealed that blood concentrations (mmol/L +/- SD) of total cholesterol (5.07 +/- 1.16 to 5.73 +/- 1.36), high-density lipoprotein cholesterol (HDL-C) (1.19 +/- 0.20 to 1.36 +/- 0.29), HDL2-C (0.24 +/- 0.08 to 0.28 +/- 0.11), HDL3-C (0.94 +/- 0.14 to 1.08 +/- 0.20), and non-HDL-C (3.88 +/- 1.24 to 4.37 +/- 1.38) were significantly elevated with exercise after the HR beef diet, but not after LR and SS diets. Thus, in healthy, untrained men the dietary beef MUFA:SFA ratio affects the blood lipid response to a single session of aerobic exercise. Copyright © 2016 Elsevier Inc. All rights reserved.

Published:

2016

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Title:

Extracellular pH Modulates Neuroendocrine Prostate Cancer Cell Metabolism and Susceptibility to the Mitochondrial Inhibitor Niclosamide

Authors:

Ippolito, Joseph E.; Brandenburg, Matthew W.; Ge, Xia; Crowley, Jan R.; Kirmess, Kristopher M.; Som, Avik; D'Avignon, D. Andre; Arbeit, Jeffrey M.; Achilefu, Samuel; Yarasheski, Kevin E.; Milbrandt, Jeffrey

Abstract:

Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6.5, 7.4, and 8.5) on neuroendocrine prostate cancer cell metabolism. We discovered that alkalinization of extracellular pH converted cellular metabolism to a nutrient consumption-dependent state that was susceptible to glucose deprivation, glutamine deprivation, and 2-deoxyglucose (2-DG) mediated inhibition of glycolysis. Conversely, acidic pH shifted cellular metabolism toward an oxidative phosphorylation (OXPHOS)-dependent state that was susceptible to OXPHOS inhibition. Based upon this mechanistic knowledge of pH-dependent metabolism, we identified that the FDA-approved anti-helminthic niclosamide depolarized mitochondrial potential and depleted ATP levels in PNEC cells whose effects were enhanced in acidic pH. To further establish relevance of these findings, we tested the effects of extracellular pH on susceptibility to nutrient deprivation and OXPHOS inhibition in a cohort of castrate-resistant prostate cancer cell lines C4-2B, PC-3, and PC-3M. We discovered similar pH-dependent toxicity profiles among all cell lines with these treatments. These findings underscore a potential importance to acidic extracellular pH in the modulation of cell metabolism in tumors and development of an emerging paradigm that exploits the synergy of environment and therapeutic efficacy in cancer.

Published:

2016

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Title:

Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan

Authors:

Longo, Valter D.; Panda, Satchidananda

Abstract:

Most animals alternate periods of feeding with periods of fasting often coinciding with sleep. Upon \textgreater24 hr of fasting, humans, rodents, and other mammals enter alternative metabolic phases, which rely less on glucose and more on ketone body-like carbon sources. Both intermittent and periodic fasting result in benefits ranging from the prevention to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in which food consumption is restricted to certain hours of the day, allows the daily fasting period to last \textgreater12 hr, thus imparting pleiotropic benefits. Understanding the mechanistic link between nutrients and the fasting benefits is leading to the identification of fasting-mimicking diets (FMDs) that achieve changes similar to those caused by fasting. Given the pleiotropic and sustained benefits of TRF and FMDs, both basic science and translational research are warranted to develop fasting-associated interventions into feasible, effective, and inexpensive treatments with the potential to improve healthspan.

Published:

2016

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Title:

Food and health in early modern Europe: diet, medicine and society, 1450-1800

Authors:

Gentilcore, David

Abstract:

Published:

2016

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Title:

Food consumption and the actual statistics of cardiovascular diseases: An epidemiological comparison of 42 European countries

Authors:

Grasgruber, Pavel; Sebera, Martin; Hrazdira, Eduard; Hrebickova, Sylva; Cacek, Jan

Abstract:

BACKGROUND The aim of this ecological study was to identify the main nutritional factors related to the prevalence of cardiovascular diseases (CVDs) in Europe, based on a comparison of international statistics. DESIGN The mean consumption of 62 food items from the FAOSTAT database (1993-2008) was compared with the actual statistics of five CVD indicators in 42 European countries. Several other exogenous factors (health expenditure, smoking, body mass index) and the historical stability of results were also examined. RESULTS We found exceptionally strong relationships between some of the examined factors, the highest being a correlation between raised cholesterol in men and the combined consumption of animal fat and animal protein (r=0.92, p\textless0.001). The most significant dietary correlate of low CVD risk was high total fat and animal protein consumption. Additional statistical analyses further highlighted citrus fruits, high-fat dairy (cheese) and tree nuts. Among other non-dietary factors, health expenditure showed by far the highest correlation coefficients. The major correlate of high CVD risk was the proportion of energy from carbohydrates and alcohol, or from potato and cereal carbohydrates. Similar patterns were observed between food consumption and CVD statistics from the period 1980-2000, which shows that these relationships are stable over time. However, we found striking discrepancies in men's CVD statistics from 1980 and 1990, which can probably explain the origin of the 'saturated fat hypothesis' that influenced public health policies in the following decades. CONCLUSION Our results do not support the association between CVDs and saturated fat, which is still contained in official dietary guidelines. Instead, they agree with data accumulated from recent studies that link CVD risk with the high glycaemic index/load of carbohydrate-based diets. In the absence of any scientific evidence connecting saturated fat with CVDs, these findings show that current dietary recommendations regarding CVDs should be seriously reconsidered.

Published:

2016

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Title:

Food consumption and the actual statistics of cardiovascular diseases: an epidemiological comparison of 42 European countries

Authors:

Grasgruber, Pavel; Sebera, Martin; Hrazdira, Eduard; Hrebickova, Sylva; Cacek, Jan

Abstract:

The aim of this ecological study was to identify the main nutritional factors related to the prevalence of cardiovascular diseases (CVDs) in Europe, based on a comparison of international statistics.The mean consumption of 62 food items from the FAOSTAT ...

Published:

2016

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Title:

Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease

Authors:

Khera, Amit V.; Emdin, Connor A.; Drake, Isabel; Natarajan, Pradeep; Bick, Alexander G.; Cook, Nancy R.; Chasman, Daniel I.; Baber, Usman; Mehran, Roxana; Rader, Daniel J.; Fuster, Valentin; Boerwinkle, Eric; Melander, Olle; Orho-Melander, Marju; Ridker, Paul M; Kathiresan, Sekar

Abstract:

BackgroundBoth genetic and lifestyle factors contribute to individual-level risk of coronary artery disease. The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown. MethodsUsing a polygenic score of DNA sequence polymorphisms, we quantified genetic risk for coronary artery disease in three prospective cohorts — 7814 participants in the Atherosclerosis Risk in Communities (ARIC) study, 21,222 in the Women's Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) — and in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available. We also determined adherence to a healthy lifestyle among the participants using a scoring system consisting of four factors: no current smoking, no obesity, regular physical activity, and a healthy diet. ResultsThe relative risk of incident coronary events was 91% higher among participants at high genetic risk (top quintile of polygenic scores) than among those at low gen...

Published:

2016

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Title:

Gluconeogenesis during endurance exercise in cyclists habituated to a long-term low carbohydrate high-fat diet

Authors:

Webster, Christopher C.; Noakes, Timothy D.; Chacko, Shaji K.; Swart, Jeroen; Kohn, Tertius A.; Smith, James A.H.

Abstract:

Endogenous glucose production (EGP) occurs via hepatic glycogenolysis (GLY) and gluconeogenesis (GNG) and plays an important role in maintaining euglycemia. Rates of GLY and GNG increase during exercise in athletes following a mixed macronutrient diet; however these processes have not been investigated in athletes following a low carbohydrate high fat (LCHF) diet. Therefore, we studied 7 well-trained male cyclists that were habituated to either a LCHF (7% carbohydrate, 72% fat, 21% protein) or mixed diet (51% carbohydrate, 33% fat, 16% protein) for longer than 8 months. After an overnight fast, participants performed a 2-hour laboratory ride at 72% of maximal oxygen consumption. Glucose kinetics were measured at rest and during the final 30 min of exercise by infusion of [6,6-(2) H2 ]-glucose and the ingestion of (2) H2 O tracers. Rates of EGP and GLY both at rest and during exercise were significantly lower in the LCHF group than the mixed diet group (Exercise EGP: LCHF, 6.0 ± 0.9; Mixed, 7.8 ± 1.1 mg kg(-1) min(-1) , P \textless 0.01. Exercise GLY: LCHF, 3.2 ± 0.7; Mixed, 5.3 ± 0.9 mg kg(-1) min(-1) , P \textless 0.01). Conversely, no difference was detected in rates of GNG between groups at rest or during exercise (Exercise: LCHF, 2.8 ± 0.4; Mixed, 2.5 ± 0.3 mg kg(-1) min(-1) , P = 0.15). We conclude that athletes on a LCHF diet do not compensate for reduced glucose availability via higher rates of glucose synthesis compared to athletes on a mixed diet. Instead, GNG remains relatively stable while glucose oxidation and GLY are influenced by dietary factors. This article is protected by copyright. All rights reserved.

Published:

2016

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Title:

Granulocyte macrophage colony-stimulating factor receptor α expression and its targeting in antigen-induced arthritis and inflammation

Authors:

Cook, Andrew D.; Louis, Cynthia; Robinson, Matthew J.; Saleh, Reem; Sleeman, Matthew A.; Hamilton, John A.

Abstract:

Background Blockade of granulocyte macrophage colony-stimulating factor (GM-CSF) and its receptor (GM-CSFRα) is being successfully tested in trials in rheumatoid arthritis (RA) with clinical results equivalent to those found with neutralization of the current therapeutic targets, TNF and IL-6. To explore further the role of GM-CSF as a pro-inflammatory cytokine, we examined the effect of anti-GM-CSFRα neutralization on myeloid cell populations in antigen-driven arthritis and inflammation models and also compared its effect with that of anti-TNF and anti-IL-6. Methods Cell population changes upon neutralization by monoclonal antibodies (mAbs) in the antigen-induced arthritis (AIA) and antigen-induced peritonitis (AIP) models were monitored by flow cytometry and microarray. Adoptive transfer of monocytes into the AIP cavity was used to assess the GM-CSF dependence of the development of macrophages and monocyte-derived dendritic cells (Mo-DCs) at a site of inflammation. Results Therapeutic administration of a neutralizing anti-GM-CSF mAb, but not of an anti-colony-stimulating factor (anti-CSF)-1 or an anti-CSF-1R mAb, ameliorated AIA disease. Using the anti-GM-CSFRα mAb, the relative surface expression of different inflammatory myeloid populations was found to be similar in the inflamed tissues in both the AIA and AIP models; however, the GM-CSFRα mAb, but not neutralizing anti-TNF and anti-IL-6 mAbs, preferentially depleted Mo-DCs from these sites. In addition, we were able to show that locally acting GM-CSF upregulated macrophage/Mo-DC numbers via GM-CSFR signalling in donor monocytes. Conclusions Our findings suggest that GM-CSF blockade modulates inflammatory responses differently to TNF and IL-6 blockade and may provide additional insight into how targeting the GM-CSF/GM-CSFRα system is providing efficacy in RA. Electronic supplementary material The online version of this article (doi:10.1186/s13075-016-1185-9) contains supplementary material, which is available to authorized users.

Published:

2016

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Title:

Gut Microbiota, Inflammation, and Colorectal Cancer

Authors:

Brennan, Caitlin A.; Garrett, Wendy S.

Abstract:

Colorectal cancer is the second-leading cause of cancer-related deaths in the United States and fourth-leading cause of cancer-related deaths worldwide. While cancer is largely considered to be a disease of genetic and environmental factors, increasing evidence has demonstrated a role for the microbiota (the microorganisms associated with the human body) in shaping inflammatory environments and promoting tumor growth and spread. Herein, we discuss both human data from meta'omics analyses and data from mechanistic studies in cell culture and animal models that support specific bacterial agents as potentiators of tumorigenesis—including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli. Further, we consider how microbes can be used in diagnosing colorectal cancer and manipulating the tumor environment to encourage better patient outcomes in response to immunotherapy treatments.

Published:

2016

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Title:

Guyton and Hall textbook of medical physiology

Authors:

Hall, John Edward; Guyton, Arthur C.

Abstract:

Published:

2016

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Title:

HHS Public Access

Authors:

Chen, Jingyuan E; Glover, Gary H

Abstract:

Published:

2016

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Title:

HHS Public Access

Authors:

Chen, Jingyuan E; Glover, Gary H

Abstract:

Published:

2016

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HHS Public Access

Authors:

Goadsby, Peter J; Kurth, Tobias; Pressman, Alice

Abstract:

Published:

2016

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Title:

Headaches: a Review of the Role of Dietary Factors

Authors:

Zaeem, Zoya; Zhou, Lily; Dilli, Esma

Abstract:

Dietary triggers are commonly reported by patients with a variety of headaches, particularly those with migraines. The presence of any specific dietary trigger in migraine patients varies from 10 to 64 % depending on study population and methodology. Some foods trigger headache within an hour while others develop within 12 h post ingestion. Alcohol (especially red wine and beer), chocolate, caffeine, dairy products such as aged cheese, food preservatives with nitrates and nitrites, monosodium glutamate (MSG), and artificial sweeteners such as aspartame have all been studied as migraine triggers in the past. This review focuses the evidence linking these compounds to headache and examines the prevalence of these triggers from prior population-based studies. Recent literature surrounding headache related to fasting and weight loss as well as elimination diets based on serum food antibody testing will also be summarized to help physicians recommend low-risk, non-pharmacological adjunctive therapies for patients with debilitating headaches.

Published:

2016

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Title:

Hepatic steatosis and insulin resistance, but not steatohepatitis, promote atherogenic dyslipidemia in NAFLD

Authors:

Bril, Fernando; Sninsky, John J.; Baca, Arthur M.; Superko, H. Robert; Sanchez, Paola Portillo; Biernacki, DIane; Maximos, Maryann; Lomonaco, Romina; Orsak, Beverly; Suman, Amitabh; Weber, Michelle H.; McPhaul, Michael J.; Cusi, Kenneth

Abstract:

Context: Patients with nonalcoholic fatty liver disease (NAFLD) are at increased risk of cardiovascular disease, and atherogenic lipoproteins may play an important role. Objective: To determine the contribution of the severity of steatohepatitis to atherogenic dyslipidemia in patients with NAFLD. Design: Cross-sectional Setting: University hospital Patients: Recruited from outpatient clinics or from the general population (n=188). Interventions: Measurement of hepatic triglyceride content by magnetic resonance spectroscopy (1H-MRS); histology (liver biopsy); metabolic profile by means of an oral glucose tolerance test and lipoprotein analyses. Outcomes: Standard lipids, lipoprotein subfraction analysis (apolipoprotein B/A1 levels, LDL particle size/phenotype, and LDL/HDL subfractions), and insulin resistance. Results: Patients with NAFLD had severe insulin resistance, especially at the level of the adipose tissue, when compared to patients without NAFLD. Despite small differences in triglycerides and HDL-...

Published:

2016

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Title:

High glucose stimulates tumorigenesis in hepatocellular carcinoma cells through ager-dependent O-glcnacylation of C-jun

Authors:

Qiao, Y.; Zhang, X.; Zhang, Y.; Wang, Y.; Xu, Y.; Liu, X.; Sun, F.; Wang, J.

Abstract:

Epidemiologic studies suggest that hepatocellular carcinoma (HCC) has a strong relationship with diabetes. However, the underlying molecular mechanisms still remain unclear. Here, we demonstrated that high glucose (HG), one of the main characteristics of diabetes, was capable of accelerating tumorigenesis in HCC cells. Advanced glycosylation end product-specific receptor (AGER) was identified as a stimulator during this process. Mechanistically, AGER activated a hexosamine biosynthetic pathway, leading to enhanced O-GlcNAcylation of target proteins. Notably, AGER was capable of increasing activity and stability of proto-oncoprotein c-Jun via O-GlcNAcylation of this protein at Ser73. Interestingly, c-Jun can conversely enhance AGER transcription. Thereby, a positive autoregulatory feedback loop that stimulates diabetic HCC was established. Finally, we found that AG490, an inhibitor of Janus kinase, has the ability to impair AGER expression and its functions in HCC cells. In conclusion, AGER and its functions to stimulate O-GlcNAcylation are important during liver tumorigenesis, when high blood glucose levels are inadequately controlled. © 2016 by the American Diabetes Association.

Published:

2016

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Title:

High intake of regular-fat cheese compared with reduced-fat cheese does not affect LDL cholesterol or risk markers of the metabolic syndrome: a randomized controlled trial

Authors:

Raziani, Farinaz; Tholstrup, Tine; Kristensen, Marlene D.; Svanegaard, Matilde L.; Ritz, Christian; Astrup, Arne; Raben, Anne

Abstract:

CONCLUSION: A high daily intake of regular-fat cheese for 12 wk did not alter LDL cholesterol or MetS risk factors differently than an equal intake of reduced-fat cheese or an isocaloric amount of carbohydrate-rich foods. This trial was registered at www.clinicaltrials.gov as NCT02616471. Copyright © 2016 American Society for Nutrition.

Published:

2016

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Title:

Histochemical evaluation of postnatal lectin-binding sites in the mouse prostate

Authors:

Sakuda, Kentaro; Muragishi, Ryoki; Yoshinaga, Kazuya

Abstract:

The prostate is a male accessory genital gland that plays an essential role in reproductive function. To understand the cytological characteristics of differentiating prostatic cells, we used lectin histochemistry combined with immunohistochemistry to examine the distribution of lectin-binding sites on prostatic cells during postnatal development in the mouse. During postnatal development, Hippeastrum Hybrid Lectin (HHL) lectin reacted consistently with the luminal cells of all prostatic lobes (regions), whereas the Ricinus Communis Agglutinin I (RCA-I) and Soybean Agglutinin (SBA) lectins showed remarkable differences with age, region, and cell type. We found that the lectin-binding pattern in differentiating prostatic cells acquired adult characteristics around 3 weeks after birth. The results indicate that prostatic cell differentiation during postnatal development in mice is characterized by the presence of cell- and region-specific lectin-binding sites in the prostate, suggesting that there may also be cellular and regional differences in their function. Furthermore, some lectins (HHL, RCA-I, and SBA) could provide useful markers for research into cell differentiation and for the pathological evaluation of prostatic diseases or in the diagnosis of male infertility.

Published:

2016

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Title:

Host-microbiome interaction and cancer: Potential application in precision medicine

Authors:

Contreras, A.V.; Cocom-Chan, B.; Hernandez-Montes, G.; Portillo-Bobadilla, T.; Resendis-Antonio, O.

Abstract:

It has been experimentally shown that host-microbial interaction plays a major role in shaping the wellness or disease of the human body. Microorganisms coexisting in human tissues provide a variety of benefits that contribute to proper functional activity in the host through the modulation of fundamental processes such as signal transduction, immunity and metabolism. The unbalance of this microbial profile, or dysbiosis, has been correlated with the genesis and evolution of complex diseases such as cancer. Although this latter disease has been thoroughly studied using different high-throughput (HT) technologies, its heterogeneous nature makes its understanding and proper treatment in patients a remaining challenge in clinical settings. Notably, given the outstanding role of host-microbiome interactions, the ecological interactions with microorganisms have become a new significant aspect in the systems that can contribute to the diagnosis and potential treatment of solid cancers. As a part of expanding precision medicine in the area of cancer research, efforts aimed at effective treatments for various kinds of cancer based on the knowledge of genetics, biology of the disease and host-microbiome interactions might improve the prediction of disease risk and implement potential microbiota-directed therapeutics. In this review, we present the state of the art of sequencing and metabolome technologies, computational methods and schemes in systems biology that have addressed recent breakthroughs of uncovering relationships or associations between microorganisms and cancer. Together, microbiome studies extend the horizon of new personalized treatments against cancer from the perspective of precision medicine through a synergistic strategy integrating clinical knowledge, HT data, bioinformatics, and systems biology. © 2016 Contreras, Cocom-Chan, Hernandez-Montes, Portillo-Bobadilla and Resendis-Antonio.

Published:

2016

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Title:

How Well Can We Control Dyslipidemias Through Lifestyle Modifications?. [Review]

Authors:

Riccardi, Gabriele; Vaccaro, Olga; Costabile, Giuseppina; Rivellese, Angela A.

Abstract:

The role for lifestyle modifications to correct dyslipidemia(s) is reviewed. Dietary composition is crucial. Replacing saturated fat with MUFA or n-6 PUFA lowers plasma low-density lipoproteins (LDL) cholesterol and ameliorates the LDL/HDL ratio. Replacing saturated fat with carbohydrates has diverging effects due to the heterogeneity of carbohydrate foods. Diets rich in refined carbohydrates increase fasting and postprandial triglycerides, whereas the consumption of fiber-rich, low GI foods lowers LDL cholesterol with no detrimental effects on triglycerides. The role of polyphenols is debated: available evidence suggests a lowering effect of polyphenol-rich foods on postprandial triglycerides. As for functional foods, health claims on a cholesterol lowering effect of psyllium, beta-glucans and phytosterols are accepted by regulatory agencies. The importance of alcohol intake, weight reduction, and physical activity is discussed. In conclusion, there is evidence that lifestyle affects plasma lipid. A multifactorial approach including multiple changes with additive effects is the best option. This may also ensure feasibility and durability. The traditional Mediterranean way of life can represent a useful model.

Published:

2016

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Title:

Human microbiome versus food-borne pathogens: friend or foe

Authors:

Josephs-Spaulding, J.; Beeler, E.; Singh, O.V.

Abstract:

As food safety advances, there is a great need to maintain, distribute, and provide high-quality food to a much broader consumer base. There is also an ever-growing “arms race” between pathogens and humans as food manufacturers. The human microbiome is a collective organ of microbes that have found community niches while associating with their host and other microorganisms. Humans play an important role in modifying the environment of these organisms through their life choices, especially through individual diet. The composition of an individual’s diet influences the digestive system—an ecosystem with the greatest number and largest diversity of organisms currently known. Organisms living on and within food have the potential to be either friends or foes to the consumer. Maintenance of this system can have multiple benefits, but lack of maintenance can lead to a host of chronic and preventable diseases. Overall, this dynamic system is influenced by intense competition from food-borne pathogens, lifestyle, overall diet, and presiding host-associated microbiota. © 2016, Springer-Verlag Berlin Heidelberg.

Published:

2016

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Title:

Hypertriglyceridemia: A simple approach to identify insulin resistance and enhanced cardio-metabolic risk in patients with prediabetes

Authors:

Abbasi, Fahim; Kohli, Payal; Reaven, Gerald M.; Knowles, Joshua W.

Abstract:

Aims Prediabetes (PreDM) is a metabolically heterogeneous condition, differing in degree of insulin resistance and risk of type 2 diabetes mellitus and coronary heart disease (CHD). This study was initiated to evaluate the hypothesis that a fasting plasma triglyceride (TG) concentration ⩾1.7 mmol/L can aid in identifying the subset of individuals with PreDM who are most insulin resistant and at greatest risk to develop CHD as well as type 2 diabetes mellitus. Methods In this cross-sectional study, measurements were made of: (1) steady-state plasma glucose (SSPG) concentration during the insulin suppression test to ascertain degree of insulin resistance and (2) conventional CHD risk factors in 587 apparently healthy individuals with normal fasting plasma glucose (NFG, n = 370) or PreDM (n = 217). Results Subjects with PreDM were significantly (P \textless 0.001) more insulin resistant (higher SSPG concentrations) and had a more adverse CHD risk profile than those with NFG. A TG concentration ⩾1.7 mmol/L identified a subset of individuals with PreDM (38%) who had a higher mean SSPG concentration (11.3 ± 3.5 mmol/L vs. 9.3 ± 3.9 mmol/L, P \textless 0.001), were more likely to be insulin resistant (66% vs. 39%, P \textless 0.001), and had a more adverse CHD risk factor profile. Conclusions Measurement of fasting TG concentration in individuals with PreDM may provide a simple clinical approach to identify those who are insulin resistant, at enhanced risk of CHD, and more likely to develop type 2 diabetes mellitus.

Published:

2016

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Title:

Impact of dietary sodium restriction on heart failure outcomes

Authors:

Doukky, Rami; Avery, Elizabeth; Mangla, Ashvarya; Collado, Fareed M.; Ibrahim, Zeina; Poulin, Marie France; Richardson, De Juran; Powell, Lynda H.

Abstract:

Objectives: This study sought to evaluate the impact of sodium restriction on heart failure (HF) outcomes. Background: Although sodium restriction is advised for patients with HF, data on sodium restriction and HF outcomes are inconsistent. Methods: We analyzed data from the multihospital HF Adherence and Retention Trial, which enrolled 902 New York Heart Association functional class II/III HF patients and followed them up for a median of 36 months. Sodium intake was serially assessed by a food frequency questionnaire. Based on the mean daily sodium intake prior to the first event of death or HF hospitalization, patients were classified into sodium restricted (\textless2,500 mg/d) and unrestricted (≥2,500 mg/d) groups. Study groups were propensity score matched according to plausible baseline confounders. The primary outcome was a composite of death or HF hospitalization. The secondary outcomes were cardiac death and HF hospitalization. Results: Sodium intake data were available for 833 subjects (145 sodium restricted, 688 sodium unrestricted), of whom 260 were propensity matched into sodium restricted (n = 130) and sodium unrestricted (n = 130) groups. Sodium restriction was associated with significantly higher risk of death or HF hospitalization (42.3% vs. 26.2%; hazard ratio [HR]: 1.85; 95% confidence interval [CI]: 1.21 to 2.84; p = 0.004), derived from an increase in the rate of HF hospitalization (32.3% vs. 20.0%; HR: 1.82; 95% CI: 1.11 to 2.96; p = 0.015) and a nonsignificant increase in the rate of cardiac death (HR: 1.62; 95% CI: 0.70 to 3.73; p = 0.257) and all-cause mortality (p = 0.074). Exploratory subgroup analyses suggested that sodium restriction was associated with increased risk of death or HF hospitalization in patients not receiving angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (HR: 5.78; 95% CI: 1.93 to 17.27; p = 0.002). Conclusions: In symptomatic patients with chronic HF, sodium restriction may have a detrimental impact on outcome. A randomized clinical trial is needed to definitively address the role of sodium restriction in HF management. (A Self-management Intervention for Mild to Moderate Heart Failure [HART]; NCT00018005).

Published:

2016

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Title:

Impulsivity is associated with blood pressure and waist circumference among adolescents with bipolar disorder

Authors:

Naiberg, Melanie R.; Newton, Dwight F.; Collins, Jordan E.; Bowie, Christopher R.; Goldstein, Benjamin I.

Abstract:

OBJECTIVE: Cardiovascular risk factors (CVRFs) and impulsivity are common in bipolar disorder (BD), and CVRFs are also linked with impulsivity through a number of mechanisms, both behavioral and biological. This study examines the association between CVRFs and impulsivity in adolescents with BD. METHODS: Subjects were 34 adolescents with BD and 35 healthy control (HC) adolescents. CVRFs were based on International Diabetes Federation metabolic syndrome criteria (triglycerides, high-density lipoprotein cholesterol, waist circumference, blood pressure (BP) and glucose). Impulsivity was measured using the computerized Cambridge Gambling Task (CGT). Analyses controlled for age, IQ, lifetime attention deficit hyperactivity disorder, and current antipsychotic use. RESULTS: Adolescents with BD had higher diastolic BP (73.36 ± 9.57 mmHg vs. 67.91 ± 8.74 mmHg, U = 401.0, p = 0.03), higher triglycerides (1.13 ± 0.60 mmol/L vs. 0.78 ± 0.38 mmol/L, U = 373.5, p = 0.008), and were more likely to meet high-risk criteria for waist circumference (17.6% vs. 2.9%, p = 0.04) vs. HC. Within the BD group, CGT sub-scores were correlated with CVRFs. For example, overall proportion bet was positively correlated with systolic (r = 0.387, p = 0.026) and diastolic (ρ = 0.404, p = 0.020) BP. Quality of decision-making was negatively correlated with systolic BP (ρ = -0.401, p = 0.021) and waist circumference (ρ = -0.534, p = 0.003). Significant interactions were observed, such that BD diagnosis moderates the relationship between both waist circumference and BP with CGT sub-scores. CONCLUSION: BP and waist circumference are associated with impulsivity in BD adolescents, but not in HC adolescents. Future studies are warranted to determine temporality and to evaluate whether optimizing CVRFs improves impulsivity among BD adolescents.

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2016

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Influence of diet and supplements on iron status after gastric bypass surgery

Authors:

Mischler, R.A.; Armah, S.M.; Wright, B.N.; Mattar, S.G.; Rosen, A.D.; Gletsu-Miller, N.

Abstract:

Background Iron deficiency is common after Roux-en-Y gastric bypass (RYGB) surgery, but there is no consensus on the optimal diet quality and quantity for restoring and preserving iron status. Objectives The authors explored the impact of dietary and supplemental sources of iron and absorptive factors on iron status. Setting Academic, United States. Methods In a cross-sectional cohort of individuals who underwent RYGB, nutrient intakes from food and supplements were measured using 3-day food records. Blood biomarkers of iron status, including concentrations of ferritin, total iron binding capacity, serum transferrin receptor (sTfR), and the sTfR:ferritin ratio, were assessed by a reference laboratory; iron deficiency was defined as having at least 2 abnormal measures. Associations between iron status biomarkers and dietary predictors were determined using regression analysis. Results Of the 36 participants, 97% were female, the mean age was 45 years (95% confidence interval, 41-48 years), and body mass index was 32 (30-35) kg/m 2 . Iron deficiency was found in 42% of participants. Dietary intake of heme iron, found in meats, was favorably associated with 3 iron status biomarkers (ferritin, β =.366; sTfR:ferritin ratio, β = -.459; and total iron binding capacity, β = -18.26; all P<.05), independent of obesity-induced inflammation. Intake of Vitamin C from food contributed to iron status (ferritin, β =.010 and sTfR:ferritin ratio, β = -.011; P<.05). Use of supplementary non-heme iron, at doses recommended for prophylaxis (45 mg/d), was positively associated with serum ferritin (β =.964; P =.029). Conclusions For patients who have undergone RYGB, consuming high, but realistic amounts of heme iron in meat, Vitamin C from food, and adherence to recommended iron supplements can prevent iron deficiency. © 2016 American Society for Bariatric Surgery.

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2016

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Influence of diet on leukocyte telomere length, markers of inflammation and oxidative stress in individuals with varied glucose tolerance: A Chinese population study

Authors:

Zhou, M.; Zhu, L.; Cui, X.; Feng, L.; Zhao, X.; He, S.; Ping, F.; Li, W.; Li, Y.

Abstract:

Objectives: To explore influence of carbohydrates/fat proportions, dietary ingredients on telomere length shortening, oxidative stress and inflammation in a Chinese population with different glucose tolerance status. Methods: Five hundred and fifty-six Chinese subjects without diabetes history underwent a 75 g, 2 h Oral Glucose Tolerance Test (OGTT). Subjects with diabetes (n = 159), pre-diabetes (n = 197), and normal glucose tolerance (n = 200) were screened. Dietary intakes were evaluated using a semi-quantitative food frequency questionnaire (FFQ). Peripheral blood leukocyte telomere length (LTL) was assessed using a real-time PCR assay. Blood lipid profile, levels of the oxidative stress indicators superoxide dismutase (SOD), glutathione reductase (GR), 8-oxo-2′-deoxyguanosine (8-oxo-dG) and inflammation indicators tumor necrosis factor (TNF-α), interleukine-6 (IL-6) were measured. Levels of HbA1c, plasma glucose, insulin, and C peptide were also determined. Measurements were taken at 0 min, 30 min, 60 min, and 120 min after 75 g OGTT. Insulin sensitivity was evaluated by HOMA-IR. Basal insulin secretion index (HOMA-β), early phase disposition index (DI30) and total phase disposition index (DI120) indicate insulin levels at different phases of insulin secretion. Results: In patients with newly diagnosed diabetes, LTL adjusted by age was longer in HbA1c < 7 % group (log (LTL): 1.93 ± 0.25) than in HbA1 c ≥ 7 % group (log (LTL): 1.82 ± 0.29). LTL was not associated with daily energy intake, diet fat, carbohydrates and protein proportions. Multiple linear regression analysis indicated that legumes, nuts, fish and seaweeds were protective factors for LTL shortening, and sweetened carbonated beverage was a risk factor for LTL shortening (legumes: β = 0.105, p = 0.018; nuts: β = 0.110, p = 0.011; fish: β = 0.118, p = 0.007; seaweeds: β = 0.116, p = 0.009; sweetened carbonated beverage: β = -0.120, p = 0.004). Daily energy intake was positively associated with TNF-α, IL-6 (TNF-α: r= 0.125, p = 0.006;IL-6: r= 0.092, p = 0.04). Fat, carbohydrate proportions were positively associated with TNF-α (fat: r= 0.119, p = 0.008; carbohydrate: r= 0.094, p = 0.043). Seaweeds and dairy intake were negatively associated with 8-oxo-dG (seaweed: r = -0.496, p = 0.001;dairy: r = -0.246, p = 0.046), vegetables and fruits were positively associated with GR (vegetables: r = 0.101, p = 0.034;fruits: r = 0.125, p = 0.045). Cereal, meat were positively associated with TNF-α (cereal: r= 0.091, p = 0.048; meat: r = 0.405, p = 0.009). Conclusion: Diabetes patients with better plasma glucose (HbA1c < 7 %) had longer LTL, LTL could reflect plasma glucose status in diabetes patients. LTL were probably not influenced by diet carbohydrates/fat proportions but was associated with diet ingredients. Diet ingredients significantly impacted on markers of inflammation and oxidative stress, which probably had an effect on LTL. © 2016 Zhou et al.

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2016

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Insulin resistance: The linchpin between prediabetes and cardiovascular disease

Authors:

Salazar, Martin R.; Carbajal, Horacio A.; Espeche, Walter G.; Aizpurúa, Marcelo; Leiva Sisnieguez, Carlos E.; Leiva Sisnieguez, Betty C.; Stavile, Rodolfo N.; March, Carlos E.; Reaven, Gerald M.

Abstract:

The aim of this study was to test the hypothesis that cardiovascular disease occurs to the greatest extent in persons with prediabetes mellitus who are also insulin resistant. In 2003, 664 non-diabetic women (n = 457) and men (n = 207), aged 52 ± 16 and 53 ± 15 years, were surveyed during a programme for cardiovascular disease prevention. Fasting plasma glucose concentrations defined participants as having normal fasting plasma glucose (fasting plasma glucose \textless5.6 mmol/L) or prediabetes mellitus (fasting plasma glucose ⩾5.6 and \textless7.0 mmol/L). The tertile of prediabetes mellitus subjects with the highest fasting plasma insulin concentration was classified as insulin resistant. Baseline cardiovascular disease risk factors were accentuated in prediabetes mellitus versus normal fasting glucose, particularly in prediabetes mellitus/insulin resistant. In 2012, 86% of the sample were surveyed again, and the crude incidence for cardiovascular disease was higher in subjects with prediabetes mellitus versus normal fasting glucose (13.7 vs 6.0/100 persons/10 years; age- and sex-adjusted hazard ratio = 1.88, p = 0.052). In prediabetes mellitus, the crude incidences were 22.9 versus 9.6/100 persons/10 years in insulin resistant versus non-insulin resistant persons (age- and sex-adjusted hazard ratio = 2.36, p = 0.040). In conclusion, cardiovascular disease risk was accentuated in prediabetes mellitus/insulin resistant individuals, with a relative risk approximately twice as high compared to prediabetes mellitus/non-insulin resistant subjects.

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2016

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Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes

Authors:

Manowsky, Julia; Camargo, Rodolfo Gonzalez; Kipp, Anna P.; Henkel, Janin; Püschel, Gerhard P.

Abstract:

Overweight and obesity are associated with hyperinsulinemia, insulin resistance, and a low-grade inflammation. Although hyperinsulinemia is generally thought to result from an attempt of the β-cell to compensate for insulin resistance, there is evidence that hyperinsulinaemia itself may contribute to the development of insulin resistance and possibly the low-grade inflammation. To test this hypothesis, U937 macrophages were exposed to insulin. In these cells, insulin induced expression of the proinflammatory cytokines IL-1β, IL-8, CCL2, and OSM. The insulin-elicited induction of IL-1β was independent of the presence of endotoxin and most likely mediated by an insulin-dependent activation of NF-κB. Supernatants of the insulin-treated U937 macrophages rendered primary cultures of rat hepatocytes insulin resistant; they attenuated the insulin-dependent induction of glucokinase by 50%. The cytokines contained in the supernatants of insulin-treated U937 macrophages activated ERK1/2 and IKKβ, resulting in an inhibitory serine phosphorylation of the insulin receptor substrate. In addition, STAT3 was activated and SOCS3 induced, further contributing to the interruption of the insulin receptor signal chain in hepatocytes. These results indicate that hyperinsulinemia per se might contribute to the low-grade inflammation prevailing in overweight and obese patients and thereby promote the development of insulin resistance particularly in the liver, because the insulin concentration in the portal circulation is much higher than in all other tissues.

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2016

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Intake of different types of dairy and its prospective association with risk of type 2 diabetes: The Rotterdam Study

Authors:

Brouwer-Brolsma, E. M.; van Woudenbergh, G. J.; Oude Elferink, S. J. W. H.; Singh-Povel, C. M.; Hofman, A.; Dehghan, A.; Franco, O. H.; Feskens, E. J. M.

Abstract:

CONCLUSIONS: This prospective cohort study did not point towards an association between dairy consumption and T2DM. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

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2016

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Integrated metabolomic and transcriptome analyses reveal finishing forage affects metabolic pathways related to beef quality and animal welfare

Authors:

Carrillo, J.A.; He, Y.; Li, Y.; Liu, J.; Erdman, R.A.; Sonstegard, T.S.; Song, J.

Abstract:

Beef represents a major dietary component and source of protein in many countries. With an increasing demand for beef, the industry is currently undergoing changes towards naturally produced beef. However, the true differences between the feeding systems, especially the biochemical and nutritional aspects, are still unclear. Using transcriptome and metabolome profiles, we identified biological pathways related to the differences between grass- and grain-fed Angus steers. In the latissimus dorsi muscle, we have recognized 241 differentially expressed genes (FDR < 0.1). The metabolome examinations of muscle and blood revealed 163 and 179 altered compounds in each tissue (P

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2016

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Integrative analysis of metabolomic, proteomic and genomic data to reveal functional pathways and candidate genes for drip loss in pigs

Authors:

Welzenbach, J.; Neuhoff, C.; Heidt, H.; Cinar, M.U.; Looft, C.; Schellander, K.; Tholen, E.; Große-Brinkhaus, C.

Abstract:

The aim of this study was to integrate multi omics data to characterize underlying functional pathways and candidate genes for drip loss in pigs. The consideration of different omics levels allows elucidating the black box of phenotype expression. Metabolite and protein profiling was applied in Musculus longissimus dorsi samples of 97 Duroc × Pietrain pigs. In total, 126 and 35 annotated metabolites and proteins were quantified, respectively. In addition, all animals were genotyped with the porcine 60 k Illumina beadchip. An enrichment analysis resulted in 10 pathways, amongst others, sphingolipid metabolism and glycolysis/gluconeogenesis, with significant influence on drip loss. Drip loss and 22 metabolic components were analyzed as intermediate phenotypes within a genome-wide association study (GWAS). We detected significantly associated genetic markers and candidate genes for drip loss and for most of the metabolic components. On chromosome 18, a region with promising candidate genes was identified based on SNPs associated with drip loss, the protein “phosphoglycerate mutase 2” and the metabolite glycine. We hypothesize that association studies based on intermediate phenotypes are able to provide comprehensive insights in the genetic variation of genes directly involved in the metabolism of performance traits. In this way, the analyses contribute to identify reliable candidate genes. © 2016 by the authors; licensee MDPI, Basel, Switzerland.

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2016

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Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice

Authors:

Seimon, Radhika V.; Shi, Yan-Chuan; Slack, Katy; Lee, Kailun; Fernando, Hamish A.; Nguyen, Amy D.; Zhang, Lei; Lin, Shu; Enriquez, Ronaldo F.; Lau, Jackie; Herzog, Herbert; Sainsbury, Amanda

Abstract:

BACKGROUND: Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled. METHODS: Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD) provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID) provided cycles of 82% of control intake for 5-6 consecutive days, and ad libitum intake for 1-3 days. Weight loss efficiency during this phase was calculated as (total weight change) ÷ [(total energy intake of mice on CD or ID)-(total average energy intake of controls)]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding. RESULTS: Mice on the ID showed transient hyperphagia relative to controls during each 1-3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05). There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P

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2016

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Title:

Intermittent energy restriction and weight loss: A systematic review

Authors:

Davis, C. S.; Clarke, R. E.; Coulter, S. N.; Rounsefell, K. N.; Walker, R. E.; Rauch, C. E.; Huggins, C. E.; Ryan, L.

Abstract:

BACKGROUND/OBJECTIVES: Intermittent energy restriction (IER) is an eating pattern of regular daily periods of restricted energy intake followed by periods of unrestricted energy intake. This is gaining prominence as an alternative weight-loss strategy to daily energy restriction (DER). The aim of this systematic review was to determine the effectiveness of IER on weight loss in overweight and obese adults and compare this with DER.$\backslash$n$\backslash$nSUBJECTS/METHODS: A systematic literature search was conducted using the CINAHL, Embase, Medline, PsycINFO, Cochrane and Scopus databases. Eight studies that assigned overweight or obese adults to IER or to a DER 'control' were deemed eligible for inclusion.$\backslash$n$\backslash$nRESULTS: All studies reported significant weight loss for IER groups. Average weight loss was approximately 0.2-0.8 kg per week. IER resulted in comparable weight loss to DER when overall energy restriction remained similar between diets. The majority of studies that reported body composition outcomes have shown equal efficacy for fat mass, fat-free mass and waist circumference.$\backslash$n$\backslash$nCONCLUSIONS: Weight loss was achieved in overweight and obese adults following IER and this loss was comparable to a DER diet. IER may be an effective alternative strategy for health practitioners to promote weight loss for selected overweight and obese people.European Journal of Clinical Nutrition advance online publication, 25 November 2015; doi:10.1038/ejcn.2015.195.

Published:

2016

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Is There a Relationship between Vegetarianism and Seasonal Affective Disorder? A Pilot Study

Authors:

Meesters, Alie N. R.; Maukonen, Mirkka; Partonen, Timo; Männistö, Satu; Gordijn, Marijke C. M.; Meesters, Ybe

Abstract:

Background and Aim: Seasonal patterns of food intake are found in healthy individuals and particularly in patients with seasonal affective disorder (SAD). One nutritional choice is a vegetarian diet. Methods: In a Finnish population study, FINRISK 2012, information about diet and SAD was collected. In a Dutch outpatient clinic, SAD patients were asked if they were vegetarian. Results: The percentage of SAD patients among Finnish vegetarians was 4 times higher than in the normal population. The percentage of vegetarians among the SAD patients in a Dutch outpatient clinic was 3 times higher than in the normal population. In the Dutch population, the seasonal loss of energy, in particular, is related to vegetarianism. Conclusion: These findings suggest a possible link between vegetarianism and SAD.

Published:

2016

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Is breakfast the most important meal of the day?

Authors:

Betts, James A.; Chowdhury, Enhad A.; Gonzalez, Javier T.; Richardson, Judith D.; Tsintzas, Kostas; Thompson, Dylan

Abstract:

The Bath Breakfast Project is a series of randomised controlled trials exploring the effects of extended morning fasting on energy balance and health. These trials were categorically not designed to answer whether or not breakfast is the most important meal of the day. However, this review will philosophise about the meaning of that question and about what questions we should be asking to better understand the effects of breakfast, before summarising how individual components of energy balance and health respond to breakfast v. fasting in lean and obese adults. Current evidence does not support a clear effect of regularly consuming or skipping breakfast on body mass/composition, metabolic rate or diet-induced thermogenesis. Findings regarding energy intake are variable, although the balance of evidence indicates some degree of compensatory feeding later in the day such that overall energy intake is either unaffected or slightly lower when breakfast is omitted from the diet. However, even if net energy intake is reduced, extended morning fasting may not result in expected weight loss due to compensatory adjustments in physical activity thermogenesis. Specifically, we report that both lean and obese adults expended less energy during the morning when remaining in the fasted state than when consuming a prescribed breakfast. Further research is required to examine whether particular health markers may be responsive to breakfast-induced responses of individual components of energy balance irrespective of their net effect on energy balance and therefore body mass.

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2016

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Title:

Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome

Authors:

Lustig, Robert H.; Mulligan, Kathleen; Noworolski, Susan M.; Tai, Viva W.; Wen, Michael J.; Erkin-Cakmak, Ayca; Gugliucci, Alejandro; Schwarz, Jean Marc

Abstract:

OBJECTIVE Dietary fructose is implicated in metabolic syndrome, but intervention studies are confounded by positive caloric balance, changes in adiposity, or artifactually high amounts. This study determined whether isocaloric substitution of starch for sugar would improve metabolic parameters in Latino (n = 27) and African-American (n = 16) children with obesity and metabolic syndrome. METHODS Participants consumed a diet for 9 days to deliver comparable percentages of protein, fat, and carbohydrate as their self-reported diet; however, dietary sugar was reduced from 28% to 10% and substituted with starch. Participants recorded daily weights, with calories adjusted for weight maintenance. Participants underwent dual-energy X-ray absorptiometry and oral glucose tolerance testing on Days 0 and 10. Biochemical analyses were controlled for weight change by repeated measures ANCOVA. RESULTS Reductions in diastolic blood pressure (-5 mmHg; P = 0.002), lactate (-0.3 mmol/L; P \textless 0.001), triglyceride, and LDL-cholesterol (-46% and -0.3 mmol/L; P \textless 0.001) were noted. Glucose tolerance and hyperinsulinemia improved (P \textless 0.001). Weight reduced by 0.9 ± 0.2 kg (P \textless 0.001) and fat-free mass by 0.6 kg (P = 0.04). Post hoc sensitivity analysis demonstrates that results in the subcohort that did not lose weight (n = 10) were directionally consistent. CONCLUSIONS Isocaloric fructose restriction improved surrogate metabolic parameters in children with obesity and metabolic syndrome irrespective of weight change.

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2016

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Isolation of Mouse and Human Tumor-Associated Macrophages

Authors:

Cassetta, Luca; Noy, Roy; Swierczak, Agnieszka; Sugano, Gaël; Smith, Harriet; Wiechmann, Lisa; Pollard, Jeffrey W.

Abstract:

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2016

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Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity

Authors:

Greco, Tiffany; Glenn, Thomas C.; Hovda, David A.; Prins, Mayumi L.

Abstract:

Cerebral metabolism of ketones after traumatic brain injury (TBI) improves neuropathology and behavior in an age-dependent manner. Neuroprotection is attributed to improved cellular energetics, although other properties contribute to the beneficial effects. Oxidative stress is responsible for mitochondrial dysfunction after TBI. Ketones decrease oxidative stress, increase antioxidants and scavenge free radicals. It is hypothesized that ketogenic diet (KD) will decrease post-TBI oxidative stress and improve mitochondria. Postnatal day 35 (PND35) male rats were given sham or controlled cortical impact (CCI) injury and placed on standard (STD) or KD. Ipsilateral cortex homogenates and mitochondria were assayed for markers of oxidative stress, antioxidant expression and mitochondrial function. Oxidative stress was significantly increased at 6 and 24 h post-injury and attenuated by KD while inducing protein expression of antioxidants, NAD(P)H dehydrogenase quinone 1 (NQO1) and superoxide dismutase (SOD1/2). Complex I activity was inhibited in STD and KD groups at 6 h and normalized by 24 h. KD significantly improved Complex II-III activity that was reduced in STD at 6 h. Activity remained reduced at 24 h in STD and unchanged in KD animals. These results strongly suggest that ketones improve post-TBI cerebral metabolism by providing alternative substrates and through antioxidant properties, preventing oxidative stress-mediated mitochondrial dysfunction.

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2016

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Ketogenic diets: From cancer to mitochondrial diseases and beyond

Authors:

Branco, Ana F.; Ferreira, André; Simões, Rui F.; Magalhães-Novais, Sílvia; Zehowski, Cheryl; Cope, Elisabeth; Silva, Ana Marta; Pereira, Daniela; Sardão, Vilma A.; Cunha-Oliveira, Teresa

Abstract:

© 2016 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd. Background: The employment of dietary strategies such as ketogenic diets, which force cells to alter their energy source, has shown efficacy in the treatment of several diseases. Ketogenic diets are composed of high fat, moderate protein and low carbohydrates, which favour mitochondrial respiration rather than glycolysis for energy metabolism. Design: This review focuses on how oncological, neurological and mitochondrial disorders have been targeted by ketogenic diets, their metabolic effects, and the possible mechanisms of action on mitochondrial energy homeostasis. The beneficial and adverse effects of the ketogenic diets are also highlighted. Results and conclusions: Although the full mechanism by which ketogenic diets improve oncological and neurological conditions still remains to be elucidated, their clinical efficacy has attracted many new followers, and ketogenic diets can be a good option as a co-adjuvant therapy, depending on the situation and the extent of the disease.

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2016

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Title:

Ketones Step to the Plate: A Game Changer for Metabolic Remodeling in Heart Failure?

Authors:

Kolwicz, Stephen C.; Airhart, Sophia; Tian, Rong

Abstract:

It is increasingly recognized that metabolic remodeling is integral to heart failure (HF) development and progression.1,2 In particular, impairments in the ability of cardiac mitochondria to oxidize fatty acids have been noted, along with an increase in glycolysis that is uncoupled from glucose oxidation.3,4 This overall reduction in the myocardial oxidative capacity is purported to be the root cause of energy deficiency in the failing heart. Although past research has focused primarily on myocardial use of glucose and fatty acids, the heart is an omnivore and capable of oxidizing other substrates such as lactate, ketone bodies, and amino acids. The current understanding of the contribution of lactate, ketone bodies, and amino acids to cardiac metabolism is limited, particularly in the setting of HF. In this issue of Circulation , 2 independent studies provide new insights into the reliance of the failing heart on ketone bodies for energy supply. Proteomics analysis in mouse models of HF by Aubert et al5 and metabolomics analysis of end-stage human failing hearts by Bedi et al6 demonstrate strong and concordant evidence of increased ketone oxidation in the failing heart.$\backslash$n$\backslash$nArticles, see p 698 and 706 $\backslash$n$\backslash$nKetone bodies, that is, acetoacetate, β-hydroxybutyrate (βOHB), and acetone (in low abundance), are produced in the liver and used in peripheral tissues as an energy source when glucose is not readily available because of either a limited exogenous supply or impaired insulin signaling or when fatty acids are in surplus, which occurs in marked activation of lipolysis. On entering the cell, they rapidly form acetyl CoA via a series of reactions catalyzed by βOHB dehydrogenase (BDH1), succinyl-CoA:3-oxoacid-CoA transferase (SCOT), and mitochondrial acetyl-CoA acetyltransferase 1 (also known as thiolase), as shown in the Figure. All enzymes are present in the heart, and \ldots

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2016

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Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review

Authors:

Ravnskov, Uffe; Diamond, David M.; Hama, Rokura; Hamazaki, Tomohito; Hammarskjöld, Björn; Hynes, Niamh; Kendrick, Malcolm; Langsjoen, Peter H.; Malhotra, Aseem; Mascitelli, Luca; McCully, Kilmer S.; Ogushi, Yoichi; Okuyama, Harumi; Rosch, Paul J.; Schersten, Tore; Sultan, Sherif; Sundberg, Ralf

Abstract:

OBJECTIVE: It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue. SETTING, PARTICIPANTS AND OUTCOME MEASURES: We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population. RESULTS: We identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found. CONCLUSIONS: High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

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2016

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Lean-seafood intake decreases urinary markers of mitochondrial lipid and energy metabolism in healthy subjects: Metabolomics results from a randomized crossover intervention study

Authors:

Schmedes, Mette; Aadland, Eli Kristin; Sundekilde, Ulrik Kraemer; Jacques, Hélène; Lavigne, Charles; Graff, Ingvild Eide; Eng, Øyvin; Holthe, Asle; Mellgren, Gunnar; Young, Jette Feveile; Bertram, Hanne Christine; Liaset, Bjørn; Clausen, Morten Rahr

Abstract:

SCOPE: Proteins constitute an important part of the human diet, but understanding of the effects of different dietary protein sources on human metabolism is sparse. We aimed to elucidate diet-induced metabolic changes through untargeted urinary metabolomics after four weeks of intervention with lean-seafood or nonseafood diets. It is shown that lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects. METHODS: In a randomized controlled trial with crossover design, 20 healthy subjects consumed two balanced diets that varied in main protein sources for 4 weeks. Morning spot urine samples were collected before and after each intervention period. Untargeted metabolomics based on (1) H NMR spectroscopy and LC-MS analyses were applied to characterize the urinary metabolic response to the interventions. RESULTS: The lean-seafood diet period reduced the urinary level of l-carnitine, 2,6-dimethylheptanoylcarnitine, and N-methyl-2-pyridone-5-carboxamide, relative to the nonseafood period. The dietary analysis revealed that the higher urinary level of trimethylamine-N-oxide after the lean-seafood diet period and guanidinoacetate and 3-methylhistidine after the nonseafood diet period was related to the endogenous content of these compounds in the diets. CONCLUSIONS: Our data reveal that 4 weeks of lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects after the lean-seafood intake.

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2016

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Lecithin (Phosphatidylcholine): Healthy dietary supplement or dangerous toxin?

Authors:

Smith, R.E.; Rouchotas, P.; Fritz, H.

Abstract:

Phosphatidylcholine (PC) is an essential part of human cell membranes and an important dietary source of choline, an important biochemical. Its common name is lecithin. It can be made from phosphatidylethanolamine (PE) by methylation of the ethanolamine moiety in a reaction catalyzed by phosphatidylethanolamine N-methyltransferase. There is a decrease in phosphatidylethanolamine (PE) and ether-linked PC concentrations, as well as an increase in lysophosphatidylethanolamine during chronic stress. PC and choline are important for healthy brains, hearts, skeletal muscles, livers and metabolism. For example, Alzheimer’s disease patients have lower concentrations of three different PCs in their blood serum than healthy control subjects. Choline is important in maintaining cell structure and synthesizing the neurotransmitter acetylcholine. Choline supplementation during critical periods of neonatal development can have long-term beneficial effects on memory. A lack of sufficient dietary choline can cause signs of subclinical organ dysfunction (fatty liver or muscle damage). The need for choline is especially high during pregnancy and lactation. If there is insufficient choline stored in the body, the ability to methylate homocysteine to make methionine decreases, and plasma concentrations of homocysteine increase. This can increase the risk for cardiovascular disease, cancer, cognitive decline and bone fractures. On the other hand, over-consumption of red meat and other dietary sources of PC can lead to the production of trimethylamine oxide (TMAO) by gut bacteria. TMAO is both a kidney toxin and a biomarker for kidney diseases. So, PC and choline must be present in sufficient concentrations to support life, but not be too high to be toxic. Moreover, not everybody is equally susceptible to TMAO toxicity. People who have a kidney disease or are highly susceptible to cardiovascular disease may want to restrict their consumption of red meat and egg yolks, as well as avoid lecithin dietary supplements. Still, vegetarians who don’t eat egg yolks may want to take such supplements. On the other hand, another supplement called citicoline (cytidine diphosphocholine, CDP-choline) may be a better option since it is not metabolized into TMAO and may help brain function. Citicoline supplementation may improve memory, including verbal memory in patients with age related cognitive impairment, as well as improving cognitive function in elderly patients with vascular related mild cognitive impairment. © 2016 Bentham Science Publishers.

Published:

2016

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Title:

Length of Residence in the United States is Associated With a Higher Prevalence of Cardiometabolic Risk Factors in Immigrants: A Contemporary Analysis of the National Health Interview Survey

Authors:

Commodore‐Mensah Yvonne; Ukonu Nwakaego; Obisesan Olawunmi; Aboagye Jonathan Kumi; Agyemang Charles; Reilly Carolyn M.; Dunbar Sandra B.; Okosun Ike S.

Abstract:

BackgroundCardiometabolic risk (CMR) factors including hypertension, overweight/obesity, diabetes mellitus, and hyperlipidemia are high among United States ethnic minorities, and the immigrant population continues to burgeon.Methods and ResultsHypothesizing that acculturation (length of residence) would be associated with a higher prevalence of CMR factors, the authors analyzed data on 54, 984 US immigrants in the 2010–2014 National Health Interview Surveys. The main predictor was length of residence. The outcomes were hypertension, overweight/obesity, diabetes mellitus, and hyperlipidemia. The authors used multivariable logistic regression to examine the association between length of US residence and these CMR factors.The mean (SE) age of the patients was 43 (0.12) years and half were women. Participants residing in the United States for ≥10 years were more likely to have health insurance than those with <10 years of residence (70% versus 54%, P<0.001). After adjusting for region of birth, poverty income ratio, age, and sex, immigrants residing in the United States for ≥10 years were more likely to be overweight/obese (odds ratio [OR], 1.19; 95% CI, 1.10–1.29), diabetic (OR, 1.43; 95% CI, 1.17–1.73), and hypertensive (OR, 1.18; 95% CI, 1.05–1.32) than those residing in the United States for

Published:

2016

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Title:

Lipids Reprogram Metabolism to Become a Major Carbon Source for Histone Acetylation

Authors:

McDonnell, Eoin; Crown, Scott B.; Fox, Douglas B.; Kitir, Betül; Ilkayeva, Olga R.; Olsen, Christian A.; Grimsrud, Paul A.; Hirschey, Matthew D.

Abstract:

Cells integrate nutrient sensing and metabolism to coordinate proper cellular responses to a particular nutrient source. For example, glucose drives a gene expression program characterized by activating genes involved in its metabolism, in part by increasing glucose-derived histone acetylation. Here, we find that lipid-derived acetyl-CoA is a major source of carbon for histone acetylation. Using 13C-carbon tracing combined with acetyl-proteomics, we show that up to 90% of acetylation on certain histone lysines can be derived from fatty acid carbon, even in the presence of excess glucose. By repressing both glucose and glutamine metabolism, fatty acid oxidation reprograms cellular metabolism, leading to increased lipid-derived acetyl-CoA. Gene expression profiling of octanoate-treated hepatocytes shows a pattern of upregulated lipid metabolic genes, demonstrating a specific transcriptional response to lipid. These studies expand the landscape of nutrient sensing and uncover how lipids and metabolism are integrated by epigenetic events that control gene expression.

Published:

2016

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Title:

Long-Term Low Intake of Dietary Calcium and Fracture Risk in Older Adults With Plant-Based Diet: A Longitudinal Study From the China Health and Nutrition Survey

Authors:

Fang, Aiping; Li, Keji; Guo, Meihan; He, Jingjing; Li, He; Shen, Xin; Song, Jie

Abstract:

The aim of this longitudinal study was to investigate long-term associations between low dietary calcium intake and fracture risk in older adults with plant-based diet. Data of self-reported first fracture events of any type from 6210 Chinese men and women, aged 50 years or older and free from fracture at baseline, in a subcohort based on the China Health and Nutrition Survey (CHNS), were analyzed. Diet was repeatedly assessed by a combination of three consecutive 24-hour individual dietary recalls and a weighing and measuring of household food inventory in each round. The older men and women habitually ingested mean (SD) of 415 (147) mg/d and 373 (140) mg/d of calcium from plant-based diet, respectively. During a median follow-up of 7.0 years, 127 men (4.34%) and 232 women (7.06%) experienced first fracture events. The crude rates were 4.88, 2.55, and 6.83 per 1000 person-years at risk for men, and 6.72, 7.10, and 11.0 per 1000 person-years at risk for women in the lowest, third, and highest quintile of dietary calcium intake. In nonlinear regressions, an increased risk of fracture was associated with dietary calcium intake more than 778 mg/d (multivariable adjusted hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.00-4.41) or lower than 275 mg/d (1.74, 95% CI 1.00-3.01) for men and more than 651 mg/d for women (1.54, 95% CI 1.00-2.38). A nonsignificant trend of increase in fracture risk was found below 248 mg/d (1.00, 95% CI 0.67-1.50) in women using restricted cubic spline Cox regression. A relatively low fracture risk is observed in men with dietary calcium intakes of 275 to 780 mg/d and in women with intakes of 250 to 650 mg/d, and higher intakes may have no further benefit for fracture prevention. The patterns of dietary calcium with fracture risk are U-shaped in men and possibly in women. © 2016 American Society for Bone and Mineral Research.

Published:

2016

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Title:

Long-term benefit of liposuction in patients with lipoedema: a follow-up study after an average of 4 and 8 years

Authors:

Baumgartner, A.; Hueppe, M.; Schmeller, W.

Abstract:

Background Long-term results following liposuction in patients with lipoedema are available only for an average period of 4 years. Objective To find out whether the improvement of complaints persists for a further 4 years. Methods In a single-centre study, 85 patients with lipoedema had already been examined after 4 years. A mail questionnaire – often in combination with clinical controls – was repeated after another 4 years (8 years after liposuction). Results Compared with the results after 4 years, the improvement in spontaneous pain, sensitivity to pressure, oedema, bruising and restriction of movement persisted. The same held true for patient self-assessment of cosmetic appearance, quality of life and overall impairment. Eight years after surgery, the reduction in the amount of conservative treatment (combined decongestive therapy, compression garments) was similar to that observed 4 years earlier. Conclusion These results demonstrate for the first time the long-lasting positive effects of liposuction in patients with lipoedema.

Published:

2016

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