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Title:

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Authors:

Zewinger, Stephen; Kleber, Marcus E; Tragante, Vinicius; McCubrey, Raymond O; Schmidt, Amand F; Direk, Kenan; Laufs, Ulrich; Werner, Christian; Koenig, Wolfgang; Rothenbacher, Dietrich; Mons, Ute; Breitling, Lutz P; Brenner, Herrmann; Jennings, Richard T; Petrakis, Ioannis; Triem, Sarah; Klug, Mira; Filips, Alexandra; Blankenberg, Stefan; Waldeyer, Christoph; Sinning, Christoph; Schnabel, Renate B; Lackner, Karl J; Vlachopoulou, Efthymia; Nygård, Ottar; Svingen, Gard Frodahl Tveitevåg; Pedersen, Eva Ringdal; Tell, Grethe S; Sinisalo, Juha; Nieminen, Markku S; Laaksonen, Reijo; Trompet, Stella; Smit, Roelof A J; Sattar, Naveed; Jukema, J Wouter; Groesdonk, Heinrich V; Delgado, Graciela; Stojakovic, Tatjana; Pilbrow, Anna P; Cameron, Vicky A; Richards, A Mark; Doughty, Robert N; Gong, Yan; Cooper-DeHoff, Rhonda; Johnson, Julie; Scholz, Markus; Beutner, Frank; Thiery, Joachim; Smith, J Gustav; Vilmundarson, Ragnar O; McPherson, Ruth; Stewart, Alexandre F R; Cresci, Sharon; Lenzini, Petra A; Spertus, John A; Olivieri, Oliviero; Girelli, Domenico; Martinelli, Nicola I; Leiherer, Andreas; Saely, Christoph H; Drexel, Heinz; Mündlein, Axel; Braund, Peter S; Nelson, Christopher P; Samani, Nilesh J; Kofink, Daniel; Hoefer, Imo E; Pasterkamp, Gerard; Quyyumi, Arshed A; Ko, Yi-An; Hartiala, Jaana A; Allayee, Hooman; Tang, W H Wilson; Hazen, Stanley L; Eriksson, Niclas; Held, Claes; Hagström, Emil; Wallentin, Lars; Åkerblom, Axel; Siegbahn, Agneta; Karp, Igor; Labos, Christopher; Pilote, Louise; Engert, James C; Brophy, James M; Thanassoulis, George; Bogaty, Peter; Szczeklik, Wojciech; Kaczor, Marcin; Sanak, Marek; Virani, Salim S; Ballantyne, Christie M; Lee, Vei-Vei; Boerwinkle, Eric; Holmes, Michael V; Horne, Benjamin D; Hingorani, Aroon; Asselbergs, Folkert W; Patel, Riyaz S; Krämer, Bernhard K; Scharnagl, Hubert; Fliser, Danilo; März, Winfried; Speer, Thimoteus

Abstract:

Published:

2017-07

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Title:

The potential of organoids in urological cancer research

Authors:

Wang, Shangqian; Gao, Dong; Chen, Yu

Abstract:

Technical advances in the development of organoid systems enable cell lines, primary adult cells, or stem or progenitor cells to develop into diverse, multicellular entities, which can self-renew, self-organize, and differentiate. These 3D organoid cultures have proven to be of value in increasing our understanding of the biology of disease and offer the potential of regenerative and genetic therapies. The successful application of 3D organoids derived from adult tissue into urological cancer research can further our understanding of these diseases and could also provide preclinical cancer models to realize the precision medicine paradigm by therapeutic screening of individual patient samples ex vivo. Kidney organoids derived from induced pluripotent stem cells provide personalized biomarkers, which can be correlated with genetic and clinical information. Organoid models can also improve our comprehension of aspects of particular diseases; for example, in prostate cancer, 3D organoids can aid in the identification of tumour-initiating cells from an epithelial cell lineage. Furthermore, kidney organoid differentiation from human pluripotent stem cells enables gene editing to model disease in kidney tubular epithelial cells. State-of-the-art human organoid cultures have potential as tools in basic and clinical research in renal, bladder, and prostatic diseases.

Published:

2017-07

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Title:

Attitudes of Brazilian Medical Students Towards Psychiatric Patients and Mental Illness: A Quantitative Study Before and After Completing the Psychiatric Clerkship

Authors:

da Rocha Neto, Helio Gomes; Rosenheck, Robert A.; Stefanovics, Elina A.; Cavalcanti, Maria Tavares

Abstract:

Objective The authors evaluated whether a psychiatric clerkship reduces stigmatized attitudes towards people with mental illness among medical students. Methods A 56-item questionnaire was used to assess the attitudes of medical students towards patients with mental illness and their beliefs about its causes before and after their participation in their psychiatric clerkship at a major medical school in Rio de Janeiro. Exploratory factor analysis identified four factors, reflecting “social acceptance of people with mental illness,” “normalizing roles for people with mental illness in society,” “non-belief in supernatural causes for mental illness,” and “belief in bio-psychosocial causes for mental illness.” Analysis of variance was used to evaluate changes in these factors before and after the clerkship. Results One significant difference was identified with a higher score on the factor representing social acceptance after as compared to before the clerkship (p = 0.0074). No significant differences were observed on the other factors. Conclusion Participation in a psychiatric clerkship was associated with greater social acceptance but not with improvement on other attitudinal factors. This may reflect ceiling effects in responses before the clerkship concerning

Published:

2017-06

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Title:

Attitudes of Students at a US Medical School Toward Mental Illness and Its Causes

Authors:

Chiles, Catherine; Stefanovics, Elina; Rosenheck, Robert

Abstract:

Objectives Stigma among health care providers toward people with mental illness is a worldwide problem. This study at a large US university examined medical student attitudes toward mental illness and its causes, and whether student attitudes change as they progress in their education.

Published:

2017-06

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Title:

Effective Research Mentorship for Residents: Meeting the Needs of Early Career Physicians

Authors:

van Schalkwyk, Gerrit I.; Katz, Rachel B.; Resignato, Joseph; van Schalkwyk, Susan C.; Rohrbaugh, Robert M.

Abstract:

Objective Challenges in pursuing research during residency may contribute to the shortage of clinician-scientists. Although the importance of mentorship in facilitating academic research careers has been described, little is understood about early career research mentorship for residents. The aim of this study was to better understand the mentorship process in the context of psychiatry residency. Method Semi-structured interviews were conducted with experienced faculty mentors in a psychiatry department at a large academic medical center. Interviews were analyzed using inductive thematic analysis. Results from faculty interviews identified several key themes that were explored with an additional sample of resident mentees. Results Five themes emerged in our study: (1) being compatible: shared interests, methods, and working styles; (2) understanding level of development and research career goals in the context of residency training; (3) establishing a shared sense of expectations about time commitment, research skills, and autonomy; (4) residents’ identity as a researcher; and (5) the diverse needs of a resident mentee. There was considerable congruence between mentor and mentee responses. Conclusions There is an opportunity to improve research mentoring practice by providing guidance to both mentors and mentees that facilitates a more structured approach to the mentorship relationship.

Published:

2017-06

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Title:

Foods contributing to vitamin B6, folate, and vitamin B12 intakes and biomarkers status in European adolescents: The HELENA study

Authors:

Iglesia, Iris; Huybrechts, Inge; Breidenassel, Christina; Hällström, Lena; Moreno, Luis; Mouratidou, Theodora; Molnar, Denes; Stehle, Peter; González-Gross, Marcela; Santabárbara, Javier; Díaz, Ligia-Esperanza; Henauw, Stefaan; Gottrand, Frédéric; Kafatos, Anthony; Widhalm, Kurt; Manios, Yannis

Abstract:

Purpose: To examine the association between food groups consumption and vitamin B6, folate and B12 intakes and biomarkers in adolescents. Methods: In total 2189 individuals participating in the cross-sectional Healthy Lifestyle in Europe by Nutrition in Adolescence study met the eligibility criteria for analysis of dietary intakes (46 % males) and 632 for biomarker analysis (47 % males). Food intakes were assessed by two non-consecutive 24-h recalls. Biomarkers were measured by chromatography and immunoassay. Food groups which best discriminated participants in the extreme tertiles of the distribution of vitamins were identified by discriminant analyses. Food groups with standardised canonical coefficients higher or equal to 0.3 were selected as valid discriminators of vitamins intake and biomarkers extreme tertiles. Linear mixed model elucidated the association between food groups and vitamins intakes and biomarkers. Results: Vitamin B6 intakes and biomarkers were best discriminated by meat (males and females), margarine and mixed origin lipids only in males and breakfast cereals (females). Breakfast cereals (males), and fruits, margarine and mixed origin lipids, vegetables excluding potatoes, breakfast cereals, and soups/bouillon (females) determined the most folate intakes and biomarkers. Considering vitamin B12 intakes and biomarkers, meat, and white and butter milk (males and females), snacks (males), and dairy products (females) best discriminated individual in the extremes of the distribution. Fewer associations were obtained with mixed model for biomarkers than for vitamins intakes with food groups. Conclusions: Whereas B-vitamin intakes were associated with their food sources, biomarkers did with overall food consumption. Low-nutrient-density foods may compromise adolescents' vitamin status.

Published:

2017-06

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Title:

Glycated albumin: a potential biomarker in diabetes

Authors:

Freitas, Priscila Aparecida Correa; Ehlert, Lethicia Rozales; Camargo, Joíza Lins; Freitas, Priscila Aparecida Correa; Ehlert, Lethicia Rozales; Camargo, Joíza Lins

Abstract:

Published:

2017-06

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Title:

Inhibition of prostate cancer proliferation by Deferiprone

Authors:

Simões, Rui V.; Veeraperumal, Suresh; Serganova, Inna S.; Kruchevsky, Natalia; Varshavsky, Joseph; Blasberg, Ronald G.; Ackerstaff, Ellen; Koutcher, Jason A.

Abstract:

Cancer growth and proliferation rely on intracellular iron availability. We studied the effects of Deferiprone (DFP), a chelator of intracellular iron, on three prostate cancer cell lines: murine, metastatic TRAMP-C2; murine, non-metastatic Myc-CaP; and human, non-metastatic 22rv1. The effects of DFP were evaluated at different cellular levels: cell culture proliferation and migration; metabolism of live cells (time-course multi-nuclear magnetic resonance spectroscopy cell perfusion studies, with 1-13 C-glucose, and extracellular flux analysis); and expression (Western blot) and activity of mitochondrial aconitase, an iron-dependent enzyme. The 50% and 90% inhibitory concentrations (IC50 and IC90 , respectively) of DFP for the three cell lines after 48 h of incubation were within the ranges 51-67 μM and 81-186 μM, respectively. Exposure to 100 μM DFP led to: (i) significant inhibition of cell migration after different exposure times, ranging from 12 h (TRAMP-C2) to 48 h (22rv1), in agreement with the respective cell doubling times; (ii) significantly decreased glucose consumption and glucose-driven tricarboxylic acid cycle activity in metastatic TRAMP-C2 cells, during the first 10 h of exposure, and impaired cellular bioenergetics and membrane phospholipid turnover after 23 h of exposure, consistent with a cytostatic effect of DFP. At this time point, all cell lines studied showed: (iii) significant decreases in mitochondrial functional parameters associated with the oxygen consumption rate, and (iv) significantly lower mitochondrial aconitase expression and activity. Our results indicate the potential of DFP to inhibit prostate cancer proliferation at clinically relevant doses and plasma concentrations.

Published:

2017-06

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Title:

Lipoprotein(a)-Associated Molecules Are Prominent Components in Plasma and Valve Leaflets in Calcific Aortic Valve Stenosis

Authors:

Torzewski, Michael; Ravandi, Amir; Yeang, Calvin; Edel, Andrea; Bhindi, Rahul; Kath, Stefan; Twardowski, Laura; Schmid, Jens; Yang, Xiaohong; Franke, Ulrich F.W.; Witztum, Joseph L.; Tsimikas, Sotirios

Abstract:

Published:

2017-06

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Title:

Listening: An Underlying Competency in Psychiatry Education

Authors:

Brenner, Adam M.

Abstract:

Published:

2017-06

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Title:

Metabolomic profiling distinction of human nonalcoholic fatty liver disease progression from a common rat model

Authors:

Han, JianHua; Dzierlenga, Anika L.; Lu, Zhengqiang; Billheimer, Dean D.; Torabzadeh, Elmira; Lake, April D.; Li, Hui; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lehman‐McKeeman, Lois D.; Cherrington, Nathan J.

Abstract:

Objective: Characteristic pathological changes define the progression of steatosis to nonalcoholic steatohepatitis (NASH) and are correlated to metabolic pathways. A common rodent model of NASH is the methionine and choline deficient (MCD) diet. The objective of this study was to perform full metabolomic analyses on liver samples to determine which pathways are altered most pronouncedly in this condition in humans, and to compare these changes to rodent models of nonalcoholic fatty liver disease (NAFLD).Methods: A principal component analysis for all 91 metabolites measured indicated that metabolome perturbation is greater and less varied for humans than for rodents.Results: Metabolome changes in human and rat NAFLD were greatest for the amino acid and bile acid metabolite families (e.g., asparagine, citrulline, gamma-aminobutyric acid, lysine); although, in many cases, the trends were reversed when compared between species (cholic acid, betaine).Conclusions: Overall, these results indicate that metabolites of specific pathways may be useful biomarkers for NASH progression, although these markers may not correspond to rodent NASH models. The MCD model may be useful when studying certain end points of NASH; however, the metabolomics results indicate important differences between humans and rodents in the biochemical pathogenesis of the disease.

Published:

2017-06

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Title:

PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment

Authors:

Fan, Hui-Hui; Li, Ling; Zhang, Yu-Ming; Yang, Jie; Li, Mao-Cheng; Zeng, Fang-Yin; Deng, Fan

Abstract:

Tumor-associated macrophages are key regulators of the complex interplay between tumor and tumor microenvironment. M2 Macrophages, one type of tumor-associated macrophages, are involved in prostate cancer growth and progression. Protein kinase C zeta has been shown to suppress prostate cancer cell growth, invasion, and metastasis as a tumor suppressor; however, its role in chemotaxis and activation of tumor-associated macrophages remains unclear. Here, we investigated the role of protein kinase C zeta of prostate cancer cells in regulation of macrophage chemotaxis and M2 phenotype activation. Immunohistochemistry was performed to analyze the expression of protein kinase C zeta and the number of CD206+ M2 macrophages in human prostate tissue. Macrophage chemotaxis and polarization were examined using Transwell migration assays and a co-culture system. Quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were used to detect M2 markers, protein kinase C zeta, interleukin-4, and interleukin-10 expression. We found the expression of protein kinase C zeta increased in prostate cancer tissues, especially in the early stage, and was negatively associated with tumor grade and the number of CD206+ macrophages. Inhibition of protein kinase C zeta expression in prostate cancer cells promoted chemotaxis of peripheral macrophages and acquisition of M2 phenotypic features. These results were further supported by the finding that silencing of endogenous protein kinase C zeta promoted the expression of prostate cancer cell-derived interleukin-4 and interleukin-10. These results suggest that protein kinase C zeta plays an important role in reducing infiltration of tumor-associated macrophages and activation of a pro-tumor M2 phenotype, which may constitute an important mechanism by which protein kinase C zeta represses cancer progression.

Published:

2017-06

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Title:

Perceived Benefits and Factors that Influence the Ability to Establish and Maintain Patient Support Groups in Rare Diseases: A Scoping Review

Authors:

Delisle, Vanessa C.; Gumuchian, Stephanie T.; Rice, Danielle B.; Levis, Alexander W.; Kloda, Lorie A.; Körner, Annett; Thombs, Brett D.

Abstract:

Background: Support groups are an important resource for many people living with rare diseases. The perceived benefits of participating in support groups for people with rare diseases and factors that may influence the ability to successfully establish and maintain these groups are not well understood. Thus, the objective of this scoping review was to provide a mapping of the available evidence on the (1) benefits or perceived benefits of participating in rare disease support groups and (2) barriers and facilitators of establishing and maintaining these groups. Methods: CINAHL and PubMed were searched from January 2000 to August 2015, with no language restrictions. Publications that described the benefits or perceived benefits of participating in rare disease support groups or the barriers and facilitators of establishing and maintaining them were eligible for inclusion. Two investigators independently evaluated titles/abstracts and full-text publications for eligibility, and extracted data from each included publication. Results: Ten publications were included in the scoping review. There was no trial evidence on support group benefits. All ten publications reported on the perceived benefits of participating in rare disease support groups. Three reported on barriers and facilitators of establishing and maintaining them. Overall, seven different perceived benefits of participating in rare disease support groups were identified: (1) meeting and befriending other people with the same rare disease and similar experiences; (2) learning about the disease and related treatments; (3) giving and receiving emotional support; (4) having a place to speak openly about the disease and one's feelings; (5) learning coping skills; (6) feeling empowered and hopeful; and (7) advocating to improve healthcare for other rare disease patients. Several facilitators (e.g., meeting via teleconference) and barriers (e.g., getting patients and/or family members to lead the group) of establishing and maintaining these groups were identified. Conclusions: Rare disease support groups are an important source of emotional and practical support for many patients. There is no trial evidence on the benefits of these groups and limited evidence on the perceived benefits and barriers and facilitators to establishing and maintaining them.

Published:

2017-06

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Title:

Trans-fatty acid levels in erythrocytes in Europe

Authors:

Schacky, Clemens; Kiefl, Rosemarie; Passow, Adrian

Abstract:

Purpose: High, but not low levels of trans-fatty acids (TFA) in erythrocytes are associated with increased mortality. Current erythrocyte TFA levels in Europe are not known. Methods: TFA levels in samples submitted by physicians for erythrocyte omega-3 fatty acid analyses are reported, as analysed with a method (HS-Omega-3 Index) previously used in pertinent prospective epidemiologic studies. From Germany, 6754 samples were included from 2008 through 2015, and 496 samples from 10 other European countries. Results: In Germany, mean levels of C16:1n-7t, a marker for dairy and meat intake, decreased, as did mean levels of industrially produced (IP)-TFA, as did the percentage of individuals with IP-TFA > 1.04 %. Mean levels of IP-TFA in Austria and Switzerland were low before and after measures were taken to reduce them. Average levels of C16:1n-7t were low, and at levels associated with increased risk of death in previous studies. A limitation of our study is that samples were not obtained in a specific or representative manner. Conclusions: Levels of IP-TFA appear to be decreasing, as are those of ruminant-derived C16:1n-7t, a marker for dairy and meat intake. Few individuals had high levels of IP-TFA above a safe range, while many had low levels of C16:1n-7t. Our data argue against further action against TFA in the countries studied. More systematic biomarker-based studies are needed.

Published:

2017-06

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Title:

Workshop Report: Modulation of Antitumor Immune Responses by Dietary and Microbial Metabolites

Authors:

Kumar, Amit; Smith, Carolyne; Jobin, Christian; Trinchieri, Giorgio; Howcroft, T. Kevin; Seifried, Harold; Espey, Michael Graham; Flores, Roberto; Kim, Young S.; Daschner, Phillip J.

Abstract:

The human microbiota maintains an enormous and diverse capacity to produce a diet-dependent metabolome that impacts both host tissue and microbial community homeostasis. Recent discoveries support a growing appreciation that microbial metabolites derived from bioactive foods are also important regulators of host immune and metabolic functions. To gain a better understanding of the current evidence for the roles of dietary and microbial metabolites in tumor immunity, the Division of Cancer Biology and the Division of Cancer Prevention, National Cancer Institute, cosponsored a workshop on August 31 and September 1, 2016, in Bethesda, Maryland. Workshop participants examined several lines of converging science that link nutrition, microbiology, and tumor immunology and identified key concepts and research opportunities that will accelerate our understanding of these interactions. In addition, the participants identified some of the critical gaps and research challenges that could be addressed through interdisciplinary collaborations, including future opportunities for translating new information into novel cancer prevention and treatment strategies based on targeting host immune functions that are altered by metabolite sensing pathways.

Published:

2017-06

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Title:

A plant-based diet for overweight and obesity prevention and treatment

Authors:

Turner-McGrievy, Gabrielle; Mandes, Trisha; Crimarco, Anthony

Abstract:

The goal of this paper is to review the evidence related to the effect of plant-based dietary patterns on obesity and weight loss, including both observational and intervention trials. Literature from plant-based diets (PBDs) epidemiological and clinical trial research was used to inform this review. In addition, data on dietary quality, adherence, and acceptability were evaluated and are presented. Both clinical trials and observational research indicate an advantage to adoption of PBDs for preventing overweight and obesity and promoting weight loss. PBDs may also confer higher levels of diet quality than are observed with other therapeutic diet approaches, with similar levels of adherence and acceptability. Future studies should utilize health behavior theory to inform intervention development and delivery of PBDs studies and new technologies to bring interventions to scale for greater public health impact. Research examining PBDs and weight loss is also needed with more diverse populations, including older adults. Based on the available evidence, PBDs should be considered a viable option for the treatment and prevention of overweight and obesity.

Published:

2017-05

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Title:

Accumulation of the advanced glycation end product carboxymethyl lysine in breast cancer is positively associated with estrogen receptor expression and unfavorable prognosis in estrogen receptor-negative cases

Authors:

Nass, Norbert; Ignatov, Atanas; Andreas, Ludwig; Weißenborn, Christine; Kalinski, Thomas; Sel, Saadettin

Abstract:

Advanced glycation end products (AGEs) accumulate as a result of high concentrations of reactive aldehydes, oxidative stress, and insufficient degradation of glycated proteins. AGEs are therefore accepted biomarkers for aging, diabetes, and several degenerative diseases. Due to the Warburg effect and increased oxidative stress, cancer cells frequently accumulate significant amounts of AGEs. As the accumulation of AGEs may reflect the metabolic state and receptor signaling, we evaluated the potential prognostic and predictive value of this biomarker. We used immunohistochemistry to determine the AGE Nε-carboxymethyl lysine (CML) in 213 mammary carcinoma samples and Western blotting to detect AGEs in cell cultures. Whereas no significant correlation between hormone receptor status and CML was observed in cell lines, CML accumulation in tumors was positively correlated with the presence of estrogen receptor alpha, the postmenopausal state, and age. A negative correlation was found for grade III carcinomas and triple-negative cases. In a retrospective Kaplan-Meier survival analysis, there was a statistical trend that high CML accumulation correlated with a more favorable prognosis (relapse-free survival, RFS) under tamoxifen treatment (p = 0.1). In estrogen receptor-negative cases, the high CML content was significantly correlated with an unfavorable outcome (RFS) of chemotherapy (p = 0.046). CML is a therefore a potentially predictive marker for the treatment of breast cancer patients with tamoxifen or chemotherapy.

Published:

2017-05

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Title:

Association between consumption of soy and risk of cardiovascular disease: A meta-analysis of observational studies

Authors:

Yan, Zhaoli; Zhang, Xinyue; Li, Chunlin; Jiao, Shouchun; Dong, Wenyao

Abstract:

Background The relationships between dietary intake of soy foods and risk of cardiovascular disease are uncertain. The aims of this study were to evaluate and summarize the evidence on the association between consumption of soy and risk of cardiovascular disease (including stroke and coronary heart disease). Methods We systematically searched the MEDLINE and EMBASE databases from their inception up to 22 February 2016. We included only observational studies, and used random-effects models to calculate summary relative risks (SRRs) and 95% confidence intervals (CIs). Results A total of 10 prospective cohort and seven case-control studies met the inclusion criteria. There were a total of 17,269 cardiovascular disease events, including 6265 stroke events, 10,806 coronary heart disease events, and 198 other cardiovascular disease events. A significant negative association was shown between soy intake and risk of cardiovascular disease (SRR = 0.84 95% CI: 0.75-0.94; pheterogeneity

Published:

2017-05

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Title:

Correlation of insulin resistance and motor function in spinal and bulbar muscular atrophy

Authors:

Nakatsuji, Hideaki; Araki, Amane; Hashizume, Atsushi; Hijikata, Yasuhiro; Yamada, Shinichiro; Inagaki, Tomonori; Suzuki, Keisuke; Banno, Haruhiko; Suga, Noriaki; Okada, Yohei; Ohyama, Manabu; Nakagawa, Tohru; Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro; Okano, Hideyuki; Katsuno, Masahisa; Sobue, Gen

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Published:

2017-05

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Title:

Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies. [Review]

Authors:

Kosinski, Christophe; Jornayvaz, Francois R.

Abstract:

The treatment of obesity and cardiovascular diseases is one of the most difficult and important challenges nowadays. Weight loss is frequently offered as a therapy and is aimed at improving some of the components of the metabolic syndrome. Among various diets, ketogenic diets, which are very low in carbohydrates and usually high in fats and/or proteins, have gained in popularity. Results regarding the impact of such diets on cardiovascular risk factors are controversial, both in animals and humans, but some improvements notably in obesity and type 2 diabetes have been described. Unfortunately, these effects seem to be limited in time. Moreover, these diets are not totally safe and can be associated with some adverse events. Notably, in rodents, development of nonalcoholic fatty liver disease (NAFLD) and insulin resistance have been described. The aim of this review is to discuss the role of ketogenic diets on different cardiovascular risk factors in both animals and humans based on available evidence.

Published:

2017-05

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Title:

Lipoprotein(a) concentrations in rheumatoid arthritis on biologic therapy: Results from the CARdiovascular in rheuMAtology study project

Authors:

García-Gómez, Carmen; Martín-Martínez, Maria A.; Castañeda, Santos; Sanchez-Alonso, Fernando; Uriarte-Ecenarro, Miren; González-Juanatey, Carlos; Romera-Baures, Montserrat; Santos-Rey, José; Pinto-Tasende, José Antonio; Quesada-Masachs, Estefanía; Tornero-Molina, Jesús; Martínez-González, Olga; Cobo-Ibáñez, Tatiana; Chamizo-Carmona, Eugenio; Manrique-Arija, Sara; Fábregas-Canales, Dolores; Díaz-González, Federico; Llorca, Javier; González-Gay, Miguel A.; de Rábago, Eugenia Gonzalez; Blanco Morales, Elena Alonso; Fernández López, J. Carlos; Villar, Natividad Oreiro; Sandoval, Antonio Atanes; Blanco García, Francisco J.; De Miquel, Cayetano Alegre; González Fernández, María J.; Codina, Ramón Huguet; Yoldi, Beatriz; Ramentol, Mercedes; Ávila, Gabriela; Barril, Sara Marsal; Steiner, Martina; Muñoz, Santiago; Gamero, Fernando; Torón, José García; Moreno Gil, María P.; Mas, Antonio J.; Espiño, Pilar; Ros, Inmaculada; Ibañez, Mónica; Murillo, Claudia; Piqueras, José A.; Sanmartí, Raimon; Berman, Horacio; Cabrera, Sonia; Ruiz, Virginia; Patón, Oscar Fontseré; Gutiérrez, Benjamín Fernández; Abasolo, Lydia; Fábregas, María D.; Nolla, Joan M.; Arias, Miriam García; García Vadillo, Jesús A.; de Vicuña, Rosario García; Nebro, Antonio Fernández; Belmonte López, Maria Angeles; Ureña, Inmaculada; Irigoyen, María V.; Cagigal, Virginia Coret; González, Ruth López; Garrido, Daniel Pielfort; Alvarez, Juana Sampedro; García Aparicio, Ángel María; Gómez, Rebeca Belmonte; Bautista, Pastora Granados; Sanz, Azucena Hernández; Sánchez González, Carmen O.; Bachiller, Javier; Zea, Antonio; Manero, Francisco J.; Zorzo, Fernando Jimenez; Ubeda, Eugenio Giménez; Gracía, Jesús Marzo; Audera, Chesús Beltrán; Medrano, Marta; Pecondón, Ángela; Erausquin, Celia; Ojeda, Soledad; Quevedo, Juan Carlos; Francisco, Félix; Lozano, Carlos Rodríguez; Herráez, Jesús Babío; López Longo, Francisco J.; Gerona, Delia; Fernández, Carlos González; Carreño, Luis; Monteagudo, Indalecio; del Pino, Javier; Sánchez González, María Dolores; Corrales, Alfonso; Peiró, María Enriqueta; Senabre, José M.; Rosas, José C.; Rotés, Isabel; Moreno, Estefanía; Erra, Alba; Grado, Dolors; Calvo, Javier; Rueda, Amalia; Möller, Ingrid; Rodríguez, Isabel; Barbadillo, Carmen; Raya, Enrique; Morales, Pilar; Nieto, Ana; Jiménez, Inmaculada; magro, Cesar; Escribano, Ana Ruibal; Expósito, Sergio Ros; Nievas, Ginés Sánchez; Navarro, Enrique Júdez; Fernández, Manuela Sianes; García Morales, María Ángeles; Bastero, Isabel Labiano; Consuegra, Gloria García; Palmou, Natalia; Pardo, Silvia Martínez; Pujol, Manel; Alonso, Elena Riera; Salvador, Georgina; Alvarez, Beatriz González; Cantabrana, Alberto; Bustabad, Sagrario; Delgado, Esmeralda; Muñoz, Alejandro; Montero, Sergio Rodríguez; Jiménez, Luis María; Redondo, Javier Rivera; Hernández, Teresa González; González Polo, Francisco J.; Almagro, Raúl Menor; Moreno, José M.; Serret, Emilio Giner; Barroso, Carla Lannuzzelli; Méndez, Laura Cebrián; Navío, María Teresa; Carballido, Cristina Fernández; Pagán, Encarnación; del Castillo, Pablo Mesa; Naredo, Esperanza; Cruz, Ana; Turrión, Ana; Mateo, Isabel; Sánchez, Julio; Galindo, María; González, Javier García; Collantes, Eduardo; Ruíz, Desireé; Font, Pilar; Bonilla, Gema; Meseguer, Antonio López; Moreno, Manuel J.; Martínez, Ma José Moreno; Fernández, Ma Dolores Beteta; Linares, Luis F.; Morcillo, Mercedes; González Gómez, María L.; Aramburu, José M.; Rivera, Natalia A.; Berrizbeitia, Olaia Fernández; García Vivar, María Luz; Riera, Manel; León, Yolanda María; Maymó, Joan; Amirall, Miriam; Escolano, Silvia Iniesta; Serrano, Silvia Sánchez; Lis Bona, María Pilar; Fiter, Jordi; Melón, Julia Fernández; Espadaler, Luis; Maiz, Olga; Belzunegui, Joaquín; Bañegil, Inmaculada; Díaz, César; Valls, Ramón; Castellví, Iván; Bonet, María; Ruzafa, Estefania Moreno; Alen, Jaime Calvo; Sandoval, Trinidad Pérez; Evrard, Eva Revuelta; Godo, Javier R.; Espartero, Cruz Fernández; Navarro Blasco, Francisco J.; González, José Antonio; Miranda-Filloy, José A.

Abstract:

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2017-05

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Title:

Non-invasive monitoring of physiological markers in primates

Authors:

Behringer, Verena; Deschner, Tobias

Abstract:

The monitoring of endocrine markers that inform about an animal's physiological state has become an invaluable tool for studying the behavioral ecology of primates. While the collection of blood samples usually requires the animal to be caught and immobilized, non-invasively collected samples of saliva, urine, feces or hair can be obtained without any major disturbance of the subject of interest. Such samples enable repeated collection which is required for matching behavioral information over long time periods with detailed information on endocrine markers. We start our review by giving an overview of endocrine and immune markers that have been successfully monitored in relation to topics of interest in primate behavioral ecology. These topics include reproductive, nutritional and health status, changes during ontogeny, social behavior such as rank relationships, aggression and cooperation as well as welfare and conservation issues. We continue by explaining which hormones can be measured in which matrices, and potential problems with measurements. We then describe different methods of hormone measurements and address their advantages and disadvantages. We finally emphasize the importance of thorough validation procedures when measuring a specific hormone in a new species or matrix.

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2017-05

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Title:

Racial Differences in Circulating Levels of the Soluble Receptor for Advanced Glycation Endproducts in Middle-Aged and Older Adults

Authors:

Brinkley, Tina E.; Leng, Xiaoyan; Nicklas, Barbara J.; Kritchevsky, Stephen B.; Ding, Jingzhong; Kitzman, Dalane W.; Hundley, W. Gregory

Abstract:

Background Low levels of the soluble receptor for advanced glycation endproducts (sRAGE) have been implicated in a number of chronic diseases. Previous studies indicate that sRAGE levels are ~30% lower in Blacks compared to Whites. However, the reasons for these differences are unclear. Purpose We aimed to identify predictors of circulating sRAGE biomarkers among Black and White adults at high cardiac risk. Methods Serum levels of total sRAGE, endogenous secretory RAGE (esRAGE), carboxymethyl-lysine (CML, a major RAGE ligand), and their ratios were measured in 99 Blacks and 454 Whites. Results Blacks had a more adverse cardiovascular risk profile, as well as lower median levels of total sRAGE (972 vs. 1564 pg/ml) and esRAGE (474 vs. 710 pg/ml) compared to Whites (p<0.0001). In addition, the proportion of esRAGE was higher in Blacks (47% vs. 44%, p=0.02), as were the CML/total sRAGE (0.89 vs. 0.56 ng/pg) and CML/esRAGE (1.72 vs. 1.20 ng/pg) ratios (p<0.0001). Racial differences persisted after adjustment for key covariates including age, gender, tobacco use, comorbidities, BMI, blood pressure, glucose, insulin, triglycerides, C-reactive protein, and renal function (p

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2017-05

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Title:

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations

Authors:

Troisi, Jacopo; Pierri, Luca; Landolfi, Annamaria; Marciano, Francesca; Bisogno, Antonella; Belmonte, Federica; Palladino, Carmen; Nuzio, Salvatore Guercio; Campiglia, Pietro; Vajro, Pietro

Abstract:

To get insight into still elusive pathomechanisms of pediatric obesity and non-alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and food preferences (Kid-Med). Intestinal permeability (IP), small intestinal bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance were investigated in forty children (mean age 9.8 years) categorized as normal weight (NW) or obese (body mass index 95th percentile, respectively) ± ultrasonographic bright liver and hypertransaminasemia (NAFLD). SIBO was increased in all obese children (p = 0.0022), IP preferentially in those with NAFLD (p = 0.0002). The partial least-square discriminant analysis of urinary metabolome correctly allocated children based on their obesity, NAFLD, visceral fat, pathological IP and SIBO. Compared to NW, obese children had (1) higher levels of glucose/1-methylhistidine, the latter more markedly in NAFLD patients; and (2) lower levels of xylitol, phenyl acetic acid and hydroquinone, the latter especially in children without NAFLD. The metabolic pathways of BCAA and/or their metabolites correlated with excess of visceral fat centimeters (leucine/oxo-valerate), and more deranged IP and SIBO (valine metabolites). Urinary metabolome analysis contributes to define a metabolic fingerprint of pediatric obesity and related NAFLD, by identifying metabolic pathways/metabolites reflecting typical obesity dietary habits and GLA perturbations.

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2017-05

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Validation of blood vitamin A concentrations in cattle: comparison of a new cow-side test (iCheckTM FLUORO) with high-performance liquid chromatography (HPLC)

Authors:

Raila, Jens; Kawashima, Chiho; Sauerwein, Helga; Hulsmann, Nadine; Knorr, Christoph; Myamoto, Akio; Schweigert, Florian J.

Abstract:

CONCLUSIONS: With the new rapid cow-side test (iCheckTM FLUORO) retinol concentrations in cattle can be reliably assessed within a few minutes and directly in the barn using even whole blood without the necessity of prior centrifugation. The ease of the application of the new rapid cow-side test and its portability can improve the diagnostic of vitamin A status and will help to control vitamin A supplementation in specific vitamin A feeding regimes such as used to optimize health status in calves or meat marbling in Japanese Black cattle.

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2017-05

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A systematic review of yoga for major depressive disorder

Authors:

Cramer, Holger; Anheyer, Dennis; Lauche, Romy; Dobos, Gustav

Abstract:

Background The purpose of this review was to investigate the efficacy and safety of yoga interventions in treating patients with major depressive disorder. Methods MEDLINE, Scopus, and the Cochrane Library were screened through December 2016. Randomized controlled trials (RCTs) comparing yoga to inactive or active comparators in patients with major depressive disorder were eligible. Primary outcomes included remission rates and severity of depression. Anxiety and adverse events were secondary outcomes. Risk of bias was assessed using the Cochrane tool. Results Seven RCTs with 240 participants were included. Risk of bias was unclear for most RCTs. Compared to aerobic exercise, no short- or medium-term group differences in depression severity was found. Higher short-term depression severity was found for yoga compared to electro-convulsive therapy; remission rates did not differ between groups. No short-term group differences occurred when yoga was compared to antidepressant medication. Conflicting evidence was found when yoga was compared to attention-control interventions, or when yoga as an add-on to antidepressant medication was compared to medication alone. Only two RCTs assessed adverse events and reported that no treatment-related adverse events were reported. Limitations Few RCTs with low sample size. Conclusions This review found some evidence for positive effects beyond placebo and comparable effects compared to evidence-based interventions. However, methodological problems and the unclear risk-benefit ratio preclude definitive recommendations for or against yoga as an adjunct treatment for major depressive disorder. Larger and adequately powered RCTs using non-inferiority designs are needed.

Published:

2017-04

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Assessment of Lean Patients with Non-alcoholic Fatty Liver Disease in a Middle Income Country; Prevalence and Its Association with Metabolic Disorders: A Cross-sectional Study

Authors:

Naderian, Mohammadreza; Kolahdoozan, Shadi; Sharifi, Amir Sina; Garmaroudi, Gholamreza; Yaseri, Mehdi; Poustchi, Hossein; Sohrabpour, Amir Ali

Abstract:

BACKGROUND: Recent data has proven that the WHO (world health organization) cut-off for obesity is not applicable to the Asian population. This study aims to estimate the prevalence of lean NAFLD (non-alcoholic fatty liver disease) in the capital of Iran and extract probable predictors for this growing health issue in this population. METHODS: This is a population-based cross-sectional study on apparently healthy subjects over 18 years of age. The participants were interviewed for baseline demographic and clinical information. They were subsequently referred for physical examination and blood sampling. NAFLD was diagnosed using abdominal ultrasonography by a single expert radiologist. RESULTS: Of 927 eligible participants who entered the study, 314 were lean; BMI (body mass index) <25 kg/m2. The prevalence of NAFLD was 17.52% (95% Exact CI: 13.48%-22.18%). BMI, SBP (systolic blood pressure), DBP (diastolic blood pressure), total cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein) and triglyceride were significantly different in patients with NAFLD. In the final multiple analysis, higher levels of triglyceride, upper SBP and higher BMI even in the range of less than 25 kg/m2 were independent predictors of NAFLD in lean participants. In lean participants with more components of metabolic syndrome, the prevalence of NAFLD increased significantly (all P < 0.01). BMI cut-offs in men and women along with waist circumference cut-off in men could significantly predict the presence of NAFLD in lean patients. After comparing these values, McNemar test showed that BMI cut-offs are more robust than waist circumference cut-offs for predicting the presence of NAFLD in lean subjects (P

Published:

2017-04

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Title:

Differential Regulation of Macrophage Glucose Metabolism by Macrophage Colony-stimulating Factor and Granulocyte-Macrophage Colony-stimulating Factor: Implications for 18F FDG PET Imaging of Vessel Wall Inflammation

Authors:

Tavakoli, Sina; Short, John D.; Downs, Kevin; Nguyen, Huynh Nga; Lai, Yanlai; Zhang, Wei; Jerabek, Paul; Goins, Beth; Sadeghi, Mehran M.; Asmis, Reto

Abstract:

Despite the significant differences in the immunologic and metabolic profiles of macrophages stimulated with macrophage colony-stimulating factor (M-CSF) versus granulocyte-M-CSF, their phenotypes are not distinguishable with fluorine 18 fluorodeoxyglucose PET because of their similar level of glucose uptake.

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2017-04

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Title:

First Dutch guidelines on lipedema using the international classification of functioning, disability and health

Authors:

Halk, Anne B; Damstra, Robert J

Abstract:

Published:

2017-04

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Title:

Interaction between epigenetic and metabolism in aging stem cells

Authors:

Brunet, Anne; Rando, Thomas A

Abstract:

Aging is accompanied by a decline in tissue function, regeneration, and repair. A large part of this decline is caused by the deterioration of tissue stem cell function. Understanding the mechanisms that drive stem cell aging and how to counteract them is a critical step for enhancing tissue repair and maintenance during aging. Emerging evidence indicates that epigenetic modifiers and metabolism regulators interact to impact lifespan, suggesting that this mechanism may also affect stem cell function with age. This review focuses on the interaction between chromatin and metabolism in the regulation of tissue stem cells during aging. We also discuss how these mechanisms integrate environmental stimuli such as nutrient stress to regulate stem cell function. Finally, this review examines new perspectives for regeneration, rejuvenation, and treatment of age-related decline of stem cell function.

Published:

2017-04

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Title:

Lymphangiogenesis: fuel, smoke, or extinguisher of inflammation’s fire?

Authors:

Abouelkheir, Gabriella R; Upchurch, Bradley D; Rutkowski, Joseph M

Abstract:

Lymphangiogenesis is a recognized hallmark of inflammatory processes in tissues and organs as diverse as the skin, heart, bowel, and airways. In clinical and animal models wherein the signaling processes of lymphangiogenesis are manipulated, most studies demonstrate that an expanded lymphatic vasculature is necessary for the resolution of inflammation. The fundamental roles that lymphatics play in fluid clearance and immune cell trafficking from the periphery make these results seemingly obvious as a mechanism of alleviating locally inflamed environments: the lymphatics are simply providing a drain. Depending on the tissue site, lymphangiogenic mechanism, or induction timeframe, however, evidence shows that inflammation-associated lymphangiogenesis (IAL) may worsen the pathology. Recent studies have identified lymphatic endothelial cells themselves to be local regulators of immune cell activity and its consequential phenotypes – a more active role in inflammation regulation than previously thought. Indeed, results focusing on the immunocentric roles of peripheral lymphatic function have revealed that the basic drainage task of lymphatic vessels is a complex balance of locally processed and transported antigens as well as interstitial cytokine and immune cell signaling: an interplay that likely defines the function of IAL. This review will summarize the latest findings on how IAL impacts a series of disease states in various tissues in both preclinical models and clinical studies. This discussion will serve to highlight some emerging areas of lymphatic research in an attempt to answer the question relevant to an array of scientists and clinicians of whether IAL helps to fuel or extinguish inflammation.

Published:

2017-04

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Title:

Medical School Factors Associated with Higher Rates of Recruitment into Psychiatry

Authors:

Spollen, John J.; Beck Dallaghan, Gary L.; Briscoe, Gregory W.; Delanoche, Nancy D.; Hales, Deborah J.

Abstract:

Objective The medical school a student attends appears to be a factor in whether students eventually match into psychiatry. Knowledge of which factors are associated with medical schools with higher recruitment rates into psychiatry may assist in developing strategies to increase recruitment. Methods Psychiatry leaders in medical student education in the 25 highest and lowest recruiting US allopathic schools were surveyed concerning various factors that could be important such as curriculum, educational leadership, and presence of anti-psychiatry stigma. The relationship between the survey results of high recruiting schools versus those of low recruiting schools was evaluated using Mann-Whitney U tests. Results Factors significantly associated (p

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2017-04

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Title:

On the history of gout: paleopathological evidence from the Medici family of Florence

Authors:

Giuffra, Valentina; Minozzi, Simona; Vitiello, Angelica; Fornaciari, Antonio

Abstract:

OBJECTIVES: Throughout history, gout has been referred to as the "disease of the kings", and has been clearly associated with the lifestyle of the aristocratic social classes. According to the written sources, several members of the famous Medici family of Florence suffered from an arthritic disease that contemporary physicians called "gout". A paleopathological study carried out on the skeletal remains of some members of the family, exhumed from their tombs in the Church of San Lorenzo in Florence, offered a unique opportunity to directly investigate the evidence of the arthritic diseases affecting this elite group. METHODS: The skeletal remains of several members of the family were examined macroscopically and submitted to x-ray investigation. RESULTS: The results of the study allowed us to ascertain that the so-called "gout of the Medici" should be considered the clinical manifestation of three different joint conditions: diffuse idiopathic skeletal hyperostosis, rheumatoid arthritis and uratic gout. In particular, uric acid gout was diagnosed in the Grand Duke Ferdinand I (1549-1609). Recently, a new case of this disease was diagnosed in Anton Francesco Maria (1618-1659), a probable illegitimate member of the family. CONCLUSIONS: With this new case, uratic gout was observed in 2 out of 9 adult males, leading to suppose that the disease should have been a common health problem within the family. The aetiology of the disease has to be searched in environmental factors, since both historical and paleonutritional studies demonstrated that the diet of this aristocratic court was rich in meat and wine.

Published:

2017-04

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Title:

Polycystic ovary syndrome (PCOS)

Authors:

Balen, Adam H

Abstract:

Published:

2017-04

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Title:

Resistance Training-Induced Elevations in Muscular Strength in Trained Men Are Maintained After 2 Weeks of Detraining and Not Differentially Affected by Whey Protein Supplementation

Authors:

Hwang, Paul S.; Andre, Thomas L.; McKinley-Barnard, Sarah K.; Morales Marroquín, Flor E.; Gann, Joshua J.; Song, Joon J.; Willoughby, Darryn S.

Abstract:

Hwang, PS, Andre, TL, McKinley-Barnard, SK, Morales Marroquín, FE, Gann, JJ, Song, JJ, and Willoughby, DS. Resistance training-induced elevations in muscular strength in trained men are maintained after 2 weeks of detraining and not differentially affected by whey protein supplementation. J Strength Cond Res 31(4): 869-881, 2017-Resistance training (RT) with nutritional strategies incorporating whey protein intake postexercise can stimulate muscle protein synthesis and elicit hypertrophy. The early phases of training-induced anabolic responses can be attenuated with longer-term training. It is currently unknown if short-term detraining (DT) can restore these blunted anabolic responses during a subsequent retraining (ReT) period. Twenty resistance-trained men (age 20.95 ± 1.23 years; n = 20) were randomized into one of 2 groups (PRO or CHO; 25 g) in a double-blind manner. Participants followed a 4-day per week RT program (4-week RT; 2-week DT; 4-week ReT) while consuming their respective supplement only on workout days during RT and ReT, but every day during DT. At baseline, 4 weeks after RT (post-RT), 2 weeks after DT (post-2-week DT), and after 4 weeks of ReT after DT (post-ReT), leg press strength (LPS) was assessed and rectus femoris cross-sectional area and lean mass changes were assessed by ultrasonography and dual-energy x-ray absorptiometry, respectively. A factorial 2 × 4 (group by time) analyses of variance with repeated measures were used with a probability level at ≤0.05. LPS was elevated throughout the 10-week training study (p = 0.003) with no decrease in LPS after DT in both groups. Although not statistically significant, both groups retained lean mass after DT. A 2-week period of DT appeared to retain muscular strength in resistance-trained men. Therefore, a short-term period of DT can potentially retain lower-body strength in young resistance-trained men irrespective of supplementing with 25 g of whey protein postexercise.

Published:

2017-04

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Title:

The Effects of Ketogenic Dieting on Body Composition, Strength, Power, and Hormonal Profiles in Resistance Training Males:

Authors:

Wilson, Jacob M.; Lowery, Ryan P.; Roberts, Michael D.; Sharp, Matthew H.; Joy, Jordan M.; Shields, Kevin A.; Partl, Jeremy; Volek, Jeff S; D’Agostino, Dominic

Abstract:

Published:

2017-04

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Title:

"Media Addiction" in a 10-Year-Old Boy

Authors:

Brown, Scott; Scharf, Michael A.; Bustos, Cristina; Chavira, Denise; Stein, Martin T.

Abstract:

CASE: Bryan is a 10-year-old boy who is brought to his pediatrician by his parents with concerns about oppositional behaviors. Bryan's parents report that he has always been hyperactive and oppositional since a very young age. He has been previously diagnosed with attention-deficit hyperactivity disorder and has been treated with appropriate stimulant medications for several years; however, despite this, his parents feel increasingly unable to manage his difficult behaviors. He refuses to do chores or follow through with household routines. He refuses to go to bed at night. His family feels unable to take him to public places because he "climbs all over everything." At school, he acts up in class, is often disruptive, and requires close supervision by teachers. He was recently kicked off of the school bus. He has very few friends, and his parents state that other children do not enjoy to be around him.Bryan's parents also report that he is "obsessed" with electronics. He spends most his free time watching TV and movies and playing computer games. He has a television in his bedroom because otherwise he "monopolizes" the family television. The family also owns several portable electronic devices that he frequently uses. Bryan insists on watching TV during meals and even that the TV stays on in an adjacent room while showering. He gets up early each morning and turns on the television. He refuses to leave the house unless he can take a portable screen device with him. His parents admit to difficulty placing limits on this behavior because they feel it is the only way to keep his other behaviors under control. His mother explains "it is our only pacifier" and that attempts to place restrictions are met with explosive tantrums and have thus been short lived. These efforts have also been impeded due to the habits of his parents and older sibling, who also enjoy spending a significant amount of time watching television.

Published:

2017-03

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Title:

Citrus leaf extract reduces blood pressure and vascular damage in repeatedly heated palm oil diet-Induced hypertensive rats

Authors:

Siti, Hawa Nordin; Kamisah, Yusof; Nur Iliyani, Mohd Ishak; Mohamed, Suhaila; Jaarin, Kamsiah

Abstract:

Prolonged consumption of repeatedly heated vegetable oil increases blood pressure. This study aimed to determine the effects of Citrus leaf extract, (CLE) on blood pressure, blood pressure-regulating enzymes and mediators, as well as aortic histomorphometry in heated palm oil induced-hypertension. Male Sprague Dawley rats (n=56) were divided into seven groups; control group was given normal diet and the other groups were fed with palm oil-enriched diet (15% w/w) either fresh (FPO), five-time-heated (5HPO) or ten-time-heated (10HPO) with or without CLE (0.15%, w/w) supplementation. CLE supplementation reduced the heated oil-raising effect of blood pressure, plasma TBARS, thromboxane and angiotensin-1 converting enzyme in 5HPO but not in 10HPO group. CLE increased serum heme oxygenase-1 in both 5HPO and 10HPO groups. CLE supplementation reduced the increase in aortic intima-media thickness, intima-media area and circumferential wall tension in 5HPO group but not in 10HPO group. These findings suggested that CLE supplementation reduces the blood pressure-raising effects of 5HPO and vascular damage, possibly through its antioxidant effect by modulating vasoactive mediators and blood pressure-regulating enzymes.

Published:

2017-03

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Title:

Comparative efficacy and acceptability of electroconvulsive therapy versus repetitive transcranial magnetic stimulation for major depression: A systematic review and multiple-treatments meta-analysis

Authors:

Chen, Jian-jun; Zhao, Li-bo; Liu, Yi-yun; Fan, Song-hua; Xie, Peng

Abstract:

Backgrounds: The effects of electroconvulsive therapy (ECT) and bilateral, left prefrontal, and right prefrontal repetitive transcranial magnetic stimulation (rTMS) on major depressive disorder (MDD) have not been adequately addressed by previous studies. Here, a multiple-treatments meta-analysis, which incorporates evidence from direct and indirect comparisons from a network of trials, was performed to assess the efficacy and acceptability of these four treatment modalities on MDD. Method: The literature was searched for randomized controlled trials (RCTs) on ECT, bilateral rTMS, and unilateral rTMS for treating MDD up to May 2016. The main outcome measures were response and drop-out rates. Results: Data were obtained from 25 studies consisting of 1288 individuals with MDD. ECT was non-significantly more efficacious than B-rTMS, R-rTMS, and L-rTMS. Left prefrontal rTMS was non −significantly less efficacious than all other treatment modalities. In terms of acceptability, R-rTMS was non-significantly better tolerated than ECT, B-rTMS, and L-rTMS. ECT was the most efficacious treatment with the cumulative probabilities of being the most efficacious treatment being: ECT (65%), B-rTMS (25%), R-rTMS (8%), and L-rTMS (2%). R-rTMS was the best-tolerated treatment with the cumulative probabilities of being the best-tolerated treatment being: R-rTMS (52%), B-rTMS (17%), L-rTMS (16%), and ECT (14%). Coherence analysis detected no statistically significant incoherence in any comparisons of direct with indirect evidence for the response rate and drop-out rate. Conclusions: ECT was the most efficacious, but least tolerated, treatment, while R-rTMS was the best tolerated treatment for MDD. B-rTMS appears to have the most favorable balance between efficacy and acceptability.

Published:

2017-03

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Title:

Comparison of HbA1c detection in whole blood and dried blood spots using an automated ion-exchange HPLC system

Authors:

Maleska, Aleksandra; Hirtz, Christophe; Casteleyn, Elise; Villard, Orianne; Ducos, Jacques; Avignon, Antoine; Sultan, Ariane; Lehmann, Sylvain

Abstract:

AIM: Hemoglobin A1c (HbA1c) is a widely recognized analyte for diagnosing and monitoring diabetes. Dried blood spot (DBS) constitutes a useful alternative to blood collection by venipuncture. Analytical and clinical validation of DBS use is, however, necessary before implementation. Results/methodology: HbA1c levels from whole blood or DBS from a cohort patients with diabetes were compared. DBS specimens were stable at ambient temperature. HbA1c detection on DBS was accurate, robust, and the correlation and agreement with whole blood values was excellent. CONCLUSION: This study provides for the first time a complete method comparison and validation under the ISO15189 guideline using an automated HPLC system. This approach constitutes, therefore, a useful tool for diagnosing diabetes.

Published:

2017-03

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Title:

Effects of Two Different Dietary Patterns on Inflammatory Markers, Advanced Glycation End Products and Lipids in Subjects without Type 2 Diabetes: A Randomised Crossover Study

Authors:

Kim, Yoona; Keogh, Jennifer B.; Clifton, Peter M.

Abstract:

Epidemiological studies suggest that consumption of red and processed meat and refined grains are associated with type 2 diabetes and metabolic syndrome and increased inflammatory and fibrinolytic markers. We hypothesised that a diet high in red and processed meat and refined grains (HMD) would increase inflammatory markers and advanced glycation end products (AGEs) compared with a diet high in dairy, whole grains, nuts and legumes (HWD). We performed a randomised crossover study of two four-week interventions in 51 participants without type 2 diabetes (15 men and 36 women aged 35.1 +/- 15.6 years; body mass index: 27.7 +/- 6.9 kg/m2). No baseline measurements were performed. Plasma fluorescent AGEs, carboxymethyllysine, glucose, insulin, lipids, hs-CRP, interleukin 6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) were analysed after four weeks on each diet. IL-6, hs-CRP, AGEs and carboxymethyllysine were not different between diets but PAI-1 was higher after the HMD than after HWD ((median and interquartile range) 158, 81 vs. 121, 53 ng/mL p

Published:

2017-03

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Title:

Incidence of elevated lipoprotein (a) levels in a large cohort of patients with cardiovascular disease

Authors:

van Buuren, Frank; Horstkotte, Dieter; Knabbe, Cornelius; Hinse, Dennis; Mellwig, Klaus Peter

Abstract:

BACKGROUND: Recently it has been demonstrated that elevated lipoprotein (a) (LPA) levels are associated with an increased risk of cardiovascular disease across multiple ethnic groups. However, there is only scanty data about the incidence of elevated LPA levels in different patient cohorts. As a consequence, we aimed to examine whether patients with elevated LPA levels might be seen more often in a cardiovascular center in comparison to the general population. METHODS: We reviewed LPA concentrations of 52,898 consecutive patients who were admitted to our hospital between January 2004 and December 2014. We subdivided them into different groups according to their LPA levels. Data was compared to available information in medical literature. RESULTS: 26.4% of the patients had LPA levels >30 mg/dl which is in line with the data from literature. Mean level of LPA concentration in our study was twice as high in comparison to the general population (25.8% vs. 13.3%). 4.6% had LPA levels >98 mg/dl (general population 30 mg/dl is comparable to the general population but mean levels over all are twice as high and the proportion of patients with LPA levels of >98 mg/dl is extremely higher.

Published:

2017-03

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Title:

Lipoprotein(a) and its role in inflammation, atherosclerosis and malignancies

Authors:

Orsó, Evelyn; Schmitz, Gerd

Abstract:

Published:

2017-03

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Title:

Metabolomics for the masses: The future of metabolomics in a personalized world

Authors:

Trivedi, Drupad K.; Hollywood, Katherine A.; Goodacre, Royston

Abstract:

Current clinical practices focus on a small number of biochemical directly related to the pathophysiology with patients and thus only describe a very limited metabolome of a patient and fail to consider the interations of these small molecules. This lack of extended information may prevent clinicians from making the best possible therapeutic interventions in sufficient time to improve patient care. Various post-genomics ‘(’omic)’ approaches have been used for therapeutic interventions previously. Metabolomics now a well-established’omics approach, has been widely adopted as a novel approach for biomarker discovery and in tandem with genomics (especially SNPs and GWAS) has the potential for providing systemic understanding of the underlying causes of pathology. In this review, we discuss the relevance of metabolomics approaches in clinical sciences and its potential for biomarker discovery which may help guide clinical interventions. Although a powerful and potentially high throughput approach for biomarker discovery at the molecular level, true translation of metabolomics into clinics is an extremely slow process. Quicker adaptation of biomarkers discovered using metabolomics can be possible with novel portable and wearable technologies aided by clever data mining, as well as deep learning and artificial intelligence; we shall also discuss this with an eye to the future of precision medicine where metabolomics can be delivered to the masses.

Published:

2017-03

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Title:

Methylation analysis in fatty-acid-related genes reveals their plasticity associated with conjugated linoleic acid and calcium supplementation in adult mice

Authors:

Chaplin, Alice; Palou, Andreu; Serra, Francisca

Abstract:

PURPOSE: DNA methylation is one of the most extensively studied mechanisms within epigenetics, and it is suggested that diet-induced changes in methylation status could be involved in energy metabolism regulation. Conjugated linoleic acid (CLA) and calcium supplementation counteract body weight gain, particularly under a high-fat (HF) diet, in adult mice. The aim was to determine whether the modulation of DNA methylation pattern in target genes and tissues could be an underlying mechanism of action. METHODS: Mice (C57BL/6J) were divided into five groups according to diet and treatment: normal fat as the control group (12 % kJ content as fat), HF group (43 % kJ content as fat), HF + CLA (6 mg CLA/day), HF + calcium (12 g/kg of calcium) and HF with both compounds. Gene expression and methylation degree of CpG sites in promoter sequences of genes involved in fatty acid metabolism, including adiponectin (Adipoq), stearoyl-CoA desaturase (Scd1) and fatty acid synthase (Fasn), were determined by bisulphite sequencing in liver and epididymal white adipose tissue. RESULTS: Results showed that the methylation profile of promoters was significantly altered by dietary supplementation in a gene- and tissue-specific manner, whereas only slight changes were observed in the HF group. Furthermore, changes in specific CpG sites were also associated with an overall healthier metabolic profile, in particular for calcium-receiving groups. CONCLUSIONS: Both CLA and calcium were able to modify the methylation pattern of genes involved in energy balance in adulthood, which opens a novel area for increasing efficiency in body weight management strategies.

Published:

2017-03

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Title:

A Test in Context: Lipoprotein(a)

Authors:

Tsimikas, Sotirios

Abstract:

Published:

2017-02

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Title:

Effects of selenium supplementation on the oxidative state of acute heat stress-exposed quails

Authors:

Del Vesco, A. P.; Gasparino, E.; Zancanela, V.; Grieser, D. O.; Stanquevis, C. E.; Pozza, P. C.; Oliveira Neto, A. R.

Abstract:

This study aimed to evaluate the effect of heat stress (HS) and selenium supplementation on markers of stress, meat quality and gene expression. For this, meat quails of 42 days of age were fed a diet that either met [0.33 mg/kg, nutritional demand for selenium (SS)] or did not meet [0.11 mg/kg, selenium deficient (SD)] the nutritional demands for selenium during the 7 days of evaluation. In addition, the animals were kept at either a thermal comfort temperature (25 degreeC) or exposed to HS (38 degreeC for 24 h). Glutathione synthetase (GSS), glutathione reductase (GSR) and uncoupling protein (UCP) gene expression were influenced by the interaction between temperature and diet. Animals subjected to HS and fed the SS diet exhibited the highest GSS and GSR gene expression. In terms of UCP gene expression, the lowest values were observed in HS animals on the SD diet. Glutathione peroxidase 7 (GPX7) gene expression, body temperature (BT) and creatine kinase (CK) activity were influenced by both selenium supplementation and HS. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) activity and creatinine content all were influenced by the diet/environment interaction. The highest AST activity, ALT activity and creatinine levels were observed in animals that were both on the SD diet and exposed to HS. HS animals also exhibited an increased heterophil/lymphocyte ratio and lower triiodothyronine (T3) hormone levels than birds that remained at the comfortable temperature. Animals subjected to HS and fed with selenium supplemented diet showed better results regarding gene expression and, thus, better results for the activities of enzymes used as stress markers, which could be due to the higher antioxidant capacity provided by the action of the studied genes. Copyright Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Published:

2017-02

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Title:

Factors shaping the composition of the cutaneous microbiota

Authors:

Szabó, K.; Erdei, L.; Bolla, B. Sz; Tax, G.; Bíró, T.; Kemény, L.

Abstract:

From birth, we are constantly exposed to bacteria, fungi and viruses, some of which are capable of transiently or permanently inhabiting our different body parts as our microbiota. The majority of our microbial interactions occur during and after birth, and several different factors, including age, sex, genetic constitution, environmental conditions and lifestyle, have been suggested to shape the composition of this microbial community. Propionibacterium acnes is one of the most dominant lipophilic microbes of the postadolescent, sebum-rich human skin regions. Currently, the role of this bacterium in the pathogenesis of the most common inflammatory skin disease, acne vulgaris, is a topic of intense scientific debate. Recent results suggest that Westernization strongly increases the dominance of the Propionibacterium genus in human skin compared with natural populations living more traditional lifestyles. According to the disappearing microbiota hypothesis proposed by Martin Blaser, such alterations in the composition of our microbiota are the possible consequences of socioeconomic and lifestyle changes occurring after the industrial revolution. Evanescence of species that are important elements of the human ecosystem might lead to the overgrowth and subsequent dominance of others because of the lack of ecological competition. Such changes can disturb the fine-tuned balance of the human body and, accordingly, our microbes developed through a long co-evolutionary process. These processes might lead to the transformation of a seemingly harmless species into an opportunistic pathogen through bacterial dysbiosis. This might have happened in the case of P. acnes in acne pathogenesis.

Published:

2017-02

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Title:

Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study

Authors:

van den Berg, Eline H.; van Tienhoven-Wind, Lynnda J. N.; Amini, Marzyeh; Schreuder, Tim C. M. A.; Faber, Klaas Nico; Blokzijl, Hans; Dullaart, Robin P. F.

Abstract:

OBJECTIVE: Overt hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a number of health issues, including atherosclerosis development and biochemical markers of increased cardiovascular risk. However, the association of thyroid hormones with NAFLD in euthyroid subjects has not been unequivocally established. We therefore determined associations of thyroid hormone parameters with NAFLD among euthyroid subjects. METHODS: The study was conducted in the Lifelines Cohort Study, a population-based cohort study of participants living in the North of the Netherlands. Only euthyroid subjects (thyroid-stimulating hormone (TSH) 0.5-4.0mU/L, free thyroxine (FT4) 11-19.5pmol/L and free triiodothyronine (FT3) 4.4-6.7pmol/L) older than 18years were included. Exclusion criteria were participants with excessive alcohol use, known hepatitis or cirrhosis, liver functions ≥ three times the upper limit, current cancer, non-white ancestry, previous or current use of thyroid medication and current use of lipid or glucose lowering medication. A priori defined liver biochemistry, thyroid function parameters and metabolic syndrome (MetS) were studied. NAFLD was defined by using the validated Fatty Liver Index (FLI); FLI≥60 was categorized as NAFLD. A P<0.01 was considered significant. RESULTS: FLI≥60 was found in 4274 (21.1%) of 20,289 individuals (62.1% male, median age 46years) with increased prevalence of MetS (P<0.0001). In age- and sex-adjusted analysis FLI≥60 was independently associated with a higher FT3 (OR 1.34, 95% CI 1.29-1.39, per SD increment, P<0.0001) and a lower FT4 (OR 0.73, 95% CI 0.70-0.75, P<0.0001) but not by TSH. The strongest association was found for the FT3/FT4 ratio (OR 1.44, 95% CI 1.39-1.49, P<0.0001). These associations remained similar after additional adjustment for the presence of MetS. In subjects with enlarged waist circumference, TSH and FT4 were lower while FT3 was higher, resulting in an increased FT3/FT4 ratio (P

Published:

2017-02

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Title:

Increasing Scholarly Activity Productivity During Residency: A Systematic Review

Authors:

Stevenson, Michelle D.; Smigielski, Elizabeth M.; Naifeh, Monique M.; Abramson, Erika L.; Todd, Christopher; Li, Su-Ting T.

Abstract:

Purpose Although resident participation in scholarly activity is mandated by the Accreditation Council for Graduate Medical Education, programmatic factors associated with success are not defined. This systematic review’s objective was to determine which interventions are effective in increasing resident scholarly activity productivity (RSAP), as measured by participation in scholarly activity, presentations, or publications.

Published:

2017-02

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