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1. Insulin-like peptide 3 (INSL3) as an indicator of leydig cell insufficiency (LCI) in Middle-aged and older men with hypogonadism: reference range and threshold

Author

Ravinder Anand-Ivell, Kee Heng, Leen Antonio, Gyorgy Bartfai, Felipe F. Casanueva, Mario Maggi, Terence W. O’Neill, Margus Punab, Giulia Rastrelli, Jolanta Slowikowska-Hilczer, Jos Tournoy, Dirk Vanderschueren, Frederick CW. Wu, Ilpo T. Huhtaniemi, and Richard Ivell

Subjects
INSL3, hypogonadism, leydig cell, HPG axis, Medicine (General), R5-920, Physiology, QP1-981
Abstract

Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of biological and technical variance, and establish a reference range for adult men. It is constitutively secreted with little within-individual variation and reflects testicular capacity to produce testosterone. The main INSL3 assays available indicate good concordance with low technical variance; there is no effect of ethnicity. INSL3 declines with age from 35 years at about 15% per decade. Like low calculated free testosterone, and to a lesser extent low total testosterone, reduced INSL3 is significantly associated with increasing age-related morbidity, including lower overall sexual function, reflecting LCI. Consequently, low INSL3 (≤0.4 ng/ml; ca. 35 years) reference range (serum) for INSL3 in the eugonadal population of 0.4 − 2.3 ng/ml, with low INSL3 prospectively identifying individuals at risk of increased future morbidity.

Published
2024
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2. Does testosterone influence the association between sleep and frailty in men: results from the European Male Aging Study

Author

Seema D. Sharma, Michael J. Cook, Leen Antonio, Evelien Gielen, Gyorgy Bartfai, Felipe F. Casanueva, Ilpo T. Huhtaniemi, Mario Maggi, Margus Punab, Giulia Rastrelli, Jolanta Slowikowska-Hilczer, Jos Tournoy, Dirk Vanderschueren, Frederick C. Wu, and Terence W. O’Neill

Subjects
Sleep, Frailty, Ageing, Testosterone, EMAS study, Geriatrics, RC952-954.6
Abstract

Abstract Background Previous studies have suggested an association between sleep disturbance and frailty. The mechanism is unknown, although it has been suggested that hormonal factors may play a role. Methods The aim was to determine the association between sleep duration, sleep quality and frailty, and to determine whether testosterone influenced this association. Males aged 40–79 years were recruited from eight European centres to the European Male Aging Study (EMAS). Subjects completed an interviewer-assisted questionnaire including questions regarding sleep quality and duration. Sleep quality was scored 0–20 and categorised as 0–4, 5–9, 10–14, and 15–20, with higher scores indicating poorer quality. A 39-component frailty index (FI) was constructed. Total testosterone levels were measured. The association between sleep duration, sleep quality and the FI was assessed using negative binomial regression, with adjustment for putative confounders including testosterone level. Results Two thousand three hundred ninety-three participants contributed data to the analysis. The mean age was 63.3 years and mean sleep duration was 7.01 h. The mean frailty index was 0.15. Mean testosterone levels declined with decreasing sleep quality. After adjustment, compared to those with a sleep score of 0–4, the FI was 57% (95% CI 38%, 78%) higher among those with a sleep score of 15–20. After adjustment compared to those with normal sleep duration (6–9 h), those with a short (

Published
2023
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3. Sarcopenia‐defining parameters, but not sarcopenia, are associated with cognitive domains in middle‐aged and older European men

Author

Nadjia Amini, Jolan Dupont, Laurence Lapauw, Laura Vercauteren, Leen Antonio, Terence W. O'Neill, Dirk Vanderschueren, Neil Pendleton, Giulia Rastrelli, Mario Maggi, Felipe F. Casanueva, Jolanta Słowikowska‐Hilczer, Margus Punab, Ilpo T. Huhtaniemi, Frederick C.W. Wu, Sabine Verschueren, Jos Tournoy, and Evelien Gielen

Subjects
Sarcopenia, Cognition, Older adults, Muscle strength, Physical performance, Muscle mass, Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695
Abstract

Abstract Background Previous research suggests that sarcopenia is associated with lower cognitive functioning. Evidence on the longitudinal relationship between cognition and sarcopenia, according to the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2), is scarce. This study aimed to investigate both cross‐sectional and longitudinal associations between sarcopenia and its defining parameters (muscle strength, muscle mass and physical performance) and cognitive performance in middle‐aged and older men. Methods This was a secondary analysis of data from the European Male Ageing Study (EMAS), a multicentre cohort study of men aged 40–79 years, recruited from population registers in eight European centres. Cognitive functioning was assessed by using a battery of three neuropsychological tests, measuring fluid intelligence: Rey–Osterrieth Complex Figure (ROCF‐Copy and ROCF‐Recall), Camden Topographical Recognition Memory (CTRM) and Digit Symbol Substitution Test (DSST). Sarcopenia‐defining parameters appendicular lean mass (aLM), gait speed (GS), chair stand test (CST) and handgrip strength (HGS) were measured. Sarcopenia was diagnosed according to the criteria of the EWGSOP2. All measurements were performed at baseline and after a follow‐up of 4.3 years. Cross‐sectional associations between cognition, sarcopenia‐defining parameters and prevalent sarcopenia (EWGSOP2) were analysed. Longitudinally, the predictive value of baseline cognition on decline in sarcopenia‐defining parameters, onset of new sarcopenia and vice versa was examined. Linear and logistic regression were used and adjusted for putative confounders. Results In the whole cohort (n = 3233), ROCF‐Copy (β = 0.016; P

Published
2023
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4. Natural history and comorbidities of generalised and partial lipodystrophy syndromes in Spain

Author

Antía Fernández-Pombo, Sofía Sánchez-Iglesias, Ana I. Castro-Pais, Maria José Ginzo-Villamayor, Silvia Cobelo-Gómez, Teresa Prado-Moraña, Everardo Josué Díaz-López, Felipe F. Casanueva, Lourdes Loidi, and David Araújo-Vilar

Subjects
generalised lipodystrophy, partial lipodystrophy, body composition, diabetes mellitus, hypertriglyceridaemia, atherosclerotic cardiovascular disease, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

The rarity of lipodystrophies implies that they are not well-known, leading to delays in diagnosis/misdiagnosis. The aim of this study was to assess the natural course and comorbidities of generalised and partial lipodystrophy in Spain to contribute to their understanding. Thus, a total of 140 patients were evaluated (77.1% with partial lipodystrophy and 22.9% with generalised lipodystrophy). Clinical data were collected in a longitudinal setting with a median follow-up of 4.7 (0.5-17.6) years. Anthropometry and body composition studies were carried out and analytical parameters were also recorded. The estimated prevalence of all lipodystrophies in Spain, excluding Köbberling syndrome, was 2.78 cases/million. The onset of phenotype occurred during childhood in generalised lipodystrophy and during adolescence-adulthood in partial lipodystrophy, with the delay in diagnosis being considerable for both cohorts. There are specific clinical findings that should be highlighted as useful features to take into account when making the differential diagnosis of these disorders. Patients with generalised lipodystrophy were found to develop their first metabolic abnormalities sooner and a different lipid profile has also been observed. Mean time to death was 83.8 ± 2.5 years, being shorter among patients with generalised lipodystrophy. These results provide an initial point of comparison for ongoing prospective studies such as the ECLip Registry study.

Published
2023
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5. DNA methylome in visceral adipose tissue can discriminate patients with and without colorectal cancer

Author

Andrea G Izquierdo, Hatim Boughanem, Angel Diaz-Lagares, Isabel Arranz-Salas, Manel Esteller, Francisco J Tinahones, Felipe F Casanueva, Manuel Macias-Gonzalez, and Ana B Crujeiras

Subjects
dna methylation, adipose tissue, cancer, obesity, microarray, Genetics, QH426-470
Abstract

Adipose tissue dysfunction, particularly the visceral (VAT) compartment, has been proposed to play a relevant role in colorectal cancer (CRC) development and progression. Epigenetic mechanisms could be involved in this association. The current study aimed to evaluate if specific epigenetic marks in VAT are associated with colorectal cancer (CRC) to identify epigenetic hallmarks of adipose tissue-related CRC. Epigenome-wide DNA methylation was evaluated in VAT from 25 healthy participants and 29 CRC patients, using the Infinium HumanMethylation450K BeadChip. The epigenome-wide methylation analysis identified 170,184 sites able to perfectly separate the CRC and healthy samples. The differentially methylated CpG sites (DMCpGs) showed a global trend for increased methylated levels in CRC with respect to healthy group. Most of the genes encoded by the DMCpGs belonged to metabolic pathways and cell cycle, insulin resistance, and adipocytokine signalling, as well as tumoural transformation processes. In gene-specific analyses, involved genes biologically relevant for the development of CRC include PTPRN2, MAD1L1, TNXB, DIP2C, INPP5A, HDCA4, PRDM16, RPTOR, ATP11A, TBCD, PABPC3, and IER2. The methylation level of some of them showed a discriminatory capacity for detecting CRC higher than 90%, showing IER2 to have the highest capacity. This study reveals that a specific methylation pattern of VAT is associated with CRC. Some of the epigenetic marks identified could provide useful tools for the prediction and personalized treatment of CRC connected to excess adiposity.

Published
2022
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6. Inflammatory markers are associated with quality of life, physical activity, and gait speed but not sarcopenia in aged men (40–79 years)

Author

Jolan Dupont, Leen Antonio, Lenore Dedeyne, Terence W. O'Neill, Dirk Vanderschueren, Giulia Rastrelli, Mario Maggi, György Bártfai, Felipe F. Casanueva, Aleksander Giwercman, Jolanta Słowikowska‐Hilczer, Margus Punab, Ilpo T. Huhtaniemi, Frederick C.W. Wu, Jos Tournoy, Katrien Koppo, and Evelien Gielen

Subjects
Inflammation, Sarcopenia, Muscle strength, Older adult, Ageing, Inflammaging, Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695
Abstract

Abstract Background Age‐related chronic low‐grade inflammation (inflammaging) is one of the proposed mechanisms behind sarcopenia. However, findings regarding inflammatory markers in sarcopenic older adults are conflicting. This study aimed to determine the association between inflammatory markers, prevalent as well as incident sarcopenia, sarcopenia‐defining parameters, quality of life (QoL), and physical activity in middle‐aged and older men. Methods Men aged 40–79 years (mean 59.66 ± 11.00y) were recruited from population registers in eight European centres for participation in the European Male Aging study (EMAS). Subjects were assessed at baseline (2003–2005) and again after a median follow‐up of 4.29 years. In 2577 participants, associations between baseline inflammatory markers [high‐sensitive C‐reactive protein (hs‐CRP), white blood cell count (WBC), albumin] and baseline physical activity (PASE) and QoL (SF‐36) were analysed. In the Leuven and Manchester cohort (n = 447), data were available on muscle mass (whole‐body dual X‐ray absorptiometry) and strength. In this subgroup, cross‐sectional associations between baseline inflammatory markers and sarcopenia‐defining parameters (handgrip strength, chair stand test, appendicular lean mass, and gait speed) and prevalent sarcopenia were examined. In a further subgroup (n = 277), associations with knee extensor strength were explored. Longitudinally, predictive value of baseline inflammation on functional decline, physical activity, QoL, and incident sarcopenia was examined. Subgroup analyses were performed in subgroups with chronic inflammation and stratified by age. Linear and logistic regressions were used, adjusted for age, body mass index, centre, and smoking. Results At baseline, hs‐CRP and WBC were negatively associated with PASE score (hs‐CRP: β = −7.920, P

Published
2021
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7. The Leydig cell biomarker INSL3 as a predictor of age-related morbidity: Findings from the EMAS cohort

Author

Richard Ivell, Kee Heng, Katie Severn, Leen Antonio, Gyorgy Bartfai, Felipe F. Casanueva, Ilpo T. Huhtaniemi, Aleksander Giwercman, Mario Maggi, Daryl B. O’Connor, Terence W. O’Neill, Margus Punab, Giulia Rastrelli, Jolanta Slowikowska-Hilczer, Jos Tournoy, Dirk Vanderschueren, Frederick C. W. Wu, and Ravinder Anand-Ivell

Subjects
sexual function, hypertension, hypogonadism, cardiovascular disease, frailty, bone mineral density, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

BackgroundInsulin-like peptide 3 (INSL3) is a constitutive hormone secreted in men by the mature Leydig cells of the testes. It is an accurate biomarker for Leydig cell functional capacity, reflecting their total cell number and differentiation status.ObjectivesTo determine the ability of INSL3 to predict hypogonadism and age-related morbidity using the EMAS cohort of older community-dwelling men.Materials & methodsCirculating INSL3 was assessed in the EMAS cohort and its cross-sectional and longitudinal relationships to hypogonadism, here defined by testosterone (T)

Published
2022
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8. Fibroblast growth factor 21 levels and liver inflammatory biomarkers in obese subjects after weight loss

Author

Irene Cantero, Itziar Abete, Vanesa Bullon-Vela, Ana B. Crujeiras, Felipe F. Casanueva, Angeles M. Zulet, and J. Alfredo Martinez

Subjects
ck-18, non-alcoholic fatty liver disease, m30-fragment, obesity, metabolic syndrome, inflammation, Medicine
Abstract

Introduction Previous studies have hypothesized fibroblast growth factor 21 (FGF-21) as a potential biomarker of the inflammation associated with liver diseases, which is also receiving considerable attention for its potential application concerning the management of obesity and co-morbidities. This study aimed to analyze the response of FGF-21 after a weight loss intervention and the relationships with other putative inflammatory liver biomarkers. Material and methods Sixty-six obese participants from the RESMENA study were evaluated at baseline and following a 6-month energy restriction treatment. Anthropometric, body composition by DXA, routine laboratory measurements, which included transaminases and -glutamyl transferase (GGT) were analyzed by standardized methods. Moreover, FGF-21, M30 fragment (M30) and plasminogen activator inhibitor-1 (PAI-I) were analyzed as recognized liver inflammatory related biomarkers with specific ELISA kits. Results Most measurements related to hepatic damage, inflammation and adiposity status improved at the end of the 6-month nutritional intervention. In addition, ΔFGF-21 shifts showed statistical relationships with changes in ΔM30, ΔGGT and ΔPAI. The reduction of M30 showed significant associations with changes in transaminases. Furthermore, PAI-I changes were associated with ΔM30 and ΔGGT regardless of weight loss. A linear regression model was set up to assess the influence of ΔPAI-I and ΔM30 on the variability of ΔFGF-21 (23.8%) adjusted by weight loss. Conclusions These results demonstrated interactions of some liver inflammatory mediators, specifically M30 and PAI-I with FGF-21. Thus, more investigation about FGF-21 is required given that this protein could be a biomarker of the obesity-inflammation-liver process.

Published
2021
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9. GLP-1 Increases Circulating Leptin Levels in Truncal Vagotomized Rats

Author

Tiago Morais, Sofia S. Pereira, Sara Andrade, Diogo Neves, Marta Guimarães, Mário Nora, Marcos C. Carreira, Felipe F. Casanueva, and Mariana P. Monteiro

Subjects
leptin, GLP-1, vagotomy, rat, adipose tissue, Biology (General), QH301-705.5
Abstract

GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body energy homeostasis and in mediating GLP-1 effects. For this, rats submitted to truncal vagotomy and sham-operated controls underwent a comprehensive evaluation, including eating behavior, body weight, percentage of white (WAT) and brown adipose tissue (BAT), resting energy expenditure (REE) and acute response to GLP-1. Truncal vagotomized rats had significantly lower food intake, body weight, body weight gain, WAT and BAT, with a higher BAT/WAT ratio, but no significant difference in REE when compared to controls. Vagotomized rats also had significantly higher fasting ghrelin and lower glucose and insulin levels. After GLP-1 administration, vagotomized rats depicted a blunted anorexigenic response and higher plasma leptin levels, as compared to controls. However, in vitro stimulation of VAT explants with GLP-1 resulted in no significant changes in leptin secretion. In conclusion, the vagus nerve influences whole-body energy homeostasis by modifying food intake, body weight and body composition and by mediating the GLP-1 anorectic response. The higher leptin levels in response to acute GLP-1 administration observed after truncal vagotomy suggest the existence of a putative GLP-1-leptin axis that relies on the integrity of gut–brain vagal pathway.

Published
2023
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10. DNA methylation screening after roux-en Y gastric bypass reveals the epigenetic signature stems from genes related to the surgery per se

Author

C. F. Nicoletti, M. A. S. Pinhel, A. Diaz-Lagares, F. F. Casanueva, A. Jácome, V. C. Pinhanelli, B. A. P. de Oliveira, A. B. Crujeiras, and C. B. Nonino

Subjects
Obesity, Bariatric surgery, Epigenetics, DNA methylation, Pathway, Weight loss, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background/objectives Obesity has been associated with gene methylation regulation. Recent studies have shown that epigenetic signature plays a role in metabolic homeostasis after Roux-en Y gastric bypass (RYGB). To conduct a genome-wide epigenetic analysis in peripheral blood to investigate whether epigenetic changes following RYGB stem from weight loss or the surgical procedure per se. Subjects/methods By means of the Infinium Human Methylation 450 BeadChip array, global methylation was analyzed in blood of 24 severely obese women before and 6 months after RYGB and in 24 normal-weight women (controls). Results In blood cells, nine DMCpG sites showed low methylation levels before surgery, methylation levels increased after RYGB and neared the levels measured in the controls. Additionally, 44 CpG sites associated with the Wnt and p53 signaling pathways were always differently methylated in the severely obese patients as compared to the controls and were not influenced by RYGB. Finally, 1638 CpG sites related to inflammation, angiogenesis, and apoptosis presented distinct methylation in the post-surgery patients as compared to the controls. Conclusion Bariatric surgery per se acts on CpGs related to inflammation, angiogenesis, and endothelin-signaling. However, the gene cluster associated with obesity remains unchanged, suggesting that weight loss 6 months after RYGB surgery cannot promote this effect. Graphical abstract

Published
2019
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11. ZNF577 Methylation Levels in Leukocytes From Women With Breast Cancer Is Modulated by Adiposity, Menopausal State, and the Mediterranean Diet

Author

Paula M. Lorenzo, Andrea G. Izquierdo, Angel Diaz-Lagares, Marcos C. Carreira, Manuel Macias-Gonzalez, Juan Sandoval, Juan Cueva, Rafael Lopez-Lopez, Felipe F. Casanueva, and Ana B. Crujeiras

Subjects
epigenetics, obesity, cancer, nutrition, blood cells, biomarkers, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

The methylation levels of ZNF577 in breast tumors has been previously identified as a possible epigenetic mark of breast cancer associated with obesity. The aim of the current study was to investigate differences in methylation levels of ZNF577 depending on obesity, menopausal state and dietary pattern in blood leukocytes, a non-invasive sample. The methylation levels of ZNF577 of two CpG sites (CpGs) located in promoter and island previously identified as differentially methylated according to adiposity and menopausal state by 450 k array (cg10635122, cg03562414) were evaluated by pyrosequencing in DNA from the blood leukocytes of breast cancer patients [n = 90; n = 64 (71.1%) overweight/obesity and n = 26 (28.9%) normal-weight] and paired tumor tissue biopsies (n = 8 breast cancer patients with obesity; n = 3/5 premenopausal/postmenopausal women). Differences in methylation levels were evaluated at each CpGs individually and at the mean of the two evaluated CpGs. Adherence to the Mediterranean diet was evaluated using the MEDAS-validated questionnaire, and the consumption of food groups of interest was also evaluated using the recommended intakes of the Sociedad Española de Nutricion Comunitaria. The methylation levels of ZNF577 were correlated between paired leukocytes and breast tumor biopsies (r = 0.62; p = 0.001). Moreover, higher methylation was found in leukocytes from patients with obesity (p = 0.002) and postmenopausal patients (p = 0.022) than patients with normal-weight or premenopausal, respectively. After adjusting for the body mass index and age, higher levels of ZNF577 methylation were also found in women with greater adherence to the Mediterranean diet (p = 0.017) or specific foods. Relevantly, the methylation levels of ZNF577 showed a good ability for fish consumption detection [area under the ROC curve (AUC) = 0.72; p = 0.016]. In conclusion, the association between methylation of ZNF577 and adiposity, menopausal state, and adherence to the Mediterranean diet can be detected in the blood leukocytes. The results guarantee the need of performing further studies in longer longitudinal cohorts in order to elucidate the role of ZNF577 methylation in the association between breast cancer, adiposity and dietary patterns.

Published
2020
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12. Inflammatory myopathy in the context of an unusual overlapping laminopathy

Author

Cristina Guillín-Amarelle, Sofía Sánchez-Iglesias, Antonio Mera, Elena Pintos, Ana Castro-Pais, Leticia Rodríguez-Cañete, Julio Pardo, Felipe F. Casanueva, and David Araújo-Vilar

Subjects
Medicine, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Summary Laminopathies are genetic disorders associated with alterations in nuclear envelope proteins, known as lamins. The LMNA gene encodes lamins A and C, and LMNA mutations have been linked to diseases involving fat (type 2 familial partial lipodystrophy [FPLD2]), muscle (type 2 Emery–Dreifuss muscular dystrophy [EDMD2], type 1B limb-girdle muscular dystrophy [LGMD1B], and dilated cardiomyopathy), nerves (type 2B1 Charcot–Marie–Tooth disease), and premature aging syndromes. Moreover, overlapping syndromes have been reported. This study aimed to determine the genetic basis of an overlapping syndrome in a patient with heart disease, myopathy, and features of lipodystrophy, combined with severe metabolic syndrome. We evaluated a 54-year-old woman with rheumatoid arthritis, chronic hypercortisolism (endogenous and exogenous), and a history of cured adrenal Cushing syndrome. The patient presented with a complex disorder, including metabolic syndrome associated with mild partial lipodystrophy (Köbberling-like); mild hypertrophic cardiomyopathy, with Wolff–Parkinson– White syndrome and atrial fibrillation; and limb-girdle inflammatory myopathy. Mutational analysis of the LMNA gene showed a heterozygous c.1634G>A (p.R545H) variant in exon 10 of LMNA. This variant has previously been independently associated with FPLD2, EDMD2, LGMD1B, and heart disease. We describe a new, LMNA-associated, complex overlapping syndrome in which fat, muscle, and cardiac disturbances are related to a p.R545H variant.

Published
2018
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13. Resting metabolic rate of obese patients under very low calorie ketogenic diet

Author

Diego Gomez-Arbelaez, Ana B. Crujeiras, Ana I. Castro, Miguel A. Martinez-Olmos, Ana Canton, Lucia Ordoñez-Mayan, Ignacio Sajoux, Cristobal Galban, Diego Bellido, and Felipe F. Casanueva

Subjects
Ketogenic diet, Very low-energy diet, Pronokal method, Protein diet, Obesity, Metabolic adaptation, Nutrition. Foods and food supply, TX341-641, Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Abstract Background The resting metabolic rate (RMR) decrease, observed after an obesity reduction therapy is a determinant of a short-time weight regain. Thus, the objective of this study was to evaluate changes in RMR, and the associated hormonal alterations in obese patients with a very low-calorie ketogenic (VLCK)-diet induced severe body weight (BW) loss. Method From 20 obese patients who lost 20.2 kg of BW after a 4-months VLCK-diet, blood samples and body composition analysis, determined by DXA and MF-Bioimpedance, and RMR by indirect calorimetry, were obtained on four subsequent visits: visit C-1, basal, initial fat mass (FM) and free fat mass (FFM); visit C-2, − 7.2 kg in FM, − 4.3 kg in FFM, maximal ketosis; visit C-3, − 14.4 kg FM, − 4.5 kg FFM, low ketosis; visit C-4, − 16.5 kg FM, − 3.8 kg FFM, no ketosis. Each subject acted as his own control. Results Despite the large BW reduction, measured RMR varied from basal visit C-1 to visit C-2, − 1.0%; visit C-3, − 2.4% and visit C-4, − 8.0%, without statistical significance. No metabolic adaptation was observed. The absent reduction in RMR was not due to increased sympathetic tone, as thyroid hormones, catecholamines, and leptin were reduced at any visit from baseline. Under regression analysis FFM, adjusted by levels of ketonic bodies, was the only predictor of the RMR changes (R2 = 0.36; p

Published
2018
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14. Evolution and bad prognostic value of advanced glycation end products after acute heart failure: relation with body composition

Author

Beatriz Paradela-Dobarro, Ángel Fernández-Trasancos, Diana Bou-Teen, Sonia Eiras, Rocío González-Ferreiro, Rosa M. Agra, Alfonso Varela-Román, Ana I. Castro-Pais, Marcos C. Carreira, Felipe F. Casanueva, Ezequiel Álvarez, and José R. González-Juanatey

Subjects
Acute heart failure, Advanced glycation end products, Soluble RAGE, Heart failure progression, Heart failure prognosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aim The role of advanced glycation end products (AGEs) and their soluble receptor (sRAGE) on the progression and prognosis of acute heart failure (HF) was analysed in relation with metabolic parameters as body composition and nutritional status. Methods A hundred and fifty consecutive patients were included in a prospective clinical study during hospitalization by acute HF. Detailed medical history, physical examination, electrocardiogram, echocardiogram and vein peripheral blood were taken for all patients. During the follow-up period [297 days (88–422 days)] blood samples for biochemical measurements were obtained 1 and 6 months after the inclusion. Dual-energy X-ray absorptiometry analyses were performed 1 week after discharge. Results AGEs and sRAGE levels continuously increased, up to 6 months, after acute HF, but AGEs increase was mainly observed in those patients with incident HF. Both AGEs and sRAGE levels were related with bad renal function and clinical malnutrition (CONUT score) and they were negatively related with body mass index or percentage of body fat. AGEs levels (≥40 a.u.) 1 month after discharge and basal sRAGE levels (>1000 pg/mL) were related with worse prognosis in terms of patient death and HF readmission (Log-rank

Published
2017
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15. Data on hyper-activation of GPVI signalling in obese patients: Towards the identification of novel antiplatelet targets in obesity

Author

María N. Barrachina, Irene Izquierdo, Lidia Hermida-Nogueira, Aurelio M. Sueiro, Esteban Guitián, Felipe F. Casanueva, Richard W. Farndale, Masaaki Moroi, Stephanie M. Jung, María Pardo, and Ángel García

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract

This data article is associated with the manuscript “GPVI surface expression and signalling pathway activation are increased in platelets from obese patients: elucidating potential anti-atherothrombotic targets in obesity” [1]. The study refers to a combination of different approaches in order to identify platelet-derived biomarkers in obesity. A total of 34 obese patients and their lean-matched controls were included in the study. We carried out a proteomic and functional (aggregation assays) analysis to find alterations in platelet-derived signalling pathways. After that, biochemical and mechanistic (flow cytometry assays) approaches were done in order to confirm a hyperactivation of the GPVI-related signalling pathway.

Published
2019
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16. Validation of criteria for defining Pituitary Tumors Centers of Excellence (PTCOE)

Author

Andrea Giustina, Melin Meliha Uygur, Stefano Frara, Ariel Barkan, Nienke R. Biermasz, Philippe Chanson, Pamela U. Freda, Monica Gadelha, Ursula B. Kaiser, Steven W.J. Lamberts, Edward Laws, Lisa B. Nachtigall, Vera Popovic, Martin Reincke, Christian Strasburger, Aart J. van der Lely, John A.H. Wass, Shlomo Melmed, and Felipe F. Casanueva

Abstract

Purpose The Pituitary Society established the concept and mostly qualitative parameters for defining uniform criteria for pituitary tumor centers of excellence (PTCOEs) based on expert consensus. To validate those previously proposed criteria through collection and evaluation of self-reported activity of several internationally-recognized tertiary pituitary centers, thereby transforming the qualitative 2017 definition into a validated quantitative one, which could serve as the basis for future objective PTCOE accreditation. Methods An ad-hoc prepared database protocol was distributed to 9 Pituitary Centers chosen by the project scientific committee and comprising Centers of worldwide repute, which agreed to provide activity information derived from registries related to the years 2018-2020 and completing the database within 60 days. The database, composed of Excel® spreadsheets with requested specific information on leading and supporting teams provided by each Center, was reviewed by two blinded referees and all 9 of 9 candidate centers satisfied the overall PTCOE definition, according to referees’ evaluations. To obtain objective numerical criteria, median values for each activity/parameter were considered as the ideal PTCOE definition target, whereas the low limit of the range was selected as the acceptable target for each respective parameter. Results Three dedicated pituitary neurosurgeons were considered ideal, whereas one dedicated surgeon was acceptable. Moreover, 100 surgical procedures per year is ideal, while the results indicated that 50 surgeries per year is acceptable. Acute post-surgery complications, including mortality and readmission rates, should ideally be negligible or nonexistent, but acceptable criterion was a rate lower than 10% of patients with complications requiring readmission within 30 days after surgery. Four endocrinologists devoted to pituitary diseases are requested in a PTCOE and the total population of patients followed in a PTCOE should not be less than 850. It appears acceptable that at least one dedicated/expert in pituitary diseases is required in neuroradiology, pathology, and ophthalmology groups, whereas at least two expert radiation oncologists are needed. Conclusion This is, to our knowledge, the first study to survey and evaluate the activity of a relevant number of high-volume centers in the pituitary field. This effort, internally validated by ad-hocreviewers, allowed for transformation of previously formulated theoretical criteria for the definition of a PTCOE to precise numerical definitions based on real-life evidence. The application of a derived objective model can be used by external bodies for accreditation of pituitary centers as PTCOEs.

Published
2023
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17. Prolonged breastfeeding protects from obesity by hypothalamic action of hepatic FGF21

Author

Veronica Pena-Leon, Cintia Folgueira, Silvia Barja-Fernández, Raquel Pérez-Lois, Natália Da Silva Lima, Marion Martin, Violeta Heras, Sara Martinez-Martinez, Paola Valero, Cristina Iglesias, Mannon Duquenne, Omar Al-Massadi, Daniel Beiroa, Yara Souto, Miguel Fidalgo, Rasika Sowmyalakshmi, Diana Guallar, Juan Cunarro, Cecilia Castelao, Ana Senra, Patricia González-Saenz, Rocío Vázquez-Cobela, Rosaura Leis, Guadalupe Sabio, Helge Mueller-Fielitz, Markus Schwaninger, Miguel López, Sulay Tovar, Felipe F. Casanueva, Emmanuel Valjent, Carlos Diéguez, Vincent Prevot, Rubén Nogueiras, Luisa M. Seoane, Complejo Hospitalario Universitario de Santiago de Compostela [Saint-Jacques-de-Compostelle, Espagne] (CHUS), Universidade de Santiago de Compostela [Spain] (USC ), Equipe 'Development and Plasticity of the Neuroendocrine Brain' - LilNCog, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain] (CNIC), Instituto de Salud Carlos III [Madrid] (ISC), Universität zu Lübeck = University of Lübeck [Lübeck], Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Guerineau, Nathalie C., Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Xunta de Galicia (España), Fundación BBVA, Atresmedia, Fundación Jesús Serra, European Foundation for the Study of Diabetes, Unión Europea. Comisión Europea. H2020, Unión Europea. Comisión Europea. European Research Council (ERC), and Centro de Investigación Biomédica en Red - CIBEROBN (Fisiopatología de la Obesidad y Nutrición)

Subjects
[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Hypothalamus, Cell Biology, Rats, Fibroblast Growth Factors, [SDV] Life Sciences [q-bio], Mice, Breast Feeding, Liver, Physiology (medical), [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Internal Medicine, Animals, Humans, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Obesity, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract

Early-life determinants are thought to be a major factor in the rapid increase of obesity. However, while maternal nutrition has been extensively studied, the effects of breastfeeding by the infant on the reprogramming of energy balance in childhood and throughout adulthood remain largely unknown. Here we show that delayed weaning in rat pups protects them against diet-induced obesity in adulthood, through enhanced brown adipose tissue thermogenesis and energy expenditure. In-depth metabolic phenotyping in this rat model as well as in transgenic mice reveals that the effects of prolonged suckling are mediated by increased hepatic fibroblast growth factor 21 (FGF21) production and tanycyte-controlled access to the hypothalamus in adulthood. Specifically, FGF21 activates GABA-containing neurons expressing dopamine receptor 2 in the lateral hypothalamic area and zona incerta. Prolonged breastfeeding thus constitutes a protective mechanism against obesity by affecting long-lasting physiological changes in liver-to-hypothalamus communication and hypothalamic metabolic regulation. This work was supported by grants from: L.M.S.: Instituto de Salud Carlos III and co-funded by FEDER (PI18/00998), FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación (C.D.: BFU2017-87721; M.L.: RTI2018–101840-B-I00; R.N.: RTI2018-099413-B-I00 and RED2018-102379-T), Xunta de Galicia (M.L.: 2016-PG068; R.N.: 2016-PG057 and 2020-PG015), Fundación BBVA (R.N.: Fundación Atresmedia (to M.L. and R.N.), Fundación La Caixa (to M.L. and R.N.), Fundación Jesus Serra and European Foundation for the Study of Diabetes (to R.N.). The research leading to these results also received funding from the European Community’s H2020 Framework Programme under the following grant: ERC Synergy Grant-2019-WATCH- 810331 to M.S., V.P. and R.N. Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBERobn). CIBERobn is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain, which is supported by FEDER funds. This work was supported by Inserm, Fondation pour la Recherche Médicale, ANR-EPITRACES (to E.V.). Research from the M.F. laboratory was supported by the Spanish Agencia Estatal de Investigación, co-funded by the FEDER Programme of the EU (BFU2016-80899-P and PID2019-105739GB-I00 grants; AEI/FEDER, UE). M.F. is recipient of a Ramón y Cajal award (RYC-2014-16779). C.F. is a recipient of a Sara Borrel award (ISCIII CD19/0078). O.A. is a recipient of the Miguel Servet grant (ISCIIII). Sí

Published
2022
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19. Immunomodulatory effect of a very-low-calorie ketogenic diet compared with bariatric surgery and a low-calorie diet in patients with excessive body weight

Author

Paula M. Lorenzo, Ignacio Sajoux, Andrea G. Izquierdo, Diego Gomez-Arbelaez, M Angeles Zulet, Itziar Abete, Ana I. Castro, Javier Baltar, María P. Portillo, Francisco J. Tinahones, J Alfredo Martinez, Felipe F. Casanueva, Ana B. Crujeiras, Masira, and Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina

Subjects
Inflammation, Lipid Peroxides, Nutrition and Dietetics, Diet, Reducing, Carcinogenesis, PnK method, Bariatric Surgery, Ketosis, Weight Gain, Critical Care and Intensive Care Medicine, Nutritional ketosis, Immunonutrition, Oxidative stress, Weight Loss, Cytokines, Humans, Obesity, Diet, Ketogenic, Biomarkers, Caloric Restriction
Abstract

Digital, Background & aim Inflammation and oxidative stress are the most probable mechanistic link between obesity and its co-diseases with cancer among them. The aim of this study was to evaluate whether the nutritional ketosis and weight loss induced by a very-low-calorie ketogenic diet (VLCKD) modulates the inflammatory and oxidative stress profile, compared with a standard, balanced hypocaloric diet (LCD) or bariatric surgery (BS) in patients with obesity. Methods The study was performed in 79 patients with overweight or obesity and 32 normal-weight volunteers as the control group. Patients with obesity underwent a weight reduction therapy based on VLCKD, LCD or BS. The quantification of the circulating levels of a multiplexing test of cytokines and carcinogenesis/aging biomarkers, as well as of lipid peroxides and total antioxidant power, was carried out. Results First, we observed that pro-inflammatory cytokines increase, while anti-inflammatory cytokines decrease under excessive body weight. Relevantly, when patients underwent weight loss strategies, it was shown that energy-restricted and surgical strategies of weight loss induced changes in circulating cytokine and lipid peroxides. This effect was more notable in patients following the VLCKD than the LCD or BS and it was observed mainly in the ketosis phase of the intervention. Particularly, IL-11, IL-12, IL-2, INF-γ, INF-β, Pentraxin-3 or MMP1 changed after VLCKD. Whereas, APRIL, TWEAK, osteocalcin and IL-28A increased after BS. Conclusion As far as we know, this is the first study that evaluate the time-course of cytokines and oxidative stress markers after a VLCKD as compared with a standard LCD and BS. The observed results support the immunomodulatory effect of nutritional ketosis induced by a VLCKD synergistically with weight loss as a strategy to improve innate-immunity and to prevent infections and carcinogenesis in patients with obesity., Ciencias Médicas y de la Salud

Published
2022
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20. Corrigendum: Validation of the Spanish Version of the Yale Food Addiction Scale 2.0 (YFAS 2.0) and Clinical Correlates in a Sample of Eating Disorder, Gambling Disorder and Healthy Control Participants

Author

Roser Granero, Susana Jiménez-Murcia, Ashley N. Gearhardt, Zaida Agüera, Neus Aymamí, Mónica Gómez-Peña, María Lozano-Madrid, Núria Mallorquí-Bagué, Gemma Mestre-Bach, Maria I. Neto-Antao, Nadine Riesco, Isabel Sánchez, Trevor Steward, Carles Soriano-Mas, Cristina Vintró-Alcaraz, José M. Menchón, Felipe F. Casanueva, Carlos Diéguez, and Fernando Fernández-Aranda

Subjects
eating disorders, food addiction, gambling disorder, psychometric properties, validation, YFAS 2.0, Psychiatry, RC435-571
Published
2018
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21. Validation of the Spanish Version of the Yale Food Addiction Scale 2.0 (YFAS 2.0) and Clinical Correlates in a Sample of Eating Disorder, Gambling Disorder, and Healthy Control Participants

Author

Roser Granero, Susana Jiménez-Murcia, Ashley N. Gearhardt, Zaida Agüera, Neus Aymamí, Mónica Gómez-Peña, María Lozano-Madrid, Núria Mallorquí-Bagué, Gemma Mestre-Bach, Maria I. Neto-Antao, Nadine Riesco, Isabel Sánchez, Trevor Steward, Carles Soriano-Mas, Cristina Vintró-Alcaraz, José M. Menchón, Felipe F. Casanueva, Carlos Diéguez, and Fernando Fernández-Aranda

Subjects
eating disorders, food addiction, gambling disorder, psychometric properties, validation, YFAS 2.0, Psychiatry, RC435-571
Abstract

Aims: Due to the increasing evidence of shared vulnerabilities between addictive behaviors and excessive food intake, the concept of food addiction in specific clinical populations has become a topic of scientific interest. The aim of this study was to validate the Yale Food Addiction Scale (YFAS) 2.0 in a Spanish sample. We also sought to explore food addiction and its clinical correlates in eating disorder (ED) and gambling disorder (GD) patients.Methods: The sample included 301 clinical cases (135 ED and 166 GD), diagnosed according to DSM-5 criteria, and 152 healthy controls (HC) recruited from the general population.Results: Food addiction was more prevalent in patients with ED, than in patients with GD and HC (77.8, 7.8, and 3.3%, respectively). Food addiction severity was associated with higher BMI, psychopathology and specific personality traits, such as higher harm avoidance, and lower self-directedness. The psychometrical properties of the Spanish version of the YFAS 2.0 were excellent with good convergent validity. Moreover, it obtained good accuracy in discriminating between diagnostic subtypes.Conclusions: Our results provide empirical support for the use of the Spanish YFAS 2.0 as a reliable and valid tool to assess food addiction among several clinical populations (namely ED and GD). The prevalence of food addiction is heterogeneous between disorders. Common risk factors such as high levels of psychopathology and low self-directedness appear to be present in individuals with food addiction.

Published
2018
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22. Human obese white adipose tissue sheds depot-specific extracellular vesicles and reveals candidate biomarkers for monitoring obesity and its comorbidities

Author

Alberto Molares-Vila, Eelipe F Casanueva, Aurelio M. Sueiro, Tamara Camino, Nerea Lago-Baameiro, María Pardo, Javier Baltar, Iván Couto, and Susana B. Bravo

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Syntenins, Adipose Tissue, White, Subcutaneous Fat, Adipokine, Adipose tissue, Inflammation, White adipose tissue, Intra-Abdominal Fat, Extracellular Vesicles, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Transforming Growth Factor beta, Physiology (medical), Internal medicine, Humans, Medicine, Obesity, Extracellular Matrix Proteins, business.industry, Biochemistry (medical), Public Health, Environmental and Occupational Health, Proteins, General Medicine, Middle Aged, medicine.disease, Obesity, Morbid, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, 030220 oncology & carcinogenesis, Proteome, Intercellular Signaling Peptides and Proteins, Female, medicine.symptom, business, Biomarkers, TGFBI
Abstract

Extracellular vesicles (EVs) have been recently postulated as key players in metabolic disorders emerging as an alternative way of paracrine/endocrine communication. However, the nature of EVs shed by adipose tissue (AT) and their role in obesity is still very limited. Here, we isolated human morbid obese visceral (VAT) and subcutaneous (SAT) whole AT shed EVs from donors submitted to bariatric surgery to characterize their protein cargo by qualitative and quantitative/SWATH mass spectrometry analysis. We identified 574 different proteins shed by morbid obese VAT and 401 proteins in those from SAT, establishing the first obese AT EV proteome reference map. Only 50% of identified proteins in VAT vesicles were common to those in SAT; additionally, EVs shed by obese VAT showed more AT and obesity-related adipokines than SAT. Functional classification shows that obese VAT vesicles exhibit an enrichment of proteins implicated in AT inflammation and insulin resistance such as TGFBI, CAVN1, CD14, mimecan, thrombospondin-1, FABP-4 or AHNAK. Selected candidate biomarkers from the quantitative-SWATH analysis were validated in EVs from independent morbid obese and from moderate obese to lean individuals showing that morbid obese VAT vesicles are characterized by a diminution of syntenin 1 and the elevation of TGFBI and mimecan. Interestingly, TGFBI and mimecan containing vesicles could be detected and quantified at circulating level in plasma. Thus, a significant elevation of -TGFBI-EVs was detected on those obese patients with a history of T2D compared to nondiabetic, and an augmentation of mimecan-EVs in obese plasma compared to those in healthy lean individuals. Thus, we conclude that obese AT release functional EVs carrying AT and obesity candidate biomarkers which vary regarding the AT of origin. Our findings suggest that circulating EV-TGFBI may facilitate monitoring T2D status in obese patients, and EV-mimecan may be useful to track adiposity, and more precisely, visceral obesity.

Published
2022
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23. Comparative secretome analysis of rat stomach under different nutritional status

Author

Lucia L. Senin, Arturo Roca-Rivada, Cecilia Castelao, Jana Alonso, Cintia Folgueira, Felipe F. Casanueva, Maria Pardo, and Luisa M. Seoane

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract

The fact that gastric surgery is at the moment the most effective treatment to fight against obesity highlights the relevance of gastric derived proteins as potential targets to treat this pathology. Taking advantage of a previously established gastric explant model for endocrine studies, the proteomic analysis of gastric secretome was performed. To validate this gastric explant system for proteomic analysis, the identification of ghrelin, a classical gastric derived peptide, was performed by MS. In addition, the differential analysis of gastric secretomes under differential nutritional status (control feeding vs fasting vs re-feeding) was performed. The MS identified proteins are showed in the present manuscript. The data supplied in this article is related to the research article entitled “Comparative secretome analysis of rat stomach under different nutritional status” [1].

Published
2015
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24. Relevance of nutritional assessment and treatment to counteract cardiac cachexia and sarcopenia in chronic heart failure

Author

Ana I. Castro, Antía Fernández-Pombo, M.A. Martinez-Olmos, Luisa M. Seoane, Felipe F. Casanueva, Ana Cantón-Blanco, Ana B. Crujeiras, Gemma Rodriguez-Carnero, and Universidade de Santiago de Compostela. Departamento de Química Analítica, Nutrición e Bromatoloxía

Subjects
Adult, Male, Sarcopenia, medicine.medical_specialty, Cachexia, Population, Cardiac cachexia, Disease, Refeeding syndrome, Critical Care and Intensive Care Medicine, Muscle wasting, medicine, Humans, Intensive care medicine, education, Wasting, Aged, Aged, 80 and over, Heart Failure, education.field_of_study, Nutrition and Dietetics, Nutritional Support, business.industry, Malnutrition, Middle Aged, Prognosis, medicine.disease, Micronutrient, Chronic heart failure, Nutrition Assessment, Heart failure, Dietary Supplements, Body Composition, Female, medicine.symptom, business, Biomarkers
Abstract

Chronic heart failure (CHF) is frequently associated with the involuntary loss of body weight and muscle wasting, which can determine the course of the disease and its prognosis. While there is no gold standard malnutrition screening tool for their detection in the CHF population, several bioelectrical and imaging methods have been used to assess body composition in these patients (such as Dual Energy X-Ray Absorptiometry and muscle ultrasound, among other techniques). In addition, numerous nutritional biomarkers have been found to be useful in the determination of the nutritional status. Nutritional considerations include the slow and progressive supply of nutrients, avoiding high volumes, which could ultimately lead to refeeding syndrome and worsen the clinical picture. If oral feeding is insufficient, hypercaloric and hyperproteic supplementation should be considered. β-Hydroxy-β-methylbutyrate and omega-3 polyunsaturated fatty acid administration prove to be beneficial in certain patients with CHF, and several interventional studies with micronutrient supplementation have also described their possible role in these subjects. Taking into account that CHF is sometimes associated with gastrointestinal dysfunction, parenteral nutritional support may be required in selected cases. In addition, potential therapeutic options regarding nutritional state and muscle wasting have also been tested in clinical studies. This review summarises the scientific evidence that demonstrates the necessity to carry out a careful nutritional evaluation and nutritional treatment to prevent or improve cardiac cachexia and sarcopenia in CHF, as well as improve its course SI

Published
2021
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25. Epigenetic landscape in blood leukocytes following ketosis and weight loss induced by a very low calorie ketogenic diet (VLCKD) in patients with obesity

Author

Alfredo Fernández-Quintela, Andrea G. Izquierdo, David Primo, María P. Portillo, Fermín I. Milagro, A. Jácome, J. Alfredo Martínez, Ana B. Crujeiras, D.A. de Luis, Felipe F. Casanueva, M.A. Martinez-Olmos, and Ignacio Sajoux

Subjects
Male, 0301 basic medicine, epigenome-wide association, Methyltransferase, Calorie, dna methylation microarray, medicine.medical_treatment, Protein metabolism, nutritional intervention, Critical Care and Intensive Care Medicine, adipose-tissue, responders, Epigenesis, Genetic, chemistry.chemical_compound, Basal (phylogenetics), 0302 clinical medicine, Weight loss, Leukocytes, Adiposity, validation, adiposity, Nutritional intervention, Nutrition and Dietetics, exercise, Middle Aged, Circulating blood cells, cpg sites, Obesity, Morbid, Female, medicine.symptom, Diet, Ketogenic, performance, medicine.medical_specialty, 030209 endocrinology & metabolism, Methylation, 03 medical and health sciences, Internal medicine, Weight Loss, medicine, Humans, 030109 nutrition & dietetics, business.industry, biomarkers, Ketosis, medicine.disease, Obesity, Endocrinology, chemistry, ketone-bodies, responses, circulating blood cells, methylation, business, Biomarkers, Ketogenic diet
Abstract

Background: The molecular mechanisms underlying the potential health benefits of a ketogenic diet are unknown and could be mediated by epigenetic mechanisms. Objective: To identify the changes in the obesity-related methylome that are mediated by the induced weight loss or are dependent on ketosis in subjects with obesity underwent a very-low calorie ketogenic diet (VLCKD). Methods: Twenty-one patients with obesity (n ¼ 12 women, 47.9 ± 1.02 yr, 33.0 ± 0.2 kg/m2 ) after 6 months on a VLCKD and 12 normal weight volunteers (n ¼ 6 women, 50.3 ± 6.2 yrs, 22.7 ± 1.5 kg/m2 ) were studied. Data from the Infinium MethylationEPIC BeadChip methylomes of blood leukocytes were obtained at time points of ketotic phases (basal, maximum ketosis, and out of ketosis) during VLCKD (n ¼ 10) and at baseline in volunteers (n ¼ 12). Results were further validated by pyrosequencing in representative cohort of patients on a VLCKD (n ¼ 18) and correlated with gene expression. Results: After weight reduction by VLCKD, differences were found at 988 CpG sites (786 unique genes). The VLCKD altered methylation levels in patients with obesity had high resemblance with those from normal weight volunteers and was concomitant with a downregulation of DNA methyltransferases (DNMT)1, 3a and 3b. Most of the encoded genes were involved in metabolic processes, protein metabolism, and muscle, organ, and skeletal system development. Novel genes representing the top scoring associated events were identified, including ZNF331, FGFRL1 (VLCKD-induced weight loss) and CBFA2T3, C3orf38, JSRP1, and LRFN4 (VLCKD-induced ketosis). Interestingly, ZNF331 and FGFRL1 were validated in an independent cohort and inversely correlated with gene expression. Conclusions: The beneficial effects of VLCKD therapy on obesity involve a methylome more suggestive of normal weight that could be mainly mediated by the VLCKD-induced ketosis rather than weight loss. This work was supported by the PronoKal Group® and grants from the Fondo de Investigacion Sanitaria as well as PI17/01287, PI20/00628 and PI20/00650 research projects and CIBERobn from the Instituto de Salud Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento de la Investigación; Fondo Europeo de Desarrollo Regional (FEDER) Ana B Crujeiras is funded by a research contract “Miguel Servet” (CP17/00088) from the ISCIII, co-financed by the European Regional Development Fund (FEDER) and Xunta de Galicia-GAIN (IN607B2020). The funding source had no involvement in the study design or interpretation of the results

Published
2021
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26. Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort

Author

Ravinder Anand‐Ivell, Kee Heng, Katie Severn, Leen Antonio, Gyorgy Bartfai, Felipe F. Casanueva, Ilpo T. Huhtaniemi, Aleksander Giwercman, Mario Maggi, Terence W. O'Neill, Margus Punab, Giulia Rastrelli, Jolanta Slowikowska‐Hilczer, Jos Tournoy, Dirk Vanderschueren, Frederick C. W. Wu, and Richard Ivell

Subjects
Adult, Male, aging male, Aging, Urology, Endocrinology, Diabetes and Metabolism, Leydig Cells, Proteins, Luteinizing Hormone, Leydig cell, Endocrinology, Diabetes Mellitus, Type 2, Reproductive Medicine, Sex Hormone-Binding Globulin, testosterone, Humans, Insulin, hypogonadism, Testosterone, Obesity, HPG axis, Follicle Stimulating Hormone, INSL3, Life Style, Biomarkers
Abstract

BACKGROUND: Aging in men is accompanied by a broad range of symptoms, including sexual dysfunction, cognitive and musculoskeletal decline, obesity, type 2 diabetes, cardiovascular disease and hypertension, organ degeneration/failure, and increasing neoplasia, some of which are associated with declining levels of Leydig cell-produced testosterone. High natural biological variance, together with multiple factors that can modulate circulating testosterone concentration, may influence its interpretation and clinical implications. Insulin-like peptide 3 is a biomarker of Leydig cell function that might provide complementary information on testicular health and its downstream outcomes. OBJECTIVES: To characterize insulin-like peptide 3 as a biomarker to assess gonadal status in aging men. METHODS AND MATERIALS: A large European multicenter (European Male Aging Study) cohort of community-dwelling men was analyzed to determine how insulin-like peptide 3 relates to a range of hormonal, anthropometric, and lifestyle parameters. RESULTS AND DISCUSSION: Insulin-like peptide 3 declines cross-sectionally and longitudinally within individuals at approximately 15% per decade from age 40 years, unlike testosterone (1.9% per decade), which is partly compensated by increasing pituitary luteinizing hormone production. Importantly, lower insulin-like peptide 3 in younger men appears to persist with aging. Multiple regression analysis shows that, unlike testosterone, insulin-like peptide 3 is negatively dependent on luteinizing hormone and sex hormone-binding globulin and positively dependent on follicle-stimulating hormone, suggesting a different mechanism of gonadotropic regulation. Circulating insulin-like peptide 3 is negatively associated with increased body mass index or waist circumference and with smoking, and unlike testosterone, it is not affected by weight loss in obese individuals. Geographic variation in mean insulin-like peptide 3 within Europe appears to be largely explained by differences in these parameters. The results allowed the establishment of a European-wide reference range for insulin-like peptide 3 (95% confidence interval) adjusted for increasing age. CONCLUSION: Insulin-like peptide 3 is a constitutive biomarker of Leydig cell functional capacity and is a robust, reliably measurable peptide not subject to gonadotropin-dependent short-term regulation and within-individual variation in testosterone. ispartof: ANDROLOGY vol:10 issue:7 pages:1328-1338 ispartof: location:England status: published

Published
2022

27. Genetic Variants in Folate and Cobalamin Metabolism-Related Genes in Pregnant Women of a Homogeneous Spanish Population: The Need for Revisiting the Current Vitamin Supplementation Strategies

Author

Gemma Rodriguez-Carnero, Paula M. Lorenzo, Ana Canton-Blanco, Leire Mendizabal, Maddi Arregi, Mirella Zulueta, Laureano Simon, Manuel Macia-Cortiñas, Felipe F. Casanueva, and Ana B. Crujeiras

Subjects
Nutrition and Dietetics, Genotype, Infant, Newborn, Vitamins, Vitamin B 12, Folic Acid, Pregnancy, vitamin B9, vitamin B12, pregnancy, newborn, polymorphism, one-carbon metabolism, MTHFR, MTR, CUBN, SLC10A1, Dietary Supplements, Humans, Premature Birth, Female, Pregnant Women, Methylenetetrahydrofolate Reductase (NADPH2), Food Science
Abstract

Polymorphisms of genes involved in the metabolism and transport of folate and cobalamin could play relevant roles in pregnancy outcomes. This study assessed the prevalence of genetic polymorphisms of folate and cobalamin metabolism-related genes such as MTHFR, MTR, CUBN, and SLC19A1 in pregnant women of a homogeneous Spanish population according to conception, pregnancy, delivery, and newborns complications. This study was conducted on 149 nulliparous women with singleton pregnancies. Sociodemographic and obstetrics variables were recorded, and all patients were genotyped in the MTHFR, MTR, CUBN, and SLC10A1 polymorphisms. The distribution of genotypes detected in this cohort was similar to the population distribution reported in Europe, highlighting that more than 50% of women were carriers of risk alleles of the studied genes. In women with the MTHFR risk allele, there was a statistically significant higher frequency of assisted fertilisation and a higher frequency of preeclampsia and preterm birth. Moreover, CUBN (rs1801222) polymorphism carriers showed a statistically significantly lower frequency of complications during delivery. In conclusion, the prevalence of genetic variants related to folic acid and vitamin B12 metabolic genes in pregnant women is related to mother and neonatal outcomes. Knowing the prevalence of these polymorphisms may lead to a personalised prescription of vitamin intake.

Published
2022

28. An increase in visceral fat is associated with a decrease in the taste and olfactory capacity.

Author

Jose Carlos Fernandez-Garcia, Juan Alcaide, Concepcion Santiago-Fernandez, M M Roca-Rodriguez, Zaida Aguera, Rosa Baños, Cristina Botella, Rafael de la Torre, Jose M Fernandez-Real, Gema Fruhbeck, Javier Gomez-Ambrosi, Susana Jimenez-Murcia, Jose M Menchon, Felipe F Casanueva, Fernando Fernandez-Aranda, Francisco J Tinahones, and Lourdes Garrido-Sanchez

Subjects
Medicine, Science
Abstract

INTRODUCTION:Sensory factors may play an important role in the determination of appetite and food choices. Also, some adipokines may alter or predict the perception and pleasantness of specific odors. We aimed to analyze differences in smell-taste capacity between females with different weights and relate them with fat and fat-free mass, visceral fat, and several adipokines. MATERIALS AND METHODS:179 females with different weights (from low weight to morbid obesity) were studied. We analyzed the relation between fat, fat-free mass, visceral fat (indirectly estimated by bioelectrical impedance analysis with visceral fat rating (VFR)), leptin, adiponectin and visfatin. The smell and taste assessments were performed through the "Sniffin' Sticks" and "Taste Strips" respectively. RESULTS:We found a lower score in the measurement of smell (TDI-score (Threshold, Discrimination and Identification)) in obese subjects. All the olfactory functions measured, such as threshold, discrimination, identification and the TDI-score, correlated negatively with age, body mass index (BMI), leptin, fat mass, fat-free mass and VFR. In a multiple linear regression model, VFR mainly predicted the TDI-score. With regard to the taste function measurements, the normal weight subjects showed a higher score of taste functions. However a tendency to decrease was observed in the groups with greater or lesser BMI. In a multiple linear regression model VFR and age mainly predicted the total taste scores. DISCUSSION:We show for the first time that a reverse relationship exists between visceral fat and sensory signals, such as smell and taste, across a population with different body weight conditions.

Published
2017
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29. Correction: An increase in visceral fat is associated with a decrease in the taste and olfactory capacity.

Author

Jose Carlos Fernandez-Garcia, Juan Alcaide, Concepcion Santiago-Fernandez, M M Roca-Rodriguez, Zaida Aguera, Rosa Baños, Cristina Botella, Rafael de la Torre, Jose M Fernandez-Real, Gema Fruhbeck, Javier Gomez-Ambrosi, Susana Jimenez-Murcia, Jose M Menchon, Felipe F Casanueva, Fernando Fernandez-Aranda, Francisco J Tinahones, and Lourdes Garrido-Sanchez

Subjects
Medicine, Science
Abstract

[This corrects the article DOI: 10.1371/journal.pone.0171204.].

Published
2017
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30. 'Food addiction' in patients with eating disorders is associated with negative urgency and difficulties to focus on long-term goals

Author

Ines eWolz, Ines eHilker, Roser eGranero, Susana eJiménez-Murcia, Ashley Nicole Gearhardt, Carlos eDieguez, Felipe F Casanueva, Ana B Crujeiras, Jose M Menchon, and Fernando eFernandez-Aranda

Subjects
Eating Disorders, Personality, impulsivity, food addiction, Negative urgency, Psychology, BF1-990
Abstract

Objectives: The present study aimed to investigate if eating disorder patients differ in specific personality traits depending on a positive screening of food addiction and to find a model to predict food addiction in eating disorder patients using measures of personality and impulsivity. Methods: 278 patients having an eating disorder self-reported on food addiction, impulsivity, personality, eating and general psychopathology. Patients were then split into two groups, depending on a positive or negative result on the food addiction screening. Analysis of variance was used to compare means between the two groups. Stepwise binary logistic regression was used to obtain a predictive model for the presence of food addiction. Results: Patients with food addiction had lower self-directedness, and more negative urgency and lack of perseverance than patients not reporting addictive eating. The probability of food addiction can be predicted by high negative urgency, high reward dependence, and low lack of premeditation. Conclusions: Eating disorder patients who have more problems to pursue tasks to the end and to focus on long-term goals seem to be more likely to develop addictive eating patterns.

Published
2016
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31. Pituitary Tumors Centers of Excellence

Author

Andrea Giustina, Ana M. Formenti, Gemma Rodriguez-Carnero, Stefano Frara, Felipe F. Casanueva, M.A. Martinez-Olmos, Frara, S., Rodriguez-Carnero, G., Formenti, A. M., Martinez-Olmos, M. A., Giustina, A., and Casanueva, F. F.

Subjects
Adenoma, Quality Control, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, education, 030209 endocrinology & metabolism, Cancer Care Facilities, Medical Oncology, Medical care, Hypopituitarism, Pituitary radiotherapy, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Excellence, Patient-Centered Care, Humans, Medicine, Pituitary Neoplasms, Quality (business), Precision Medicine, health care economics and organizations, Quality of Health Care, media_common, Medical education, Health professionals, business.industry, Cushing disease, Reference Standards, Patient organization, Pituitary adenoma, humanities, Professional satisfaction, Work (electrical), Publishing, Transsphenoidal surgery, 030220 oncology & carcinogenesis, Acromegaly, business
Abstract

Pituitary tumors are common and require complex and sophisticated procedures for both diagnosis and therapy. To maintain the highest standards of quality, it is proposed to manage patients in pituitary tumors centers of excellence (PTCOEs) with patient-centric organizations, with expert clinical endocrinologists and neurosurgeons forming the core. That core needs to be supported by experts from different disciplines such as neuroradiology, neuropathology, radiation oncology, neuro-ophthalmology, otorhinolaryngology, and trained nursing. To provide high-level medical care to patients with pituitary tumors, PTCOEs further pituitary science through research publication, presentation of results at meetings, and performing clinical trials.

Published
2020
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32. Ketogenic diets as treatment of obesity and type 2 diabetes mellitus

Author

Marco Castellana, Felipe F. Casanueva, Gemma Rodriguez-Carnero, Ana I. Castro, Diego Bellido, Pierpaolo Trimboli, Ignacio Sajoux, Diego Gomez-Arbelaez, Ana B. Crujeiras, and M.A. Martinez-Olmos

Subjects
Pediatrics, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Type 2 diabetes, Overweight, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Weight loss, Diabetes mellitus, Weight Loss, medicine, Humans, Obesity, Caloric Restriction, business.industry, Type 2 Diabetes Mellitus, medicine.disease, Malnutrition, Diabetes Mellitus, Type 2, medicine.symptom, Diet, Ketogenic, business, Ketogenic diet
Abstract

During the last decades, several interventions for the management of overweight and obesity have been proposed. Among diets, the first studies focused on the effect of water only and total fasting diets with or without proteins. Unfortunately, they were found to be associated with adverse events which lead to the abandon of these strategies. Interestingly, despite the radical approach, total fasting was effective and generally well tolerated. A strict connection between protein-calorie malnutrition and increased in morbidity and mortality in hospitalized patients was found at that time. Then, the seminal works of Blackburn and his collaborators lead to the introduction of the protein-sparing modified fast. Encouraged by the early results using this intervention, diets evolved to the current very-low-calorie ketogenic diets (VLCKD). In the present review, results of studies on the VLCKDs are presented and discussed, with a particular reference to the protocolled VLCKD. Also, a recent proposal on the nomenclature on the ketogenic diets is reported. Available evidence suggests VLCKDs to be effective in achieving a rapid and significant weight loss by means of an easily reversible intervention which could be repeated, if needed. Muscle mass and strength are preserved, resting metabolic rate is not impaired, hunger, appetite and mood are not worsened. Symptoms and abnormal laboratory findings can be there, but they have generally been reported as of mild intensity and transient. Preliminary studies suggest VLCKDs to be a potential game-changer in the management of type 2 diabetes too. Therefore, VLCKDs should be considered as an excellent initial step in properly selected and motivated patients with obesity or type 2 diabetes, to be delivered as a part of a multicomponent strategy and under strict medical supervision.

Published
2020
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33. Weight loss normalizes enhanced expression of the oncogene survivin in visceral adipose tissue and blood leukocytes from individuals with obesity

Author

Marcos C. Carreira, Ana B. Crujeiras, Andrea G. Izquierdo, María P. Portillo, Carla Barbosa Nonino, Carolina Ferreira Nicoletti, Alfredo Fernández-Quintela, Francisco Ortega, D.A. de Luis, Felipe F. Casanueva, Marcela Augusta de Souza Pinhel, German Guzman, Gemma Rodriguez-Carnero, José Manuel Fernández-Real, M.A. Martinez-Olmos, and Aurelio M. Sueiro

Subjects
Adult, Male, medicine.medical_specialty, Survivin, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medicine (miscellaneous), Adipose tissue, 030209 endocrinology & metabolism, Intra-Abdominal Fat, Peripheral blood mononuclear cell, Article, Rats, Sprague-Dawley, Mice, 03 medical and health sciences, 0302 clinical medicine, Weight loss, Internal medicine, Weight Loss, medicine, Animals, Humans, Obesity, 030212 general & internal medicine, Nutrition and Dietetics, Oncogene, business.industry, Cancer, Middle Aged, medicine.disease, Rats, Rats, Zucker, Mice, Inbred C57BL, Endocrinology, Leukocytes, Mononuclear, Female, medicine.symptom, business, Ketogenic diet
Abstract

BACKGROUND/OBJECTIVES: Survivin is an oncogene associated with a decrease in apoptosis, an increase in tumor growth, and poor clinical outcome of diverse malignancies. A correlation between obesity, cancer, and survivin is reported in the literature. To date, the impact of weight loss on change in survivin levels is understudied. This study was aimed at: (1) comparing survivin levels in adipose tissue (AT) from lean and obese animal models and evaluating changes after weight loss induced by energy restriction and/or exercise; (2) comparing survivin levels in normal weighted and obese humans and evaluating changes in survivin levels after weight loss induced by a very-low-calorie ketogenic diet (VLCKD) or bariatric surgery in AT and/or blood leukocytes (PBL/PBMCs). SUBJECTS/METHODS: Survivin expression was evaluated in subcutaneous (SAT) and visceral (VAT) AT derived from animal models of monogenic (Zucker rats) and diet-induced obesity (Sprague Dawley rats and C57BL/6J mice) and after a 4-week weight-loss protocol of energy restriction and/or exercise. Plasma was used to measure the inflammatory status. Survivin expression was also evaluated in PBMCs from patients with obesity and compared with normal weight, in PBLs after VLCKD, and in SAT and/or PBLs after bariatric surgery. RESULTS: Survivin expression was specifically higher in VAT from obese that lean animals, without differences in SAT. It decreased after weight loss induced by energy restriction and correlated with adiposity and inflammatory markers. In humans, the correlation between being obese and higher levels of survivin was confirmed. In obese subjects, survivin levels were reduced following weight loss after either VLCKD or bariatric surgery. Particularly, a decrease in PBMCs expression (not in SAT one) was found after surgery. CONCLUSIONS: Weight loss is effective in decreasing survivin levels. Also, PBL/PBMC should be regarded as appropriate mirror of survivin levels in VAT for the identification of an obesity-related protumoral microenvironment.

Published
2020
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34. Aging Men With Insufficient Vitamin D Have a Higher Mortality Risk: No Added Value of its Free Fractions or Active Form

Author

Dirk Vanderschueren, Jos Tournoy, Felipe F. Casanueva, Hannes Moors, Marian Dejaeger, Jolanta Słowikowska-Hilczer, Gianni Forti, Ilpo Huhtaniemi, Giulia Rastrelli, Frederick C. W. Wu, Roger Bouillon, Evelien Gielen, Leen Antonio, Mario Maggi, Terence W O'Neill, and Margus Punab

Subjects
Survival Status, Adult, Male, medicine.medical_specialty, Vitamin D-binding protein, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Context (language use), Total 25(OH)D, Biochemistry, Risk Assessment, DBP, vitamin D deficiency, Endocrinology, Risk Factors, Internal medicine, medicine, Vitamin D and neurology, Humans, Prospective Studies, Mortality, Vitamin D, Prospective cohort study, Aged, business.industry, Vitamin D-Binding Protein, Biochemistry (medical), Outcome measures, Middle Aged, medicine.disease, Vitamin D Deficiency, mortality, Ageing, 25(OH)2D, business, free 25(OH)D, Follow-Up Studies
Abstract

Context Low total 25-hydroxyvitamin D (25(OH)D) has been associated with mortality. Whether vitamin D in its free form or 1,25-dihydroxyvitamin D (1,25(OH)2D), provide any additional information is unclear. Objective To determine what level of 25(OH)D is predictive for mortality and if free 25(OH)D or 1,25(OH) 2 D concentrations have any added value. Methods This prospective cohort comprised 1915 community-dwelling men, aged 40 to 79 years. Intervention included determination of association of total and free 25(OH)D and 1,25(OH) 2 D concentrations with survival status. Vitamin D results were grouped into quintiles. For total 25(OH)D, specific cutoff values were also applied. Cox proportional hazard models were used adjusted for center, body mass index, smoking, alcohol, physical activity, season of blood sample, kidney function, and number of comorbidities. Results A total of 469 (23.5%) men died during a mean follow-up of 12.3 ± 3.4 years. Compared to those with normal vitamin D values (> 30 µg/L), men with a total 25(OH)D of less than 20 µg/L had an increased mortality (hazard ratio [HR] 2.03 [95% CI, 1.39-2.96]; P Conclusion Aging men with vitamin D deficiency have a 2-fold increased mortality risk. Determinations of either the free fractions of vitamin D or measurement of its active form offer no additional information on mortality risks.

Published
2022

35. The Ghrelin System

Author

A. Benso, F. F. Casanueva, E. Ghigo, R. Granata

Published
2013

36. Epigenetic effects of healthy foods and lifestyle habits from the southern european atlantic diet pattern: a narrative review

Author

Paula M Lorenzo, Andrea G Izquierdo, Gemma Rodriguez-Carnero, Antía Fernández-Pombo, Alba Iglesias, Marcos C Carreira, Cristina Tejera, Diego Bellido, Miguel A Martinez-Olmos, Rosaura Leis, Felipe F Casanueva, Ana B Crujeiras, and Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría

Subjects
Nutrition and Dietetics, Healthy foods, Prevention, Medicine (miscellaneous), Precision nutrition, Lifestyle, Bioactive compounds, Diet, Epigenesis, Genetic, Habits, Atlantic diet, Humans, Epigenetics, Diet, Healthy, Life Style, Biomarkers, Food Science, Nutri-epigenetics
Abstract

Recent scientific evidence has shown the importance of diet and lifestyle habits for the proper functioning of the human body. A balanced and healthy diet, physical activity, and psychological well-being have a direct beneficial effect on health and can have a crucial role in the development and prognosis of certain diseases. The Southern European Atlantic diet, also named the Atlantic diet, is a unique dietary pattern that occurs in regions that present higher life expectancy, suggesting that this specific dietary pattern is associated with positive health effects. In fact, it is enriched with nutrients of high biological value, which, together with its cooking methods, physical activity promotion, reduction in carbon footprint, and promoting of family meals, promote these positive effects on health. The latest scientific advances in the field of nutri-epigenetics have revealed that epigenetic markers associated with food or nutrients and environmental factors modulate gene expression and, therefore, are involved with both health and disease. Thus, in this review, we evaluated the main aspects that define the Southern European Atlantic diet and the potential epigenetic changes associated with them based on recent studies regarding the main components of these dietary patterns. In conclusion, based on the information existing in the literature, we postulate that the Southern European Atlantic diet could promote healthy aging by means of epigenetic mechanisms. This review highlights the necessity of performing longitudinal studies to demonstrate this proposal SI

Published
2022

37. Pituitary tumor centers of excellence for Cushing’s disease

Author

Marcos, Couselo, Stefano, Frara, Andrea, Giustina, Felipe F, Casanueva, and Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina

Subjects
Adenoma, Endocrinology, Adrenocorticotropic Hormone, Endocrinology, Diabetes and Metabolism, Humans, Pituitary Neoplasms, Pituitary ACTH Hypersecretion
Abstract

Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature SI

Published
2022

38. A Lower Olfactory Capacity Is Related to Higher Circulating Concentrations of Endocannabinoid 2-Arachidonoylglycerol and Higher Body Mass Index in Women.

Author

Antoni Pastor, Fernando Fernández-Aranda, Montserrat Fitó, Susana Jiménez-Murcia, Cristina Botella, Jose M Fernández-Real, Gema Frühbeck, Francisco J Tinahones, Ana B Fagundo, Joan Rodriguez, Zaida Agüera, Klaus Langohr, Felipe F Casanueva, and Rafael de la Torre

Subjects
Medicine, Science
Abstract

The endocannabinoid (eCB) system can promote food intake by increasing odor detection in mice. The eCB system is over-active in human obesity. Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system. The study sample was made up of 161 females with five groups of body mass index sub-categories ranging from under-weight to morbidly obese. We assessed olfactory capacity with the "Sniffin´Sticks" test, which measures olfactory threshold-discrimination-identification (TDI) capacity. We measured plasma concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine or anandamide (AEA), and several eCB-related compounds, 2-acylglycerols and N-acylethanolamines. 2-AG and other 2-acylglycerols fasting plasma circulating plasma concentrations were higher in obese and morbidly obese subjects. AEA and other N-acylethanolamine circulating concentrations were lower in under-weight subjects. Olfactory TDI scores were lower in obese and morbidly obese subjects. Lower TDI scores were independently associated with higher 2-AG fasting plasma circulating concentrations, higher %body fat, and higher body mass index, after controlling for age, smoking, menstruation, and use of contraceptives. Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity. In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects.

Published
2016
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39. Decision Making Impairment: A Shared Vulnerability in Obesity, Gambling Disorder and Substance Use Disorders?

Author

Nuria Mallorquí-Bagué, Ana B Fagundo, Susana Jimenez-Murcia, Rafael de la Torre, Rosa M Baños, Cristina Botella, Felipe F Casanueva, Ana B Crujeiras, Jose C Fernández-García, Jose M Fernández-Real, Gema Frühbeck, Roser Granero, Amaia Rodríguez, Iris Tolosa-Sola, Francisco J Ortega, Francisco J Tinahones, Eva Alvarez-Moya, Cristian Ochoa, Jose M Menchón, and Fernando Fernández-Aranda

Subjects
Medicine, Science
Abstract

INTRODUCTION:Addictions are associated with decision making impairments. The present study explores decision making in Substance use disorder (SUD), Gambling disorder (GD) and Obesity (OB) when assessed by Iowa Gambling Task (IGT) and compares them with healthy controls (HC). METHODS:For the aims of this study, 591 participants (194 HC, 178 GD, 113 OB, 106 SUD) were assessed according to DSM criteria, completed a sociodemographic interview and conducted the IGT. RESULTS:SUD, GD and OB present impaired decision making when compared to the HC in the overall task and task learning, however no differences are found for the overall performance in the IGT among the clinical groups. Results also reveal some specific learning across the task patterns within the clinical groups: OB maintains negative scores until the third set where learning starts but with a less extend to HC, SUD presents an early learning followed by a progressive although slow improvement and GD presents more random choices with no learning. CONCLUSIONS:Decision making impairments are present in the studied clinical samples and they display individual differences in the task learning. Results can help understanding the underlying mechanisms of OB and addiction behaviors as well as improve current clinical treatments.

Published
2016
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40. Olfaction in Eating Disorders and Abnormal Eating Behaviour: A Systematic Review

Author

Mohammed Anisul eIslam, Ana Beatriz Fagundo, Jon eArcelus, Zaida eAguera, Susana eJiménez-Murcia, Jose Manuel Fernandez-Real, Francisco J Tinahones, Rafael eDe La Torre, Cristina eBotella, Gema eFrühbeck, Felipe F Casanueva, Jose M Menchon, and Fernando eFernandez-Aranda

Subjects
Anorexia, Anorexia Nervosa, Bulimia, Bulimia Nervosa, Eating, Eating Disorders, Psychology, BF1-990
Abstract

The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insights with regard to the complex etiopathology of ED and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1,352 articles, 14 articles were selected (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN (35.7%) and obesity (14.3%). The general findings support that olfaction is altered in AN and Obesity and indicates towards there being no differences in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior.

Published
2015
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41. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author

Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. Gregor, Vayia Rarra, Seyed Mohammad Hashemi-Shahri, Loreto Santa Marina, Galina Obreja, Rudolf Kaaks, Aya Mostafa, Maria do Carmo Franco, Beata Gurzkowska, Chien-Jen Chen, Marie Moitry, Nizal Sarrafzadegan, Xiangjun Wang, Diego Giulliano Destro Christofaro, Imperia Brajkovich, Fangfang Chen, Francesco Panza, Ling Yang, Holly E. Syddall, Cecily Kelleher, Michael Tornaritis, Ningli Wang, Lutgarde Thijs, Marjolein Visser, Angelika Schaffrath Rosario, María José Tormo, Jostein Steene-Johannessen, Norbert Amougou, Emmanuella Magriplis, Mar Alvarez-Pedrerol, Jingli Gao, Stig E. Bojesen, Giuseppe Grosso, Seongjun Ha, Lauren Lissner, Mikhail Benet, Anastasia Markaki, Sanjay Rampal, Antônio Augusto Moura da Silva, Maria Lorenza Muiesan, Angelique Chan, Yvonne T. van der Schouw, Annamari Lundqvist, Philippe Amouyel, Kristyna Zejglicova, Charalambos Hadjigeorgiou, João Breda, Jørgen Meisfjord, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Vilma Irazola, Leng Huat Foo, Óscar Lopes, Dickman Gareta, Flavio Nervi, Imre Janszky, Ruzena Kubinova, Terho Lehtimäki, Mario V. Capanzana, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Shuohua Chen, Arvind Pandey, Luigi Palmieri, Roya Kelishadi, Srinivasan Kannan, Jie Mi, Robert Beaglehole, Liliana Dacica, Jyrki K. Virtanen, Mohan Deepa, Peter Ueda, Isti Ilmiati Fujiati, Hermann Pohlabeln, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, Mohsen Azimi-Nezhad, Henry Völzke, Karolina Milkowska, Zahra Mohammadi, Belgin Ünal, Magda Gasull, George S. Stergiou, Marshall K. Tulloch-Reid, Seppo Koskinen, James E. Bennett, Marcela González-Gross, Virginija Dulskiene, Idris Guessous, Assembekov Batyrbek, Kamarul Imran Musa, Jeannette Lee, Josep Redon, Bihungum Bista, Luisa M Macieira, Johan Sundström, Andres Metspalu, Lariane M Ono, Flora A. Ukoli, Salar Rahimikazerooni, Andrea Gualtieri, Trevor S. Ferguson, Félicité Tchibindat, Eliza Cinteza, Ha Tp Do, Tajana Zeljkovic Vrkic, Tuyen D Le, Alison J. Hayes, Abdul Basit, Chandini Nekkantti, Teresa Norat, Eunice Ugel, Gulmira Aitmurzaeva, Mariachiara Di Cesare, Abdul Hamid Zargar, Vincenzo Solfrizzi, Garry L. Jennings, Aline Meirhaeghe, Kaare Christensen, Päivi Mäki, Xu Lin, Ali Esmaeili, Joanna Baran, Aneta Grajda, Renata Cifkova, Alexandre C. Pereira, Martin Bobak, Iuliia A Rusakova, Keiu Nelis, Damian K Francis, Guansheng Ma, Axel C. Carlsson, Alejandro Diaz, Alireza Ansari-Moghaddam, N Capkova, Zumin Shi, Maria Turley, Imelda A. Agdeppa, Helena I. S. Nogueira, Marcia Scazufca, Katharina Maruszczak, Natascia Rinaldo, Paulo A. Lotufo, Nuno Lunet, Thor Aspelund, Caroline H.D. Fall, Antonio Cabrera de León, Ahmad Faudzi Yusoff, Holger Theobald, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Mihai Gafencu, Tandi E. Matsha, Ana B. Crujeiras, Ahmad Reza Dorosty, Alain Morejon, Weili Yan, Dominique Hange, Bekbolat Zholdin, Frédéric Gottrand, Jorge Mota, Jana Námešná, Stevo Popovic, Louise Eriksen, Line Lund Kårhus, Cihangir Erem, Juergen Breckenkamp, Mathilde Kersting, Yi Song, Martin McKee, Aleksandra Gomula, Rafaela Rosário, Enzo Manzato, S. Goya Wannamethee, Sounnia Mediene Benchekor, Azim Nejatizadeh, Krishna Kumar Aryal, Juan P. González-Rivas, Vedrana Sember, Stephen T. McGarvey, Jukka T. Salonen, Patrick Pasquet, Patricia Varona-Pérez, Amelia C. Crampin, Ramin Heshmat, Violeta Iotova, Juvenal Soares Dias-da-Costa, Oye Gureje, Aletta E. Schutte, João Luiz Bastos, Anelise Reis Gaya, Konrad Jamrozik, Dalia Luksiene, Amina Barkat, Maria Paula Santos, José Camolas, Azli Baharudin, Diego Vanuzzo, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, Albertino Damasceno, Davood Khalili, Simona Bo, Martina Müller-Nurasyid, Dominique Cottel, Markku Peltonen, Fikru Tullu, Ana Isabel Rito, Angélica Ochoa-Avilés, Annette J. Dobson, Christopher T. Cowell, Charumathi Sabanayagam, Rildo de Souza Wanderley Júnior, Oanh T. H. Trinh, Farahnaz Joukar, Mostafa K. Mohamed, Mostafa Qorbani, Jeongseon Kim, Helmut Schröder, Machi Suka, Natasja M. van Schoor, Jussi Kauhanen, Teresa Haugsgjerd, Goodarz Danaei, M. Fernanda Lima-Costa, Yong Tao, Elisabetta L. Romeo, Grazyna Jasienska, Victor Guillermo Sequera, Kazem Mohammad, Yanina Zócalo, Fernanda Cunha Soares, Jianfeng Wu, Mohammad Esmaeel Motlagh, María Elena Díaz-Sánchez, Monika Zuziak, Eldridge Ferrer, Anette Varbo, Leila Beltrami Moreira, Jeremy M. Jacobs, Kenneth James, Elena Sacchini, Pascal Bovet, Mahboubeh Parsaeian, Tania Lopez, Ya Xing Wang, Wojciech Drygas, Jody C Miller, Svetlana A. Shalnova, Maria Elisa Zapata, Chung T Nguyen, Nimmathota Arlappa, Edwige Landais, Thorkild I. A. Sørensen, Jeannette Klimont, Amirabbas Momenan, Erik J. Timmermans, Mari-Liis Tammesoo, Jost B. Jonas, Stefania Toselli, Maria Teresa Anselmo Olinto, Bahman Cheraghian, Kouamelan Doua, Esteban Carmuega, Marjeta Mišigoj-Duraković, Bo Werner, M. Arfan Ikram, Breige A. McNulty, Christa Meisinger, Clara Homs, Namuna Shrestha, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Alicia Matijasevich, Alison J Price, Ala'a Alkerwi, Kristine H. Allin, Lorenza Pilotto, Mohannad Al Nsour, Ingunn Holden Bergh, Marianna Noale, Heba Fouad, Vilnis Dzerve, Novie O. Younger-Coleman, Peter Willeit, Andrea R. V. R. Horimoto, Freda Pitakaka, Habiba Ben Romdhane, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Cristina Padez, Sarah P. Garnett, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tien Yin Wong, Rosa Haghshenas, Jonathan Giovannelli, Christina Howitt, Marleen E. Hendriks, Fadia AlBuhairan, Huashuai Chen, Gretchen A Stevens, Luís B. Sardinha, David Goltzman, Jenny M. Kindblom, Karina Mary de Paiva, Yousef Khader, Eric Monterrubio-Flores, Rajendra Pradeepa, Yi-Ting Lin, Martin Neovius, Juan Francisco Miquel, Ellis Owusu-Dabo, Anil Poudyal, Marzieh Katibeh, Tanja Stocks, Veronica Mocanu, Ulla Roggenbuck, Robespierre Ribeiro, Gabriele Eiben, Mary Simon, Christine Cameron, Hamid Hakimi, Kamel Ajlouni, Jakub Stokwiszewski, Iulia Jurca Simina, Pietro Amedeo Modesti, Frederick C. W. Wu, Peter Kristensen, Charles Mondo, Felix Gutzwiller, Mariana Sbaraini, Martijn Huisman, Betina H. Thuesen, Queenie Chan, Antonisamy Belavendra, Artur Mazur, Ulf Ekelund, Laura A. Rodríguez-Villamizar, Marcos André Moura-dos-Santos, Jean Ferrières, Farhad Zamani, Shina Avi, Yves Kameli, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Thomas Meinertz Dantoft, Hossein Poustchi, Farid Najafi, Giovanni de Gaetano, Azaliia M Tuliakova, Vera Lanska, Tint Swe Latt, Matthias Bopp, Abbas Rezaianzadeh, Rod Jackson, Johan Van der Heyden, Reecha Sofat, Koen Van Herck, Allan G. Hill, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Stela McLachlan, Ulrike Gehring, Ranko Stevanovic, Nagalla Balakrishna, Lekhraj Rampal, Marjolijn C. E. Bragt, Saeid Eslami, Napoleón Pérez-Farinós, G. K. Mini, Viktoria Anna Kovacs, Rosemarie Martin, Nahla Hwalla, Wei Zheng, Hoang Van Minh, Edward D Janus, Laetitia Huiart, Farhad Pourfarzi, Sudha Ramachandra Rao, Fred Paccaud, Marcia Makdisse, Aye Aye Sein, Enrique Gutiérrez-González, Yang Yang, Anneke Blokstra, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Wan Nazaimoon Wan Mohamud, Jesús Ibarluzea, Julio Zuñiga Cisneros, Laura Lauria, Argyro Karakosta, Dragana P Jovic, Jun Hata, Elio Riboli, Piotr Bandosz, Xun Tang, Parvina Mukhtorova, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Aleksandra Piwońska, Dusan Grafnetter, Mette Rasmussen, Daniel Weghuber, Sherali Rakhmatulloev, Martine Vrijheid, Johann Willeit, Motahareh Kheradmand, Małgorzata Mossakowska, Lechaba Tshepo, Dongfeng Gu, Hyeon Chang Kim, Vilmundur Gudnason, Maria Forsner, Peter Bjerregaard, Leon A. Simons, Rachael McLean, Japhet Killewo, Ramón Suárez-Medina, Y Nikitin, Eng Joo Tan, Jean Claude Mbanya, Aroor Bhagyalaxmi, Renata Kuciene, Kairat Davletov, Jose Eugenio Lozano, Afshin Ostovar, Niloofar Peykari, Guy De Backer, Soheir H Ahmed, Nicholas J. Wareham, Sai Yin Ho, Constanta Huidumac Petrescu, Maria Hassapidou, Iris Pigeot, Myriam Galfo, Susana Cararo Confortin, Blanca Sandra Ruiz-Betancourt, W. M. Monique Verschuren, Catterina Ferreccio, Fabio Galvano, Leila Houti, Daniel Bia, Annika Rosengren, Marcin Rutkowski, Biruta Velika, Joana Araújo, Fernando Rigo, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Marie Kunešová, Boban Mugoša, Sania Nishtar, Mangesh S. Pednekar, Shahla AlDhukair, Helle-Mai Loit, Antonis Zampelas, Altan Onat, Maciej Banach, Shohreh Naderimagham, Hajer Aounallah-Skhiri, Maja Bæksgaard Jørgensen, Yin Guo, Ewelina Czenczek-Lewandowska, Parasmani Dasgupta, Elvis Oa Wambiya, Inge Huybrechts, Raimund Erbel, Jari Jokelainen, Ana P. Ortiz, Stefan Kiechl, Emmanuel Cohen, Caleb Ochimana, Shynar Abdrakhmanova, Laura Censi, Iqbal Bata, Geetha R Menon, Snehalatha Chamukuttan, Pedro Plans-Rubio, Domenico Palli, Ana Azevedo, Slawomir Koziel, Benoît Salanave, Parinaz Mehdipour, Shu Ti Chiou, Lela Sturua, Lubica Ticha, Felipe Vogt Cureau, Jin Soo Moon, Ming-Hui Zhao, Urho M. Kujala, Nathalie Michels, Ertugrul Celikcan, Jaakko Tuomilehto, Judith Benedics, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, Andrea Rodriguez-Martinez, Tai Hing Lam, Yn-Tz Sung, Jürgen König, Kodavanti Mallikharjuna Rao, Hazzaa M. Al-Hazzaa, Karen Morgan, Bogdan Wojtyniak, Cynthia M. Pérez, Ilse Khouw, Manoli Garcia-de-la-Hera, Dong Wook Shin, Genc Burazeri, Ausra Petrauskiene, Charles Sossa Jérome, Kenisha Russell Jonsson, José Boggia, Daniela Galeone, Alice Bonilla-Vargas, Han Cg Kemper, Rahman Shiri, Stefaan Demarest, Else Karin Grøholt, San-Lin You, Adelheid Weber, Juha Auvinen, Aida Pilav, Sibel Gogen, Suzanne N Morin, Wan Mohamad Wan Bebakar, Viviane Cunha Cardoso, Kavumpurathu Raman Thankappan, Hana Zamrazilová, Frank Claessens, Karien Stronks, Helen Gonçalves, Tahir Aris, Luis Revilla, Sérgio Viana Peixoto, Zhamilya Battakova, Jing Liu, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Priscilla Duboz, Sandjaja, Tiina Laatikainen, Rafel Ramos, Sareh Eghtesad, Judith Simons, Orn Olafsson, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Aung Soe Htet, Bente Sparboe-Nilsen, Paul Elliott, Soon-Woo Park, Angel R. Gonzalez, Ying-Wei Wang, Rob M. van Dam, Ryutaro Ohtsuka, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Lynell V Maniego, Fariborz Mansour-Ghanaei, Maria Dorobantu, Giovanni Viegi, Xiaoguang Yang, Honor Bixby, Prakash C. Gupta, Ofra Kalter-Leibovici, Eugene Sobngwi, Ričardas Radišauskas, Jurate Medzioniene, Roy A Wong-McClure, Kim F. Michaelsen, Antonia Trichopoulou, Tania Tello, Francesco Branca, Johanna Gunnlaugsdottir, Els Clays, Wei-Yen Lim, Suzanne C. Ho, Toomas Veidebaum, Rebecca Goldsmith, Margot González-León, Matthias Nauck, Alibek Mereke, Marta Buoncristiano, Jakob Tarp, Rosalba Rojas-Martínez, Maya Tanrygulyyeva, Reza Malekzadeh, Abdonas Tamosiunas, Dimitrios Poulimeneas, Pedro Ordunez, Isabelle Herter-Aeberli, Khanh Le Nguyen Bao, Anne Juolevi, Vassilis Zafiropulos, Emanuela Gualdi-Russo, Jordi Sunyer, Manu Raj, Chaoqiang Jiang, Sofia Malyutina, Efthymios Kapantais, Maria Lazo-Porras, Maung Maung Than Htike, Michael Hobbs, Ranjit Mohan Anjana, Merike Liivak, Johan G. Eriksson, Margarita Samoutian, Andreia N. Pizarro, Mohammed Rasoul Tarawneh, Jean Woo, Kaspar Staub, Maria Teresa Menzano, Mojtaba Farjam, Adroaldo Cesar Araujo Gaya, Mohammad El-khateeb, Zulfiqar A Bhutta, Mukharram M. Bikbov, Hsien-Ho Lin, Oscar Noboa, Thomas Waldhör, Garry Brian, Simona Costanzo, Frank Tanser, Nor Azwany Yaacob, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ioannis Pagkalos, Ivan Pećin, Carlo M. Barbagallo, Abla M. Sibai, Yuna He, Matsuda Fumihiko, Bharathi Viswanathan, Ali Reza Safarpour, Wei Cheng Lo, Abdullatif Husseini, Jiang He, Liv Elin Torheim, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, William R. Tebar, Yingfeng Zheng, Eha Nurk, Bhawesh Koirala, Ana Jelakovic, Suhad Bahijri, Freja B Kampmann, Qi Sheng You, Marika Ferrari, María-Elena González-Villalpando, Aline Wagner, Olfa Saidi, Anwar Batieha, Eduardo Capuano, Coimbatore Subramaniam Shanthirani, Dong Wook Kim, Albina A Fakhretdinova, Tom Wilsgaard, Maria Avdicova, Moesijanti Soekatri, Chiara Donfrancesco, Salim Mohanna, Paola Russo, Uruwan Yamborisut, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Khairil Si-Ramlee, Kirsten Mehlig, Christina Mavrogianni, Raluca Pop, Lèlita Santos, Graziella Bruno, Valentina Peterkova, Iná S. Santos, Georg Lappas, Alberto Palloni, Malay K. Mridha, Andrzej Pajak, Marta García-Solano, Stefaan De Henauw, Daniel Ferrante, Rute Santos, Anders Grøntved, Lucjan Szponar, Mihaela Vladulescu, Chien-An Sun, Jan A. Staessen, Paula Duarte de Oliveira, Norazizah Ibrahim Wong, Maria Nordendahl, Elaine M. Dennison, Jeonghee Lee, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Noushin Mohammadifard, Igor Spiroski, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Valéria Regecová, Cláudia S. Minderico, Johanna A. Otero, Jamila Abubakar Garba, Vesselka Duleva, Rui Ornelas, Ilpo Huhtaniemi, Cesar G. Victora, Lijuan Liu, Rody G. Sy, Mahmood Moosazadeh, Ali Ahmadi, Antonio Pedro Graça, Natalia Nowak-Szczepanska, Miao Li Chee, Michael Sjöström, Charles Agyemang, Shiqi Zhen, Xiu-Hua Guo, Pawel Kurjata, Jardena J. Puder, Mehrdad Azmin, Neil Murphy, Kaosar Afsana, Alireza Sadjadi, Johanna M. Geleijnse, Prashant Mathur, Elysée Claude Bika Lele, Raphael Mendes Ritti-Dias, Yannis Manios, Majid Shirani, Rosemary B. Duda, Liis Nelis, Jurate Klumbiene, Zhengming Chen, Wichai Aekplakorn, Alun Evans, Andrzej Wiecek, Lars Lind, Denise Eldemire-Shearer, Bernardo L. Horta, Macia Enguerran, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Kumiko Ohara, Ursula Kiechl-Kohlendorfer, Hermann Brenner, Przemyslaw Slusarczyk, Espen Bjertness, Jutta Stieber, Augusto Di Castelnuovo, Joel G. R. Roy, Aryeh D. Stein, Ruth Frikke-Schmidt, Vera Musil, Amaneh Shayanrad, Marcel Goldberg, Ramon O. Jimenez, Mohammad Reza Fattahi, Jolanda Hyska, Amir Houshang Mehrparvar, Elin Kolle, Mohamed Bamoshmoosh, Michelle Holdsworth, Felipe F. Casanueva, Børge G. Nordestgaard, Niels Wedderkopp, Eva Corpeleijn, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Larissa Pruner Marques, Slavica Sović, Olli T. Raitakari, Marco Aurélio Peres, Alexandra Cucu, Gregorio Varela-Moreiras, Janine Clarke, Andrea Gazzinelli, Mieczysław Litwin, Sara Schramm, Xenophon Theodoridis, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Dimitrios Papandreou, Peter T. Katzmarzyk, Benjamin Acosta-Cazares, Ben Schöttker, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Sadaf G. Sepanlou, Adolfo Rubinstein, Francis Delpeuch, Julianne Williams, Abbas Dehghan, Leanne M. Riley, Heloisa Bettiol, Gabriele Nagel, Ellisiv B. Mathiesen, Ekaterina Stoyanova, Alisha N. Wade, Zhamyila Usupova, Arnaud Chiolero, Oonagh Markey, Jacqueline Ramke, Elena Bogova, Niveen M E Abu-Rmeileh, Nguyen D Nguyen, Tomasz Zdrojewski, Marjo-Riitta Järvelin, Jose Sanchez-Abanto, Rômulo Araújo Fernandes, Lourdes Ribas-Barba, Nalan Uysal, Mohamad Hasnan Ahmad, Krista Fischer, Maria Wany Louzada Strufaldi, Ramiro Guerrero, Farnam Mohebi, Tran Quoc Bao, Flávio Danni Fuchs, Salim Berkinbayev, Enisa Kujundzic, Sari Voutilainen, Farzad Hadaegh, Robert Lundqvist, Saeid Safiri, Iraj Mohebbi, George Luiz Lins Machado-Coelho, Annette Peters, Gonzalo Valdivia, Magdalena Korzycka, Rajiv T Erasmus, Masanori Iwasaki, Charmaine A. Duante, Sheikh Mohammed Shariful Islam, Quang Ngoc La, Ricky Eddie, Petra Rust, Daniela Rodrigues, Dirk De Bacquer, Karen Sparrenberger, Agneta Sjöberg, Thet Thet Mu, Katarzyna Dereń, Cora L. Craig, Jorge Motta, Janina Petkeviciene, Boyd Swinburn, Paibul Suriyawongpaisal, Visnja Djordjic, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Daan Kromhout, Marius B. Bjertness, Stefano Marventano, Juel Jarani, Alireza Khosravi, Eva Martos, David De Ridder, Lizzy M. Brewster, Nico Dragano, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Hashem Jaddou, Grzegorz Sobek, Dimitrios Trichopoulos, Marvin Cervantes-Loaiza, Abu Am Hanif, Elaine M. Murtagh, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Kyungwon Oh, Heiner Boeing, Regina Heidinger-Felso, André Luiz Sena Guimarães, Balkish M. Naidu, Avula Laxmaiah, Ana M. B. Menezes, Marie Eliasen, Francesco Pistelli, Yuan He, Dusko Bjelica, José A. Casajús, Guang Ning, Lutgart Braeckman, Dirk Vanderschueren, Jochanan Stessman, Ivana Radic, Yi Zeng, Hans Concin, Damaskini Valvi, Sari Hantunen, Catherine Kyobutungi, Diego Augusto Santos Silva, Wenhua Zhao, Sok King Ong, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Mattias Johansson, Samuel C. Dumith, Magdalena Muc, Sabine Schipf, Idowu O Senbanjo, Jim Mann, Rajaa Al-Raddadi, Yih Chung Tham, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Sahar Saeedi Moghaddam, Reza Mohammadpourhodki, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Camilla T. Damsgaard, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Constance Schultsz, Santiago F. Gomez, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Pierre Traissac, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Eleonora d'Orsi, Irene G. M. van Valkengoed, Anna Fijałkowska, Wen-Harn Pan, Gregor Starc, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Abdullah Alkandari, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Saeed Dastgiri, Lien Braeckevelt, Nasheeta Peer, Radka Taxová Braunerová, Mohamed M. Ali, Steiner Krokstad, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Silvana Donoso, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paola Nardone, Alberto Barceló, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Miquel Porta, Vesna Jureša, Alexander D. Deev, David Faeh, Antonio Bernabe-Ortiz, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Anjani Kumar Jha, Thamara Hubler Figueiró, Jana Kratenova, Claudia M. Hormiga, Maria Tsigga, Zivka Dika, Indrapal I. Meshram, Ei Ei K. Nang, Ian Rouse, Rusidah Selamat, Paul Korrovits, Grethe S. Tell, Julie Taylor, Anabela Mota-Pinto, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Frank J Rühli, Shelly R. McFarlane, Sara Santos Sanz, Edyta Łuszczki, Maria G. Stathopoulou, Tara Coppinger, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Muhammad Islam, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Maria Ruiz-Castell, Daniela Pierannunzio, Cristina Taddei, Gowri Mahasampath, Gustavo Velasquez-Melendez, Hanna Tolonen, Sudhir Kowlessur, Bagher Larijani, Laura Torres-Collado, Susi Kriemler, Ali Akbar Shayesteh, Cynthia Robitaille, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Line Tang Møllehave, Vincent Jr DeGennaro, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Kodanda R Kanala, Gert B. M. Mensink, Abhijit Sen, Sergej M. Ostojic, Hanan F. Abdul Rahim, Hélène Delisle, Francisco J. Félix-Redondo, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Bethlehem D. Solomon, Erik Lykke Mortensen, Nikhil D. Patel, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Son Thai Pham, Simona Giampaoli, Dong Zhao, Indah Suci Widyahening, Merete Osler, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, Giota Touloumi, Janice Luisa Lukrafka, Adela Chirita-Emandi, Maryam Kavousi, Sanja Musić Milanović, Jean-Michel Gaspoz, Jalila El Ati, Sauli Herrala, Liang Xu, Pilar Guallar-Castillón, Bee Koon Poh, Luis Serra-Majem, Jonathan E. Shaw, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Yuki Fujita, Tiffany K. Gill, Nish Chaturvedi, Erkin M. Mirrakhimov, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Deepak Amarapurkar, Deepa Weerasekera, Diana A. Santos, Marjeta Majer, Herman Schargrodsky, Bruna Gonçalves Cordeiro da Silva, Ebrahim Eftekhar, Jesús Vioque, Marisa K. Sophiea, Teresa Shamah-Levy, María Dolores Chirlaque, Mohd Azahadi Omar, Stefan Söderberg, Isabel O. Oliveira, Joanne Katz, Xingwang Ye, Christophe Tzourio, Marie Zins, Aneta Weres, Ulrich Keil, Haiquan Xu, Akihiro Yoshihara, Rachel Dankner, Gabriella Gruden, Maroje Sorić, Hanspeter Stamm, Kim Overvad, Yanping Li, Carsten Oliver Schmidt, Christa L. Lilly, Veikko Salomaa, Gilad Twig, Senthil K Vasan, Qian Wang, Liufu Cui, Andrzej Galbarczyk, Sylvain Sebert, Wilma M. Hopman, Karl-Heinz Jöckel, Ari Voutilainen, Peter Schnohr, Jerzy Chudek, Katia Vergetti Bloch, Vincenzo Capuano, Jyh Eiin Wong, Torben Jørgensen, Anja Schienkiewitz, Nader Saki, Carolina Tarqui-Mamani, Maria Cecília Formoso Assunção, Kazi M. Jamil, Juraci Almeida Cesar, Pedro J Ortiz, Delphine De Smedt, Luciana Zaccagni, Lynne M. Boddy, Jie Hao, David Alejandro González-Chica, Romana Roccaldo, Sara Magnacca, Peter Stehle, Victoria Farrugia Sant'Angelo, Gry Skodje, Maryam Keramati, Tabara Yasuharu, Ali Ghanbari, Gyulli M. Kazakbaeva, Takuro Furusawa, Felicia Cañete, Kari Kuulasmaa, Justina Vaitkeviciute, (NCD-RisC), NCD Risk Factor Collaboration, Imperial College London, Harvard T.H. Chan School of Public Health, Middlesex University [London], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Wellcome TrustEuropean Commission, Clinical Developmental Psychology, APH - Mental Health, Sociology, The Social Context of Aging (SoCA), Nutrition and Health, Iurilli, Maria LC [0000-0003-0409-1635], Zhou, Bin [0000-0002-1741-8628], Ezzati, Majid [0000-0002-2109-8081], Apollo - University of Cambridge Repository, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Public and occupational health, APH - Health Behaviors & Chronic Diseases, VU University medical center, APH - Personalized Medicine, AGEM - Endocrinology, metabolism and nutrition, ACS - Diabetes & metabolism, APH - Global Health, ARD - Amsterdam Reproduction and Development, Adult Psychiatry, Global Health, APH - Quality of Care, APH - Methodology, ACS - Atherosclerosis & ischemic syndromes, Gómez Santos, Santiago Felipe, NCD Risk Factor Collaboration (NCD-RisC), Faculdade de Desporto, Faculdade de Ciências da Nutrição e Alimentação, Faculdade de Medicina, Tampere University, Clinical Medicine, Department of Clinical Chemistry, Eye Centre, Harvard TH Chan School of Public Health, Middlesex University, World Health Organization, Ministry of Health, University of Lausanne, Eduardo Mondlane University, Victor Babes University of Medicine and Pharmacy Timisoara, University of Sydney, Health and Nutrition, University of Auckland, Seoul National University, ICMR - National Institute of Nutrition, Capital Medical University Beijing An Zhen Hospital, Universidad Peruana Cayetano Heredia, University 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Ltd, Orebro University, University of London, Universitas Indonesia, Institute of Food and Nutrition Development of Ministry of Agriculture and Rural Affairs, Children’s Hospital of Fudan University, University of Cyprus, Niigata University, International Medical University, Iran University of Medical Sciences, Center for Diabetes and Endocrine Care, Peking University First Hospital, Jiangsu Provincial Center for Disease Control and Prevention, Sun Yat-sen University, West Kazakhstan Medical University, Inner Mongolia Medical University, University of Ghana, Maria Lc Iurilli , Bin Zhou , James E Bennett , Rodrigo M Carrillo-Larco , Marisa K Sophiea , Andrea Rodriguez-Martinez , Honor Bixby , Bethlehem D Solomon , Cristina Taddei , Goodarz Danaei , Mariachiara Di Cesare , Gretchen A Stevens , Leanne M Riley , Stefan Savin , Melanie J Cowan , Pascal Bovet , Albertino Damasceno , Adela Chirita-Emandi , Alison J Hayes , Nayu Ikeda , Rod T Jackson , Young-Ho Khang , Avula Laxmaiah , Jing 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Enrique Gutiérrez-González , Laura Gutierrez , Felix Gutzwiller , Seongjun Ha , Farzad Hadaegh , Charalambos A Hadjigeorgiou , Rosa Haghshenas , Hamid Hakimi , Jytte Halkjær , Ian R Hambleton , Behrooz Hamzeh , Dominique Hange , Abu Am Hanif , Sari Hantunen , Jie Hao , Rachakulla Hari Kumar , Seyed Mohammad Hashemi-Shahri , Maria Hassapidou , Jun Hata , Teresa Haugsgjerd , Jiang He , Yuan He , Yuna He , Regina Heidinger-Felso , Mirjam Heinen , Tatjana Hejgaard , Marleen Elisabeth Hendriks , Rafael Dos Santos Henrique , Ana Henriques , Leticia Hernandez Cadena , Sauli Herrala , Victor M Herrera , Isabelle Herter-Aeberli , Ramin Heshmat , Allan G Hill , Sai Yin Ho , Suzanne C Ho , Michael Hobbs , Michelle Holdsworth , Reza Homayounfar , Clara Homs , Wilma M Hopman , Andrea Rvr Horimoto , Claudia M Hormiga , Bernardo L Horta , Leila Houti , Christina Howitt , Thein Thein Htay , Aung Soe Htet , Maung Maung Than Htike , Yonghua Hu , José María Huerta , Ilpo Tapani Huhtaniemi , Laetitia Huiart , Constanta Huidumac Petrescu , Martijn Huisman , Abdullatif Husseini , Chinh Nguyen Huu , Inge Huybrechts , Nahla Hwalla , Jolanda Hyska , Licia Iacoviello , Jesús M Ibarluzea , Mohsen M Ibrahim , Norazizah Ibrahim Wong , M Arfan Ikram , Violeta Iotova , Vilma E Irazola , Takafumi Ishida , Muhammad Islam , Sheikh Mohammed Shariful Islam , Masanori Iwasaki , Jeremy M Jacobs , Hashem Y Jaddou , Tazeen Jafar , Kenneth James , Kazi M Jamil , Konrad Jamrozik , Imre Janszky , Edward Janus , Juel Jarani , Marjo-Riitta Jarvelin , Grazyna Jasienska , Ana Jelakovic , Bojan Jelakovic , Garry Jennings , Anjani Kumar Jha , Chao Qiang Jiang , Ramon O Jimenez , Karl-Heinz Jöckel , Michel Joffres , Mattias Johansson , Jari J Jokelainen , Jost B Jonas , Jitendra Jonnagaddala , Torben Jørgensen , Pradeep Joshi , Farahnaz Joukar , Dragana P Jovic , Jacek J Jóźwiak , Anne Juolevi , Gregor Jurak , Iulia Jurca Simina , Vesna Juresa , Rudolf Kaaks , Felix O Kaducu , Anthony Kafatos , Eero O Kajantie , Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , Jelena Kos , Seppo Koskinen , Katsuyasu Kouda , Viktoria A Kovacs , Sudhir Kowlessur , Slawomir Koziel , Jana Kratenova , Wolfgang Kratzer , Susi Kriemler , Peter Lund Kristensen , Steinar Krokstad , Daan Kromhout , Herculina S Kruger , Ruzena Kubinova , Renata Kuciene , Urho M Kujala , Enisa Kujundzic , Zbigniew Kulaga , R Krishna Kumar , Marie Kunešová , Pawel Kurjata , Yadlapalli S Kusuma , Kari Kuulasmaa , Catherine Kyobutungi , Quang Ngoc La , Fatima Zahra Laamiri , Tiina Laatikainen , Carl Lachat , Youcef Laid , Tai Hing Lam , Christina-Paulina Lambrinou , Edwige Landais , Vera Lanska , Georg Lappas , Bagher Larijani , Tint Swe Latt , Laura Lauria , Maria Lazo-Porras , Gwenaëlle Le Coroller , Khanh Le Nguyen Bao , Agnès Le Port , Tuyen D Le , Jeannette Lee , Jeonghee Lee , Paul H Lee , Nils Lehmann , Terho Lehtimäki , Daniel Lemogoum , Naomi S Levitt , Yanping Li , Merike Liivak , Christa L Lilly , Wei-Yen Lim , M Fernanda Lima-Costa , Hsien-Ho Lin , Xu Lin , Yi-Ting Lin , Lars Lind , Allan Linneberg , Lauren Lissner , Mieczyslaw Litwin , Lijuan Liu , Wei-Cheng Lo , Helle-Mai Loit , Khuong Quynh Long , Luis Lopes , Oscar Lopes , Esther Lopez-Garcia , Tania Lopez , Paulo A Lotufo , José Eugenio Lozano , Janice L Lukrafka , Dalia Luksiene , Annamari Lundqvist , Robert Lundqvist , Nuno Lunet , Charles Lunogelo , Michala Lustigová , Edyta Łuszczki , Guansheng Ma , Jun Ma , Xu Ma , George Ll Machado-Coelho , Aristides M Machado-Rodrigues , Luisa M Macieira , Ahmed A Madar , Stefania Maggi , Dianna J Magliano , Sara Magnacca , Emmanuella Magriplis , Gowri Mahasampath , Bernard Maire , Marjeta Majer , Marcia Makdisse , Päivi Mäki , Fatemeh Malekzadeh , Reza Malekzadeh , Rahul Malhotra , Kodavanti Mallikharjuna Rao , Sofia K Malyutina , Lynell V Maniego , Yannis Manios , Jim I Mann , Fariborz Mansour-Ghanaei , Enzo Manzato , Paula Margozzini , Anastasia Markaki , Oonagh Markey , Eliza Markidou Ioannidou , Pedro Marques-Vidal , Larissa Pruner Marques , Jaume Marrugat , Yves Martin-Prevel , Rosemarie Martin , Reynaldo Martorell , Eva Martos , Katharina Maruszczak , Stefano Marventano , Luis P Mascarenhas , Shariq R Masoodi , Ellisiv B Mathiesen , Prashant Mathur , Alicia Matijasevich , Tandi E Matsha , Christina Mavrogianni , Artur Mazur , Jean Claude N Mbanya , Shelly R McFarlane , Stephen T McGarvey , Martin McKee , Stela McLachlan , Rachael M McLean , Scott B McLean , Breige A McNulty , Sounnia Mediene Benchekor , Jurate Medzioniene , Parinaz Mehdipour , Kirsten Mehlig , Amir Houshang Mehrparvar , Aline Meirhaeghe , Jørgen Meisfjord , Christa Meisinger , Ana Maria B Menezes , Geetha R Menon , Gert Bm Mensink , Maria Teresa Menzano , Alibek Mereke , Indrapal I Meshram , Andres Metspalu , Haakon E Meyer , Jie Mi , Kim F Michaelsen , Nathalie Michels , Kairit Mikkel , Karolina Milkowska , Jody C Miller , Cláudia S Minderico , G K Mini , Juan Francisco Miquel , Mohammad Reza Mirjalili , Daphne Mirkopoulou , Erkin Mirrakhimov , Marjeta Mišigoj-Durakovic , Antonio Mistretta , Veronica Mocanu , Pietro A Modesti , Sahar Saeedi Moghaddam , Bahram Mohajer , Mostafa K Mohamed , Shukri F Mohamed , Kazem Mohammad , Zahra Mohammadi , Noushin Mohammadifard , Reza Mohammadpourhodki , Viswanathan Mohan , Salim Mohanna , Muhammad Fadhli Mohd Yusoff , Iraj Mohebbi , Farnam Mohebi , Marie Moitry , Drude Molbo , Line T Møllehave , Niels C Møller , Dénes Molnár , Amirabbas Momenan , Charles K Mondo , Michele Monroy-Valle , Eric Monterrubio-Flores , Kotsedi Daniel K Monyeki , Jin Soo Moon , Mahmood Moosazadeh , Leila B Moreira , Alain Morejon , Luis A Moreno , Karen Morgan , Suzanne N Morin , Erik Lykke Mortensen , George Moschonis , Malgorzata Mossakowska , Aya Mostafa , Anabela Mota-Pinto , Jorge Mota , Mohammad Esmaeel Motlagh , Jorge Motta , Marcos André Moura-Dos-Santos , Malay K Mridha , Kelias P Msyamboza , Thet Thet Mu , Magdalena Muc , Boban Mugoša , Maria L Muiesan , Parvina Mukhtorova , Martina Müller-Nurasyid , Neil Murphy , Jaakko Mursu , Elaine M Murtagh , Kamarul Imran Musa , Sanja Music Milanovic , Vera Musil , Norlaila Mustafa , Iraj Nabipour , Shohreh Naderimagham , Gabriele Nagel , Balkish M Naidu , Farid Najafi , Harunobu Nakamura , Jana Námešná , Ei Ei K Nang , Vinay B Nangia , Martin Nankap , Sameer Narake , Paola Nardone , Matthias Nauck , William A Neal , Azim Nejatizadeh , Chandini Nekkantti , Keiu Nelis , Liis Nelis , Ilona Nenko , Martin Neovius , Flavio Nervi , Chung T Nguyen , Nguyen D Nguyen , Quang Ngoc Nguyen , Ramfis E Nieto-Martínez , Yury P Nikitin , Guang Ning , Toshiharu Ninomiya , Sania Nishtar , Marianna Noale , Oscar A Noboa , Helena Nogueira , Teresa Norat , Maria Nordendahl , Børge G Nordestgaard , Davide Noto , Natalia Nowak-Szczepanska , Mohannad Al Nsour , Irfan Nuhoglu , Eha Nurk , Terence W O'Neill , Dermot O'Reilly , Galina Obreja , Caleb Ochimana , Angélica M Ochoa-Avilés , Eiji Oda , Kyungwon Oh , Kumiko Ohara , Claes Ohlsson , Ryutaro Ohtsuka , Örn Olafsson , Maria Teresa A Olinto , Isabel O Oliveira , Mohd Azahadi Omar , Altan Onat , Sok King Ong , Lariane M Ono , Pedro Ordunez , Rui Ornelas , Ana P Ortiz , Pedro J Ortiz , Merete Osler , Clive Osmond , Sergej M Ostojic , Afshin Ostovar , Johanna A Otero , Kim Overvad , Ellis Owusu-Dabo , Fred Michel Paccaud , Cristina Padez , Ioannis Pagkalos , Elena Pahomova , Karina Mary de Paiva , Andrzej Pajak , Domenico Palli , Alberto Palloni , Luigi Palmieri , Wen-Harn Pan , Songhomitra Panda-Jonas , Arvind Pandey , Francesco Panza , Dimitrios Papandreou , Soon-Woo Park , Suyeon Park , Winsome R Parnell , Mahboubeh Parsaeian , Ionela M Pascanu , Patrick Pasquet , Nikhil D Patel , Ivan Pecin , Mangesh S Pednekar , Nasheeta Peer , Gao Pei , Sergio Viana Peixoto , Markku Peltonen , Alexandre C Pereira , Marco A Peres , Napoleón Pérez-Farinós , Cynthia M Pérez , Valentina Peterkova , Annette Peters , Astrid Petersmann , Janina Petkeviciene , Ausra Petrauskiene , Emanuela Pettenuzzo , Niloofar Peykari , Son Thai Pham , Rafael N Pichardo , Daniela Pierannunzio , Iris Pigeot , Hynek Pikhart , Aida Pilav , Lorenza Pilotto , Francesco Pistelli , Freda Pitakaka , Aleksandra Piwonska , Andreia N Pizarro , Pedro Plans-Rubió , Bee Koon Poh , Hermann Pohlabeln , Raluca M Pop , Stevo R Popovic , Miquel Porta , Georg Posch , Anil Poudyal , Dimitrios Poulimeneas , Hamed Pouraram , Farhad Pourfarzi , Akram Pourshams , Hossein Poustchi , Rajendra Pradeepa , Alison J Price , Jacqueline F Price , Rui Providencia , Jardena J Puder , Iveta Pudule , Soile E Puhakka , Maria Puiu , Margus Punab , Radwan F Qasrawi , Mostafa Qorbani , Tran Quoc Bao , Ivana Radic , Ricardas Radisauskas , Salar Rahimikazerooni , Mahfuzar Rahman , Mahmudur Rahman , Olli Raitakari , Manu Raj , Ellina Rakhimova , Sherali Rakhmatulloev , Ivo Rakovac , Sudha Ramachandra Rao , Ambady Ramachandran , Jacqueline Ramke , Elisabete Ramos , Rafel Ramos , Lekhraj Rampal , Sanjay Rampal , Vayia Rarra , Ramon A Rascon-Pacheco , Mette Rasmussen , Cassiano Ricardo Rech , Josep Redon , Paul Ferdinand M Reganit , Valéria Regecová , Luis Revilla , Abbas Rezaianzadeh , Lourdes Ribas-Barba , Robespierre Ribeiro , Elio Riboli , Adrian Richter , Fernando Rigo , Natascia Rinaldo , Tobias F Rinke de Wit , Ana Rito , Raphael M Ritti-Dias , Juan A Rivera , Cynthia Robitaille , Romana Roccaldo , Daniela Rodrigues , Fernando Rodríguez-Artalejo , María Del Cristo Rodriguez-Perez , Laura A Rodríguez-Villamizar , Ulla Roggenbuck , Rosalba Rojas-Martinez , Nipa Rojroongwasinkul , Dora Romaguera , Elisabetta L Romeo , Rafaela V Rosario , Annika Rosengren , Ian Rouse , Joel Gr Roy , Adolfo Rubinstein , Frank J Rühli , Jean-Bernard Ruidavets , Blanca Sandra Ruiz-Betancourt , Maria Ruiz-Castell , Emma Ruiz Moreno , Iuliia A Rusakova , Kenisha Russell Jonsson , Paola Russo , Petra Rust , Marcin Rutkowski , Charumathi Sabanayagam , Elena Sacchini , Harshpal S Sachdev , Alireza Sadjadi , Ali Reza Safarpour , Saeid Safiri , Nader Saki , Benoit Salanave , Eduardo Salazar Martinez , Diego Salmerón , Veikko Salomaa , Jukka T Salonen , Massimo Salvetti , Margarita Samoutian , Jose Sánchez-Abanto , Sandjaja , Susana Sans , Loreto Santa Marina , Diana A Santos , Ina S Santos , Lèlita C Santos , Maria Paula Santos , Osvaldo Santos , Rute Santos , Sara Santos Sanz , Jouko L Saramies , Luis B Sardinha , Nizal Sarrafzadegan , Thirunavukkarasu Sathish , Kai-Uwe Saum , Savvas Savva , Mathilde Savy , Norie Sawada , Mariana Sbaraini , Marcia Scazufca , Beatriz D Schaan , Angelika Schaffrath Rosario , Herman Schargrodsky , Anja Schienkiewitz , Sabine Schipf , Carsten O Schmidt , Ida Maria Schmidt , Peter Schnohr , Ben Schöttker , Sara Schramm , Stine Schramm , Helmut Schröder , Constance Schultsz , Aletta E Schutte , Aye Aye Sein , Rusidah Selamat , Vedrana Sember , Abhijit Sen , Idowu O Senbanjo , Sadaf G Sepanlou , Victor Sequera , Luis Serra-Majem , Jennifer Servais , Ludmila Ševcíková , Svetlana A Shalnova , Teresa Shamah-Levy , Morteza Shamshirgaran , Coimbatore Subramaniam Shanthirani , Maryam Sharafkhah , Sanjib K Sharma , Jonathan E Shaw , Amaneh Shayanrad , Ali Akbar Shayesteh , Lela Shengelia , Zumin Shi , Kenji Shibuya , Hana Shimizu-Furusawa , Dong Wook Shin , Majid Shirani , Rahman Shiri , Namuna Shrestha , Khairil Si-Ramlee , Alfonso Siani , Rosalynn Siantar , Abla M Sibai , Antonio M Silva , Diego Augusto Santos Silva , Mary Simon , Judith Simons , Leon A Simons , Agneta Sjöberg , Michael Sjöström , Gry Skodje , Jolanta Slowikowska-Hilczer , Przemyslaw Slusarczyk , Liam Smeeth , Hung-Kwan So , Fernanda Cunha Soares , Grzegorz Sobek , Eugène Sobngwi , Morten Sodemann , Stefan Söderberg , Moesijanti Ye Soekatri , Agustinus Soemantri , Reecha Sofat , Vincenzo Solfrizzi , Mohammad Hossein Somi , Emily Sonestedt , Yi Song , Thorkild Ia Sørensen , Elin P Sørgjerd , Charles Sossa Jérome , Victoria E Soto-Rojas , Aïcha Soumaré , Slavica Sovic , Bente Sparboe-Nilsen , Karen Sparrenberger , Angela Spinelli , Igor Spiroski , Jan A Staessen , Hanspeter Stamm , Maria G Stathopoulou , Kaspar Staub , Bill Stavreski , Jostein Steene-Johannessen , Peter Stehle , Aryeh D Stein , George S Stergiou , Jochanan Stessman , Ranko Stevanovic , Jutta Stieber , Doris Stöckl , Tanja Stocks , Jakub Stokwiszewski , Ekaterina Stoyanova , Gareth Stratton , Karien Stronks , Maria Wany Strufaldi , Lela Sturua , Ramón Suárez-Medina , Machi Suka , Chien-An Sun , Johan Sundström , Yn-Tz Sung , Jordi Sunyer , Paibul Suriyawongpaisal , Boyd A Swinburn , Rody G Sy , Holly E Syddall , René Charles Sylva , Moyses Szklo , Lucjan Szponar , E Shyong Tai , Mari-Liis Tammesoo , Abdonas Tamosiunas , Eng Joo Tan , Xun Tang , Maya Tanrygulyyeva , Frank Tanser , Yong Tao , Mohammed Rasoul Tarawneh , Jakob Tarp , Carolina B Tarqui-Mamani , Radka Taxová Braunerová , Anne Taylor , Julie Taylor , Félicité Tchibindat , William R Tebar , Grethe S Tell , Tania Tello , Yih Chung Tham , K R Thankappan , Holger Theobald , Xenophon 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, Luxia Zhang , Zhen-Yu Zhang , Dong Zhao , Ming-Hui Zhao , Wenhua Zhao , Shiqi Zhen , Wei Zheng , Yingfeng Zheng , Bekbolat Zholdin , Maigeng Zhou , Dan Zhu , Marie Zins , Emanuel Zitt , Yanina Zocalo , Julio Zuñiga Cisneros , Monika Zuziak , Majid Ezzati , Sarah Filippi, Epidemiology, Iurilli, Maria LC, Zhou, Bin, Bennett, James E, Carrillo-Larco, Rodrigo M, Sophiea, Marisa K, Rodriguez-Martinez, Andrea, Bixby, Honor, Solomon, Bethlehem D, Taddei, Cristina, Danaei, Goodarz, Di Cesare, Mariachiara, Stevens, Gretchen A, Riley, Leanne M, Savin, Stefan, Cowan, Melanie J, Bovet, Pascal, Damasceno, Albertino, Chirita-Emandi, Adela, Hayes, Alison J, Ikeda, Nayu, Jackson, Rod T, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Miranda, J Jaime, Saidi, Olfa, Sebert, Sylvain, Sorić, Maroje, Starc, Gregor, Gregg, Edward W, Abarca-Gómez, Leandra, Abdeen, Ziad A, Abdrakhmanova, Shynar, Ghaffar, Suhaila Abdul, Rahim, Hanan F Abdul, Abu-Rmeileh, Niveen M, Garba, Jamila Abubakar, Acosta-Cazares, Benjamin, Adams, Robert J, Aekplakorn, Wichai, Afsana, Kaosar, Afzal, Shoaib, Agdeppa, Imelda A, Aghazadeh-Attari, Javad, Aguilar-Salinas, Carlos A, Agyemang, Charle, Ahmad, Mohamad Hasnan, Ahmad, Noor Ani, Ahmadi, Ali, Ahmadi, Naser, Ahmed, Soheir H, Ahrens, Wolfgang, Aitmurzaeva, Gulmira, Ajlouni, Kamel, Al-Hazzaa, Hazzaa M, Al-Lahou, Badreya, Al-Raddadi, Rajaa, Alarouj, Monira, AlBuhairan, Fadia, AlDhukair, Shahla, Ali, Mohamed M, Alkandari, Abdullah, Alkerwi, Ala'a, Allin, Kristine, Alvarez-Pedrerol, Mar, Aly, Eman, Amarapurkar, Deepak N, Amiri, Parisa, Amougou, Norbert, Amouyel, Philippe, Bo Andersen, Lar, Anderssen, Sigmund A, Ängquist, Lar, Anjana, Ranjit Mohan, Ansari-Moghaddam, Alireza, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arku, Raphael E, Arlappa, Nimmathota, Aryal, Krishna K, Aspelund, Thor, Assah, Felix K, Assunção, Maria Cecília F, Aung, May Soe, Auvinen, Juha, Avdicová, Mária, Avi, Shina, Azevedo, Ana, Azimi-Nezhad, Mohsen, Azizi, Fereidoun, Azmin, Mehrdad, Babu, Bontha V, Jørgensen, Maja Bæksgaard, Baharudin, Azli, Bahijri, Suhad, Baker, Jennifer L, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, José R, Baran, Joanna, Barbagallo, Carlo M, Barceló, Alberto, Barkat, Amina, Barros, Aluisio JD, Barros, Mauro Virgílio Gome, Basit, Abdul, Bastos, Joao Luiz D, Bata, Iqbal, Batieha, Anwar M, Batista, Rosangela L, Battakova, Zhamilya, Batyrbek, Assembekov, Baur, Louise A, Beaglehole, Robert, Bel-Serrat, Silvia, Belavendra, Antonisamy, Romdhane, Habiba Ben, Benedics, Judith, Benet, Mikhail, Bergh, Ingunn Holden, Berkinbayev, Salim, Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloísa, Bezerra, Jorge, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K, Bhutta, Zulfiqar A, Bi, Hongsheng, Bi, Yufang, Bia, Daniel, Lele, Elysée Claude Bika, Bikbov, Mukharram M, Bista, Bihungum, Bjelica, Dusko J, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B, Björkelund, 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Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savva, Savy, Mathilde, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schmidt, Ida Maria, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schramm, Stine, Schröder, Helmut, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Selamat, Rusidah, Sember, Vedrana, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sequera, Victor, Serra-Majem, Lui, Servais, Jennifer, Ševcíková, Ludmila, Shalnova, Svetlana A, Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shengelia, Lela, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinu, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed

Published
2021
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42. Consensus on Diagnosis and Management of Cushing’s Disease: A Guideline Update

Author

Stylianos Tsagarakis, Ashley B. Grossman, André Lacroix, Maria Chiara Zatelli, Hershel Raff, Lynnette K. Nieman, Eliza B Geer, Cesar Luiz Boguszewski, Beverly M. K. Biller, Marily Theodoropoulou, Mark E. Molitch, Daniel F. Kelly, Alberto M. Pereira, Marcello D. Bronstein, Brooke Swearingen, Stephan Petersenn, Irina Bancos, Adriana G. Ioachimescu, Frederic Castinetti, Ken K. Y. Ho, Ilan Shimon, Martin Reincke, Susan M. Webb, Richard J. Auchus, John Newell-Price, Roberto Salvatori, Shlomo Melmed, Carla Scaroni, Maria Fleseriu, Ursula B. Kaiser, Greisa Vila, Jérôme Bertherat, Anat Ben-Shlomo, Andrea Giustina, Mônica R. Gadelha, Michael Buchfelder, James W. Findling, Mark Gurnell, Rosario Pivonello, Philippe Chanson, Yutaka Takahashi, John A.H. Wass, Nienke R. Biermasz, Ann McCormack, Niki Karavitaki, Felipe F. Casanueva, Laurence Katznelson, Elena Valassi, Antoine Tabarin, John D. Carmichael, Pietro Mortini, Constantine A. Stratakis, Elena V. Varlamov, Fleseriu, M., Auchus, R., Bancos, I., Ben-Shlomo, A., Bertherat, J., Biermasz, N. R., Boguszewski, C. L., Bronstein, M. D., Buchfelder, M., Carmichael, J. D., Casanueva, F. F., Castinetti, F., Chanson, P., Findling, J., Gadelha, M., Geer, E. B., Giustina, A., Grossman, A., Gurnell, M., Ho, K., Ioachimescu, A. G., Kaiser, U. B., Karavitaki, N., Katznelson, L., Kelly, D. F., Lacroix, A., Mccormack, A., Melmed, S., Molitch, M., Mortini, P., Newell-Price, J., Nieman, L., Pereira, A. M., Petersenn, S., Pivonello, R., Raff, H., Reincke, M., Salvatori, R., Scaroni, C., Shimon, I., Stratakis, C. A., Swearingen, B., Tabarin, A., Takahashi, Y., Theodoropoulou, M., Tsagarakis, S., Valassi, E., Varlamov, E. V., Vila, G., Wass, J., Webb, S. M., Zatelli, M. C., and Biller, B. M. K.

Subjects
medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Medizin, Treatment options, Guideline, Disease, Cushing's disease, medicine.disease, Article, NO, Clinical Practice, Endocrinology, Pituitary, cushing disease, Internal Medicine, Medicine, Medical physics, LS4_3, business
Abstract

Summary Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants. During the meeting, concise summaries of the recorded lectures were presented, followed by small group breakout discussions. Consensus opinions from each group were collated into a draft document, which was reviewed and approved by all participants. Recommendations regarding use of laboratory tests, imaging, and treatment options are presented, along with algorithms for diagnosis of Cushing's syndrome and management of Cushing's disease. Topics considered most important to address in future research are also identified.

Published
2021

43. Adipose tissue and blood leukocytes ACE2 DNA methylation in obesity and after weight loss

Author

Ana B. Crujeiras, D.A. de Luis, Paula Oliver, J. Alfredo Martínez, Hatim Boughanem, José Manuel Fernández-Real, Carolina Ferreira Nicoletti, Manuel Macias-Gonzalez, Carla Barbosa Nonino, Francisco J. Tinahones, Felipe F. Casanueva, M.A. Martinez-Olmos, José María Moreno-Navarrete, María P. Portillo, Andrea G. Izquierdo, and Marcos C. Carreira

Subjects
Adult, Male, medicine.medical_specialty, Diet, Reducing, medicine.medical_treatment, Clinical Biochemistry, Subcutaneous Fat, Adipose tissue, Bariatric Surgery, Intra-Abdominal Fat, Biochemistry, Weight loss, Internal medicine, Weight Loss, medicine, Humans, Epigenetics, Obesity, Aged, Aged, 80 and over, business.industry, SARS-CoV-2, COVID-19, General Medicine, Methylation, DNA Methylation, Middle Aged, medicine.disease, Obesity, Morbid, Endocrinology, CpG site, Gene Expression Regulation, DNA methylation, Leukocytes, Mononuclear, Female, Angiotensin-Converting Enzyme 2, medicine.symptom, business, Diet, Ketogenic, hormones, hormone substitutes, and hormone antagonists, Ketogenic diet, Receptors, Coronavirus
Abstract

Background: Obesity was consistently associated with a poor prognosis in patients with COVID-19. Epigenetic mechanisms were proposed as the link between obesity and comorbidities risk. Aim: To evaluate the methylation levels of angiotensin-converting enzyme 2 (ACE2) gene, the main entry receptor of SARS-CoV-2, in different depots of adipose tissue (AT) and leukocytes (PBMCs) in obesity and after weight loss therapy based on a very-low-calorie ketogenic diet (VLCKD), a balanced hypocaloric diet (HCD) or bariatric surgery (BS). Materials and Methods: DNA methylation levels of ACE2 were extracted from our data sets generated by the hybridization of subcutaneous (SAT) (n = 32) or visceral (VAT; n = 32) adipose tissue, and PBMCs (n = 34) samples in Infinium HumanMethylation450 BeadChips. Data were compared based on the degree of obesity and after 4–6 months of weight loss either by following a nutritional or surgical treatment and correlated with ACE2 transcript levels. Results: As compared with normal weight, VAT from patients with obesity showed higher ACE2 methylation levels. These differences were mirrored in PBMCs but not in SAT. The observed obesity-associated methylation of ACE2 was reversed after VLCKD and HCD but not after BS. Among the studied CpG sites, cg16734967 and cg21598868, located at the promoter, were the most affected and correlated with BMI. The observed DNA methylation pattern was inversely correlated with ACE2 expression. Conclusion: Obesity-related VAT shows hypermethylation and downregulation of the ACE2 gene that is mirrored in PBMCs and is restored after nutritional weight reduction therapy. The results warrant the necessity to further evaluate its implication for COVID-19 pathogenesis.

Published
2021

44. Erectile dysfunction predicts mortality in middle-aged and older men independent of their sex steroid status

Author

Leen, Antonio, Frederick C W, Wu, Hannes, Moors, Cathy, Matheï, Ilpo T, Huhtaniemi, Giulia, Rastrelli, Marian, Dejaeger, Terence W, O'Neill, Stephen R, Pye, Gianni, Forti, Mario, Maggi, Felipe F, Casanueva, Jolanta, Slowikowska-Hilczer, Margus, Punab, Jos, Tournoy, Dirk, Vanderschueren, and Paul, Korrovitz Tartu

Subjects
Male, Aging, Erectile Dysfunction, Libido, Humans, Female, Testosterone, General Medicine, Prospective Studies, Geriatrics and Gerontology, Middle Aged, Aged
Abstract

Background erectile dysfunction is associated with mortality, whereas the association between low testosterone (T) and higher mortality remains controversial. Sexual dysfunction and low T often coexist, but the relative importance of sexual symptoms versus low T in predicting mortality is not known. We studied the interrelationships between sex steroids and sexual symptoms with all-cause mortality in a large prospective cohort of European men. Design survival status was assessed in 1,788 community-dwelling men, aged 40–79, who participated in the European Male Ageing Study (EMAS). Sexual symptoms were evaluated via a validated questionnaire (EMAS-SFQ). Sex steroids were measured by mass spectrometry. Cox proportional hazard models were used to study the association between hormones, sexual symptoms and mortality. Results about 420 (25.3%) men died during a mean follow-up of 12.6 ± 3.1 years. Total T levels were similar in both groups, but free T was lower in those who died. Men with three sexual symptoms (erectile dysfunction, reduced morning erections and lower libido) had a higher mortality risk compared with men with none of these symptoms (adjusted hazard ratio (HR) and 95% confidence intervals: 1.75 (1.28–2.40, P = 0.001)). Particularly, erectile dysfunction and poor morning erections, but not lower libido, were associated with increased mortality (HR 1.40 (1.13–1.74, P = 0.002), 1.28 (1.04–1.59, P = 0.023) and 1.12 (0.90–1.39, P = 0.312), respectively). Further adjusting for total T, free T or oestradiol did not influence the observed risk. Conclusions sexual symptoms, in particular erectile dysfunction, predict all-cause mortality independently of sex steroids and can be an early warning sign of a poor health status.

Published
2021

45. Confusion in the nomenclature of ketogenic diets blurs evidence

Author

Diego Bellido, Pierpaolo Trimboli, Felipe F. Casanueva, and Marco Castellana

Subjects
medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Type 2 Diabetes Mellitus, 030209 endocrinology & metabolism, Context (language use), medicine.disease, Polycystic ovary, Obesity, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Endocrinology, Diabetes mellitus, medicine, Dementia, Intensive care medicine, business, Ketogenic diet
Abstract

Ketogenic diets have been proposed as a non-pharmacological strategy for the management of several chronic conditions. Their efficacy and safety have been evaluated in the field of neurology, oncology and endocrinology for disorders including cancer, dementia, drug-resistant epilepsy, migraines, obesity, polycystic ovary syndrome and type 2 diabetes mellitus. The nutritional requirements of these subjects are expected to differ significantly. Indeed, although all ketogenic diets restrict carbohydrates, each intervention is characterized by a specific daily calorie intake, macronutrient composition and duration. However, the adopted nomenclature was often unclear to the general reader; also, the same abbreviations for different protocols were used. This possibly resulted in mistakes in the interpretation of the available evidence and limited the impact of studies on the topic in the clinical practice. Adopting a clear and consistent vocabulary is key in any context. Here, we present a practical and clinically-based proposal for the classification and abbreviation of ketogenic diets.

Published
2020
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46. Modulation of Higher-Order Olfaction Components on Executive Functions in Humans.

Author

Ana B Fagundo, Susana Jiménez-Murcia, Cristina Giner-Bartolomé, Mohammed Anisul Islam, Rafael de la Torre, Antoni Pastor, Felipe F Casanueva, Ana B Crujeiras, Roser Granero, Rosa Baños, Cristina Botella, Jose M Fernández-Real, Gema Frühbeck, Javier Gómez-Ambrosi, José M Menchón, Francisco J Tinahones, and Fernando Fernández-Aranda

Subjects
Medicine, Science
Abstract

The prefrontal (PFC) and orbitofrontal cortex (OFC) appear to be associated with both executive functions and olfaction. However, there is little data relating olfactory processing and executive functions in humans. The present study aimed at exploring the role of olfaction on executive functioning, making a distinction between primary and more cognitive aspects of olfaction. Three executive tasks of similar difficulty were used. One was used to assess hot executive functions (Iowa Gambling Task-IGT), and two as a measure of cold executive functioning (Stroop Colour and Word Test-SCWT and Wisconsin Card Sorting Test-WCST). Sixty two healthy participants were included: 31 with normosmia and 31 with hyposmia. Olfactory abilities were assessed using the ''Sniffin' Sticks'' test and the olfactory threshold, odour discrimination and odour identification measures were obtained. All participants were female, aged between 18 and 60. Results showed that participants with hyposmia displayed worse performance in decision making (IGT; Cohen's-d = 0.91) and cognitive flexibility (WCST; Cohen's-d between 0.54 and 0.68) compared to those with normosmia. Multiple regression adjusted by the covariates participants' age and education level showed a positive association between odour identification and the cognitive inhibition response (SCWT-interference; Beta = 0.29; p = .034). The odour discrimination capacity was not a predictor of the cognitive executive performance. Our results suggest that both hot and cold executive functions seem to be associated with higher-order olfactory functioning in humans. These results robustly support the hypothesis that olfaction and executive measures have a common neural substrate in PFC and OFC, and suggest that olfaction might be a reliable cognitive marker in psychiatric and neurologic disorders.

Published
2015
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47. Changes in Body Composition in Anorexia Nervosa: Predictors of Recovery and Treatment Outcome.

Author

Zaida Agüera, Xandra Romero, Jon Arcelus, Isabel Sánchez, Nadine Riesco, Susana Jiménez-Murcia, Jana González-Gómez, Roser Granero, Nuria Custal, Monica Montserrat-Gil de Bernabé, Salomé Tárrega, Rosa M Baños, Cristina Botella, Rafael de la Torre, José C Fernández-García, José M Fernández-Real, Gema Frühbeck, Javier Gómez-Ambrosi, Francisco J Tinahones, Ana B Crujeiras, Felipe F Casanueva, José M Menchón, and Fernando Fernández-Aranda

Subjects
Medicine, Science
Abstract

The restoration of body composition (BC) parameters is considered to be one of the most important goals in the treatment of patients with anorexia nervosa (AN). However, little is known about differences between AN diagnostic subtypes [restricting (AN-R) and binge/purging (AN-BP)] and weekly changes in BC during refeeding treatment. Therefore, the main objectives of our study were twofold: 1) to assess the changes in BC throughout nutritional treatment in an AN sample and 2) to analyze predictors of BC changes during treatment, as well as predictors of treatment outcome. The whole sample comprised 261 participants [118 adult females with AN (70 AN-R vs. 48 AN-BP), and 143 healthy controls]. BC was measured weekly during 15 weeks of day-hospital treatment using bioelectrical impedance analysis (BIA). Assessment measures also included the Eating Disorders Inventory-2, as well as a number of other clinical indices. Overall, the results showed that AN-R and AN-BP patients statistically differed in all BC measures at admission. However, no significant time×group interaction was found for almost all BC parameters. Significant time×group interactions were only found for basal metabolic rate (p = .041) and body mass index (BMI) (p = .035). Multiple regression models showed that the best predictors of pre-post changes in BC parameters (namely fat-free mass, muscular mass, total body water and BMI) were the baseline values of BC parameters. Stepwise predictive logistic regressions showed that only BMI and age were significantly associated with outcome, but not with the percentage of body fat. In conclusion, these data suggest that although AN patients tended to restore all BC parameters during nutritional treatment, only AN-BP patients obtained the same fat mass values as healthy controls. Put succinctly, the best predictors of changes in BC were baseline BC values, which did not, however, seem to influence treatment outcome.

Published
2015
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48. Peripheral Signals Mediate the Beneficial Effects of Gastric Surgery in Obesity

Author

Silvia Barja-Fernández, Cintia Folgueira, Cecilia Castelao, Rosaura Leis, Felipe F. Casanueva, and Luisa M. Seoane

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Obesity is nowadays a public health problem both in the industrialized world and developing countries. The different treatments to fight against obesity are not very successful with the exception of gastric surgery. The mechanism behind the achievement of this procedure remains unclear although the modifications in the pattern of gastrointestinal hormones production appear to be responsible for the beneficial effect. The gastrointestinal tract has emerged in the last time as an endocrine organ in charge of response to the different stimulus related to nutritional status by the modulation of more than 30 signals acting at central level to modulate food intake and body weight. The production of some of these gastric derived signals has been proved to be altered in obesity (ghrelin, CCK, and GLP-1). In fact, bariatric surgery modifies the production of both gastrointestinal and adipose tissue peripheral signals beyond the gut microbiota composition. Through this paper the main peripheral signals altered in obesity will be reviewed together with their modifications after bariatric surgery.

Published
2015
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49. An energy restriction‐based weight loss intervention is able to reverse the effects of obesity on the expression of liver tumor‐promoting genes

Author

Maria Amil, Andrea G. Izquierdo, Alfredo Fernández-Quintela, Felipe F. Casanueva, Carlos S. Mosteiro, María P. Portillo, Marcos C. Carreira, Ana B. Crujeiras, and Tomás García-Caballero

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Liver tumor, Tumor suppressor gene, Inflammation, medicine.disease_cause, Biochemistry, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Weight loss, Proto-Oncogene Proteins, Internal medicine, Weight Loss, Genetics, medicine, Animals, Obesity, Molecular Biology, Caloric Restriction, business.industry, medicine.disease, Rats, Rats, Zucker, 030104 developmental biology, Endocrinology, Gene Expression Regulation, Liver, medicine.symptom, business, Carcinogenesis, 030217 neurology & neurosurgery, Oxidative stress, Biotechnology
Abstract

The epidemiological evidence regarding the association of obesity with liver disease and possibly hepatocellular carcinoma highlights the need for investigations of whether obesity itself could induce the differential expression of genes commonly associated with the initial phase of liver tumorigenesis, and whether such phenomenon could be reversed after a weight loss intervention. In this study, obese Zucker rats were found to have dysregulated cell proliferation, antioxidative defenses, and tumor suppressor gene expression in association with liver dysfunction parameters, as well as oxidative stress and inflammation. Importantly, after a 4-week weight loss protocol of energy restriction and/or exercise, this effect on the liver carcinogenesis-related genes was reversed concomitantly with reductions in the fat mass, hepatic lipid content, oxidative stress, and inflammation. The findings indicate that the oxidative stress and inflammation associated with excess adiposity promote dysregulation of the genes involved in liver tumorigenesis. This is clinically relevant because these effects were detectable in the liver without evidence of a tumoral mass and were reversed after weight loss. Consequently, this study reveals the susceptibility of obese individuals to the initiation of a hepatocarcinogenic process, and how this can be prevented by achieving a healthy body weight.

Published
2019
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50. GLP‐1 induces alpha cell proliferation and overrides leptin suppression induced by negative energy balance in vagotomized rats

Author

Tiago Morais, Felipe F. Casanueva, Sara Andrade, Marcos C. Carreira, Bárbara Patrício, Sofia S Pereira, and Mariana P. Monteiro

Subjects
Leptin, Male, 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Vagotomy, Carbohydrate metabolism, Biochemistry, Energy homeostasis, Eating, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Glucagon-Like Peptide 1, Internal medicine, Brown adipose tissue, medicine, Animals, Homeostasis, Molecular Biology, Cell Proliferation, business.industry, Insulin, Body Weight, digestive, oral, and skin physiology, Cell Biology, medicine.disease, Rats, Vagus nerve, Glucose, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Glucagon-Secreting Cells, 030220 oncology & carcinogenesis, Ghrelin, Energy Metabolism, business, hormones, hormone substitutes, and hormone antagonists
Abstract

Glucagon-like peptide-1 (GLP-1) influences energy balance by exerting effects on food intake and glucose metabolism, through mechanisms that are partially dependent on the vagal pathway. The aim of this study was to characterize the effects of chronic GLP-1 stimulation on energy homeostasis and glucose metabolism in the absence of vagal innervation. Truncal vagotomized (VGX) and sham operated rats (SHAM) received an intraperitoneal GLP-1 infusion (3.5 pmol/kg/min) trough mini-osmotic pumps. To dissect the effects derived from vagal denervation on food intake, an additional group was included consisting of sham operated rats that were PAIR FED to VGX. Food intake and body weight were recorded throughout the experimental period, while the percentage of white and brown adipose tissue, fasting glucose, insulin, gastro-intestinal hormonal profile, hypothalamic, and BAT gene expression were assessed at endpoint. VGX rats had significantly lower food intake, body weight gain, and leptin levels when compared with SHAM rats. Despite having similar body weight, PAIR-FED rats had lower fasting leptin, insulin and insulin resistance, while having higher ghrelin levels than VGX. GLP-1 infusion did not influence food intake or body weight, but was associated with lower leptin levels in VGX and lower pancreatic α-cells ki-67 staining in SHAM. Concluding, this study corroborates that the vagus nerve may modulate whole body energy homeostasis by acting in peripheral signals. Our data suggest that in the absence of vagal or parasympathetic tonus, GLP-1 mediated inhibition of cell proliferation markers in α-cells is prevented, meanwhile leptin suppression, associated with a negative energy balance, is partially overridden.

Published
2019
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