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D Benaiges,1–3 JJ Chillarón,1–3 MJ Carrera,1,3 F Cots,3,4 J Puig de Dou,1 E Corominas,1 J Pedro-Botet,1–3 JA Flores-Le Roux,1–3 C Claret,1 A Goday,1–3 JF Cano1–3 1Department of Endocrinology and Nutrition, Hospital del Mar, 2Department of Medicine, Universitat Autònoma de Barcelona, 3Institut Hospital del Mar d’Investigacions Mèdiques, 4Epidemiology and Evaluation Department, Parc de Salut Mar, Barcelona, Spain Background: The purpose of this prospective cohort study was to compare the costs of day hospital (DH) care for hyperglycemic crisis in elderly diabetic patients with those of conventional hospitalization (CH). Secondary objectives were to compare these two clinical scenarios in terms of glycemic control, number of emergency and outpatient visits, readmissions, hypoglycemic episodes, and nosocomial morbidity. Methods: The study population comprised diabetic patients aged >74 years consecutively admitted to a tertiary teaching hospital in Spain for hyperglycemic crisis (sustained hyperglycemia [>300 mg/dL] for at least 3 days with or without ketosis). The patients were assigned to DH or CH care according to time of admission and were followed for 6 months after discharge. Exclusion criteria were ketoacidosis, hyperosmolar crisis, hemodynamic instability, severe intercurrent illness, social deprivation, or Katz index >D.Results: Sixty-four diabetic patients on DH care and 36 on CH care were included, with no differences in baseline characteristics. The average cost per patient was 1,345.1±793.6 € in the DH group and 2,212.4±982.5 € in the CH group (P

Abstract Background There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the superiority of Roux-en-Y gastric bypass (RYGB) for reducing low-density lipoprotein (LDL) cholesterol. The main aim was to ascertain whether high LDL cholesterol levels should be considered when selecting the most appropriate surgical procedure for each patient (RYGB or SG). Methods In this single-center, randomized clinical trial using intention-to-treat analysis, 38 patients with severe obesity and elevated levels of LDL cholesterol were randomly assigned to undergo RYGB or SG. The primary outcome was LDL cholesterol remission at 12 months, defined as LDL cholesterol

Abstract Background The Mediterranean diet (MedDiet) has demonstrated efficacy in preventing age-related cognitive decline and modulating plasma concentrations of endocannabinoids (eCBs) and N-acylethanolamines (NAEs, or eCB-like compounds), which are lipid mediators involved in multiple neurological disorders and metabolic processes. Hypothesizing that eCBs and NAEs will be biomarkers of a MedDiet intervention and will be related to the cognitive response, we investigated this relationship according to sex and apolipoprotein E (APOE) genotype, which may affect eCBs and cognitive performance. Methods This was a prospective cohort study of 102 participants (53.9% women, 18.8% APOE-ɛ4 carriers, aged 65.6 ± 4.5 years) from the PREDIMED-Plus-Cognition substudy, who were recruited at the Hospital del Mar Research Institute (Barcelona). All of them presented metabolic syndrome plus overweight/obesity (inclusion criteria of the PREDIMED-Plus) and normal cognitive performance at baseline (inclusion criteria of this substudy). A comprehensive battery of neuropsychological tests was administered at baseline and after 1 and 3 years. Plasma concentrations of eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and N-docosahexaenoylethanolamine (DHEA), were also monitored. Baseline cognition, cognitive changes, and the association between eCBs/NAEs and cognition were evaluated according to gender (crude models), sex (adjusted models), and APOE genotype. Results At baseline, men had better executive function and global cognition than women (the effect size of gender differences was − 0.49, p = 0.015; and − 0.42, p = 0.036); however, these differences became nonsignificant in models of sex differences. After 3 years of MedDiet intervention, participants exhibited modest improvements in memory and global cognition. However, greater memory changes were observed in men than in women (Cohen’s d of 0.40 vs. 0.25; p = 0.017). In men and APOE-ε4 carriers, 2-AG concentrations were inversely associated with baseline cognition and cognitive changes, while in women, cognitive changes were positively linked to changes in DHEA and the DHEA/AEA ratio. In men, changes in the OEA/AEA and OEA/PEA ratios were positively associated with cognitive changes. Conclusions The MedDiet improved participants’ cognitive performance but the effect size was small and negatively influenced by female sex. Changes in 2-AG, DHEA, the OEA/AEA, the OEA/PEA and the DHEA/AEA ratios were associated with cognitive changes in a sex- and APOE-dependent fashion. These results support the modulation of the endocannabinoid system as a potential therapeutic approach to prevent cognitive decline in at-risk populations. Trial registration ISRCTN89898870.

Stephen Jones,1 Conxa Castell,2 Albert Goday,3 Helen T Smith,4 Claudia Nicolay,5 Alexander Simpson,4 Carole Salaun-Martin61James Cook University Hospital, Middlesborough, UK; 2Department of Health, Barcelona, Spain; 3Hospital Del Mar, Barcelona, Spain; 4Eli Lilly and Company, Erl Wood, UK; 5Lilly Deutschland GmbH, Bad Homburg, Germany; 6Lilly France, Suresnes, FranceBackground: The purpose of this study was to describe the resource use and associated direct costs of diabetes care for patients with type 2 diabetes mellitus in the 6 months before and after initiation of insulin therapy.Methods: INSTIGATE is a prospective, noninterventional, multicenter study of patients with type 2 diabetes who were initiating insulin for the first time as part of their usual care in 2006. The study was conducted in France, Germany, Greece, Spain, and the UK, and observed the course of diabetes therapy for up to 6 months. Direct medical costs were evaluated from the national health care system (third-party payer) perspective at 2006 prices.Results: Of the 1153 patients with type 2 diabetes, 1051 (91.2%) had follow-up visits in the 6 months after insulin initiation and were included in the cost analysis. In all countries in our study, mean total direct costs per patient increased in the 6-month follow-up period, compared with the 6-month period prior to insulin initiation, and ranged from €577 in Greece to €1402 in France. The incremental cost of adding insulin treatment ranged from €81 in France to €471 in Spain.Conclusion: In all countries, the mean total direct cost of care for diabetes increased after starting insulin. The breakdown of total direct costs by expenditure category varied considerably across countries, reflecting differences in resource use patterns, prices of medical resources, and different health care systems.Keywords: type 2 diabetes mellitus, costs, resource use, insulin

BackgroundBariatric surgery (BS) is the most effective intervention for severe obesity, leading to sustained weight loss, reduced obesity-related comorbidities, and cardiovascular mortality.AimTo assess changes in high-density lipoprotein (HDL) functions [cholesterol efflux capacity (CEC) and anti-inflammatory capacity] at different follow-up times in patients with severe obesity undergoing BS.MethodsA prospective observational study within a cohort of consecutively enrolled patients with severe obesity scheduled to undergo BS. In total, 62 participants (77% women), with a mean age of 42.1 years (SD 9.33 years) underwent BS. Regarding the surgical procedure, 27 (43.5%) underwent sleeve gastrectomy and 35 (56.5%) Roux-en-Y gastric bypass. All patients were evaluated preoperatively and at 1, 3, 6, and 12 months after surgery.ResultsA decrease in body mass index and an improvement in the systemic lipid profile, indicated by reductions in total cholesterol, low-density lipoprotein cholesterol (LDLc), and remnant cholesterol, and an increase in HDL cholesterol (HDLc) was observed (all p trend

IntroductionDistinct androgen formulations have been used as gender-affirming hormone treatment, but little is known about the specific changes that may occur in the ovary depending on the testosterone preparation used. The study aims to evaluate the histological modifications of the ovarian tissue and the hormonal changes after gender-affirming surgery based on the testosterone preparation employed, such as testosterone cypionate or undecanoate.DesignUnicenter transversal cohort study.Materials and methodsSixty transmasculine persons before and after gender-affirming surgery. A histological examination of the ovaries was conducted, including the follicular population and the characterization of the ovarian stroma. Hormonal status (testosterone, estradiol, FSH, and LH) were also assessed before and after the procedure.ResultsThe median age of participants was similar between the two groups (27.9 vs. 26.7 years, p = 0.27). There were no differences in all hormonal determinations before gender-affirming surgery between the groups. After surgery, FSH levels increased significantly, especially in the testosterone undecanoate group compared to the cypionate group (72.3 vs. 38.3 U/L, p = 0.02), consistent with LH determinations (43.0 vs. 23.4 U/L, p = 0.02). However, no regimen modification was required for any individual. No statistical differences were observed in any parameter concerning the follicular population, nor were there any variances in the thickness of the tunica albuginea (p = 0.85) or the proportion of luteinized stromal cells. Nevertheless, there was a tendency toward increased luteinization in the testosterone cypionate group (88.2% vs. 76.9%, p > 0.05).ConclusionsIn a cohort of transmasculine individuals using different androgen preparations, histological analysis of ovarian tissue revealed comparable findings. Both groups exhibited similar follicular populations and comparable modifications in stromal tissue. However, significant differences were observed in hormonal profiles, although no modification in testosterone dosage was needed.

Objectives: The evidence on water intake in the prevention of kidney function decline is scarce at population level in well-being individuals at high cardiovascular risk. Therefore, we aimed to longitudinally evaluate the associations between total water intake and subtypes and kidney function, through estimated-Glomerular Filtration Rate (eGFR). Methods: Three-year prospective analysis conducted in 1986 older adults (aged 55–75 year) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus study. Water intake was assessed using validated beverage and food frequency questionnaires. Serum creatinine-based eGFR (SCr-based eGFR; ml/min/1.73 m2) was estimated using the CKD-EPI equation at baseline, one-year and 3-years of follow-up. Mixed-effects linear regression models were fitted to evaluate the associations between baseline total water intake and subtypes, and SCr-based eGFR over 3-years of follow-up. Results: Participants in the highest baseline tertile of total water intake, plain water and water from all fluids showed a lower decrease in SCr-based eGFR after 3-years of follow-up, compared to those in the lowest tertile. Participants with the highest tap water consumption showed a lower SCr-based eGFR decline after 1-year and 3-years of follow-up, in comparerd to participants in the lowest intake category (T3 vs. T1: β: 1.4 ml/min/1.73 m2; 95%CI: 0.5–2.3, β: 1.0; 95%CI: 0.1–2.0, respectively). Conclusions: Plain water rather than other water sources, and especially tap water, was associated with lower kidney function decline assessed through eGFR over 3-years of follow-up, in older individuals at high cardiovascular risk. Trial registration: ISRCTN89898870. Retrospectively registered on 24 July 2014

Abstract Background Fragile X-associated primary ovarian insufficiency (FXPOI), characterized by amenorrhea before age 40 years, occurs in 20% of female FMR1 premutation carriers. Presently, there are no molecular or biomarkers that can help predicting which FMR1 premutation women will develop FXPOI. We previously demonstrated that high FMR4 levels can discriminate between FMR1 premutation carriers with and without FXPOI. In the present study the relationship between the expression levels of FMR4 and the ovarian reserve markers was assessed in female FMR1 premutation carriers under age of 35 years. Methods We examined the association between FMR4 transcript levels and the measures of total antral follicle count (AFC) and serum anti-müllerian hormone (AMH) levels as markers of ovarian follicle reserve. Results Results revealed a negative association between FMR4 levels and AMH (r = 0.45) and AFC (r = 0.64). Statistically significant higher FMR4 transcript levels were found among those FMR1 premutation women with both, low AFCs and AMH levels. Conclusions These findings reinforce previous studies supporting the association between high levels of FMR4 and the risk of developing FXPOI in FMR1 premutation carriers.

Pediatric Feeding Disorder, a common problem in children, is commoner in children with various developmental disorders. Children with pediatric feeding disorder can have food selectivity and lack dietary diversity (DD). In this paper, an understanding of DD in these children is provided along with a dietary diversity index that can be helpful in measuring and understanding the risks posed by this lack of DD. An overview of a management strategy to address decreased DD is proposed. In these children, improving DD can improve growth, micronutrient status, long-term metabolic health, and potentially quality of life.

This project aims to establish the acceptability and satiety of a hybrid snack containing plant protein and a small percentage of animal protein compared to a meat-based snack. Design: Randomised, crossover, double-blind, controlled post-prandial trial involving 24 participants (18–30 years), with two interventions: (a) a hybrid snack containing plant protein derived from chickpeas and 6.6% lean high-quality pork meat; and (b) a meat-based snack containing 90% lean pork meat. Methods: General, life-style, sensory acceptability questionnaire, and the following laboratory analyses were performed: lipid profile, endocannabinoids, and related compounds. Results: Sensory questionnaires showed in general good acceptability for both bars. Additionally, there was a greater increase in glycemia at 30, 60, and 90 min after consuming the hybrid snack compared to the meat-based snack, with no changes in the lipid profile. Regarding the endocannabinoid compounds and related compounds, the compound N-palmitoleoyl ethanolamine in the acylethanolamide group showed higher levels overall following the consumption of the hybrid snack compared to the meat-based snack, particularly at 2 h. Conclusions: The hybrid snack was associated with changes in endocannabinoid-like compounds. Therefore, it may provide a lasting satiating effect, while complementing the protein profile of plant-based foods with the quality of animal protein.

Background: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. Objective: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. Methods: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. Results: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [β-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. Discussion: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.

Background: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown. Methods: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data. Results: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001). Conclusions: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.

Abstract Background Metabolic syndrome (MetS) has become a growing risk factor of some non-communicable diseases. Increase of greenhouse gas emissions affects the planet. Aims To assess the association between MetS severity and amount of carbon dioxide (CO2) emitted in an adult population. Design Cross-sectional study (n = 6646; 55-76-year-old-men; 60-75-year-old-women with MetS). Methods Dietary habits were assessed using a pre-validated semi quantitative 143-item food frequency questionnaire. The amount of CO2 emitted due to the production of food consumed by person and day was calculated using a European database, and the severity of the MetS was calculated with the MetS Severity Score. Results Higher glycaemia levels were found in people with higher CO2 emissions. The risk of having high severe MetS was related to high CO2 emissions. Conclusions Low CO2 emissions diet would help to reduce MetS severity. Advantages for both health and the environment were found following a more sustainable diet. Trial registration ISRCTN, ISRCTN89898870 . Registered 05 September 2013.

ABSTRACTTo evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis−4 score (FIB−4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (−24.9 to −7.51), T2 (−7.5 to −1.86), T3 (−1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB−4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB−4 tertile of change: T1 (−89.60 to −5.57), T2 (−5.56 to 11.4), and T3 (11.41 to 206.24). FIB−4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB−4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.

Abstract Background Patients with type 2 diabetes mellitus and heart failure have adverse clinical outcomes, but the characteristics and prognosis of those with undiagnosed diabetes in this setting has not been established. Methods In total, 400 patients admitted consecutively with acute heart failure were grouped in three glycaemic categories: no diabetes, clinical diabetes (previously reported or with hypoglycaemic treatment) and undiagnosed diabetes. The latter was defined by the presence of at least two measurements of fasting plasma glycaemia ≥ 7 mmol/L before or after the acute episode.Group differences were tested by proportional hazards models in all-cause and cardiovascular mortality during a 7-year follow-up. Results There were 188 (47%) patients without diabetes, 149 (37%) with clinical diabetes and 63 (16%) with undiagnosed diabetes. Patients with undiagnosed diabetes had a lower prevalence of hypertension, dyslipidaemia, peripheral vascular disease and previous myocardial infarction than those with clinical diabetes and similar to that of those without diabetes. The adjusted hazards ratios for 7-year total and cardiovascular mortality compared with the group of subjects without diabetes were 1.69 (95% CI: 1.17-2.46) and 2.45 (95% CI: 1.58-3.81) for those with undiagnosed diabetes, and 1.48 (95% CI: 1.10-1.99) and 2.01 (95% CI: 1.40-2.89) for those with clinical diabetes. Conclusions Undiagnosed diabetes is common in patients requiring hospitalization for acute heart failure. Patients with undiagnosed diabetes, despite having a lower cardiovascular risk profile than those with clinical diabetes, show a similar increased mortality.

IntroductionAbdominal pain is common and is associated with high disease burden and health care costs in pediatric acute recurrent and chronic pancreatitis (ARP/CP). Despite the strong central component of pain in ARP/CP and the efficacy of psychological therapies for other centralized pain syndromes, no studies have evaluated psychological pain interventions in children with ARP/CP. The current trial seeks to 1) evaluate the efficacy of a psychological pain intervention for pediatric ARP/CP, and 2) examine baseline patient-specific genetic, clinical, and psychosocial characteristics that may predict or moderate treatment response.MethodsThis single-blinded randomized placebo-controlled multicenter trial aims to enroll 260 youth (ages 10-18) with ARP/CP and their parents from twenty-one INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE) centers. Participants will be randomly assigned to either a web-based cognitive behavioral pain management intervention (Web-based Management of Adolescent Pain Chronic Pancreatitis; WebMAP; N = 130) or to a web-based pain education program (WebED; N = 130). Assessments will be completed at baseline (T1), immediately after completion of the intervention (T2) and at 6 months post-intervention (T3). The primary study outcome is abdominal pain severity. Secondary outcomes include pain-related disability, pain interference, health-related quality of life, emotional distress, impact of pain, opioid use, and healthcare utilization.ConclusionsThis is the first clinical trial to evaluate the efficacy of a psychological pain intervention for children with CP for reduction of abdominal pain and improvement of health-related quality of life. Findings will inform delivery of web-based pain management and potentially identify patient-specific biological and psychosocial factors associated with favorable response to therapy. Clinical Trial Registration #: NCT03707431.

Abstract Background Research related to sustainable diets is is highly relevant to provide better understanding of the impact of dietary intake on the health and the environment. Aim To assess the association between the adherence to an energy-restricted Mediterranean diet and the amount of CO2 emitted in an older adult population. Design and population Using a cross-sectional design, the association between the adherence to an energy-reduced Mediterranean Diet (erMedDiet) score and dietary CO2 emissions in 6646 participants was assessed. Methods Food intake and adherence to the erMedDiet was assessed using validated food frequency questionnaire and 17-item Mediterranean questionnaire. Sociodemographic characteristics were documented. Environmental impact was calculated through greenhouse gas emissions estimations, specifically CO2 emissions of each participant diet per day, using a European database. Participants were distributed in quartiles according to their estimated CO2 emissions expressed in kg/day: Q1 (≤2.01 kg CO2), Q2 (2.02-2.34 kg CO2), Q3 (2.35-2.79 kg CO2) and Q4 (≥2.80 kg CO2). Results More men than women induced higher dietary levels of CO2 emissions. Participants reporting higher consumption of vegetables, fruits, legumes, nuts, whole cereals, preferring white meat, and having less consumption of red meat were mostly emitting less kg of CO2 through diet. Participants with higher adherence to the Mediterranean Diet showed lower odds for dietary CO2 emissions: Q2 (OR 0.87; 95%CI: 0.76-1.00), Q3 (OR 0.69; 95%CI: 0.69-0.79) and Q4 (OR 0.48; 95%CI: 0.42-0.55) vs Q1 (reference). Conclusions The Mediterranean diet can be environmentally protective since the higher the adherence to the Mediterranean diet, the lower total dietary CO2 emissions. Mediterranean Diet index may be used as a pollution level index.

BackgroundA major barrier to a healthy diet may be the higher price of healthy foods compared to low-quality foods.ObjectivesThis study aimed to assess the association between the monetary cost of food and diet quality in Spanish older adults at high risk of cardiovascular disease.MethodsCross-sectional analysis was carried out in Spanish older adults (n = 6,838; 48.6% female). A validated food frequency questionnaire was used to assess dietary intake. Metabolic syndrome severity, adherence to the Mediterranean diet (MedDiet), adherence to a provegetarian dietary pattern, and dietary inflammatory index were assessed. The economic cost of the foods was obtained from the Spanish Ministry of Agriculture Fisheries and Food database (2015–2017, the period of time when the participants were recruited). The total cost of diet adjusted per 1,000 kcal was computed.ResultsThe healthier dietary pattern was associated with a higher cost of the diet. Higher adherence to the MedDiet, anti-inflammatory diet, and the healthy version of the provegetarian dietary pattern were related to higher costs of the diet.ConclusionHigher diet quality was associated with a higher dietary cost of the diet per 1,000 kcal/day. Food prices can be an important component of interventions and policies aimed at improving people's diets and preventing diet-related chronic diseases.Clinical trial registry numberThe trial was registered in 2014 at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870) with the number 89898870.

Abstract Rothamsted Research (RRes) is the world's oldest agricultural research centre, notable for the development of the first synthetic fertilizer (superphosphate) and long‐term farming experiments (LTEs) spanning over 170 years. In 2015, RRes recruited several life cycle assessment (LCA) experts and began adopting the method to utilize high resolution agronomical data covering livestock (primarily ruminants), grassland/forage productivity and quality, and arable systems established on its North Wyke Farm Platform (NWFP) and the LTEs. The NWFP is a UK ‘National Bioscience Research Infrastructure’ (NBRI) developed for informing and testing systems science utilising high‐resolution data to determine whether it is possible to produce nutritious food sustainably. Thanks largely to the multidisciplinary knowledge at RRes, and its collaborators, its LCA Team has been at the forefront of methodological advances during a 6‐year Institute Strategic Programme (ISP) ‘Soil‐to‐Nutrition’ (S2N). While S2N investigated the co‐benefits and trade‐offs of new mechanistic understanding of efficient nutrient use across scales from pot to landscape, this commentary specifically synthesizes progress in incorporating human nutrition in the context of environmental footprinting, known as ‘nutritional LCA’ (nLCA). We conclude our commentary with a brief discussion on future pathways of exploration and methodological developments covering various activities along entire agri‐food supply‐chains.

Summary: Adipose tissue from pheochromocytoma patients acquires brown fat features, making it a valuable model for studying the mechanisms that control thermogenic adipose plasticity in humans. Transcriptomic analyses revealed a massive downregulation of splicing machinery components and splicing regulatory factors in browned adipose tissue from patients, with upregulation of a few genes encoding RNA-binding proteins potentially involved in splicing regulation. These changes were also observed in cell culture models of human brown adipocyte differentiation, confirming a potential involvement of splicing in the cell-autonomous control of adipose browning. The coordinated changes in splicing are associated with a profound modification in the expression levels of splicing-driven transcript isoforms for genes involved in the specialized metabolism of brown adipocytes and those encoding master transcriptional regulators of adipose browning. Splicing control appears to be a relevant component of the coordinated gene expression changes that allow human adipose tissue to acquire a brown phenotype.

Aims: To assess the comparative effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), 4-dipeptidyl peptidase inhibitors (DPP-4I), and metformin treatment during one year on metabolic syndrome (MetS) components and severity in MetS patients. Methods: Prospective study (n = 6165 adults) within the frame of PREDIMED-Plus trial. The major end-point was changes on MetS components and severity after one- year treatment of GLP-1RA, DPP-4I, and metformin. Anthropometric measurements (weight, height and waist circumference), body mass index (BM), and blood pressure were registered. Blood samples were collected after overnight fasting. Plasma glucose, glycosylated hemoglobin (HbA1c), plasma triglycerides and cholesterol were measured. Dietary intakes as well as physical activity were assessed through validated questionnaires. Results: MetS parameters improved through time. The treated groups improved glycaemia compared with untreated (glycaemia ∆ untreated: −1.7 mg/dL(± 13.5); ∆ metformin: − 2.5(± 23.9) mg/dL; ∆ DPP-4I: − 4.5(± 42.6); mg/dL ∆ GLP-1RA: − 4.3(± 50.9) mg/dL; and HbA1c: ∆ untreated: 0.0(± 0.3) %; ∆ metformin: − 0.1(± 0.7) %; ∆ DPP-4I: − 0.1(± 1.0) %; ∆ GLP-1RA: − 0.2(± 1.2) %. Participants decreased BMI and waist circumference. GLP-1RA and DPP-4I participants registered the lowest decrease in BMI (∆ untreated: −0.8(± 1.6) kg/m2; ∆ metformin: − 0.8(± 1.5) kg/m2; ∆ DPP-4I: − 0.6(± 1.3) kg/m2; ∆ GLP-1RA: − 0.5(± 1.2) kg/m2. and their waist circumference (∆ untreated: −2.8(± 5.2) cm; ∆ metformin: − 2.6(± 15.2) cm; ∆ DPP-4I: − 2.1(± 4.8) cm; ∆ GLP-1RA: − 2.4(± 4.1) cm. Conclusion: In patients with MetS and healthy lifestyle intervention, those treated with GLP-1RA and DPP-4I obtained better glycemic profile. Anthropometric improvements were modest.