Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement.

Persistent symptoms in patients treated for hypothyroidism are common. Despite more than 20 years of debate, the use of liothyronine for this indication remains controversial, as numerous randomised trials have failed to show a benefit of treatment regimens that combine liothyronine (T3) with levothyroxine over levothyroxine monotherapy. This consensus statement attempts to provide practical guidance to clinicians faced with patients who have persistent symptoms during thyroid hormone replacement therapy.

The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction.

Mortality in children with severe malnutrition is strongly related to signs of metabolic dysfunction, such as hypoglycemia. Lower circulating tryptophan levels in children with severe malnutrition suggest a possible disturbance in the tryptophan-nicotinamide adenine dinucleotide (TRP-NAD+) pathway and subsequently in NAD+  dependent metabolism regulator sirtuin1 (SIRT1). Here we show that severe malnutrition in weanling mice, induced by 2-weeks of low protein diet feeding from weaning, leads to an impaired TRP-NAD+  pathway with decreased NAD+ levels and affects hepatic mitochondrial turnover and function.

INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes.

Background: The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with newly diagnosed type 1 diabetes combined with centralised collection of clinical samples to determine rates of decline in beta-cell function and identify novel biomarkers, which could be used for future stratification of phase 2 clinical trials.

Methods: In this context, we have developed a Master Protocol, based on the "backbone" of the INNODIA natural history study, which we believe could improve the delivery of phase 2 studies exploring the use of single or combinations of Investigational Medicinal Products (IMPs), designed to prevent or reverse declines in beta-cell function in individuals with newly diagnosed type 1 diabetes. Although many IMPs have demonstrated potential efficacy in phase 2 studies, few subsequent phase 3 studies have confirmed these benefits.

Face Validity of Observed Meal Patterns Reported with 7-Day Diet Diaries in a Large Population-Based Cohort Using Diurnal Variation in Concentration Biomarkers of Dietary Intake.

In a cross-sectional analysis of a population-based cohort (United Kingdom, = 21,318, 1993-1998), we studied how associations between meal patterns and non-fasting triglyceride and glucose concentrations were influenced by the hour of day at which the blood sample was collected to ascertain face validity of reported meal patterns, as well as the influence of reporting bias (assessed using formula of energy expenditure) on this association. Meal size (i.e.

Initial response of young people with thyrotoxicosis to block and replace or dose titration thionamide.

Objective: Patients with thyrotoxicosis are treated with anti-thyroid drug (ATD) using block and replace (BR) or a smaller, titrated dose of ATD (dose titration, DT).

Design: A multi-centre, phase III, open-label trial of newly diagnosed paediatric thyrotoxicosis patients randomised to BR/DT. We compared the biochemical response to BR/DT in the first 6 months of therapy.

Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension.

Background: Inflammation and dysregulated immunity are important in the development of pulmonary arterial hypertension (PAH). Compelling preclinical data supports the therapeutic blockade of interleukin-6 (IL-6) signalling.

Methods: We conducted a phase 2 open-label study of intravenous tocilizumab (8 mg·kg) over 6 months in patients with group 1 PAH.

Adolescents' understanding of obesity: a qualitative study from rural South Africa.

Background: Levels of obesity are rising in South Africa, notably among adolescent females. Excessive energy-dense diets and physical inactivity are among the factors contributing to this increase. Given that these factors are largely behavioural, understanding young people's views of obesity can contribute to more targeted behavioural interventions.

In vitro metabolism of synthetic Elabela/Toddler (ELA-32) peptide in human plasma and kidney homogenates analyzed with mass spectrometry and validation of endogenous peptide quantification in tissues by ELISA.

Background: Elabela/Toddler (ELA) is a novel endogenous ligand of the apelin receptor, whose signalling has emerged as a therapeutic target, for example, in cardiovascular disease and cancer. Shorter forms of ELA-32 have been predicted, including ELA-21 and ELA-11, but metabolism and stability of ELA-32 in humans is poorly understood. We, therefore, developed an LC-MS/MS assay to identify ELA-32 metabolites in human plasma and tissues.

Caffeine Increases Exercise Performance, Maximal Oxygen Uptake, and Oxygen Deficit in Elite Male Endurance Athletes.

Purpose: The aims of the present study were to test the hypothesis that caffeine increases maximal oxygen uptake (V˙O2max) and to characterize the physiological mechanisms underpinning improved high-intensity endurance capacity.

Methods: Twenty-three elite endurance-trained male athletes were tested twice with and twice without caffeine (four tests) in a randomized, double-blinded, and placebo-controlled study with crossover design. Caffeine (4.

Randomised trial of block and replace vs dose titration thionamide in young people with thyrotoxicosis.

Objective: First-line treatment of thyrotoxicosis in young people is thionamide anti-thyroid drug (ATD) in a blocking dose with levothyroxine replacement (block and replace, BR) or in a smaller dose tailored to render the patient euthyroid (dose titration, DT). Our objective was to determine which regimen provides more stable biochemical control.

Design: A multi-centre phase III, open-label randomised trial comparing BR with DT in patients aged 2-17 years with newly diagnosed thyrotoxicosis at 15 UK centres.

The global diet and activity research (GDAR) network: a global public health partnership to address upstream NCD risk factors in urban low and middle-income contexts.

Background: Non-communicable diseases (NCDs) are the leading cause of death globally. While upstream approaches to tackle NCD risk factors of poor quality diets and physical inactivity have been trialled in high income countries (HICs), there is little evidence from low and middle-income countries (LMICs) that bear a disproportionate NCD burden. Sub-Saharan Africa and the Caribbean are therefore the focus regions for a novel global health partnership to address upstream determinants of NCDs.

What role should the commercial food system play in promoting health through better diet?

consider that the commercial food system has the potential to show leadership and support for dietary public health, but systemic change is needed first and this is likely to require governmental action

Whole-body and adipose tissue-specific mechanisms underlying the metabolic effects of fibroblast growth factor 21 in the Siberian hamster.

Objective: Fibroblast growth factor 21 (FGF21) has been shown to rapidly lower body weight in the Siberian hamster, a preclinical model of adiposity. This induced negative energy balance mediated by FGF21 is associated with both lowered caloric intake and increased energy expenditure. Previous research demonstrated that adipose tissue (AT) is one of the primary sites of FGF21 action and may be responsible for its ability to increase the whole-body metabolic rate.

Development and validation of an LC-MS/MS method for detection and quantification of in vivo derived metabolites of [Pyr]apelin-13 in humans.

[Pyr]apelin-13 is the predominant apelin peptide isoform in the human cardiovascular system and plasma. To date, few studies have investigated [Pyr]apelin-13 metabolism in vivo in rats with no studies examining its stability in humans. We therefore aimed to develop an LC-MS/MS method for detection and quantification of intact [Pyr]apelin-13 and have used this method to identify the metabolites generated in vivo in humans.

Factors predicting poor glycemic control in the first two years of childhood onset type 1 diabetes in a cohort from East London, UK: Analyses using mixed effects fractional polynomial models.

Background/objective: Poor early glycemic control in childhood onset type 1 diabetes (T1D) is associated with future risk of acute and chronic complications. Our aim was to identify the predictors of higher glycated hemoglobin (HbA1c) within 24 months of T1D diagnosis in children and adolescents.

Methods: Mixed effects models with fractional polynomials were used to analyze longitudinal data of patients <19 years of age, followed from T1D diagnosis for up to 2 years, at three diabetes clinics in East London, United Kingdom.

Photoperiodic changes in adiposity increase sensitivity of female Siberian hamsters to systemic VGF derived peptide TLQP-21.

TLQP-21, a peptide encoded by the highly conserved vgf gene, is expressed in neuroendocrine cells and has been the most prominent VGF-derived peptide studied in relation to control of energy balance. The recent discovery that TLQP-21 is the natural agonist for the complement 3a receptor 1 (C3aR1) has revived interest in this peptide as a potential drug target for obesity. We have investigated its function in Siberian hamsters (Phodopus sungorus), a rodent that displays natural seasonal changes in body weight and adiposity as an adaptation to survive winter.

Building consensus on interactions between population health researchers and the food industry: Two-stage, online, international Delphi study and stakeholder survey.

Key to scientific integrity is ensuring that research findings are considered credible by scientific peers, practitioners, policymakers and the public. Industry sponsorship of nutritional research can result in bias and raises significant professional, public and media concern. Yet, there is no international consensus on how to prevent or manage conflicts of interest for researchers considering engaging with the food industry.

In primary care, is measuring free-thyroxine plus thyroid-stimulating hormone to detect hypopituitarism cost-effective? A cost utility analysis using Markov chain models.

Objective: We examined whether it is cost-effective to measure free thyroxine (FT4) in addition to thyrotropin (thyroid-stimulating hormone (TSH)) on all requests for thyroid function tests from primary care on adult patients.

Background: Hypopituitarism occurs in about 4 people per 100 000 per year. Loss of thyrotropin (TSH) secretion may lead to secondary hypothyroidism with a low TSH and low FT4, and this pattern may help to diagnose hypopituitarism that might otherwise be missed.

Going Back to the Biology of FGF21: New Insights.

Fibroblast growth factor 21 (FGF21) is a protein highly synthesized in the liver that exerts paracrine and endocrine control of many aspects of energy homeostasis in multiple tissues. In preclinical models of obesity and type 2 diabetes, treatment with FGF21 improves glucose homeostasis and promotes weight loss, and, as a result, FGF21 has attracted considerable attention as a therapeutic agent for the treatment of metabolic syndrome in humans. An improved understanding of the biological role of FGF21 may help to explain why its therapeutic potential in humans has not been fully realized.

Genome sequencing and transcriptome analyses of the Siberian hamster hypothalamus identify mechanisms for seasonal energy balance.

Synthesis of triiodothyronine (T) in the hypothalamus induces marked seasonal neuromorphology changes across taxa. How species-specific responses to T signaling in the CNS drive annual changes in body weight and energy balance remains uncharacterized. These experiments sequenced and annotated the Siberian hamster () genome, a model organism for seasonal physiology research, to facilitate the dissection of T-dependent molecular mechanisms that govern predictable, robust, and long-term changes in body weight.

Effect of early glycemic control on HbA1c tracking and development of vascular complications after 5 years of childhood onset type 1 diabetes: Systematic review and meta-analysis.

Objective: A systematic review and meta-analysis was conducted to investigate if glycemic control measured by glycated hemoglobin (HbA1c) levels near diagnosis are predictive of future glycemic outcomes and vascular complications in childhood onset type 1 diabetes (T1D).

Methods: Evidence was gathered using electronic databases (MEDLINE, EMBASE, Web of Science, CINAHL, Scopus, and Cochrane Library up to February 2017) and snowballing techniques. Studies investigating the association between the exposure "early glycemic control" and main outcome: "tracking of early control" and secondary outcome: risk of future complications; in children and young people aged 0 to 19 years at baseline; were systematically double-reviewed, quality assessed, and outcome data extracted for synthesis and meta-analysis.

Implementing personalized medicine in diabetic kidney disease: Stakeholders' perspectives.

The promise of personalized medicine to deliver "the right treatments at the right time to the right person" is the next frontier in healthcare. However, to implement personalized medicine in chronic diseases such as diabetes mellitus and diabetic kidney disease (DKD), a number of different aspects need to be taken into account. Better risk stratification and more precise options for treatment need to be developed and included in clinical practice guidelines.