Aging selectively dampens oscillation of lipid abundance in white and brown adipose tissue

Lipid metabolism is under the control of the circadian system and circadian dysregulation has been linked to obesity and dyslipidemia. These factors and outcomes have also been associated to, or affected by, the process of aging. Here, we investigated whether murine white (WAT) and brown (BAT) adipose tissue lipids exhibit rhythmicity and if this is affected by aging. To this end, we have measured the 24 h lipid profiles of WAT and BAT using a global lipidomics analysis of >1100 lipids. We observed rhythmicity in nearly all lipid classes including glycerolipids, glycerophospholipids, sterol lipids and sphingolipids. Overall, similar to 22% of the analyzed lipids were considered rhythmic in WAT and BAT. Despite a general accumulation of lipids upon aging the fraction of oscillating lipids decreased in both tissues to 14% and 18%, respectively. Diurnal profiles of lipids in BAT appeared to depend on the lipid acyl chain length and this specific regulation was lost in aged mice. Our study revealed how aging affects the rhythmicity of lipid metabolism and could contribute to the quest for targets that improve diurnal lipid homeostasis to maintain cardiometabolic health during aging.Diabetes mellitus: pathophysiological changes and therap

Identification of metabolic biomarkers in relation to methotrexate response in early rheumatoid arthritis

This study aimed to identify baseline metabolic biomarkers for response to methotrexate (MTX) therapy in rheumatoid arthritis (RA) using an untargeted method. In total, 82 baseline plasma samples (41 insufficient responders and 41 sufficient responders to MTX) were selected from the Treatment in the Rotterdam Early Arthritis Cohort (tREACH, trial number: ISRCTN26791028) based on patients’ EULAR response at 3 months. Metabolites were assessed using high-performance liquid chromatography-quadrupole time of flight mass spectrometry. Differences in metabolite concentrations between insufficient and sufficient responders were assessed using partial least square regression discriminant analysis (PLS-DA) and Welch’s t-test. The predictive performance of the most significant findings was assessed in a receiver operating chara

Tamanho de amostras para a determinação de parâmetros físicos em planossolo por tomografia computadorizada

A técnica da tomografia computadorizada (TC) permite medir a densidade e a umidade de amostras de solo, constituindo uma importante ferramenta na Ciência do Solo. Este trabalho tem como objetivos descrever os aspectos da adequação do tamanho de amostras de um Planossolo e os procedimentos de avaliação e estudos por análise estatística, empregando-se um minitomógrafo computadorizado de raios gama com fonte de 241Am. O valor do erro atribuído ao equipamento são 0,051 e 0,046 Mg m-3, respectivamente, para os horizontes A e B. O valor teórico da espessura da amostra do Planossolo para uso na técnica de TC com fonte de 241Am é, aproximadamente, 4,0 cm para os horizontes A e B. Já a espessura ideal de amostras é de aproximadamente 6,0 cm, sendo menor para amostras do horizonte B em relação ao A. Obteve-se boa precisão e adaptabilidade no emprego da TC para estudos de Planossolos._________________________________________________________________________________ ABSTRACT: Computerized tomography (CT) is an important tool in Soil Science for noninvasive measurement of density and water content of soil samples. This work aims to describe the aspects of sample size adequacy for Planosol (Albaqualf) and to evaluate procedures for statistical analysis, using a CT scanner with a 241Am source. Density errors attributed to the equipment are 0.051 and 0.046 Mg m-3 for horizons A and B, respectively. The theoretical value for sample thickness for the Planosol, using this equipment, is 4.0 cm for the horizons A and B. The ideal thickness of samples is approximately 6.0 cm, being smaller for samples of the horizon B in relation to A. Alternatives for the improvement of the efficiency analysis and the reliability of the results obtained by CT are also discussed, and indicate good precision and adaptability of the application of this technology in Planosol (Albaqualf) studies

Deep phenotyping classical galactosemia: clinical outcomes and biochemical markers

Early diagnosis and dietary treatment do not prevent long-term complications, which mostly affect the central nervous system in classical galactosemia patients. The clinical outcome of patients is highly variable, and there is an urgent need for prognostic biomarkers. The aim of this study was first to increase knowledge on the natural history of classical galactosemia by studying a cohort of patients with varying geno- and phenotypes and second to study the association between clinical outcomes and two possible prognostic biomarkers. In addition, the association between abnormalities on brain MRI and clinical outcomes was investigated. Classical galactosemia patients visiting the galactosemia expertise outpatient clinic of the Amsterdam University Medical Centre were evaluated according to the International Classical Galactosemia guideline with the addition of an examination by a neurologist, serum immunoglobulin G N-glycan profiling and a brain MRI. The biomarkers of interest were galactose-1-phosphate levels and N-glycan profiles, and the clinical outcomes studied were intellectual outcome and the presence or absence of movement disorders and/or primary ovarian insufficiency. Data of 56 classical galactosemia patients are reported. The intellectual outcome ranged from 45 to 103 (mean 77 6 14) and was <85 in 62%. Movement disorders were found in 17 (47%) of the 36 tested patients. In females aged 12 years and older, primary ovarian insufficiency was diagnosed in 12 (71%) of the 17 patients. Significant differences in N-glycan peaks were found between controls and patients. However, no significant differences in either N-glycans or galactose-1-phosphate levels were found between patients with a poor (intellectual outcome < 85) and normal intellectual outcome (intellectual outcome 85), and with or without movement disorders or primary ovarian insufficiency. The variant patients detected by newborn screening, with previously unknown geno- and phenotypes and currently no long-term complications, demonstrated significantly lower galactose-1-phospate levels than classical patients (P < 0.0005). Qualitative analysis of the MRI’s demonstrated brain abnormalities in 18 of the 21 patients, more severely in patients with a lower intellectual outcome and/or with movement disorders. This study demonstrates a large variability in clinical outcome, which varies from a below average intelligence, movement disorders and in females primary ovarian insufficiency to a normal clinical outcome. In our cohort of classical galactosemia patients, galactose-1-phosphate levels and N-glycan variations were not associated with clinical outcomes, but galactose-1-phosphate levels did differentiate between classical and variant patients detected by newborn screening. The correlation between brain abn