Concentrations of docosahexaenoic acid are reduced in maternal liver, adipose, and heart in rats fed high-fat diets without docosahexaenoic acid throughout pregnancy

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.plefa.2018.10.003 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/Fetal accretion for DHA is high during late pregnancy due to the brain growth spurt. Prior evidence suggests that DHA is mobilized from maternal liver and adipose to meet fetal accretion and physiological requirements. However, changes in the DHA levels of various maternal tissues throughout pregnancy and into lactation of mothers on diets with and without dietary DHA, and with a background dietary fatty acid profile that resembles human intake has not been examined. Sprague Dawley rats were fed a total western diet with (TWD + ) or without DHA (TWD-) along with a commercial rodent chow control (Chow) throughout pregnancy and postpartum. The fatty acid compositions of adipose, brain, heart, liver, erythrocytes, and plasma were determined before pregnancy, at 15 and 20 days of pregnancy, and 7 days postpartum. The placenta, fetuses, and pups were also examined when available. Maternal DHA concentrations were increased in plasma at 20 days pregnancy in all the diets with TWD + > Chow > TWD-. Maternal DHA concentrations in the TWD- group were lower in adipose throughout pregnancy as compared with the other diets. At postpartum, DHA concentrations decreased below baseline levels in the heart of the TWD- and Chow dams and the liver of the TWD- dams. Whole body DHA concentrations of the fetuses did not differ but there was evidence of decreased DHA in the whole body and tissues of the TWD- and Chow 7d old pups. In conclusion, it appears that in this rodent model of pregnancy, maternal adaptations were made to meet fetal DHA requirements, but they may compromise maternal DHA status and the ability to deliver DHA during lactation.Natural Sciences and Engineering Research Council of Canada [327149-2013]Canada Research Chairs program as a Chair in Nutritional Lipidomics [950-228125

Hipocalcemia severa o sintomática secundaria a hipoparatiroidismo posoperatorio en cirugía de tiroides: experiencia en un hospital universitario de Medellín, Colombia

Objetivo: caracterizar la población de pacientes que presentan hipocalcemia severa o sintomática después de una tiroidectomía total y que requieren calcio parenteral. Diseño: estudio observacional retrospectivo realizado en un centro especializado de Medellín, Colombia. Marco de referencia: la hipocalcemia posoperatoria (POP) es una complicación bien reconocida de la tiroidectomía, que se caracteriza por la presencia de hipocalcemia, con niveles de hormona paratiroidea (Parathyroid hormone, PTH) bajos o inadecuadamente normales. La hipocalcemia sintomática o severa (calcio corregido <7,5 mg/dL) es una verdadera emergencia médica, que requiere un rápido diagnóstico y tratamiento con calcio parenteral. Pacientes: pacientes en POP de tiroidectomía que presentan hipocalcemia severa o sintomática. Intervenciones: reposición con calcio parenteral. Resultados: la hipocalcemia severa o sintomática se presentó en el 8 % de los pacientes llevados a una tiroidectomía total, con predominio en el sexo femenino. La patología tiroidea maligna se constituyó en la indicación más frecuente de la cirugía. En estos pacientes, la media de la PTH fue de 11,3 pg/ mL, mientras que los valores de calcio más bajos se presentaron a las 48 horas POP. Solo se visualizaron las paratiroides en cirugía en una tercera parte de los casos y un paciente tuvo una reintervención en las primeras 24 horas; hasta el 18 % tuvieron hipomagnesemia concomitante. Conclusión: la hipocalcemia por hipoparatiroidismo POP es una complicación frecuente después de la cirugía de tiroides, y en un grupo de pacientes será severa o sintomática, razón por la cual requiere uso de calcio parenteral. En consecuencia, esta complicación tendrá que identificarse y tratarse como una emergencia médica para disminuir la morbilidad y la potencial mortalidad asociadas

Two weeks of docosahexaenoic acid (DHA) supplementation increases synthesis-secretion kinetics of n-3 polyunsaturated fatty acids compared to 8 weeks of DHA supplementation

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.jnutbio.2018.07.002 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Docosahexaenoic acid (DHA, 22:6n-3) must be consumed in the diet or synthesized from n-3 polyunsaturated fatty acid (PUFA) precursors. However, the effect of dietary DHA on the metabolic pathway is not fully understood. Presently, 21-day-old Long Evans rats were weaned onto one of four dietary protocols: 1) 8 weeks of 2% ALA (ALA), 2) 6 weeks ALA followed by 2 weeks of 2% ALA + 2% DHA (DHA), 3) 4 weeks ALA followed by 4 weeks DHA and 4) 8 weeks of DHA. After the feeding period, 2H5-ALA and 13C20-eicosapentaenoic acid (EPA, 20:5n-3) were co-infused and blood was collected over 3 h for determination of whole-body synthesis-secretion kinetics. The synthesis-secretion coefficient (ml/min, means ± SEM) for EPA (0.238±0.104 vs. 0.021±0.001) and DPAn-3 (0.194±0.060 vs. 0.020±0.008) synthesis from plasma unesterified ALA, and DPAn-3 from plasma unesterified EPA (2.04±0.89 vs. 0.163±0.025) were higher (P<.05) after 2 weeks compared to 8 weeks of DHA feeding. The daily synthesis-secretion rate (nmol/d) of DHA from EPA was highest after 4 weeks of DHA feeding (843±409) compared to no DHA (70±22). Liver gene expression of ELOVL2 and FADS2 were lower (P<.05) after 4 vs. 8 weeks of DHA. Higher synthesis-secretion kinetics after 2 and 4 weeks of DHA feeding suggests an increased throughput of the PUFA metabolic pathway. Furthermore, these findings may lead to novel dietary strategies to maximize DHA levels while minimizing dietary requirements.Natural Sciences and Engineering Research Council of Canada || 48259

Reference materials for MS-based untargeted metabolomics and lipidomics: a review by the metabolomics quality assurance and quality control consortium (mQACC)

Introduction The metabolomics quality assurance and quality control consortium (mQACC) is enabling the identification, development, prioritization, and promotion of suitable reference materials (RMs) to be used in quality assurance (QA) and quality control (QC) for untargeted metabolomics research. Objectives This review aims to highlight current RMs, and methodologies used within untargeted metabolomics and lipidomics communities to ensure standardization of results obtained from data analysis, interpretation and cross-study, and cross-laboratory comparisons. The essence of the aims is also applicable to other ‘omics areas that generate high dimensional data. Results The potential for game-changing biochemical discoveries through mass spectrometry-based (MS) untargeted metabolomics and lipidomics are predicated on the evolution of more confident qualitative (and eventually quantitative) results from research laboratories. RMs are thus critical QC tools to be able to assure standardization, comparability, repeatability and reproducibility for untargeted data analysis, interpretation, to compare data within and across studies and across multiple laboratories. Standard operating procedures (SOPs) that promote, describe and exemplify the use of RMs will also improve QC for the metabolomics and lipidomics communities. Conclusions The application of RMs described in this review may significantly improve data quality to support metabolomics and lipidomics research. The continued development and deployment of new RMs, together with interlaboratory studies and educational outreach and training, will further promote sound QA practices in the community

Microwave Energy Increases Fatty Acid Methyl Ester Yield in Human Whole Blood Due to Increased Sphingomyelin Transesterification

Dried blood spots (DBS) by fingertip prick collection for fatty acid profiling are becoming increasingly popular due to ease of collection, minimal invasiveness and its amenability to high-throughput analyses. Herein, we assess a microwave-assisted direct transesterification method for the production of fatty acid methyl esters (FAME) from DBS. Technical replicates of human whole blood were collected and 25-μL aliquots were applied to chromatography strips prior to analysis by a standard 3-h transesterification method or microwave-assisted direct transesterification method under various power (variable vs constant), time (1-5 min) and reagent (1-10% H2SO4 in methanol) conditions. In addition, a standard method was compared to a 5-min, 30-W power microwave in 1% H2SO4 method for FAME yield from whole blood sphingomyelin, and sphingomyelin standards alone and spiked in whole blood. Microwave-assisted direct transesterification yielded no significant differences in both quantitative (nmol/100 µL) and qualitative (mol%) fatty acid assessments after as little as 1.5- and 1-min reaction times, respectively, using the variable power method and 5% H2SO4 in methanol. However, 30-W power for 5 min increased total FAME yield of the technical replicates by 14%. This increase appears largely due to higher sphingomyelin-derived FAME yield of up to 109 and 399% compared to the standard method when determined from whole blood or pure standards, respectively. In conclusion, microwave-assisted direct transesterification of DBS achieved in as little as 1-min, and 5-min reaction times increase total fatty acids primarily by significantly improving sphingomyelin-derived fatty acid yield

Stability and Free Vibration Analyses of Cantilever Shear Buildings with Semi-Rigid Support Conditions and Multiple Masses

The stability and free vibration analyses of a cantilever shear building with generalized support conditions and with multiple masses (rotational and translational) rigidly attached at both ends and along its height are presented. The proposed model includes the simultaneous effects of: (1) lateral and rotational elastic restraints at the base support; (2) a uniform distributed mass and rotary inertia plus lumped rotary and translational masses rigidly attached at both extremes and along its height; (3) linearly distributed axial load plus the concentrated vertical axial loads caused by the lumped masses; and (4) shear deformations and shear forces induced by the applied axial forces. A parametric study is carried out that shows the importance of all variables included in this work on the stability and dynamic behavior of cantilever shear buildings, particularly the effects of the attached lumped masses and the rotational and translational constraints at the base support. A comparison with results presented by other researchers in previous studies shows that the proposed method and corresponding equations can be very useful in the assessment design of cantilever shear buildings. The main objective is to present readily solutions on the static stability and free vibration of cantilever shear buildings with generalized support conditions and multiple masses rigidly attached. The proposed method and corresponding expressions for the natural frequencies and modal shapes, buckling modes and axial critical loads are extensions of those presented recently by the senior author

A Checklist for Reproducible Computational Analysis in Clinical Metabolomics Research

Clinical metabolomics emerged as a novel approach for biomarker discovery with the translational potential to guide next-generation therapeutics and precision health interventions. However, reproducibility in clinical research employing metabolomics data is challenging. Checklists are a helpful tool for promoting reproducible research. Existing checklists that promote reproducible metabolomics research primarily focused on metadata and may not be sufficient to ensure reproducible metabolomics data processing. This paper provides a checklist including actions that need to be taken by researchers to make computational steps reproducible for clinical metabolomics studies. We developed an eight-item checklist that includes criteria related to reusable data sharing and reproducible computational workflow development. We also provided recommended tools and resources to complete each item, as well as a GitHub project template to guide the process. The checklist is concise and easy to follow. Studies that follow this checklist and use recommended resources may facilitate other researchers to reproduce metabolomics results easily and efficiently

Interaction between Butyrate and Tumor Necrosis Factor α in Primary Rat Colonocytes

Butyrate, a short-chain fatty acid, is utilized by the gut epithelium as energy and it improves the gut epithelial barrier. More recently, it has been associated with beneficial effects on immune and cardiovascular homeostasis. Conversely, tumor necrosis factor alpha (TNFα) is a pro-inflammatory and pro-hypertensive cytokine. While butyrate and TNFα are both linked with hypertension, studies have not yet addressed their interaction in the colon. Here, we investigated the capacity of butyrate to modulate a host of effects of TNFα in primary rodent colonic cells in vitro. We measured ATP levels, cell viability, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial oxidative phosphorylation, and glycolytic activity in colonocytes following exposure to either butyrate or TNFα, or both. To address the potential mechanisms, transcripts related to oxidative stress, cell fate, and cell metabolism (Pdk1, Pdk2, Pdk4, Spr, Slc16a1, Slc16a3, Ppargc1a, Cs, Lgr5, Casp3, Tnfr2, Bax, Bcl2, Sod1, Sod2, and Cat) were measured, and untargeted liquid chromatography–tandem mass spectrometry (LC-MS/MS) was employed to profile the metabolic responses of colonocytes following exposure to butyrate and TNFα. We found that both butyrate and TNFα lowered cellular ATP levels towards a quiescent cell energy phenotype, characterized by decreased oxygen consumption and extracellular acidification. Co-treatment with butyrate ameliorated TNFα-induced cytotoxicity and the reduction in cell viability. Butyrate also opposed the TNFα-mediated decrease in MMP and mitochondrial-to-intracellular calcium ratios, suggesting that butyrate may protect colonocytes against TNFα-induced cytotoxicity by decreasing mitochondrial calcium flux. The relative expression levels of pyruvate dehydrogenase kinase 4 (Pdk4) were increased via co-treatment of butyrate and TNFα, suggesting the synergistic inhibition of glycolysis. TNFα alone reduced the expression of monocarboxylate transporters slc16a1 and slc16a3, suggesting effects of TNFα on butyrate uptake into colonocytes. Of the 185 metabolites that were detected with LC-MS, the TNFα-induced increase in biopterin produced the only significant change, suggesting an alteration in mitochondrial biogenesis in colonocytes. Considering the reports of elevated colonic TNFα and reduced butyrate metabolism in many conditions, including in hypertension, the present work sheds light on cellular interactions between TNFα and butyrate in colonocytes that may be important in understanding conditions of the colon