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1.
Clin Chem Lab Med ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396137

RESUMO

Coronavirus disease 2019 (COVID-19) is the third coronavirus outbreak that has emerged in the past 20 years, after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). One important aspect, highlighted by many global health organizations, is that this novel coronavirus outbreak may be especially hazardous to healthcare personnel, including laboratory professionals. Therefore, the aim of this document, prepared by the COVID-19 taskforce of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), is to provide a set of recommendations, adapted from official documents of international and national health agencies, on biosafety measures for routine clinical chemistry laboratories that operate at biosafety levels 1 (BSL-1; work with agents posing minimal threat to laboratory workers) and 2 (BSL-2; work with agents associated with human disease which pose moderate hazard). We believe that the interim measures proposed in this document for best practice will help minimazing the risk of developing COVID-19 while working in clinical laboratories.

2.
Cell Mol Biol (Noisy-le-grand) ; 66(2): 99-104, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415934

RESUMO

Reference intervals (RIs) are important tools for improving medical decision-making. Hematology reference values can be influenced by important covariates such as genetic and environmental factors, rendering it essential to define RIs for specific populations. Therefore, we aimed to establish accurate and robust RIs for hematological markers in a healthy adult male Iranian population. This cross-sectional study was conducted in a population of 723 males aged 20-60 years old. Hematological parameters were routinely measured using a Sysmex auto analyser system (KX-21 N). The quality of assays was monitored using commercial quality control samples. The nonparametric rank method, as recommended by the Clinical and Laboratory Standards Institute (CLSI) guidelines, was used to calculate the 2.5th and 97.5th percentiles as the lower and upper reference limits, respectively. Of the 12 hematological parameters assessed, only mean platelet volume (MPV) demonstrated significant age-specific differences, requiring two partitions from 20 to 35 years (8.7-12.2 fL) and 35 to 65 years (8.5-11.5 fL). The remaining hematological parameters (e.g. leukocyte, erythrocyte, and platelet parameters) could be defined by one age range. This study established RIs for 12 routinely used hematological parameters in a healthy male population living in the northeastern region of Iran. Established RIs differed from those previously reported by other cohorts, highlighting the importance of population-specific RIs.

3.
Pediatr Obes ; : e12633, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32181602

RESUMO

BACKGROUND: Rapid growth is associated with increased cardiometabolic risk (CMR) in adolescence and adulthood. Little is known about whether the association between rapid growth and increased CMR originates in early childhood. OBJECTIVES: To identify age and sex standardized body mass index (zBMI) trajectories and to examine the association between zBMI trajectories and CMR outcomes in children 0 to 60 months. STUDY DESIGN: A longitudinal cohort study was conducted through The Applied Research Group for Kids (TARGet Kids!) in Toronto, Canada. Participants had repeated measures of weight and length or height performed from birth to 60 months of age. Latent class mixed modelling was used to identify the zBMI trajectories. Linear regressions were performed to determine the association between zBMI trajectories and the primary outcome, a CMR score, quantified as the sum of age- and sex- standardized waist circumference, systolic blood pressure, glucose, log-triglycerides and negative high-density lipoprotein cholesterol (HDL-C), divided by √5. Secondary outcomes were the individual components of the CMR formula as well as diastolic blood pressure and non-HDL-C. RESULTS: Four BMI trajectories were identified among the 1166 children. After adjusting for all covariates, children in the rapidly accelerating trajectory had increased total CMR score (ß = 1.38, 95% CI 0.77; 1.99, P < .001) and increased waist circumference score (ß = 2.39, 95% CI 1.92; 2.86, P < .001) compared to the stable low group. CONCLUSIONS: Rapid growth during early childhood is associated with increased CMR in preschool children, largely driven by larger waist circumference.

4.
J Endocr Soc ; 4(2): bvz030, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32110745

RESUMO

Context: Screening for and diagnosing non classic congenital adrenal hyperplasia (NCCAH) uses serum 17-hydroxyprogesterone (17OHP) thresholds established from immunoassay data; however, a new liquid-chromatography tandem mass spectrometry (LC-MS/MS) method results in lower 17OHP values. The evolution of immunoassays is also challenging our diagnostic cut-off for glucocorticoid insufficiency and few data re-evaluate the utility of testing for glucocorticoid insufficiency in NCCAH. Objective: (1) Evaluate the 17OHP threshold that predicts NCCAH in children using LC-MS/MS, and (2) determine the prevalence of glucocorticoid insufficiency in NCCAH. Methods: A retrospective chart review of pediatric patients who underwent ACTH stimulation tests with cortisol and 17OHP measurements from 2011 to 2018 for assessment of NCCAH. Other adrenal pathologies were excluded. A cortisol < 415 nmol/L defined glucocorticoid insufficiency. Published correlation data determined a 17OHP of 3.3 nmol/L by LC-MS/MS was equivalent to 6 nmol/L by immunoassay. Data analysis was by measures of diagnostic accuracy. Results: Of 188 patients included, 23 (12%) had NCCAH (21/23 had genetic confirmation); the remaining 2 had peak 17OHP > 30 nmol/L. Baseline 17OHP ≥ 6 nmol/L most accurately screened for NCCAH-sensitivity and specificity 96%. Almost all genetically confirmed NCCAH (20/21) had peak 17OHP > 30 nmol/L; all subjects with other diagnoses peaked < 30 nmol/L. Glucocorticoid insufficiency was present in 55% with NCCAH. Conclusions: Despite the increased specificity of LC-MS/MS, a baseline 17OHP ≥ 6 nmol/L most accurately screened for NCCAH; this supports current practice guidelines. This threshold identified all with glucocorticoid insufficiency, notably prevalent in our cohort and for whom glucocorticoid stress dosing should be considered.

6.
Am J Physiol Gastrointest Liver Physiol ; 318(4): G682-G693, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32003602

RESUMO

Postprandial dyslipidemia is a common feature of insulin-resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. Although bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here, we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion. Healthy C57BL/6 mice were given an intraduodenal infusion of taurocholic acid (TA) under fat-loaded conditions, and circulating lipids were measured. Targeting of bile acid receptors was achieved with GW4064, a synthetic agonist to the farnesoid X receptor (FXR), and deoxycholic acid (DCA), an activator of the Takeda G-protein-coupled receptor 5. TA, GW4064, and DCA treatments all lowered postprandial lipemia. FXR agonism also reduced intestinal triglyceride content and activity of microsomal triglyceride transfer protein, involved in chylomicron assembly. Importantly, TA (but not DCA) effects were largely lost in FXR knockout mice. These bile acid effects are reminiscent of the antidiabetic hormone glucagon-like peptide-1 (GLP-1). Although the GLP-1 receptor agonist exendin-4 retained its ability to acutely lower postprandial lipemia during bile acid sequestration and FXR deficiency, it did raise hepatic expression of the rate-limiting enzyme for bile acid synthesis. Bile acid signaling may be an important mechanism of controlling dietary lipid absorption, and bile acid receptors may constitute novel targets for the treatment of postprandial dyslipidemia.NEW & NOTEWORTHY We present new data suggesting potentially important roles for bile acids in regulation of postprandial lipid metabolism. Specific bile acid species, particularly secondary bile acids, were found to markedly inhibit absorption of dietary lipid and reduce postprandial triglyceride excursion. These effects appear to be mediated via bile acid receptors, farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Importantly, bile acid signaling may trigger glucagon-like peptide-1 (GLP-1) secretion, which may in turn mediate the marked inhibitory effects on dietary fat absorption.

7.
Clin Biochem ; 76: 31-34, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838019

RESUMO

BACKGROUND: The urea creatinine ratio (UCR) is important in the clinical assessment of several medical conditions, including acute kidney injury and gastrointestinal bleeding. However, accurate and robust paediatric reference intervals (RIs) for this ratio have not been well established. Here, we determined age- and sex-specific discrete and continuous RIs for UCR in the Canadian Laboratory Initiative on Paediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents for the first time. METHODS: UCR was calculated for approximately 1030 CALIPER participants using retrospective urea and creatinine (both Jaffe and enzymatic methods) normative data. Partitions were determined using the Harris & Boyd statistical method. Discrete RIs were established in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. Continuous RIs were established using nonparametric quantile regression. RESULTS: Several age- and sex-specific partitions were necessary to capture dynamic physiological trends associated with this ratio throughout childhood and adolescence, highlighting the benefit of continuous RI establishment. Established UCR RIs also demonstrated marked differences between Jaffe and enzymatic assay methods. CONCLUSION: Our results clearly demonstrate the critical need for RI stratification by important covariates such as age, sex, and creatinine assay methodology for paediatric UCR test result interpretation. These data contribute to our understanding of normative UCR values in childhood and adolescence and can be expected to improve paediatric test result interpretation in clinical laboratories that report this ratio.


Assuntos
Creatinina/normas , Ureia/normas , Adolescente , Criança , Pré-Escolar , Creatinina/sangue , Humanos , Lactente , Recém-Nascido , Valores de Referência , Ureia/sangue , Adulto Jovem
8.
Am J Physiol Endocrinol Metab ; 318(2): E262-E275, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31821038

RESUMO

miR-130b is a microRNA whose expression is particularly elevated within adipose tissue and in the circulation in diabetic states. Hepatic miR-130b expression has been linked to hepatocellular carcinoma and changes in lipid metabolism. Here, we investigated the role of miR-130b in hepatic lipid homeostasis and lipoprotein export. We observed that overexpression of miR-130b-3p or -5p in HepG2 cells markedly enhanced the secretion of very-low-density lipoprotein (VLDL) particles, enhanced the secretion of [3H]glycerol metabolically labeled triglyceride (TG), and significantly increased the number or the average size of lipid droplets (LDs), respectively. Overexpression of miR-130b also altered the expression of key genes involved in lipid metabolism and in particular markedly increased both mRNA and protein expression levels of microsomal triglyceride transfer protein (MTP). Conversely, the miR-130b inhibitor decreased mRNA levels of MTP and fatty acid synthase (FAS) in HepG2 cells. However, dual-luciferase reporter assays indicated that MTP is not a direct target of miR-130b-3p. miR-130b overexpression did not alter de novo synthesized TG or the stability and secretion of apolipoprotein B 100. Interestingly, knockdown of phosphatase and tensin homolog (PTEN) blocked the upregulation of MTP mRNA induced by miR-130b. Finally, miR-130b-induced stimulation of VLDL secretion was also observed in a second hepatocyte cell culture model, immortalized human hepatocytes, confirming the effects observed in HepG2 cells. Overall, these data suggest a potential role for miR-130b in promoting hepatic VLDL assembly and secretion mediated by marked stimulation of MTP expression and TG mobilization. Thus miR-130b overexpression corrects the defect in VLDL production in HepG2 cells.

9.
J Clin Endocrinol Metab ; 105(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31845996

RESUMO

BACKGROUND: The prevalence of pediatric obesity is increasing worldwide and strongly associates with metabolic abnormalities, including inflammation, insulin resistance, and dyslipidemia. This study assessed the influence of 3 measures of adiposity on levels of routinely assessed biochemical markers in apparently healthy children and adolescents. METHODS: The influence of adiposity on 35 biochemical markers was examined in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents by comparing serum biomarker levels between subjects with a normal weight, overweight, and obese body mass index (BMI). The cohort comprised 1332 subjects 5.1 to 19.0 years of age with a BMI ranging from 13.4 to 65.0 kg/m2. The association between each biochemical marker and BMI, waist circumference, and waist-to-height ratio z-scores was assessed, while adjusting for age and sex. Reference intervals were established for all biochemical markers before and after removing overweight/obese subjects. RESULTS: In children and adolescents, levels of 13 routinely assessed biochemical markers, including alanine aminotransferase, apolipoprotein B, complement components 3 and 4, cholinesterase, high sensitivity C-reactive protein, gamma-glutamyl transferase, haptoglobin, high-density lipoprotein cholesterol, iron, transferrin, triglycerides, and uric acid, were significantly different between BMI categories. BMI, waist circumference, and/or waist-to-height ratio were significantly associated with the serum concentration of 24 of the 35 markers examined, after adjusting for age and sex. CONCLUSIONS: Excess adiposity significantly influences circulating levels of routinely assessed laboratory markers, most notably liver enzymes, lipids/lipoproteins, inflammatory markers, and uric acid in children and adolescents. Although it is unknown whether altered biochemical marker levels in subjects with overweight/obesity reflect health or indolent disease, clinicians should be aware of the effect of weight status on several laboratory tests.

10.
Clin Chem Lab Med ; 58(4): 605-617, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-31874092

RESUMO

Background Accurate pediatric reference intervals (RIs) for laboratory tests determined in a healthy pediatric population are essential for correct laboratory test interpretation and clinical decision-making. In pediatrics, RIs require partitioning by age and/or sex; however, the need for partitioning based on ethnicity is unclear. Here, we assessed the influence of ethnicity on biomarker concentrations in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents and compared the results with the National Health and Nutrition Examination Survey (NHANES). Methods A total of 52 biomarkers were measured in a multiethnic population of 846-1179 healthy children (aged 5 to <19 years) upon informed consent. Biomarker concentrations were retrospectively compared between four major ethnic groups (i.e. Black, Caucasian, East Asian, and South Asian, determined by parental ethnicity). Retrospective results were verified prospectively using an additional 500 healthy pediatric samples with equal sample size across ethnicities. Ethnic-specific differences were assessed based on statistical significance and biological and analytical variations. Appropriate age-, sex-, and ethnic-specific RIs were calculated. Results Ethnic-specific differences were not observed for 34 biomarkers examined in the retrospective analysis, while 18 demonstrated statistically significant ethnic differences. Among these, seven analytes demonstrated ethnic-specific differences in the prospective analysis: vitamin D, amylase, ferritin, follicle-stimulating hormone (FSH), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM). Analysis of select NHANES data confirmed CALIPER findings. Conclusions This is the first comprehensive Canadian pediatric study examining ethnic-specific differences in common biomarkers. While the majority of biomarkers did not require ethnic partitioning, ethnic-specific RIs were established for seven biomarkers showing marked differences. Further studies in other populations are needed to confirm our findings.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31825485

RESUMO

BACKGROUND: With increased rates of obesity and insulin resistance in youth, development of postprandial dyslipidemia, an important cardiovascular disease risk factor, is a concern. Glucagon-like peptides (i.e. GLP-1 and GLP-2) and bile acids have been shown to regulate dietary fat absorption and postprandial lipids in animal models and humans. We hypothesize that the physiological response of GLPs and bile acids to dietary fat ingestion is impaired in adolescents with obesity and this associates with marked postprandial dyslipidemia and insulin resistance. METHODS: In this cross-sectional study, normal weight adolescents and adolescents with obesity underwent a 6-hour oral fat tolerance test. The postprandial lipoprotein phenotype profile was determined using various assays, including nuclear magnetic resonance spectroscopy, to characterize lipoprotein particle number, size, lipid content, and apolipoproteins. GLP-1 and GLP-2 were quantified by electrochemiluminescent immunoassays. Total bile acids were measured by an automated enzymatic cycling colorimetric method and the bile acid profile by mass spectrometry. RESULTS: Adolescents with obesity exhibited fasting and postprandial dyslipidemia, particularly augmented postprandial excursion of large triglyceride-rich lipoproteins. Postprandial GLPs were reduced and inversely correlated with postprandial dyslipidemia and insulin resistance. Postprandial bile acids were also diminished, particularly lithocholic acid, a potent stimulator of GLP-1 secretion. CONCLUSION: Blunted postprandial GLP and bile acid response to dietary fat ingestion strongly associates with marked postprandial dyslipidemia. Further investigation is needed to assess their potential utility as early biomarkers for postprandial dyslipidemia in adolescents with obesity.

12.
Clin Biochem ; 73: 82-89, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31445880

RESUMO

BACKGROUND: Reference intervals have traditionally been partitioned by age based on statistical significance and physiological relevance. However, analyte concentration does not change abruptly with age, but rather dynamically. In this study, we establish biochemical marker continuous reference intervals for a Canadian population using healthy pediatric reference individuals and compare these to partitioned reference intervals. METHODS: Continuous reference intervals spanning 1-18.5 years of age were established using data from healthy CALIPER children and adolescents aged 6 months- < 19 years. Continuous reference intervals (i.e. 2.5th and 97.5th quantiles) were generated by nonparametric quantile regression via penalized splines with non-crossing constraints. Abnormal flagging rates of established continuous reference intervals were compared to previously established age-partitioned CALIPER reference intervals for five biochemical markers using internal (CALIPER) and external (i.e. Canadian Health Measures Survey (CHMS)) datasets. RESULTS: Continuous reference intervals were determined for 38 biochemical markers, with 21 markers requiring sex-specific reference intervals. Despite similar total flagging rates to partitioned reference intervals, continuous reference intervals appeared to provide a more consistent and accurate estimation of reference limits for biomarkers with more complex age-related changes, including alkaline phosphatase and phosphate. CONCLUSIONS: This is the first report of continuous biochemical marker reference intervals based on a healthy Canadian pediatric population. Reference limit point estimates based on continuous reference intervals are provided to aid clinical implementation. Continuous reference intervals offer a better estimation of dynamic changes in biochemical marker reference values with age, resulting in improved laboratory test result interpretation and clinical decision making in pediatrics.


Assuntos
Biomarcadores/sangue , Adolescente , Canadá , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Lactente , Masculino , Valores de Referência
13.
Clin Chem Lab Med ; 57(12): 1968-1979, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31377737

RESUMO

Background The diagnostic utility of laboratory tests in paediatric medicine relies heavily on the availability of appropriate reference intervals (RIs). The Canadian Laboratory Initiative on Paediatric Reference Intervals (CALIPER) has established a comprehensive database of covariate-stratified RIs for many paediatric laboratory tests using a large, healthy reference population. Several automated analysers in widespread use in clinical laboratories have already been studied. Here, we extend the testing to Roche immunoassays and report, for the first time, comprehensive paediatric RIs for 17 endocrine and special chemistry markers. Methods A total of 741 healthy children and adolescents (1 day to <19 years) were recruited and serum samples were analysed for 17 immunoassays on the Roche cobas 8000 e602 Immunoassay Analyzer. Age and sex-specific RIs were established and corresponding 90% confidence intervals (CIs) were calculated in accordance with Clinical and Laboratory Standards Institute guidelines. Results Reference values for all analytes measured required age partitioning, particularly during early life and throughout adolescence. Of the 17 analytes measured, eight required sex partitioning, including ferritin, thyroid stimulating hormone (TSH), total triiodothyronine (TT3) and all fertility/sex hormones, except prolactin. Conclusions This is the first study to determine accurate paediatric RIs for Roche immunoassays. RIs were generally similar to those previously published by CALIPER on other analytical platforms, highlighting the reproducibility of age- and sex-specific trends in reference values observed across the paediatric age range. The RIs established in this study will improve the accuracy of test result interpretation and clinical decision-making in clinical laboratories utilising Roche immunoassays.

14.
Am J Physiol Endocrinol Metab ; 317(4): E559-E572, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31310579

RESUMO

Nutrient sensing plays an important role in ensuring that appropriate digestive or hormonal responses are elicited following the ingestion of fuel substrates. Mechanisms of nutrient sensing in the oral cavity have been fairly well characterized and involve lingual taste receptors. These include heterodimers of G protein-coupled receptors (GPCRs) of the taste receptor type 1 (T1R) family for sensing sweet (T1R2-T1R3) and umami (T1R1-T1R3) stimuli, the T2R family for sensing bitter stimuli, and ion channels for conferring sour and salty tastes. In recent years, several studies have revealed the existence of additional nutrient-sensing mechanisms along the gastrointestinal tract. Glucose sensing is achieved by the T1R2-T1R3 heterodimer on enteroendocrine cells, which plays a role in triggering the secretion of incretin hormones for improved glycemic and lipemic control. Protein hydrolysates are detected by Ca2+-sensing receptor, the T1R1-T1R3 heterodimer, and G protein-coupled receptor 92/93 (GPR92/93), which leads to the release of the gut-derived satiety factor cholecystokinin. Furthermore, several GPCRs have been implicated in fatty acid sensing: GPR40 and GPR120 respond to medium- and long-chain fatty acids, GPR41 and GPR43 to short-chain fatty acids, and GPR119 to endogenous lipid derivatives. Aside from the recognition of fuel substrates, both the oral cavity and the gastrointestinal tract also possess T2R-mediated mechanisms of recognizing nonnutrients such as environmental contaminants, bacterial toxins, and secondary plant metabolites that evoke a bitter taste. These gastrointestinal sensing mechanisms result in the transmission of neuronal signals to the brain through the release of gastrointestinal hormones that act on vagal and enteric afferents to modulate the physiological response to nutrients, particularly satiety and energy homeostasis. Modulating these orally accessible nutrient-sensing pathways using particular foods, dietary supplements, or pharmaceutical compounds may have therapeutic potential for treating obesity and metabolic diseases.

15.
Lancet Child Adolesc Health ; 3(8): 558-567, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31231066

RESUMO

BACKGROUND: Traumatic brain injury (TBI) is a major health problem in children. Blood-based biomarkers interpreted by use of normative values might improve the accuracy of diagnosis. Ultrasensitive assays can quantify serum concentrations of the neuronal microtubule-associated protein tau, which is increased in adult brains following TBI. We aimed to determine if serum total tau correlates with TBI diagnosis, severity, and radiological findings on CT scans in children younger than 18 years. METHODS: In this case-control study, we included venous blood samples from healthy control children in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) biobank. For TBI cases, we recruited children (aged 0-17 years) who presented to the emergency department within 24 h of a TBI in three tertiary-care paediatric hospitals (Toronto, Vancouver, and Melbourne). Children were eligible if they required hospital observation for a minimum of 4 h or admission to the intensive care unit, and were excluded if they had had hospital treatment for a previous TBI, had birth trauma, or their parents could not speak English or French and therefore could not readily give consent. All available control samples were used and a case-control match was therefore not done. Venous and arterial blood samples were collected from patients with TBI within 28 h of injury (day 1). We used an ultrasensitive single-molecule immunoassay to measure serum total tau in blood samples. We first generated reference intervals of serum total tau from the control group, and used these normative data to interpret injury-associated changes in serum total tau in children with TBI. Concentrations of serum tau were measured in all CALIPER participants and patients with TBI, and no participants were excluded before analysis. FINDINGS: We included samples from 416 control participants from the CALIPER cohort. Median total tau concentrations did not differ between sexes (p=0·12), but three significant reference intervals based on age groups were identified (1-3 years [0·88-19·2 pg/mL], 4-15 years [0·93-5·31 pg/mL], and 16-19 years [0·79-4·20 pg/mL]). Blood samples were obtained from 158 patients with TBI recruited between April 30, 2011, and June 28, 2013. Serum total tau on day 1 of TBI was negatively associated with Glasgow Coma Scale (GCS) score (rs=-0·42, 95% CI -0·55 to -0·28, p<0·0001). Median total tau was 2·86 pg/mL (IQR 1·52-4·83) in patients with GCS score 13-15 points (n=114), 7·08 pg/mL (3·75-41·1) in those with GCS score 9-12 points (n=13), and 8·48 pg/mL (2·53-70·6) in those with GCS score 3-8 points (n=31). Notably, participants who had GCS scores of 15 points had median total tau concentrations (2·57 pg/mL [1·50-4·61]) indistinguishable from those of control participants (2·46 pg/mL [1·77-3·42]), whereas those with GCS score 13-14 points had elevated total tau (6·41 pg/mL [2·97-42·5]). Serum total tau was not strongly associated with CT findings in patients with mild TBI. INTERPRETATION: Serum total tau might help to differentiate between patients with mild TBI (GCS 13-14 vs GCS 15), but larger studies are needed to validate these results before this biomarker can be used for diagnosis and prognosis. FUNDING: Canadian Institutes of Health Research, Ontario Neurotrauma Foundation, and Victoria Neurotrauma Foundation.

16.
Curr Opin Clin Nutr Metab Care ; 22(4): 284-288, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31107259

RESUMO

PURPOSE OF REVIEW: To review recent evidence for the role of carbohydrates in the promotion of de novo lipogenesis and lipoprotein secretion from the intestine. RECENT FINDINGS: The consumption of diets rich in carbohydrates have been shown to promote elevations in circulating lipids. In particular, the consumption of monosaccharides, such as glucose and fructose, have been shown to induce increases in intestinal de novo lipogenesis, as well as be used as a substrate for the synthesis of triglycerides and lipoprotein export in the form of chylomicrons. Recently, various systematic reviews have analyzed the relative contribution of dietary fructose to intestinal lipogenesis. Although, there remains controversy within the literature, the body of evidence supports lipogenic effects of high fructose diets. In addition, alterations in markers of de novo lipogenesis within the jejunum of patients with insulin resistance may explain the alterations in their postprandial lipid profile. SUMMARY: Recent evidence supports the contribution of dietary carbohydrates to intestinal lipogenesis and lipoprotein secretion; however, further research is required to fully understand the mechanisms underlying this complex process.

17.
Int J Obes (Lond) ; 43(7): 1354-1362, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30940913

RESUMO

BACKGROUND/OBJECTIVES: We examined the association for rates of age- and sex-standardized body mass index (zBMI) gain between 0-3, 3-18, and 18-36 months with BP in children at 36-72 months of age. METHODS: We collected repeated measures of zBMI and BP in 2502 children. zBMI was calculated using the World Health Organization standards. Each child's zBMI at birth and rates of zBMI gain in each period from birth to 36 months were estimated using linear spline multilevel models. Generalized estimating equations were used to determine whether zBMI at birth and zBMI gain between 0-3, 3-18, and 18-36 months were each associated with repeated measures of BP at 36-72 months of age. We sequentially conditioned on zBMI at birth and zBMI gain in each period prior to each period tested, as covariates, and adjusted for important socio-demographic, familial, and study design covariates. We examined whether these associations were modified by birthweight or maternal obesity, by including interaction terms. RESULTS: After adjusting for all covariates and conditioning on prior zBMI gains, a 1 standard deviation unit faster rate of zBMI gain during 0-3 months, (ß = 0.59 mmHg; 95% CI 0.31, 0.86) and 3-18 months (ß = 0.74 mmHg; 95% CI 0.46, 1.03) were each associated with higher systolic BP at 36-72 months. No significant associations were observed, however, for zBMI at birth or zBMI gain in the 18-36 month growth period. zBMI gains from 0-3 and 3-18 months were also associated with diastolic BP. Birthweight significantly modified the relationship during the 3-18 month period (p = 0.02), with the low birthweight group exhibiting the strongest association for faster rate of zBMI gain with higher systolic BP (ß = 1.31 mmHg; 95% CI 0.14, 2.48). CONCLUSIONS: Given that long-term exposure to small elevations in BP are associated with subclinical cardiovascular disease, promoting interventions targeting healthy growth in infancy may be important.

20.
Clin Biochem ; 66: 29-36, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30763567

RESUMO

BACKGROUND: Reference intervals (i.e. normative ranges) established from a healthy reference population are essential to accurately interpret disease biomarkers. Biomarker concentration may partially depend on associations with other biomarkers due to various physiological and pathophysiological processes. In this study, a robust correlation analysis was performed to identify physiological biomarker associations in the healthy pediatric CALIPER cohort. METHODS: Population reference values for 35 biochemical and 20 fertility/endocrine markers were analyzed for correlations in all subjects, male adolescents, female adolescents, and young children. Associations between biomarkers were assessed by Spearman's rank correlation and a multivariate analysis technique, principal component analysis (PCA). RESULTS: Of 197, 90, 59, and 32 significant correlations between biochemical markers in all subjects, male adolescents, female adolescents, and children, respectively, 23, 19, 16, and 9 were moderately strong (r > 0.5 or r < -0.5). Of 98, 24, 33, and 16 significant correlations between fertility/endocrine markers in all subjects, male adolescents, female adolescents, and children, respectively, 17, 8, 11, and 5 were moderately strong. Results were agreeable between Spearman's rank method and PCA. In some cases, biomarker correlations differed between sexes. CONCLUSIONS: Using PCA, this study provides for the first time an extensive analysis of circulating biomarker associations in a healthy pediatric cohort. These data can inform future studies of potential confounding factors or particular variables that should be considered in test result interpretation for specific diseases.


Assuntos
Análise Química do Sangue/normas , Sistema Endócrino/química , Hormônios/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos de Coortes , Correlação de Dados , Bases de Dados Factuais , Feminino , Humanos , Lactente , Masculino , Análise Multivariada , Análise de Componente Principal , Valores de Referência , Adulto Jovem
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