Atypical postmortem redistribution in chronic methadone consumers.

Available literature demonstrates that methadone is prone to moderate postmortem redistribution, but subject to high interindividual variability in the central to peripheral blood concentration ratios (C/P). In this case series, 10 cases of chronic methadone users displaying C/P < 1 (range 0.26-0.82) are described. Femoral, cardiac and ante-mortem blood concentrations of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) are reported for all cases, as well as sex, age, case history, results of the pathological investigation, other toxicological findings and cause and manner of death. EDDP blood concentrations, similar in both central and peripheral blood, as well as antemortem blood concentration results in Case 4, demonstrate that this atypical C/P < 1 finding is attributable to postmortem changes and not analytical or pre-analytical artifacts. Case 4 is a particularly instructive example, with femoral blood concentration (966 ng/mL) approximately twice as high as cardiac blood (499 ng/mL) and ante-mortem blood (418 ng/mL, collected 38 min prior to death)-clearly demonstrating that cardiac blood methadone concentration is more representative of the antemortem blood concentration in this case. In Case 4 and four others, toxicological interpretation based on femoral blood concentration alone would have been misleading. Based on these results and evidence from the literature, it is hypothesized that methadone bioaccumulates in the tissues of chronic users and redistributes from thigh tissues into femoral blood, increasing the concentration postmortem. This case series highlights how femoral blood is not always preserved from postmortem changes and that the analysis of multiple blood sources is necessary to avoid a misleading toxicological interpretation-particularly for cases of chronic methadone users.

Metabolic features of adiposity and glucose homoeostasis among school-aged inuit children from Nunavik (Northern Quebec, Canada).

In contrast to most Indigenous people in Canada, Inuit appeared until recently to have been protected from type 2 diabetes (T2D) related to obesity. We assessed the associations of metabolites (amino acids, acylcarnitines) with adiposity and biomarkers of T2D in school-aged Inuit children of Nunavik (Canada). Concentrations of metabolite were measured in plasma samples from a cross-sectional analysis of 248 children (mean age = 10.8 years). We assessed associations of plasma metabolites with adiposity measures (BMI, skinfold thicknesses) and T2D markers (insulin, glucose, adiponectin). Plasma concentrations of valine and tyrosine were higher in obese and overweight children compared to those of normal weight children (P < 0.05). An increment of 1-SD in BMI (SD = 3.3 kg/m2) was statistically associated with an increment of 0.21 (95% CI: 0.08, 0.33) for valine, 0.15 (95% CI: 0.02, 0.27) for isoleucine and 0.17 (95% CI: 0.04, 0.29) for tyrosine. Insulin concentration increased with concentrations of all amino acids (P < 0.05) except methionine. None of the acylcarnitines measured were statistically significantly associated with adiposity or T2D biomarkers A signature of metabolites, particularly higher levels of branched-chain amino acids, might allow for early detection of T2D among school-aged Inuit children.

Risk of gestational diabetes mellitus in relation to plasma concentrations of amino acids and acylcarnitines: A nested case-control study.

AIMS: Gestational diabetes mellitus (GDM) affects between 5 and 10% of all pregnancies in Canada and can lead to adverse health outcomes in both the mother and fetus. Amino acids (AA) and acylcarnitines (AC) have been identified as early biomarkers of type 2 diabetes but their usefulness in screening for GDM has yet to be demonstrated. METHODS: We conducted a nested case-control study involving 50 controls and 50 GDM cases diagnosed between the 24th and 28th week of gestation. Heparinized plasma samples were obtained during the first and early second trimester of pregnancy. Case and controls were matched according to date of recruitment, maternal age, gestational age at blood sampling as well as pre-pregnancy body mass index. Eight AA and eight AC were quantified using an ultra-high pressure liquid-chromatography quadrupole time-of-flight mass spectrometry platform. Conditional regression analyses adjusted for matching factors and smoking habits during pregnancy were performed to identify plasma metabolites associated with GDM risk. RESULTS: Odds ratio (OR) and 95% confidence interval (CI) for the prediction of GDM per one standard deviation increase of AA or AC in plasma levels were 0.25 (0.08-0.79) for butyrylcarnitine, 0.31 (0.12-0.79) for glutamic acid, 2.5 (1.2-5.3) for acetylcarnitine, 2.9 (1.3-6.8) for isobutyrylcarnitine and 5.3 (1.7-17.0) for leucine. These five metabolites were selected by stepwise conditional logistic regression to create a predictive model with an OR of 2.7 (1.5-4.9). CONCLUSION: Whether the identified metabolites can predict the risk of developing GDM requires additional studies in a larger sample of pregnant women.

Is mercury exposure causing diabetes, metabolic syndrome and insulin resistance? A systematic review of the literature.

INTRODUCTION: Several populations are exposed to mercury (Hg) via their environment, occupation or diet. It is hypothesized that Hg exposure can lead to the development of diabetes mellitus (DM). Metabolic syndrome (MS) is also a possible outcome as its symptoms are closely linked to those of DM. METHOD: We conducted a systematic review of the literature by screening Web of Science, MEDLINE, SciFinder and Embase and we included original studies pertaining to the relationship of total Hg exposure (elemental, inorganic or organic) to DM, MS or insulin resistance. The studies were selected based on the PICOS (patients, intervention, comparator, outcomes and study design) criteria and their quality assessed using a nine-point scale. Study characteristics and results were extracted and presented in structured tables. We also extracted covariates entered as confounding factors to evaluate possible biases in selected studies. Finally, a weight of evidence approach was used to assess the causality of the relationship. RESULTS: A total of 34 studies were included in the present review. Epidemiological data assessment suggests a possible association between total Hg concentrations in different biological matrices and incidence of DM or MS, but the relationship is not consistent. In vivo and in vitro studies support the biological plausibility of the relation between Hg exposure and DM or MS. Five out of nine of Bradford Hill's criteria were fulfilled: strength, temporality, plausibility, coherence and analogy. CONCLUSION: Increased total Hg exposure may augment the risk of DM and MS, but the lack of consistency of the epidemiological evidence prevents inference of a causal relationship. Additional prospective cohort studies and careful consideration of confounding variables and interactions are required to conclude on the causal relationship of total Hg exposure on the development of DM or MS.

Branched-chain and aromatic amino acids in relation to behavioral problems among young Inuit from Nunavik, Canada: a cohort study.

BackgroundObesity and insulin resistance are linked with mood disorders, and elevated concentrations of branched-chain (BCAAs) and aromatic amino acids (AAAs). Our study aimed to prospectively assess the relationship between childhood plasma BCAAs and AAAs, and behavioral problems in young Inuit from Nunavik.MethodsWe analyzed data on 181 children (with a mean age of 11.4 years at baseline) involved in the Nunavik Child Development Study. Plasma BCAA and AAA concentrations were measured in childhood (2005-2010). BCAA/AAA tertiles-the ratio of total BCAAs to AAAs-were considered as surrogate categorical independent variables. Behavioral problems were assessed with the Youth Self-Report (YSR) from the Child Behavior Checklist about 7 years later during adolescence (2013-2016). ANOVA ascertained relationships between BCAA/AAA tertiles and YSR outcomes.ResultsAscending BCAA/AAA tertiles were positively associated (Ptrend<0.05) with somatic complaint scores. Scores of somatic complaints syndrome were significantly higher (Ptrend <0.05) with increasing BCAA/AAA tertiles among both normal and overweight/obese participants.ConclusionOur results suggest that higher BCAA/AAA ratios in childhood are significantly associated with somatic complaints in adolescence.

Eye fixation patterns for categorizing static and dynamic facial expressions.

Facial expressions of emotion are dynamic in nature, but most studies on the visual strategies underlying the recognition of facial emotions have used static stimuli. The present study directly compared the visual strategies underlying the recognition of static and dynamic facial expressions using eye tracking and the Bubbles technique. The results revealed different eye fixation patterns with the 2 kinds of stimuli, with fewer fixations on the eye and mouth area during the recognition of dynamic than static expressions. However, these differences in eye fixations were not accompanied by any systematic differences in the facial information that was actually processed to recognize the expressions. (PsycINFO Database Record

Quantitative analysis of amino acids and acylcarnitines combined with untargeted metabolomics using ultra-high performance liquid chromatography and quadrupole time-of-flight mass spectrometry.

Metabolomics is an "omic" technique being increasingly used in epidemiological and clinical studies. We developed a method combining untargeted metabolomics with the quantitative determination of eight amino acids (AA) and eight acylcarnitines (AC) in plasma using ultra-high pressure liquid chromatography (UHPLC), electrospray ionization (ESI) and quadrupole time-of-flight mass spectrometry (QTOFMS). Separation of metabolites is performed by ion-pair reverse phase UHPLC using a HSS T3 column (2.1×100mm, 100Å, 1.8µm particle size) and formic acid-ammonium acetate-heptafluorobutyric acid in water and formic acid-ammonium acetate in methanol as mobile phases. Metabolite identification and quantification are achieved using a QTOFMS operating in ESI-positive and full-scan mode along with MS(E) acquisition of fragmentation patterns. Targeted metabolites are quantified using the appropriate labeled standards and include branched-chain AA (leucine, isoleucine, valine), aromatic AA (phenylalanine, tyrosine) as well as acetylcarnitine and propionylcarnitine, which have been identified as biomarkers of future cardiometabolic disease risk. The inter-day precision (relative standard deviation) for the targeted method was <15% for all but one metabolite and accuracy (bias) of amino acids ranged from 0.5% to 13.9% using SRM 1950 as the external standard. Untargeted metabolomics in 30 plasma samples from the general Canadian population revealed 5018 features, of which 48 metabolites were identified using the MZmine 2.19 software including 23 by our in-house library that comprises 671 annotated metabolites. SRM 1950 analysis revealed 11,684 features, among which 154 metabolites were identified. Our method is currently applied in several epidemiological studies to better characterize cardiometabolic diseases and identify new biomarkers for disease prevention.

Overweight and Obesity Prevalence Among School-Aged Nunavik Inuit Children According to Three Body Mass Index Classification Systems.

PURPOSE: Little is known about the suitability of three commonly used body mass index (BMI) classification system for Indigenous children. This study aims to estimate overweight and obesity prevalence among school-aged Nunavik Inuit children according to International Obesity Task Force (IOTF), Centers for Disease Control and Prevention (CDC), and World Health Organization (WHO) BMI classification systems, to measure agreement between those classification systems, and to investigate whether BMI status as defined by these classification systems is associated with levels of metabolic and inflammatory biomarkers. METHODS: Data were collected on 290 school-aged children (aged 8-14 years; 50.7% girls) from the Nunavik Child Development Study with data collected in 2005-2010. Anthropometric parameters were measured and blood sampled. Participants were classified as normal weight, overweight, and obese according to BMI classification systems. Weighted kappa (κw) statistics assessed agreement between different BMI classification systems, and multivariate analysis of variance ascertained their relationship with metabolic and inflammatory biomarkers. RESULTS: The combined prevalence rate of overweight/obesity was 26.9% (with 6.6% obesity) with IOTF, 24.1% (11.0%) with CDC, and 40.4% (12.8%) with WHO classification systems. Agreement was the highest between IOTF and CDC (κw = .87) classifications, and substantial for IOTF and WHO (κw = .69) and for CDC and WHO (κw = .73). Insulin and high-sensitivity C-reactive protein plasma levels were significantly higher from normal weight to obesity, regardless of classification system. Among obese subjects, higher insulin level was observed with IOTF. CONCLUSIONS: Compared with other systems, IOTF classification appears to be more specific to identify overweight and obesity in Inuit children.

A refined examination of the facial cues contributing to vicarious effects on self-pain and spinal responses.

UNLABELLED: Vicarious pain has been shown to enhance observers' nociceptive reactivity and pain perception. We exposed healthy participants to specific parts of facial pain expressions in order to investigate which components are required to induce this modulation. We created 2 classes of stimuli: one containing the most useful information for identification of pain expressions (diagnostic) and one containing the least useful information (antidiagnostic). Twenty-eight normal volunteers received electrical stimulation of the sural nerve immediately after they viewed these stimuli. Subjective ratings (intensity and unpleasantness) as well as the nociceptive flexion reflex (NFR) evoked by the shock were recorded. Results show that diagnostic stimuli lead to higher subjective ratings of shock pain than the antidiagnostic stimuli, but the stimuli classes had no significant impact on the NFR. A control experiment showed that our facial stimuli were given very low valence and arousal ratings compared to stimuli previously used to demonstrate the effect of emotional pictures on pain. Thus, the results are unlikely to be explained by emotions felt by the observer and suggest a vicarious facilitation of supraspinal pain processing induced by key features underlying pain expressions recognition. Results provide further support to the perception-action model of empathy. PERSPECTIVE: This study demonstrates that visual features that are efficiently used for the recognition of pain expressions are sufficient to induce a vicarious facilitation of self-pain. Supraspinal pain responses were modulated by the informativeness of the areas of the pain expressions that participants viewed prior to the painful stimulations.

The eyes are not the window to basic emotions.

Facial expressions are one of the most important ways to communicate our emotional state. In popular culture and in the scientific literature on face processing, the eye area is often conceived as a very important - if not the most important - cue for the recognition of facial expressions. In support of this, an underutilization of the eye area is often observed in clinical populations with a deficit in the recognition of facial expressions of emotions. Here, we used the Bubbles technique to verify which facial cue is the most important when it comes to discriminating between eight static and dynamic facial expressions (i.e., six basic emotions, pain and a neutral expression). We found that the mouth area is the most important cue for both static and dynamic facial expressions. We conducted an ideal observer analysis on the static expressions and determined that the mouth area is the most informative. However, we found an underutilization of the eye area by human participants in comparison to the ideal observer. We then demonstrated that the mouth area contains the most discriminative motions across expressions. We propose that the greater utilization of the mouth area by the human participants might come from remnants of the strategy the brain has developed with dynamic stimuli, and/or from a strategy whereby the most informative area is prioritized due to the limited capacity of the visuo-cognitive system.