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Summary: Background: Whilst single chemical exposures are suspected to be obesogenic, the combined role of chemical mixtures in paediatric obesity is not well understood. Objectives: We aimed to evaluate the potential associations between chemical mixtures and obesity in a population‐based sample of Canadian children. Methods: We ascertained biomonitoring and health data for children aged 3–11 from the cross‐sectional Canadian Health Measures Survey from 2007 to 2019. Several chemicals of interest were measured in blood or urine and paediatric obesity was defined based on measured anthropometrics. Using quantile‐based G computational analysis, we quantified the effects of three chemical mixtures selected a priori. Models were adjusted for sociodemographic and environmental factors identified through a directed acyclic graph. Results are presented through adjusted relative risks (RR) with 95% confidence intervals (95% CI). Results: We included 9147 children. Of these, 24.1% were overweight or obese. Exposure to the mixture of bisphenol A, acrylamide, glycidamide, metals, parabens and arsenic increased the risk of childhood overweight or obesity by 45% (95% CI 1.09, 1.93), obesity by 109% (95% CI 1.27, 3.42) and central obesity by 82% (95% CI 1.30, 2.56). Conclusions: Our findings support the role of early childhood chemical exposures in paediatric obesity and the potential combined effects of chemicals. [ABSTRACT FROM AUTHOR]

Aim: Disruption of functional brain connectivity is thought to underlie disorders of consciousness (DOC) and recovery of impaired connectivity is suggested as an indicator of consciousness restoration. We recently found that rhythmic acoustic‐electric trigeminal‐nerve stimulation (i.e., musical stimulation synchronized to electrical stimulation of the trigeminal nerve) in the gamma band can improve consciousness in patients with DOC. Here, we investigated whether these beneficial stimulation effects are mediated by alterations in functional connectivity. Methods: Sixty‐three patients with DOC underwent 5 days of gamma, beta, or sham acoustic‐electric trigeminal‐nerve stimulation. Resting‐state electroencephalography was measured before and after the stimulation and functional connectivity was assessed using phase‐lag index (PLI). Results: We found that gamma stimulation induces an increase in gamma‐band PLI. Further characterization revealed that the enhancing effect is (i) specific to the gamma band (as we observed no comparable change in beta‐band PLI and no effect of beta‐band acoustic‐electric stimulation or sham stimulation), (ii) widely spread across the cortex, and (iii) accompanied by improvements in patients' auditory abilities. Conclusion: These findings show that gamma acoustic‐electric trigeminal‐nerve stimulation can improve resting‐state functional connectivity in the gamma band, which in turn may be linked to auditory abilities and/or consciousness restoration in DOC patients. [ABSTRACT FROM AUTHOR]

The assessment of consciousness states, especially distinguishing minimally conscious states (MCS) from unresponsive wakefulness states (UWS), constitutes a pivotal role in clinical therapies. Despite that numerous neural signatures of consciousness have been proposed, the effectiveness and reliability of such signatures for clinical consciousness assessment still remains an intense debate. Through a comprehensive review of the literature, inconsistent findings are observed about the effectiveness of diverse neural signatures. Notably, the majority of existing studies have evaluated neural signatures on a limited number of subjects (usually below 30), which may result in uncertain conclusions due to small data bias. This study presents a systematic evaluation of neural signatures with large‐scale clinical resting‐state electroencephalography (EEG) signals containing 99 UWS, 129 MCS, 36 emergence from the minimally conscious state, and 32 healthy subjects (296 total) collected over 3 years. A total of 380 EEG‐based metrics for consciousness detection, including spectrum features, nonlinear measures, functional connectivity, and graph‐based measures, are summarized and evaluated. To further mitigate the effect of data bias, the evaluation is performed with bootstrap sampling so that reliable measures can be obtained. The results of this study suggest that relative power in alpha and delta serve as dependable indicators of consciousness. With the MCS group, there is a notable increase in the phase lag index‐related connectivity measures and enhanced functional connectivity between brain regions in comparison to the UWS group. A combination of features enables the development of an automatic detector of conscious states. [ABSTRACT FROM AUTHOR]

Childhood obesity is a predictor of adult obesity and has its roots in the pre-pregnancy or pregnancy period. This review presents an overview of the prenatal risk factors for childhood obesity, which were categorized into 2 groups: biological risk factors (maternal pre-pregnancy body mass index, gestational weight gain, diabetes in pregnancy, and caesarean section), and environmental and behavioural risk factors (maternal smoking and exposure to obesogens, maternal dietary patterns, maternal intestinal microbiome and antibiotics exposure, and maternal psychosocial stress). Identifying modifiable predisposing prenatal factors for obesity will inform further development of inventions to prevent obesity over the life course, and future directions for research and intervention are discussed. Key words: risk factors, obesity, pregnancy, body mass index, childhood. L'obesite chez l'enfant est un facteur predictif de l'obesite chez l'adulte ayant ses racines dans les periodes de grossesse ou precedant la grossesse. Cet article de synthese presente un apercu des facteurs de risque prenataux pour l'obesite chez l'enfant, que nous avons categorises en 2 groupes : facteurs de risque biologiques (indice de masse corporelle maternel avant la grossesse, prise de poids pendant la grossesse, diabete de grossesse, ainsi que cesarienne) et facteurs de risque environnementaux et comportementaux (tabagisme chez la mere et exposition aux << obesogenes >>, habitudes alimentaires de la mere, microbiome intestinal maternel et prise d'antibiotiques, ainsi que stress psychosocial chez la mere). L'identification de facteurs predisposants modifiables prenataux d'obesite chez Ia mere apportera des donnees pour le developpement a venir d'inventions destinees a la prevention de l'obesite tout au long de la vie, et nous discutons d'avenues pour des recherches et des interventions futures. [Traduit par la Redaction] Mots-cles : facteurs de risque, obesite, grossesse, indice de masse corporelle, enfance., Introduction Obesity is generally defined as a condition in which the degree of excess body fat has the potential to negatively impact health outcomes (WHO 2017). Body mass index (BMI) [...]

Doublecortin-like kinase 1 (DCLK1) is a prominent kinase involved in carcinogenesis, serving as a diagnostic marker for early cancer detection and prevention, as well as a target for cancer therapy. Extensive research efforts have been dedicated to understanding its role in cancer development and designing selective inhibitors. In our previous work, we successfully determined the crystal structure of DCLK1 while it was bound to its autoinhibitory domain (AID) at the active site. By analyzing this structure, we were able to uncover the intricate molecular mechanisms behind specific cancer-causing mutations in DCLK1. Utilizing molecular dynamics simulations, we discovered that these mutations disrupt the smooth assembly of the AID, particularly affecting the R2 helix, into the kinase domain (KD). This disruption leads to the exposure of the D533 residue of the DFG (Asp-Phe-Gly) motif in the KD, either through steric hindrance, the rearrangement of electrostatic interactions, or the disruption of local structures in the AID. With these molecular insights, we conducted a screening process to identify potential small-molecule inhibitors that could bind to DCLK1 through an alternative binding mode. To assess the binding affinity of these inhibitors to the KD of DCLK1, we performed calculations on their binding energy and conducted SPR experiments. We anticipate that our study will contribute novel perspectives to the field of drug screening and optimization, particularly in targeting DCLK1. [ABSTRACT FROM AUTHOR]

Objective: To assess relationships between breast-feeding, rapid growth in the first year of life and overweight/obesity status at the age of 2 years. Design: As part of an observational, longitudinal study beginning in early pregnancy, multivariable logistic regressions were used to assess associations between breast-feeding duration (total and exclusive) and rapid weight gain (RWG) between birth and 1 year of age, and to determine predictors of overweight/obesity status at the age of 2 years. Setting: Nine hospitals located in the province of Quebec, Canada. Participants: A sample of 1599 term infants who participated in the 3D Cohort Study. Results: Children having RWG in the first year and those having excess weight at the age of 2 years accounted for 28 % and < 10 %, respectively. In multivariable models, children breastfed < 6 months and from 6 months to < 1 year were, respectively, 2·5 times (OR 2·45; 95 % CI 1·76, 3·41) and 1·8 times (OR 1·78; 95 % CI 1·29, 2·45) more likely to show RWG up to 1 year of age compared to children breastfed ≥ 1 year. Children exclusively breastfed < 3 months had significantly greater odds of RWG in the first year (OR 1·94; 95 % CI 1·25, 3·04) compared to children exclusively breastfed for ≥ 6 months. Associations between breast-feeding duration (total or exclusive) and excess weight at the age of 2 years were not detected. RWG in the first year was found to be the main predictor of excess weight at the age of 2 years (OR 6·98; 95 % CI 4·35, 11·47). Conclusions: The potential beneficial effects of breast-feeding on rate of growth in the first year of life suggest that interventions promoting breast-feeding are relevant for obesity prevention early in life. [ABSTRACT FROM AUTHOR]

Good diet quality during pregnancy provides adequate nutrition to support both the mothers and the fetus. The objective of this study is to describe the distribution of diet quality during pregnancy and to study the association between social factors and diet quality during pregnancy in a Canadian population. This study was based on 1535 pregnant women who provided dietary information in the 3D Cohort Study in Quebec, Canada. A 3‐day food record was used to collect dietary intake in the second trimester of pregnancy. A Canadian adaption of the Healthy Eating Index (HEI‐C) 2010 was used to quantify diet quality. Univariate and multiple linear regression models were used to calculate unadjusted and adjusted effect estimates and confidence intervals for the association between social factors and HEI‐C. The mean HEI‐C 2010 score in this study was 62.9 (SD: 11.2). Only 4.5% and 8.3% of the pregnant women consumed the recommended amounts of whole grains and 'greens and beans', respectively. Diet quality was lower in some subgroups of pregnant women. After multivariable adjustment, lower diet quality was observed in participants who were less educated, younger, overweight or obese before pregnancy, or parous. There was an interaction between ethnicity and immigration status on diet quality in pregnancy. These findings could be useful for health practitioners and policymakers in developing strategies to improve the diet quality of pregnant women. Key message: The diet of the women in Canada still needs improvement, especially regarding whole grains and 'greens and beans', where the majority of the women did not meet the recommendations.Pregnant women who were less educated, younger, overweight or obese before pregnancy, or parous should be targeted for improving diet quality in Canada.There was an interaction between ethnicity and immigration status on diet quality during pregnancy. [ABSTRACT FROM AUTHOR]

The neurophysiological basis of the association between interhemispheric connectivity and speech comprehension processing remains unclear. This prospective study examined regional cerebral blood flow (CBF), homotopic functional connectivity, and neurovascular coupling, and their effects on comprehension performance in post-stroke aphasia. Multimodal imaging data (including data from functional magnetic resonance imaging and arterial spin labeling imaging) of 19 patients with post-stroke aphasia and 22 healthy volunteers were collected. CBF, voxel-mirrored homotopic connectivity (VMHC), CBF-VMHC correlation, and CBF/VMHC ratio maps were calculated. Between-group comparisons were performed to identify neurovascular changes, and correlation analyses were conducted to examine their relationship with the comprehension domain. The correlation between CBF and VMHC of the global gray matter decreased in patients with post-stroke aphasia. The total speech comprehension score was significantly associated with VMHC in the peri-Wernicke area [posterior superior temporal sulcus (pSTS): r = 0.748, p = 0.001; rostroventral area 39: r = 0.641, p = 0.008]. The decreased CBF/VMHC ratio was also mainly associated with the peri-Wernicke temporoparietal areas. Additionally, a negative relationship between the mean CBF/VMHC ratio of the cingulate gyrus subregion and sentence-level comprehension was observed (r = −0.658, p = 0.006). These findings indicate the contribution of peri-Wernicke homotopic functional connectivity to speech comprehension and reveal that abnormal neurovascular coupling of the cingulate gyrus subregion may underly comprehension deficits in patients with post-stroke aphasia. [ABSTRACT FROM AUTHOR]

Mass suspension of anthropogenic activities is extremely rare, the quarantine due to the coronavirus disease 2019 (COVID-19) represents a natural experiment to investigate the impact of anthropogenic activities on air quality. The mitigation of air pollution during the COVID-19 lockdown has been reported from a global perspective; however, the air pollution levels vary in different regions. This study initiated a novel synthesis of multiple-year satellite observations, national ground measurements towards SO2, NO2 and O3 and meteorological conditions to evaluate the impact of the COVID-19 lockdown in Beihai, a specific city in a less developed area in southwest China, to reveal the potential implications of control strategies for air pollution. The levels of the major air pollutants during the COVID-19 lockdown (LP) and during the same period of previous years (SP) were compared and a series of statistical tools were applied to analyze the sources of air pollution in Beihai. The results show that air pollutant levels decreased with substantial diversity during the LP. Satellite-retrieved NO2 and SO2 levels during the LP decreased by 5.26% and 22.06%, while NO2, SO2, PM2.5 and PM10 from ground measurements during the LP were 25.6%, 2.7%, 22.2% and 22.2% lower than during SP, respectively. Ground measured SO2 concentrations during the LP were only 2.7% lower than during the SP, which may be attributed to uninterrupted essential industrial activities, such as power plants. Polar plots analysis shows that NO2 concentrations were strongly associated with local emission sources, such as automobiles and local industry. Additionally, the much lower levels of NO2 concentrations during the LP and the absence of an evening peak may highlight the significant impact of the traffic sector on NO2. The decrease in daily mean O3 concentrations during the LP may be associated with the reduction in NO2 concentrations. Indications in this study could be beneficial for the formulation of atmospheric protection policies. [ABSTRACT FROM AUTHOR]

Naming is a commonly impaired language domain in various types of aphasia. Emerging evidence supports the cortico‐subcortical circuitry subserving naming processing, although neurovascular regulation of the non‐dominant thalamic and basal ganglia subregions underlying post‐stroke naming difficulty remains unclear. Data from 25 subacute stroke patients and 26 age‐, sex‐, and education‐matched healthy volunteers were analyzed. Region‐of‐interest‐wise functional connectivity (FC) was calculated to measure the strength of cortico‐subcortical connections. Cerebral blood flow (CBF) was determined to reflect perfusion levels. Correlation and mediation analyses were performed to identify the relationship between cortico‐subcortical connectivity, regional cerebral perfusion, and naming performance. We observed increased right‐hemispheric subcortical connectivity in patients. FC between the right posterior superior temporal sulcus (pSTS) and lateral/medial prefrontal thalamus (lPFtha/mPFtha) exhibited significantly negative correlations with total naming score. Trend‐level increased CBF in subcortical nuclei, including that in the right lPFtha, and significant negative correlations between naming and regional perfusion of the right lPFtha were observed. The relationship between CBF in the right lPFtha and naming was fully mediated by the lPFtha‐pSTS connectivity in the non‐dominant hemisphere. Our findings suggest that perfusion changes in the right thalamic subregions affect naming performance through thalamo‐cortical circuits in post‐stroke aphasia. This study highlights the neurovascular pathophysiology of the non‐dominant hemisphere and demonstrates thalamic involvement in naming after stroke. [ABSTRACT FROM AUTHOR]

• Both static and dynamic analyses of local neural activity were investigated in patients of disorder of consciousness (DOC). • The dynamic analysis could unravel more pathological regions than the static analysis. • Sub-frequency analysis of fALFF indicated a potential frequency dependent alteration of the default mode network in DOC patients. • The DOC classifier established on fALFF achieved the highest classification accuracy. Although the resting-state networks of patients with disorders of consciousness (DOC) have been widely investigated, the underlying neural mechanisms remain unclear. Here we aimed to explore the static and dynamic alterations in the regional brain activity in patients with DOC and detect the diagnostic ability of each index. Nineteen patients in the vegetative state, 19 in the minimally conscious state (MCS), and 41 healthy controls were recruited for this study. The fractional amplitudes of the low-frequency fluctuation (fALFF) and dynamic fALFF (dfALFF) values were computed, and intergroup differences were detected by analysis of variance. Sub-frequency analysis (slow-4 band and slow-5 band) of fALFF was also performed. Machine learning classifiers were established based on these measures to explore the classification accuracies between patients and controls. The fALFF and dfALFF analyses showed significant intergroup differences in the medial prefrontal gyrus, precuneus, left angular gyrus, and right middle cingulate cortex (MCC), whereas only the dfALFF analysis revealed aberrations in the right inferior frontal gyrus (IFG), right angular gyrus, left supramarginal gyrus (SMG), and left middle occipital gyrus (MOG). Sub-frequency analysis suggested a potential frequency dependent alteration in the default mode network (DMN). The fALFF model exhibited a higher classification accuracy (ACC) (90.50%) than the dfALFF model (86.29%). The combination of fALFF and dfALFF did not improve classification performance. The strength and stability of regional brain activities were disrupted in patients with DOC. Our findings demonstrate that dynamic analysis may reveal more pathological regions and provide a better understanding of the pathophysiologic mechanisms of DOC. [ABSTRACT FROM AUTHOR]