Structural brain network lateralization across childhood and adolescence.

Developmental lateralization of brain function is imperative for behavioral specialization, yet few studies have investigated differences between hemispheres in structural connectivity patterns, especially over the course of development. The present study compares the lateralization of structural connectivity patterns, or topology, across children, adolescents, and young adults. We applied a graph theory approach to quantify key topological metrics in each hemisphere including efficiency of information transfer between regions (global efficiency), clustering of connections between regions (clustering coefficient [CC]), presence of hub-nodes (betweenness centrality [BC]), and connectivity between nodes of high and low complexity (hierarchical complexity [HC]) and investigated changes in these metrics during development.

Structural connectome differences in pediatric mild traumatic brain and orthopedic injury.

Sophisticated network-based approaches such as structural connectomics may help to detect a biomarker of mild traumatic brain injury (mTBI) in children. This study compared the structural connectome of children with mTBI or mild orthopedic injury (OI) to that of typically developing (TD) children. Children aged 8-16.

Participant factors that contribute to magnetic resonance imaging motion artifacts in children with mild traumatic brain injury or orthopedic injury.

Motion can compromise image quality and confound results, especially in pediatric research. This study evaluated qualitative and quantitative approaches to motion artifacts detection and correction, and whether motion artifacts relate to injury history, age, or sex in children with mild traumatic brain injury or orthopedic injury relative to typically developing children. The concordance between qualitative and quantitative motion ratings was also examined.

Multimodal principal component analysis to identify major features of white matter structure and links to reading.

The role of white matter in reading has been established by diffusion tensor imaging (DTI), but DTI cannot identify specific microstructural features driving these relationships. Neurite orientation dispersion and density imaging (NODDI), inhomogeneous magnetization transfer (ihMT) and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT) can be used to link more specific aspects of white matter microstructure and reading due to their sensitivity to axonal packing and fiber coherence (NODDI) and myelin (ihMT and mcDESPOT). We applied principal component analysis (PCA) to combine DTI, NODDI, ihMT and mcDESPOT measures (10 in total), identify major features of white matter structure, and link these features to both reading and age.

Brain structure and internalizing and externalizing behavior in typically developing children and adolescents.

Mental health problems often emerge in adolescence and are associated with reduced gray matter thickness or volume in the prefrontal cortex (PFC) and limbic system and reduced fractional anisotropy (FA) and increased mean diffusivity (MD) of white matter linking these regions. However, few studies have investigated whether internalizing and externalizing behavior are associated with brain structure in children and adolescents without mental health disorders, which is important for understanding the progression of symptoms. 67 T1-weighted and diffusion tensor imaging datasets were obtained from 48 typically developing participants aged 6-16 years (37M/30F; 19 participants had two visits).

A multiparametric analysis of white matter maturation during late childhood and adolescence.

White matter development has been well described using diffusion tensor imaging (DTI), but the microstructural processes driving development remain unclear due to methodological limitations. Here, using neurite orientation dispersion and density imaging (NODDI), inhomogeneous magnetization transfer (ihMT), and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT), we describe white matter development at the microstructural level in a longitudinal cohort of healthy 6-15 year olds. We evaluated age and gender-related trends in fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI), orientation dispersion index (ODI), quantitative ihMT (qihMT), myelin volume fraction (VF ), and g-ratio.

Developmental trajectories of white matter structure in children with and without reading impairments.

Left temporal-parietal white matter structure is consistently associated with reading abilities in children. A small number of longitudinal studies show that development of this area over time is altered in children with impaired reading. However, it remains unclear how brain developmental patterns relate to specific reading skills such as fluency, which is a critical part of reading comprehension.

A comparison of inhomogeneous magnetization transfer, myelin volume fraction, and diffusion tensor imaging measures in healthy children.

Sensitive and specific biomarkers of myelin can help define baseline brain health and development, identify and monitor disease pathology, and evaluate response to treatment where myelin content is affected. Diffusion measures such as radial diffusivity (RD) are commonly used to assess myelin content, but are not specific to myelin. Inhomogeneous magnetization transfer (ihMT) and multicomponent driven equilibrium single-pulse observation of T1 and T2 (mcDESPOT) offer quantitative parameters (qihMT and myelin volume fraction/VF, respectively) which are suggested to have improved sensitivity to myelin.

Detailing neuroanatomical development in late childhood and early adolescence using NODDI.

Diffusion tensor imaging (DTI) studies have provided much evidence of white and subcortical gray matter changes during late childhood and early adolescence that suggest increasing myelination, axon density, and/or fiber coherence. Neurite orientation dispersion and density imaging (NODDI) can be used to further characterize development in white and subcortical grey matter regions in the brain by improving specificity of the MRI signal compared to conventional DTI. We used measures from NODDI and DTI to examine white and subcortical gray matter development in a group of 27 healthy participants aged 8-13 years.

Low Cytochrome Oxidase 1 Links Mitochondrial Dysfunction to Atherosclerosis in Mice and Pigs.

Background: Cytochrome oxidase IV complex regulates energy production in mitochondria. Therefore, we determined the relation of COX genes with atherosclerosis in mice and pigs.

Methods And Results: First, we compared atherosclerosis in the aortic arch of age-matched (24 weeks) C57BL/6J control (n = 10), LDL-receptor deficient (n = 8), leptin-deficient ob/ob (n = 10), and double knock-out (lacking LDL-receptor and leptin) mice (n = 12).

Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent.

Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO < 10 mmHg) after the termination of seizures.

Low cytochrome oxidase 4I1 links mitochondrial dysfunction to obesity and type 2 diabetes in humans and mice.

Objectives: Cytochrome oxidase (COX) dysfunction is associated with mitochondrial oxidative stress. We determined the association between COX expression, obesity and type 2 diabetes.

Subjects/methods: COX4I1 and COX10 genes were measured in monocytes of 24 lean controls, 31 glucose-tolerant and 67 diabetic obese patients, and 17 morbidly obese patients before and after bariatric surgery.

Stevia-derived compounds attenuate the toxic effects of ectopic lipid accumulation in the liver of obese mice: a transcriptomic and metabolomic study.

There is a close interaction between Type 2 Diabetes, obesity and liver disease. We have studied the effects of the two most abundant Stevia-derived steviol glycosides, stevioside and rebaudioside A, and their aglycol derivative steviol on liver steatosis and the hepatic effects of lipotoxicity using a mouse model of obesity and insulin resistance. We treated ob/ob and LDLR-double deficient mice with stevioside (10 mg⋅kg(-1)⋅day-1 p.

Rosiglitazone and fenofibrate exacerbate liver steatosis in a mouse model of obesity and hyperlipidemia. A transcriptomic and metabolomic study.

Peroxisome proliferator-activated receptors (PPAR) play an important role in the regulation of lipid and glucose metabolism, inflammatory, and vascular responses. We show the effect of treatment with two PPAR agonists, fenofibrate (FF) and rosiglitazone (RSG), on ob/ob and LDLR-double deficient mice, by combined gene-expression and metabolomic analyses. Male mice were daily treated for 12 weeks with RSG (10 mg·kg(1-)·day(-1) per os (p.

PPAR agonist-induced reduction of Mcp1 in atherosclerotic plaques of obese, insulin-resistant mice depends on adiponectin-induced Irak3 expression.

Synthetic peroxisome proliferator-activated receptor (PPAR) agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate) and a PPARγ agonist (rosiglitazone) on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO) were treated with fenofibrate, rosiglitazone or placebo for 12 weeks.

CD36 inhibitors reduce postprandial hypertriglyceridemia and protect against diabetic dyslipidemia and atherosclerosis.

CD36 is recognized as a lipid and fatty acid receptor and plays an important role in the metabolic syndrome and associated cardiac events. The pleiotropic activity and the multiple molecular associations of this scavenger receptor with membrane associated molecules in different cells and tissues have however questioned its potential as a therapeutic target. The present study shows that it is possible to identify low molecular weight chemicals that can block the CD36 binding and uptake functions.

Interleukin-1 receptor-associated kinase-3 is a key inhibitor of inflammation in obesity and metabolic syndrome.

Background: Visceral obesity is associated with the rising incidence of type 2 diabetes and metabolic syndrome. Low-grade chronic inflammation and oxidative stress synergize in obesity and obesity-induced disorders.

Objective: We searched a cluster of molecules that support interactions between these stress conditions in monocytes.

Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin-resistant mice.

Objective: Stevioside is a non-caloric natural sweetener that does not induce a glycemic response, making it attractive as sweetener to diabetics and others on carbohydrate-controlled diets. Obesity is frequently associated with insulin resistance and increased inflammation and oxidative stress. Therefore, we investigated its effects on insulin resistance, inflammation and oxidative stress related to atherosclerosis in obese insulin-resistant mice.

Increased PAFAH and oxidized lipids are associated with inflammation and atherosclerosis in hypercholesterolemic pigs.

Objective: To study the association of PAF-acetyl hydrolase (PAFAH) activity with inflammation, oxidative stress, and atherosclerosis in hypercholesterolemic swine.

Methods And Results: Cholesterol-rich diet feeding of miniature pigs was associated with an increase in PAFAH activity and an increase of the PAFAH to PON1 ratio. PLA2G7 RNA (coding for PAFAH) expression was increased in blood monocytes and plaque macrophages.

Oxidized low-density lipoprotein-induced expression of ABCA1 in blood monocytes precedes coronary atherosclerosis and is associated with plaque complexity in hypercholesterolemic pigs.

Background: Elevated oxidized low-density lipoprotein (oxLDL) is associated with atherosclerosis and high cardiovascular risk. Previously, we identified 18 genes in coronary plaque macrophages of hypercholesterolemic pigs that correlated with plaque oxLDL.

Objective: To determine which of these genes were differentially expressed in blood monocytes and correlated with blood and plaque oxLDL and with plaque complexity.

Rosuvastatin restores superoxide dismutase expression and inhibits accumulation of oxidized LDL in the aortic arch of obese dyslipidemic mice.

Background And Purpose: Our goal was to elucidate mechanisms of the inhibitory effect of rosuvastatin on the accumulation of plaque oxidized low density lipoproteins (oxLDL) and on plaque volume, without lowering cholesterol, in mice with combined leptin and LDL-receptor deficiency (DKO).

Experimental Approach: Twelve-week old DKO mice were treated with rosuvastatin (10 mg kg(-1) day(-1), s.c.