Investigating the link between regional oxygen metabolism and cognitive speed in multiple sclerosis: Implications for fatigue.

Background: Most multiple sclerosis (MS) patients experience fatigue and cognitive decline but the underlying mechanisms remain unknown. Previous work has shown whole brain resting cerebral metabolic rate of oxygen (CMRO) is associated with the extent of these symptoms. However, it is not known if the association between global CMRO and MS-related cognitive speed and fatigue can be localized to specific brain regions.

Apolipoprotein A4 Elevates Sympathetic Activity and Thermogenesis in Male Mice.

Long-chain fatty acids induce apolipoprotein A4 (APOA4) production in the small intestine and activate brown adipose tissue (BAT) thermogenesis. The increase in BAT thermogenesis enhances triglyceride clearance and insulin sensitivity. Acute administration of recombinant APOA4 protein elevates BAT thermogenesis in chow-fed mice.

Increased BAT Thermogenesis in Male Mouse Apolipoprotein A4 Transgenic Mice.

Dietary lipids induce apolipoprotein A4 (APOA4) production and brown adipose tissue (BAT) thermogenesis. Administration of exogenous APOA4 elevates BAT thermogenesis in chow-fed mice, but not high-fat diet (HFD)-fed mice. Chronic feeding of HFD attenuates plasma APOA4 production and BAT thermogenesis in wildtype (WT) mice.

Impact of an Urban Project ECHO: Safety-Net Clinician Self-Efficacy Across Conditions.

Introduction: To mitigate the lack of specialty healthcare, Project ECHO (Extension for Community Health Outcomes) trains community-based primary care clinicians to better prevent the progression of, manage, and treat common health conditions. ECHO-Chicago launched in 2010 as the first urban-centered ECHO program, focusing on safety-net clinicians, and has trained over 5,175 community clinicians across 34 topic areas. This paper examines self-efficacy among ECHO-Chicago participants across 11 clinical series, including a novel use of qualitative themes from self-efficacy questions.

Compound-specific isotope analysis (CSIA) evaluation of degradation of chlorinated benzenes (CBs) and benzene in a contaminated aquifer.

Compound-specific isotope analysis (CSIA) has become a valuable tool in understanding the fate of organic contaminants at field sites. However, its application to chlorinated benzenes (CBs), a group of toxic and persistent groundwater contaminants, has received less attention. This study employed CSIA to investigate the occurrence of natural degradation of various CBs and benzene in a contaminated aquifer.

Creating Comics to Address Well-Being and Resilience During the COVID-19 Pandemic.

In this descriptive case series, we detail the theoretical basis, methodology, and impact of a small-scale pilot implementation of graphic medicine workshops as an innovative approach to well-being and resilience in the age of COVID-19 and increasing awareness of racial injustice. The data provided in this article are anecdotal and based on participation in the workshops. Images created during the workshops are also shared as examples of the types of reflection that graphic medicine can enable.

Multi-element isotopic evidence for monochlorobenzene and benzene degradation under anaerobic conditions in contaminated sediments.

Industrial chemicals are frequently detected in sediments due to a legacy of chemical spills. Globally, site remedies for groundwater and sediment decontamination include natural attenuation by in situ abiotic and biotic processes. Compound-specific isotope analysis (CSIA) is a diagnostic tool to identify, quantify, and characterize degradation processes in situ, and in some cases can differentiate between abiotic degradation and biodegradation.

Resting cerebral oxygen metabolism exhibits archetypal network features.

Standard magnetic resonance imaging approaches offer high-resolution but indirect measures of neural activity, limiting understanding of the physiological processes associated with imaging findings. Here, we used calibrated functional magnetic resonance imaging during the resting state to recover low-frequency fluctuations of the cerebral metabolic rate of oxygen (CMRO ). We tested whether functional connections derived from these fluctuations exhibited organization properties similar to those established by previous standard functional and anatomical connectivity studies.

BOLD signal within and around white matter lesions distinguishes multiple sclerosis and non-specific white matter disease: a three-dimensional approach.

Multiple sclerosis (MS) diagnostic criteria are based upon clinical presentation and presence of white matter hyperintensities on two-dimensional magnetic resonance imaging (MRI) views. Such criteria, however, are prone to false-positive interpretations due to the presence of similar MRI findings in non-specific white matter disease (NSWMD) states such as migraine and microvascular disease. The coexistence of age-related changes has also been recognized in MS patients, and this comorbidity further poses a diagnostic challenge.

The neurovascular basis of processing speed differences in humans: A model-systems approach using multiple sclerosis.

Behavioral studies investigating fundamental cognitive abilities provide evidence that processing speed accounts for large proportions of performance variability between individuals. Processing speed decline is a hallmark feature of the cognitive disruption observed in healthy aging and in demyelinating diseases such as multiple sclerosis (MS), neuromyelitis optica, and Wilson's disease. Despite the wealth of evidence suggesting a central role for processing speed in cognitive decline, the neural mechanisms of this fundamental ability remain unknown.

Altered task-induced cerebral blood flow and oxygen metabolism underlies motor impairment in multiple sclerosis.

The neural mechanisms underlying motor impairment in multiple sclerosis (MS) remain unknown. Motor cortex dysfunction is implicated in blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies, but the role of neural-vascular coupling underlying BOLD changes remains unknown. We sought to independently measure the physiologic factors (i.

Transformation of Chlorofluorocarbons Investigated via Stable Carbon Compound-Specific Isotope Analysis.

Compound-specific isotope analysis (CSIA) is a valuable tool in contaminant remediation studies. Chlorofluorocarbons (CFCs) are ozone-depleting substances previously thought to be persistent in groundwater under most geochemical conditions but more recently have been found to (bio)transform in some laboratory experiments. To date, limited applications of CSIA to CFCs have been undertaken.

Reduced arterial compliance along the cerebrovascular tree predicts cognitive slowing in multiple sclerosis: Evidence for a neurovascular uncoupling hypothesis.

Background: Cognitive slowing occurs in ~70% of multiple sclerosis (MS) patients. The pathophysiology of this slowing is unknown. Neurovascular coupling, acute localized blood flow increases following neural activity, is essential for efficient cognition.

Three-Dimensional Lesion Phenotyping and Physiologic Characterization Inform Remyelination Ability in Multiple Sclerosis.

Background And Purpose: Multiple sclerosis (MS) clinical management is based upon lesion characterization from 2-dimensional (2D) magnetic resonance imaging (MRI) views. Such views fail to convey the lesion-phenotype (ie, shape and surface texture) complexity, underlying metabolic alterations, and remyelination potential. We utilized a 3-dimensional (3D) lesion phenotyping approach coupled with imaging to study physiologic profiles within and around MS lesions and their impacts on lesion phenotypes.

Determination of in situ biodegradation rates via a novel high resolution isotopic approach in contaminated sediments.

A key challenge in conceptual models for contaminated sites is identification of the multiplicity of processes controlling contaminant concentrations and distribution as well as quantification of the rates at which such processes occur. Conventional protocol for calculating biodegradation rates can lead to overestimation by attributing concentration decreases to degradation alone. This study reports a novel approach of assessing in situ biodegradation rates of monochlorobenzene (MCB) and benzene in contaminated sediments.

BOLD hemodynamic response function changes significantly with healthy aging.

Functional magnetic resonance imaging (fMRI) has been used to infer age-differences in neural activity from the hemodynamic response function (HRF) that characterizes the blood-oxygen-level-dependent (BOLD) signal over time. BOLD literature in healthy aging lacks consensus in age-related HRF changes, the nature of those changes, and their implications for measurement of age differences in brain function. Between-study discrepancies could be due to small sample sizes, analysis techniques, and/or physiologic mechanisms.

Experimental studies of g-ratio MRI in ex vivo mouse brain.

This study aimed to experimentally evaluate a previously proposed MRI method for mapping axonal g-ratio (ratio of axon diameters, measured to the inner and outer boundary of myelin). MRI and electron microscopy were used to study excised and fixed brains of control mice and three mouse models of abnormal white matter. The results showed that g-ratio measured with MRI correlated with histological measures of myelinated axon g-ratio, but with a bias that is likely due to the presence of non-myelinated axons.

Loss of mTORC2 signaling in oligodendrocyte precursor cells delays myelination.

Myelin abnormalities are increasingly being recognized as an important component of a number of neurologic developmental disorders. The integration of many signaling pathways and cell types are critical for correct myelinogenesis. The PI3-K and mechanistic target of rapamycin (mTOR) pathways have been found to play key roles.

Evaluating g-ratio weighted changes in the corpus callosum as a function of age and sex.

Recent years have seen a growing interest in relating MRI measurements to the structural-biophysical properties of white matter fibers. The fiber g-ratio, defined as the ratio between the inner and outer radii of the axon myelin sheath, is an important structural property of white matter, affecting signal conduction. Recently proposed modeling methods that use a combination of quantitative-MRI signals, enable a measurement of the fiber g-ratio in vivo.

Myelin volume fraction imaging with MRI.

MRI is a valuable tool to assess myelin during development and demyelinating disease processes. While multiexponential T and quantitative magnetization transfer measures correlate with myelin content, neither provides the total myelin volume fraction. In many cases correlative measures are adequate; but to assess microstructure of myelin, (e.

Sediment Monitored Natural Recovery Evidenced by Compound Specific Isotope Analysis and High-Resolution Pore Water Sampling.

Monitoring natural recovery of contaminated sediments requires the use of techniques that can provide definitive evidence of in situ contaminant degradation. In this study, a passive diffusion sampler, called "peeper", was combined with Compound Specific Isotope Analysis to determine benzene and monochlorobenzene (MCB) stable carbon isotope values at a fine vertical resolution (3 cm) across the sediment water interface at a contaminated site. Results indicated significant decrease in concentrations of MCB from the bottom to the top layers of the sediment over 25 cm, and a 3.

Hypomyelination following deletion of Tsc2 in oligodendrocyte precursors.

Objective: While abnormalities in myelin in tuberous sclerosis complex (TSC) have been known for some time, recent imaging-based data suggest myelin abnormalities may be independent of the pathognomonic cortical lesions ("tubers"). Multiple mouse models of TSC exhibit myelination deficits, though the cell types responsible and the mechanisms underlying the myelin abnormalities remain unclear.

Methods: To determine the role of alterations in mTOR signaling in myelination, we generated a conditional knockout (CKO) mouse model using Cre-recombinase and the Olig2 promoter to inactivate the Tsc2 gene in oligodendrocyte precursor cells.

Quantitative analysis of mouse corpus callosum from electron microscopy images.

This article provides morphometric analysis of 72 electron microscopy images from control (n=4) and hypomyelinated (n=2) mouse corpus callosum. Measures of axon diameter and g-ratio were tabulated across all brains from two regions of the corpus callosum and a non-linear relationship between axon diameter and g-ratio was observed. These data are related to the accompanying research article comparing multiple methods of measuring g-ratio entitled 'A revised model for estimating g-ratio from MRI' (West et al.