Clinical and imaging correlates of EEG patterns in hospitalized patients with encephalopathy.

To identify the relationship between pathologic electroencephalographic (EEG) patterns, clinical and neuroradiological abnormalities, and outcome in hospitalized patients with acute encephalopathy. This 5-year cohort study was performed at an academic tertiary care center. EEGs in 154 patients with altered mental status were classified according to five predefined patterns: Isolated continuous slowing of background activity (theta, theta/delta, and delta activity) and patterns with slowing background activity with episodic transients [i.

Pathogenesis of A⁻β⁺ ketosis-prone diabetes.

A⁻β⁺ ketosis-prone diabetes (KPD) is an emerging syndrome of obesity, unprovoked ketoacidosis, reversible β-cell dysfunction, and near-normoglycemic remission. We combined metabolomics with targeted kinetic measurements to investigate its pathophysiology. Fasting plasma fatty acids, acylcarnitines, and amino acids were quantified in 20 KPD patients compared with 19 nondiabetic control subjects.

Assessment of white matter injury and outcome in severe brain trauma: a prospective multicenter cohort.

Background: Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI).

Methods: In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury.

Diffusion tensor imaging to predict long-term outcome after cardiac arrest: a bicentric pilot study.

Background: Prognostication in comatose survivors of cardiac arrest is a major clinical challenge. The authors' objective was to determine whether an assessment with diffusion tensor imaging, a brain magnetic resonance imaging sequence, increases the accuracy of 1 yr functional outcome prediction in cardiac arrest survivors.

Methods: Prospective, observational study in two intensive care units.

Skeletal muscle Nur77 expression enhances oxidative metabolism and substrate utilization.

Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes. Identifying novel regulators of mitochondrial bioenergetics will broaden our understanding of regulatory checkpoints that coordinate complex metabolic pathways. We previously showed that Nur77, an orphan nuclear receptor of the NR4A family, regulates the expression of genes linked to glucose utilization.

Emergency neurological life support: intracranial hypertension and herniation.

Sustained intracranial hypertension and acute brain herniation are "brain codes," signifying catastrophic neurological events that require immediate recognition and treatment to prevent irreversible injury and death. As in cardiac arrest, evidence supports the organized implementation of a stepwise management algorithm. Because there are multiple etiologies and many treatments that can potentially reverse cerebral herniation, intracranial hypertension and herniation was chosen as an Emergency Neurological Life Support (ENLS) protocol.

Emergency neurological life support: approach to the patient with coma.

Coma is an acute failure of neuronal systems governing arousal and awareness and represents a neurological emergency. When encountering a comatose patient, the clinician must have an organized approach to detect easily remedial causes, prevent ongoing neurologic injury, and determine a hierarchy of diagnostic tests, treatments, and neuromonitoring. Coma was chosen as an Emergency Neurological Life Support (ENLS) protocol because timely medical and surgical interventions can be life-saving, and the initial work-up of such patients is critical to establishing a correct diagnosis.

Mig-6 plays a critical role in the regulation of cholesterol homeostasis and bile acid synthesis.

The disruption of cholesterol homeostasis leads to an increase in cholesterol levels which results in the development of cardiovascular disease. Mitogen Inducible Gene 6 (Mig-6) is an immediate early response gene that can be induced by various mitogens, stresses, and hormones. To identify the metabolic role of Mig-6 in the liver, we conditionally ablated Mig-6 in the liver using the Albumin-Cre mouse model (Alb(cre/+)Mig-6(f/f); Mig-6(d/d)).

Daily Variation of Serum Acylcarnitines and Amino Acids.

To characterize daily variation of amino acids (AAs) and acylcarnitines (ACs) in response to feeding and activity, we measured serum metabolites at various times and after various activities during the day. Subjects were admitted overnight for serial serum sampling, collected in the evening (6-8pm, n=40), before rising from bed or eating (8AM, n=40), 1 hour after rising but before eating (9 AM, n=20), 1-2 hours after rising and breakfast (9-10 AM, n=40), and at noon (12 PM, n=20). Measurements of 15 AAs and 45 ACs were performed by quantitative tandem mass spectrometry using stable-isotope dilution.

Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium.

A peptide designed to induce apoptosis of endothelium in white adipose tissue (WAT) decreases adiposity. The goal of this work is to determine whether targeting of WAT endothelium results in impaired glucose regulation as a result of impaired WAT function. Glucose tolerance tests were performed on days 2 and 3 of treatment with vehicle (HF-V) or proapoptotic peptide (HF-PP) and mice pair-fed to HF-PP (HF-PF) in obese mice on a high-fat diet (HFD).

Analysis of serum metabolic profiles in women with endometrial cancer and controls in a population-based case-control study.

Context: Endometrial cancer is associated with metabolic disturbances related to its underlying risk factors, including obesity and diabetes. Identifying metabolite biomarkers associated with endometrial cancer may have value for early detection, risk assessment, and understanding etiology.

Objective: The objective of the study was to evaluate the reliable measurement of metabolites in epidemiological studies with nonstandardized blood collection; confirm previously reported correlations of metabolites with body size; and assess differences in metabolite levels between cases and controls.

Metabolomic profiling reveals mitochondrial-derived lipid biomarkers that drive obesity-associated inflammation.

Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to "Cafeteria diets" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation.

Workshop on laboratory protocol standards for the Molecular Methods Database.

Management of data to produce scientific knowledge is a key challenge for biological research in the 21st century. Emerging high-throughput technologies allow life science researchers to produce big data at speeds and in amounts that were unthinkable just a few years ago. This places high demands on all aspects of the workflow: from data capture (including the experimental constraints of the experiment), analysis and preservation, to peer-reviewed publication of results.

Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy.

For more than a century, thyroid hormones (THs) have been known to exert powerful catabolic effects, leading to weight loss. Although much has been learned about the molecular mechanisms used by TH receptors (TRs) to regulate gene expression, little is known about the mechanisms by which THs increase oxidative metabolism. Here, we report that TH stimulation of fatty acid β-oxidation is coupled with induction of hepatic autophagy to deliver fatty acids to mitochondria in cell culture and in vivo.

The language of gene ontology: a Zipf's law analysis.

Background: Most major genome projects and sequence databases provide a GO annotation of their data, either automatically or through human annotators, creating a large corpus of data written in the language of GO. Texts written in natural language show a statistical power law behaviour, Zipf's law, the exponent of which can provide useful information on the nature of the language being used. We have therefore explored the hypothesis that collections of GO annotations will show similar statistical behaviours to natural language.

Continuous cerebral blood flow autoregulation monitoring in patients undergoing liver transplantation.

Background: Clinical monitoring of cerebral blood flow (CBF) autoregulation in patients undergoing liver transplantation may provide a means for optimizing blood pressure to reduce the risk of brain injury. The purpose of this pilot project is to test the feasibility of autoregulation monitoring with transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) in patients undergoing liver transplantation and to assess changes that may occur perioperatively.

Methods: We performed a prospective observational study in 9 consecutive patients undergoing orthotopic liver transplantation.

Directionality and bipolarity of olfactory ensheathing cells on electrospun nanofibers.

Aim: As a preliminary to the construction of olfactory ensheathing cells (OECs) bearing scaffold for bridging larger lesions in the spinal cord, we have investigated the response of purified cultured OECs to nanoscale fibers of varying diameter using US FDA-approved, biodegradable poly(lactic-co-glycolic-acid).

Materials & Methods: Conventional electrospinning produced fibers of approximately 700 nm diameter (nano-700) while nanocomposite electrospinning with quantum dots produced significantly more uniform fibers of a reduced diameter to approximately 237 nm (nano-250). OECs from adult rat were FACS purified, cultured at low density on either a flat surface or a meshwork of randomly orientated nano-700 and nano-250 fibers, and assessed using cytomorphometric analysis of immunofluorescent confocal images and by scanning electron microscopy.

Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease.

Background: Cardiovascular risk models remain incomplete. Small-molecule metabolites may reflect underlying disease and, as such, serve as novel biomarkers of cardiovascular risk.

Methods: We studied 2,023 consecutive patients undergoing cardiac catheterization.

Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility.

The concept of "metabolic inflexibility" was first introduced to describe the failure of insulin-resistant human subjects to appropriately adjust mitochondrial fuel selection in response to nutritional cues. This phenomenon has since gained increasing recognition as a core component of the metabolic syndrome, but the underlying mechanisms have remained elusive. Here, we identify an essential role for the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT), in regulating substrate switching and glucose tolerance.

Ablation of steroid receptor coactivator-3 resembles the human CACT metabolic myopathy.

Oxidation of lipid substrates is essential for survival in fasting and other catabolic conditions, sparing glucose for the brain and other glucose-dependent tissues. Here we show Steroid Receptor Coactivator-3 (SRC-3) plays a central role in long chain fatty acid metabolism by directly regulating carnitine/acyl-carnitine translocase (CACT) gene expression. Genetic deficiency of CACT in humans is accompanied by a constellation of metabolic and toxicity phenotypes including hypoketonemia, hypoglycemia, hyperammonemia, and impaired neurologic, cardiac and skeletal muscle performance, each of which is apparent in mice lacking SRC-3 expression.

Measuring the level of activity in community built bio-ontologies.

In this paper we explore the measurement of activity in ontology projects as an aspect of community ontology building. When choosing whether to use an ontology or whether to participate in its development, having some knowledge of how actively that ontology is developed is an important issue. Our knowledge of biology grows and changes and an ontology must adapt to keep pace with those changes and also adapt with respect to other ontologies and organisational principles.

Logical Gene Ontology Annotations (GOAL): exploring gene ontology annotations with OWL.

Motivation: Ontologies such as the Gene Ontology (GO) and their use in annotations make cross species comparisons of genes possible, along with a wide range of other analytical activities. The bio-ontologies community, in particular the Open Biomedical Ontologies (OBO) community, have provided many other ontologies and an increasingly large volume of annotations of gene products that can be exploited in query and analysis. As many annotations with different ontologies centre upon gene products, there is a possibility to explore gene products through multiple ontological perspectives at the same time.

Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial.

Objectives: To determine if caloric restriction (CR) would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I)).

Methods: Forty-six volunteers were randomized to a weight maintenance diet (Control), 25% CR, or 12.5% CR plus 12.

Structure-based classification and ontology in chemistry.

Background: Recent years have seen an explosion in the availability of data in the chemistry domain. With this information explosion, however, retrieving relevant results from the available information, and organising those results, become even harder problems. Computational processing is essential to filter and organise the available resources so as to better facilitate the work of scientists.