Combination of EEG and ECG for improved automatic neonatal seizure detection.

Objective: Neonatal seizures are the most common central nervous system disorder in newborn infants. A system that could automatically detect the presence of seizures in neonates would be a significant advance facilitating timely medical intervention.

Methods: A novel method is proposed for the robust detection of neonatal seizures through the combination of simultaneously-recorded electroencephalogram (EEG) and electrocardiogram (ECG).

Construction and evaluation of the tumor imaging properties of 123I-labeled recombinant and enzymatically generated Fab fragments of the TAG-72 monoclonal antibody CC49.

Tumor-associated glycoprotein-72 (TAG-72) is overexpressed in a high percentage of epithelial cancers and has proven useful as a target for imaging and targeted radiotherapy. Our goal was to express a recombinant Fab (rFab) of the TAG-72 monoclonal antibody CC49 in Pichia pastoris and directly compare its tumor and normal tissue uptake and imaging properties with enzymatically generated Fab (eFab). In this study, the genes coding for CC49 Fab were cloned from hybridoma cells and expressed in P.

Identification of diamino chromone-2-carboxamides as MCHr1 antagonists with minimal hERG channel activity.

A series of potent 2-carboxychromone-based melanin-concentrating hormone receptor 1 (MCHr1) antagonists were synthesized and evaluated for hERG (human Ether-a-go-go Related Gene) channel affinity and functional blockade. Basic dialkylamine-terminated analogs were found to weakly bind the hERG channel and provided marked improvement in a functional patch-clamp assay versus previously reported antagonists of the series.

Optimal sustained attention is linked to the spectral content of background EEG activity: greater ongoing tonic alpha (approximately 10 Hz) power supports successful phasic goal activation.

Efficient executive control frequently requires the timely activation or re-activation of a task-goal to enable purposeful behaviour. Additionally, more generalized factors such as alertness or neurological health will influence the efficiency with which control can be implemented. Goal-directed processes have been investigated by examining event-related potentials (ERPs), but much less is known about the involvement of background or 'tonic' processes reflected in the ongoing electroencephalogram (EEG), and how these affect the phasic processes expressed in the broad-band ERP.

A comparison of covert and overt attention as a control option in a steady-state visual evoked potential-based brain computer interface.

EEG data were recorded from occipital scalp regions of subjects who attended to an alternating checkerboard stimulus in one visual field while ignoring a similar stimulus of a different frequency in the opposite visual field. Classification of left/right spatial attention is attempted by extracting steady-state visual evoked potentials (SSVEPs) elicited by the stimuli to assess the potential use of such a spatial selective attention paradigm in a brain computer interface (BCI). Experimental setup and analysis procedure in a previous study in which eye movement is permitted are replicated in order to quantify differences in classification performance using overt and covert attention.

An evaluation of 3,4-methylenedioxy phenyl replacements in the aminopiperidine chromone class of MCHr1 antagonists.

The optimization of potent MCHr1 antagonist 1 with respect to improving its in vitro profile by replacement of the 3,4-methylenedioxy phenyl (piperonyl) moiety led to the discovery of 19, a compound that showed excellent MCHr1 binding and functional potencies in addition to possessing superior hERG separation, CYP3A4 profile, and receptor cross-reactivity profiles.

Cellular penetration and nuclear importation properties of 111In-labeled and 123I-labeled HIV-1 tat peptide immunoconjugates in BT-474 human breast cancer cells.

Introduction: Our objective was to compare the cell penetration and nuclear importation properties of 111In-labeled and 123I-labeled immunoconjugates (ICs) composed of 16-mer peptides (GRKKRRQRRRPPQGYG) derived from HIV-1 transactivator of transcription (tat) protein and anti-mouse IgG (mIgG) in BT-474 breast cancer (BC) cells.

Methods: [111In]tat ICs were constructed by site-specific conjugation of tat peptides to NaIO4(-)-oxidized carbohydrates in the Fc domain of diethylenetriaminepentaacetic-acid-modified anti-mIgG antibodies. Immunoreactivity against mIgG was assessed in a competition assay.

Constrained 7-fluorocarboxychromone-4-aminopiperidine based Melanin-concentrating hormone receptor 1 antagonists: the effects of chirality on substituted indan-1-ylamines.

The incorporation of constrained tertiary amines into an existing class of N-benzyl-4-aminopiperidinyl chromone-based MCHr1 antagonists led to the identification of a series of chiral racemic compounds that displayed good to excellent functional potency, binding affinity, and selectivity over the hERG channel. Further separation of two distinct chiral racemic compounds into their corresponding pairs of enantiomers revealed a considerable selectivity for MCHr1 for one configuration, in addition to a striking difference in oral exposure between one pair of enantiomers in diet-induced obese mice. Oral administration of the most potent compound in this class in the same animal model led to significant reduction of fat mass in a semi-chronic model for weight loss.

A patient-adapting heartbeat classifier using ECG morphology and heartbeat interval features.

An adaptive system for the automatic processing of the electrocardiogram (ECG) for the classification of heartbeats into one of the five beat classes recommended by ANSI/AAMI EC57:1998 standard is presented. The heartbeat classification system processes an incoming recording with a global-classifier to produce the first set of beat annotations. An expert then validates and if necessary corrects a fraction of the beats of the recording.

Creating a learning culture for quality and leadership. Panel discussion.

Today's fast-changing health care environment requires adept and knowledgeable leadership. Leaders must develop consistent standards across the organization to ensure quality and operational excellence. This will require the adoption of new skill sets and behaviors by clinicians and other employees.

Do antisaccade deficits in schizophrenia provide evidence of a specific inhibitory function?

Background: Despite its inhibitory control requirements, antisaccade deficits have been consistently associated with working memory impairments in schizophrenia. We investigated whether variance in antisaccade performance could be better accounted for in terms of a specific inhibitory function.

Method: We assessed 48 clinically stable out-patients with schizophrenia on an antisaccade task, as well as on measures of spatial and verbal working memory, sustained selective attention, and a simple motoric go/no-go measure of response inhibition.

Optimization of chromone-2-carboxamide melanin concentrating hormone receptor 1 antagonists: assessment of potency, efficacy, and cardiovascular safety.

Evaluation of multiple structurally distinct series of melanin concentrating hormone receptor 1 antagonists in an anesthetized rat cardiovascualar assay led to the identification of a chromone-2-carboxamide series as having excellent safety against the chosen cardiovascular endpoints at high drug concentrations in the plasma and brain. Optimization of this series led to considerable improvements in affinity, functional potency, and pharmacokinetic profile. This led to the identification of a 7-fluorochromone-2-carboxamide (22) that was orally efficacious in a diet-induced obese mouse model, retained a favorable cardiovascular profile in rat, and demonstrated dramatic improvement in effects on mean arterial pressure in our dog cardiovascular model compared to other series reported by our group.

123I-labeled HIV-1 tat peptide radioimmunoconjugates are imported into the nucleus of human breast cancer cells and functionally interact in vitro and in vivo with the cyclin-dependent kinase inhibitor, p21(WAF-1/Cip-1).

Purpose: To evaluate the internalization and nuclear translocation of (123)I-tat-peptide radioimmunoconjugates in MDA-MB-468 breast cancer cells and their ability to interact with the cyclin-dependent kinase inhibitor, p21(WAF-1/Cip-1).

Methods: Peptides [GRKKRRQRRRPPQGYGC] harboring the nuclear-localizing sequence from HIV tat domain were conjugated to anti-p21(WAF-1/Cip-1) antibodies. Immunoreactivity was assessed by Western blot using lysate from MDA-MB-468 cells exposed to EGF to induce p21(WAF-1/Cip-1).

Survey of 1276 shoeprint impressions and development of an automatic shoeprint pattern matching facility.

1276 shoeprints were collected at a scientific exhibition. Details regarding the age groups of the participants, style, size and manufacturer/brand of their shoes were recorded. The impressions were assigned to pattern groups showing that the most common pattern was present in only 1% of the population studied and most patterns were much less common.

HIV-1 Tat peptide immunoconjugates differentially sensitize breast cancer cells to selected antiproliferative agents that induce the cyclin-dependent kinase inhibitor p21WAF-1/CIP-1.

In this study, we evaluated the ability of anti-p21 antibodies conjugated to 17-mer peptides [GRKKRRQRRRPPQGYGC] harboring the membrane-translocating and nuclear import sequences [underlined] of HIV-1 tat protein to inhibit the cyclin-dependent kinase inhibitor, p21(WAF-1/Cip-1) (p21) and differentially sensitize MDA-MB-468 and MCF-7 human breast cancer (BC) cells to the antiproliferative effects of treatments that induce or do not induce p21. BC cells were treated with increasing concentrations of epidermal growth factor (EGF; 0.5-10 nM), the topoisomerase I inhibitor, camptothecin (CPT; 0.

99mTc-Sestamibi, a sensitive probe for in vivo imaging of P-glycoprotein inhibition by modulators and mdr1 antisense oligodeoxynucleotides.

Purpose: We tested the suitability of (99m)Tc-sestamibi to image the inhibition of P-glycoprotein (Pgp)-mediated multidrug resistance in tumor cells and xenografts after antisense treatment and/or inhibition with a novel Pgp modulator WK-X-34.

Procedure: Pgp inhibition was measured by daunorubicin transport assays and fluorescence microscopy in resistant A2780/Adr cells treated with WK-X-34 and antisense. A2780/Adr xenograft mice were dosed with mdr1 antisense oligodeoxynucleotides intratumorally for three days; next, mice were treated with WK-X-34, followed by (99m)Tc-sestamibi injection.

Hepatic knockdown of mitochondrial GPAT1 in ob/ob mice improves metabolic profile.

Glycerol-3-phosphate acyltransferase (GPAT) controls the first step of triglyceride (TAG) synthesis. Three distinct GPAT activities have been identified, two localized in mitochondria and one in microsomes. Mitochondrial GPAT1 (mtGPAT1) is abundantly expressed in the liver and constitutes approximately 50% of total GPAT activities in this organ.

Hypophosphatemia: an evidence-based approach to its clinical consequences and management.

Optimal cellular function is dependent on maintenance of a normal serum phosphorus concentration. Serum phosphorus concentration is affected by several determinants, the most important of which is regulation of phosphorus reabsorption by the kidney. The majority of this reabsorption (80%) occurs in the proximal tubule and is mediated by an isoform of the sodium-phosphate cotransporter (NaPi-II).

Retroperitoneal fibrosis presenting as acute renal failure.

Background: A 60-year-old man with a history of atherosclerotic disease of the carotid and coronary vasculature presented with lower back pain and acute renal failure. Imaging studies revealed bilateral ureteral obstruction by a large retroperitoneal mass.

Investigations: Physical examination, urine and blood analysis, catheterization, radiography of the chest, abdominal and pelvic CT, magnetic resonance angiography, renal ultrasound and biopsy of mass.

Heart and respiration rate changes in the neonate during electroencephalographic seizure.

An investigation of changes in the neonatal electrocardiogram (ECG) and respiration signals from labelled seizure data for five neonatal patient records is reported. A decrease during seizure of 5.70% in the mean RR-interval was found.

Characterization of ghrelin receptor activity in a rat pituitary cell line RC-4B/C.

Ghrelin, a 28 amino acid, octanoylated peptide, is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). In addition to various endocrine functions, including stimulation of GH release, ghrelin has been characterized as an important regulator of energy homeostasis. Ghrelin administration has been shown to increase adiposity in rodents and stimulate food intake in humans.

Anticoagulation and continuous renal replacement therapy.

More than half of patients with acute renal failure in the intensive care unit require dialysis, and the majority of them have significant hemodynamic instability. Continuous renal replacement therapy (CRRT) is often the preferred dialysis modality in these patients. One requirement for CRRT is anticoagulation, which can expose patients to the risk of bleeding.

The VESPA: a method for the rapid estimation of a visual evoked potential.

Faster and less obtrusive means for measuring a Visual Evoked Potential would be valuable in clinical testing and basic neuroscience research. This study presents a method for accomplishing this by smoothly modulating the luminance of a visual stimulus using a stochastic process. Despite its visually unobtrusive nature, the rich statistical structure of the stimulus enables rapid estimation of the visual system's impulse response.

Equality of the psychological model underlying depressive symptoms in patients with temporal lobe epilepsy versus heterogeneous neurological disorders.

Controversy surrounds the question of whether there is a specific pattern of psychopathology or personality style observed in patients with temporal lobe epilepsy (TLE) or whether the symptoms of psychological distress reflect a common disorder such as depression. Measurement equivalence was examined to test the hypothesis that the latent variable model underlying scores on the Beck Depression Inventory (BDI) was equivalent across samples of patients with TLE (n = 187) and patients with heterogeneous neurological disorders (n = 150). A well-replicated model of depression or psychological distress comprising three related variables, negative attitude, performance difficulty, and somatic elements, displayed a pattern of strict metric invariance.