OpenClinical.net: Artificial intelligence and knowledge engineering at the point of care.

Objective: OpenClinical.net is a way of disseminating clinical guidelines to improve quality of care whose distinctive feature is to combine the benefits of clinical guidelines and other human-readable material with the power of artificial intelligence to give patient-specific recommendations. A key objective is to empower healthcare professionals to author, share, critique, trial and revise these 'executable' models of best practice.

Specificity of elevated cerebrospinal fluid bilirubin in the investigation of subarachnoid haemorrhage.

Background: The spectrophotometric examination of cerebrospinal fluid for bilirubin is an established investigation in patients with suspected subarachnoid haemorrhage. This study assesses the diagnostic specificity of an elevated cerebrospinal fluid bilirubin and how this may be influenced by the presence of oxyhaemoglobin and the concentration of cerebrospinal fluid total protein.

Methods: One thousand cerebrospinal fluid spectroscopy reports were reviewed.

Conditional Expression of Human PPARδ and a Dominant Negative Variant of hPPARδ In Vivo.

The nuclear receptor, NR1C2 or peroxisome proliferator-activated receptor (PPAR)-δ, is ubiquitously expressed and important for placental development, fatty acid metabolism, wound healing, inflammation, and tumour development. PPARδ has been hypothesized to function as both a ligand activated transcription factor and a repressor of transcription in the absence of agonist. In this paper, treatment of mice conditionally expressing human PPARδ with GW501516 resulted in a marked loss in body weight that was not evident in nontransgenic animals or animals expressing a dominant negative derivative of PPARδ.

Markers of cardiovascular risk are not changed by increased whole-grain intake: the WHOLEheart study, a randomised, controlled dietary intervention.

Recommendations for whole-grain (WG) intake are based on observational studies showing that higher WG consumption is associated with reduced CVD risk. No large-scale, randomised, controlled dietary intervention studies have investigated the effects on CVD risk markers of substituting WG in place of refined grains in the diets of non-WG consumers. A total of 316 participants (aged 18-65 years; BMI>25 kg/m2) consuming < 30 g WG/d were randomly assigned to three groups: control (no dietary change), intervention 1 (60 g WG/d for 16 weeks) and intervention 2 (60 g WG/d for 8 weeks followed by 120 g WG/d for 8 weeks).

Late onset Leigh syndrome and ataxia due to a T to C mutation at bp 9,185 of mitochondrial DNA.

A T-to-C missense mutation at nucleotide position 9,185 in the protein-coding ATP6 gene of the mitochondrial genome was present at high heteroplasmy in members of a Canadian family with Leigh syndrome with predominant ataxia and peripheral neuropathy. This mutation results in the substitution of a proline residue for an evolutionary-conserved leucine at position of amino acid 220 near the carboxyl terminus of the mitochondrial protein. The index patient and brother, who had an identical clinical presentation, had >90% mutant mtDNA in cultured skin fibroblasts, lymphocytes, and whole blood.

Acrylamide: update on selected research activities conducted by the European food and drink industry.

This paper reviews the progress made by the European food and drink industry (CIAA) on acrylamide with regard to analytical methods, mechanisms of formation, and mitigation research in the major food categories. It is an update on the first CIAA review paper, "A Review of Acrylamide: An Industry Perspective on Research, Analysis, Formation and Control." Initial difficulties with the establishment of reliable analytical methods, in most cases, have now been overcome, but challenges remain in terms of the need to develop simple and rapid test methods and certified reference materials.

A review of acrylamide: an industry perspective on research, analysis, formation, and control.

Acrylamide is a synthetic monomer with a wide scope of industrial applications, mainly as a precursor in the production of several polymers, such as polyacrylamide. The main uses of polyacrylamides are in water and wastewater treatment processes, pulp and paper processing, and mining and mineral processing. The announcement by the Swedish National Food Administration in April 2002 of the presence of acrylamide predominantly in heat-treated carbohydrate-rich foods sparked intensive investigations into acrylamide, encompassing the occurrence, chemistry, agricultural practices, and toxicology, in order to establish if there is a potential risk to human health from the presence of this contaminant in the human diet.

Very fast oscillations evoked by median nerve stimulation in the human thalamus and subthalamic nucleus.

Very fast oscillations (VFOs; 500-1,500 Hz) are associated with sensory-evoked potentials (SEPs), but their origin is unknown. To characterize the origins of VFOs, we studied 35 patients with deep brain stimulation (DBS) electrodes [15 with thalamic and 20 with the subthalamic nucleus (STN) electrodes]. We recorded median nerve stimulation-evoked SEPs from the thalamus and STN with microelectrodes during stereotactic surgery and from the contacts of the DBS electrodes postoperatively.

Single pulse stimulation of the human subthalamic nucleus facilitates the motor cortex at short intervals.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). The mechanism is poorly understood. High-frequency STN DBS has been reported to affect motor cortex excitability in a complex way, but the timing between STN stimuli and changes in motor cortical (M1) excitability has not been investigated.

The in vivo role of PtdIns(3,4,5)P3 binding to PDK1 PH domain defined by knockin mutation.

We generated homozygous knockin ES cells expressing a form of 3-phosphoinositide-dependent protein kinase-1 (PDK1) with a mutation in its pleckstrin homology (PH) domain that abolishes phosphatidylinositol 3,4,5-tris-phosphate (PtdIns(3,4,5)P3) binding, without affecting catalytic activity. In the knockin cells, protein kinase B (PKB) was not activated by IGF1, whereas ribosomal S6 kinase (RSK) was activated normally, indicating that PtdIns(3,4,5)P3 binding to PDK1 is required for PKB but not RSK activation. Interestingly, amino acids and Rheb, but not IGF1, activated S6K in the knockin cells, supporting the idea that PtdIns(3,4,5)P3 stimulates S6K through PKB-mediated activation of Rheb.

Somatosensory evoked potentials (SEPs) recorded from deep brain stimulation (DBS) electrodes in the thalamus and subthalamic nucleus (STN).

Objective: To examine the location of deep brain stimulation (DBS) electrode somatosensory evoked potentials (SEPs) and determine the generators of the median nerve SEPs recorded in thalamus and subthalamic nucleus (STN).

Methods: SEPs were recorded from contacts of DBS electrodes and microelectrodes in thalamus and STN to establish the latencies of N13, N18 and N20 in 24 patients (8 tremor, 4 chronic pain, 12 Parkinson disease) undergoing chronic DBS.

Results: A large SEP with a mean latency of 17.

Knockout of ERK5 causes multiple defects in placental and embryonic development.

Background: ERK5 is a member of the mitogen activated protein kinase family activated by certain mitogenic or stressful stimuli in cells, but whose physiological role is largely unclear.

Results: To help determine the function of ERK5 we have used gene targeting to inactivate this gene in mice. Here we report that ERK5 knockout mice die at approximately E10.

Simulation of brain death from fulminant de-efferentation.

Background: Guillain-Barré syndrome (GBS) classically presents with a subacutely evolving areflexic paralysis, with typical laboratory findings of elevated cerebrospinal fluid protein and abnormal nerve conduction studies. There is now an increasing recognition of GBS variants that differ in clinical presentation, prognosis, electrophysiology and presumed pathogenesis. Fulminant cases of GBS have been reported in which a rapid deterioration evolves to a clinical state resembling "brain death".

Unique form of propriospinal myoclonus as a possible complication of an enteropathogenic toxin.

Propriospinal myoclonus is an uncommon form of spinal myoclonus propagated, presumably, by slowly conducting polysynaptic intraspinal pathways. Although most patients demonstrate no clear etiology, a variety of disorders have been linked to this abnormal movement, including trauma, multiple sclerosis, tumors, and infectious disorders such as herpes zoster, human immunodeficiency virus, and Lyme disease. We describe 2 young male patients from the same town in Northern Ontario, Canada, exposed to an outbreak of Escherichia coli O157:H7 from contaminated municipal water, who developed identical clinical and electrophysiological features suggestive of a rhythmic form of propriospinal myoclonus with activity alternating between abdominal and paraspinal muscles.

Deep brain stimulation for Parkinson's disease: disrupting the disruption.

Many people are disabled by Parkinson's disease (PD) despite the drug treatments that are currently available. For these patients, neurosurgery has the potential to help restore their function. The most effective neurosurgical procedures to date use electrical stimulation--deep brain stimulation (DBS)--of small targets in the brain by use of a pacemaker-like device to deliver constant stimulation.

Acute effect of transcutaneous electrical nerve stimulation on tremor.

Based on the claims that transcutaneous electrical nerve stimulation is effective in myoclonic dystonia and essential tremor, we evaluated its acute effects in 5 patients with essential tremor and 2 patients with tremor attributed to peripheral neuropathy using as parameters the Washington Heights-Inwood Genetic Study of Essential Tremor rating scale, self-reported impression, and recording of electromyographic activity. We found no significant improvement in any of the parameters tested.

Essential role of PDK1 in regulating cell size and development in mice.

PDK1 functions as a master kinase, phosphorylating and activating PKB/Akt, S6K and RSK. To learn more about the roles of PDK1, we generated mice that either lack PDK1 or possess PDK1 hypomorphic alleles, expressing only approximately 10% of the normal level of PDK1. PDK1(-/-) embryos die at embryonic day 9.

Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson's disease.

Local field potentials and pairs of neurones in the subthalamic nucleus (STN) of patients with Parkinson's disease show high-frequency oscillations (HFOs) at 15-30 Hz. This study explores how these HFOs are modulated by voluntary movements and by dopaminergic medication. We examined 15 patients undergoing implantation of bilateral deep brain stimulating electrodes using microelectrode recordings of pairs of STN neurones (eight patients) and macroelectrode recordings of local field potentials from the STN (14 patients).