Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology.

Background: The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination.

Mediterranean diet has no effect on markers of inflammation and metabolic risk factors in patients with coronary artery disease.

Objective: Mediterranean diet is associated with decreased levels of inflammatory markers and metabolic risk factors in epidemiologic studies and recent trials on patients with metabolic syndrome. Given the recent improvements in medical treatments, it is unclear if such beneficial effects are also present in patients with coronary artery disease (CAD). We therefore investigated the effect of Mediterranean diet on markers of inflammation and metabolic risk factors in patients with treated CAD.

Expression of endothelins and their receptors promotes an invasive phenotype of breast tumor cells but is insufficient to induce invasion in benign cells.

There is increased staining of endothelins (ET-1, -2, and -3) and receptors (ET-RA and -RB) in invasive breast tumors compared to nonneoplastic tissue, and ETs stimulate MCF-7 cell invasion in vitro. We analyzed ETstimulation of benign and transformed mammary epithelial cells, and whether expression of ETs is sufficient to induce invasiveness. In breast cancer patient serum, ET-1 was increased in those patients with lymph node metastases compared to those with no lymph node involvement; ETs, however, had no mitogenic effect on breast tumor cell lines in vitro.

Plasma N-terminal pro-brain natriuretic peptide as a marker of right ventricular dysfunction in patients with tetralogy of Fallot after surgical repair.

Objective: Chronic heart failure is associated with neurohormonal activation that is not only related to outcome but is also a therapeutic target. We have attempted to demonstrate whether a similar pattern of neurohormonal activation exists in adult congenital heart disease (ACHD) and, if so, whether it relates to disease severity determined by cardiopulmonary exercise testing.

Methods And Results: Concentrations of N-terminal pro-atrial natriuretic peptide, N-terminal pro-brain natriuretic peptide (NT-proBNP), endothelin (ET)-1, renin, aldosterone, adrenalin, and noradrenalin were determined in 50 adults (mean age, 27.

Site-specific nitration differentially influences tau assembly in vitro.

Previously, we reported that the microtubule-associated tau protein, the major constituent of neurofibrillary tangles (NFTs) in Alzheimer's brain, undergoes site-selective nitration by peroxynitrite (ONOO-) and that this event inhibits tau polymerization in vitro [Reynolds et al. (2005) Biochemistry 44, 1690-1700]. In the present study, we extend our analysis of tau nitration to include mutant tau proteins singly nitrated at each residue targeted by ONOO- in vitro (Tyr18, Tyr29, Tyr197, and Tyr394).

Impact of the Liaison Committee on Medical Education requirements for emergency medicine education at U.S. schools of medicine.

The Liaison Committee on Medical Education (LCME) accredits complete and independent medical education programs leading to the MD degree. The LCME standards for accreditation are described in the online document "Functions and Structure of a Medical School." There are ongoing minor and major changes to these standards.

N-terminal pro-brain natriuretic peptide or troponin testing followed by echocardiography for risk stratification of acute pulmonary embolism.

Background: Brain natriuretic peptide (BNP) and N-terminal (NT)-proBNP have recently emerged as promising parameters for risk assessment in acute pulmonary embolism (PE). However, their positive predictive value is low, and the prognostic implications of NT-proBNP or troponin elevation alone are questionable.

Methods And Results: To determine whether the combination of NT-proBNP testing with echocardiography may identify both low-risk and high-risk patients with PE, we examined 124 consecutive patients with proved PE.

Galanin plasticity in the cholinergic basal forebrain in Alzheimer's disease and transgenic mice.

Galanin (GAL) is a biologically active 29 amino acid (30 in humans) which participates in the modulation of several ascending neurotransmitter systems including cholinergic basal forebrain (CBF) neurons, which undergo extensive degeneration in Alzheimer's disease (AD). GAL immunoreactive fibers within the CBF display hypertrophy and hyperinnervate surviving CBF neurons in late AD. Over the years, this unique neuronal plasticity response has been an active area of research for our group.

Tau truncation during neurofibrillary tangle evolution in Alzheimer's disease.

The microtubule-associated protein, tau, is a highly soluble molecule that is nonetheless capable of self-association into filamentous deposits characteristic of a number of neurodegenerative diseases. This state change is thought to be driven by phosphorylation and/or C-terminal truncation events resulting in intracellular inclusions, such as the neurofibrillary tangles (NFTs) in Alzheimer's disease (AD). Previously, we reported the existence of a novel truncation event, cleavage at aspartic acid(421), presumably by a caspase, and also described a monoclonal antibody (Tau-C3) specific for tau cleaved at this site.

Political and budget issues associated with educating medical students.

Unfortunately for medical educators, medical student clerkships in emergency medicine (EM) do not occur in isolation from the key institutional issues of organizational politics and resource support. This article discusses some of the political and resource issues in proposing and obtaining support for a mandatory EM student clerkship. Political issues of importance include: 1) securing intradepartmental support from all faculty and the chair for the priority and teaching commitment of a mandatory clerkship; 2) strategizing the different steps and their sequencing for achieving clerkship approval, including cultivation of key supporters, content of a clerkship proposal, and resource support needs; 3) identifying and collecting data from existing EM teaching efforts that will support a mandatory clerkship proposal; 4) establishing a connection between the overall educational outcome objectives for students of the school and the educational outcomes for students taking the EM clerkship; and 5) developing solutions to logistic issues in clerkship implementation (availability of an adequate number of teaching sites; establishment of equivalence of educational experiences across all sites).

Site-specific nitration and oxidative dityrosine bridging of the tau protein by peroxynitrite: implications for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive amnestic disorder typified by the pathological misfolding and deposition of the microtubule-associated tau protein into neurofibrillary tangles (NFTs). While numerous post-translational modifications influence NFT formation, the molecular mechanisms responsible for tau aggregation remain enigmatic. Since nitrative and oxidative injury have previously been shown to play a mechanistic role in neurodegeneration, we examined whether these events influence tau aggregation.

Tau, tangles, and Alzheimer's disease.

Neurofibrillary tangles (NFT) are comprised of the microtubule-associated protein tau, in the form of filamentous aggregates. In addition to the well-known changes in phosphorylation state, tau undergoes multiple truncations and shifts in conformation as it transforms from an unfolded monomer to the structured polymer characteristic of NFT. Truncations at both the amino- and carboxy-termini directly influence the conformation into which the molecule folds, and hence the ability of tau to polymerize into fibrils.

Medically unexplained symptoms and neuropsychological assessment.

Several illnesses expressed somatically that do not have clearly demonstrated pathophysiological origin and that are associated with neuropsychological complaints are reviewed. Among them are nonepileptic seizures, fibromyalgia, chronic fatigue syndrome, Persian Gulf War unexplained illnesses, toxic mold and sick building syndrome, and silicone breast implant disease. Some of these illnesses may be associated with objective cognitive abnormalities, but it is not likely that these abnormalities are caused by traditionally defined neurological disease.

Tau epitope display in progressive supranuclear palsy and corticobasal degeneration.

Filamentous aggregates of the protein tau are a prominent feature of Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). However, the extent to which the molecular structure of the tau in these aggregates is similar or differs between these diseases is unclear. We approached this question by examining these disorders with a panel of antibodies that represent different structural, conformational, and cleavage-specific tau epitopes.

BCG lymphadenitis in an HIV-infected child 9.5 years after vaccination.

Complications of Bacillus Calmette-Guerin (BCG) vaccination have been reported in immunocompetent as well as in immunocompromised individuals. Severe and/or late complications have been associated with impairment of cell-mediated immunity. A case of BCG lymphadenitis in a vertically infected HIV-positive boy 9.

Elevated concentrations of serum relaxin are associated with metastatic disease in breast cancer patients.

Relaxin (RLX) is known to induce remodeling of benign stromal tissues through upregulation of matrix metalloproteases (MMPs). Recently, we could show that RLX also induces MMPs in breast cancer cells and enhances in vitro invasiveness. To investigate its potential role for progression of breast cancer in vivo, RLX serum concentrations were determined in 160 breast cancer patients during post-surgical follow-up.

Early N-terminal changes and caspase-6 cleavage of tau in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive amnestic dementia that involves post-translational hyperphosphorylation, enzymatic cleavage, and conformational alterations of the microtubule-associated protein tau. The truncation state of tau influences many of its pathologic characteristics, including its ability to assume AD-related conformations and to assemble into filaments. Cleavage also appears to be an important marker in AD progression.

Integrating the Accreditation Council for Graduate Medical Education Core competencies into the model of the clinical practice of emergency medicine.

In response to public pressure for greater accountability from the medical profession, a transformation is occurring in the approach to medical education and assessment of physician competency. Over the past 5 years, the Accreditation Council for Graduate Medical Education (ACGME) has implemented the Outcomes and General Competencies projects to better ensure that physicians are appropriately trained in the knowledge and skills of their specialties. Concurrently, the American Board of Medical Specialties, including the American Board of Emergency Medicine (ABEM), has embraced the competency concept.

Neuropsychologic impairment in patients with nonepileptic seizures.

Patients with nonepileptic seizures (NES), those with epileptic seizures (ES), and normal controls were compared on a battery of neuropsychologic tests. Diagnoses were made after intensive electroencephalogram (EEG) monitoring. Excluded from the study were patients with both ES and NES, as well as patients with ES who had evidence of structural brain damage.

Subjective cognitive complaints, affective distress, and objective cognitive performance in Persian Gulf War veterans.

We examined subjective cognitive complaints, affective distress, and cognitive performance in Persian Gulf veterans who reported illness and cognitive complaints. We predicted a stronger relationship between subjective cognitive complaints and affective distress than between subjective cognitive complaints and objective cognitive performance. This prediction was confirmed in a sample of 100 veterans.

Comment: Warning malingerers produces more sophisticated malingering.

Warning persons that attempts to malinger on neuropsychological testing will be detected is not an effective way of reducing malingering behavior. Rather, the literature on coaching consistently shows that malingerers who are warned of the presence of symptom validity assessment techniques are able to feign deficits in a less exaggerated and more believable fashion and therefore elude detection. Warning persons about the presence of these techniques reduces the validity and scientific quality of forensic evaluations.