Severe CTE and TDP-43 pathology in a former professional soccer player with dementia: a clinicopathological case report and review of the literature

In the last decades, numerous post-mortem case series have documented chronic traumatic encephalopathy (CTE) in former contact-sport athletes, though reports of CTE pathology in former soccer players are scarce. This study presents a clinicopathological case of a former professional soccer player with young-onset dementia. The patient experienced early onset progressive cognitive decline and developed dementia in his mid-50 s, after playing soccer for 12 years at a professional level. While the clinical picture mimicked Alzheimer's disease, amyloid PET imaging did not provide evidence of elevated beta-amyloid plaque density. After he died in his mid-60 s, brain autopsy showed severe phosphorylated tau (p-tau) abnormalities fulfilling the neuropathological criteria for high-stage CTE, as well as astrocytic and oligodendroglial tau pathology in terms of tufted astrocytes, thorn-shaped astrocytes, and coiled bodies. Additionally, there were TAR DNA-binding protein 43 (TDP-43) positive cytoplasmic inclusions in the frontal lobe and hippocampus, and Amyloid Precursor Protein (APP) positivity in the axons of the white matter. A systematic review of the literature revealed only 13 other soccer players with postmortem diagnosis of CTE. Our report illustrates the complex clinicopathological correlation of CTE and the need for disease-specific biomarkers

An Evolutionarily Conserved Arginine Is Essential for Tre1 G Protein-Coupled Receptor Function During Germ Cell Migration in Drosophila melanogaster

BACKGROUND: G protein-coupled receptors (GPCRs) play central roles in mediating cellular responses to environmental signals leading to changes in cell physiology and behaviors, including cell migration. Numerous clinical pathologies including metastasis, an invasive form of cell migration, have been linked to abnormal GPCR signaling. While the structures of some GPCRs have been defined, the in vivo roles of conserved amino acid residues and their relationships to receptor function are not fully understood. Trapped in endoderm 1 (Tre1) is an orphan receptor of the rhodopsin class that is necessary for primordial germ cell migration in Drosophila melanogaster embryos. In this study, we employ molecular genetic approaches to identify residues in Tre1 that are critical to its functions in germ cell migration. METHODOLOGY/PRINCIPAL FINDINGS: First, we show that the previously reported scattershot mutation is an allele of tre1. The scattershot allele results in an in-frame deletion of 8 amino acids at the junction of the third transmembrane domain and the second intracellular loop of Tre1 that dramatically impairs the function of this GPCR in germ cell migration. To further refine the molecular basis for this phenotype, we assayed the effects of single amino acid substitutions in transgenic animals and determined that the arginine within the evolutionarily conserved E/N/DRY motif is critical for receptor function in mediating germ cell migration within an intact developing embryo. CONCLUSIONS/SIGNIFICANCE: These structure-function studies of GPCR signaling in native contexts will inform future studies into the basic biology of this large and clinically important family of receptors

Do decision support systems influence variation in prescription?

<p>Abstract</p> <p>Background</p> <p>Translating scientific evidence into daily practice is problematic. All kinds of intervention strategies, using educational and/or directive strategies, aimed at modifying behavior, have evolved, but have been found only partially successful. In this article the focus is on (computerized) decision support systems (DSSs). DSSs intervene in physicians' daily routine, as opposed to interventions that aim at influencing knowledge in order to change behavior. We examined whether general practitioners (GPs) are prescribing in accordance with the advice given by the DSS and whether there is less variation in prescription when the DSS is used.</p> <p>Methods</p> <p>Data were used from the Second Dutch National Survey of General Practice (DNSGP2), collected in 2001. A total of 82 diagnoses, 749811 contacts, 133 physicians, and 85 practices was included in the analyses. GPs using the DSS daily were compared to GPs who do not use the DSS. Multilevel analyses were used to analyse the data. Two outcome measures were chosen: whether prescription was in accordance with the advice of the DSS or not, and a measure of concentration, the Herfindahl-Hirschman Index (HHI).</p> <p>Results</p> <p>GPs who use the DSS daily prescribe more according to the advice given in the DSS than GPs who do not use the DSS. Contradictory to our expectation there was no significant difference between the HHIs for both groups: variation in prescription was comparable.</p> <p>Conclusion</p> <p>We studied the use of a DSS for drug prescribing in general practice in the Netherlands. The DSS is based on guidelines developed by the Dutch College of General Practitioners and implemented in the Electronic Medical Systems of the GPs. GPs using the DSS more often prescribe in accordance with the advice given in the DSS compared to GPs not using the DSS. This finding, however, did not mean that variation is lower; variation is the same for GPs using and for GPs not using a DSS. Implications of the study are that DSSs can be used to implement guidelines, but that it should not be expected that variation is limited.</p

HETEROGENEITY AMONG THE ACUTE NONLYMPHOCYTIC LEUKEMIAS - VALUE OF IMMUNOPHENOTYPE FOR DIAGNOSIS, PROGNOSIS, AND THERAPY

Immunophenotyping of acute nonlymphocytic leukemia has confirmed previous observations on the heterogeneity of this disease. The lack of leukemia-specific monoclonal antibodies as well as antibodies reactive with early myeloid cells is reflected in poor correlation of morphologically and cytochemically defined FAB classes with the immunophenotype of the leukemic cells. Possible exceptions are the microgranular variant of FAB-M3, megakaryocytic leukemia (FAB-M7), and early erythroid leukemias (FAB-M6). The use of antibody panels can alleviate the differential diagnosis of acute lymphoid and myeloid leukemias, especially those occurring in infants, and the discrimination of FAB-L2 and FAB-MI. Also, the immunophenotyping of presumptive hybrid leukemias can help to resolve the many questions about these leukemias with a particularly poor prognosis. The challenge for multiinstitutional groups is to define those clinically relevant subgroups of acute nonlymphocytic leukemia in children that have general acceptance and could provide the basis for new treatment strategies