Elevated G2 chromosomal radiosensitivity in Irish breast cancer patients: a comparison with other studies

Previous studies have shown that a significant proportion of breast cancer patients exhibit elevated G2 chromosomal radiosensitivity in contrast to controls (approximately 40%). In this study, the G2 assay was applied to a small number of Irish breast cancer patients who were recorded as sporadic cases and they were compared with a control group to compare and contrast with the previous documented studies. Lymphocyte cultures were set up on whole blood samples and stimulated with phytohaemagglutinin. The cultures were irradiated 74?h later with 0.5?Gy gamma-radiation and cells were arrested in metaphase by treating the cultures with colcemid. The chromosomes were harvested and the aberrations scored per 100 metaphases to assign a G2 score. The assay was first carried out on four donor controls to estimate intra-individual variation and then ten controls for inter-individual variation to measure assay reproducibility. The G2 assay was then applied to 27 breast cancer patients. Good intrinsic assay reproducibility was observed in the coefficient of variation (CV) data in three out of four controls. Intra-individual variation was similar in three out of four of the donors (4.6?–?5.1%) with one donor showing a higher CV compared with the others (22.9%). Inter-individual variation was calculated at 30.5% for all controls. No significant difference was observed between intra- and inter-individual variation using the variance ratio F-test. A G2 radiosensitivity cut-off of 110 aberrations/100 metaphases was calculated from the controls, and from this 70.4% of breast cancer patients and 7.7% of controls were calculated as G2 radiosensitive. This proportion of G2-sensitive breast cancer patients is the highest recorded in studies to date. It is thought that the G2 radiosensitivity assay is a biomarker of breast cancer predisposition genes of low penetrance, suggesting the presence of these genes in the Irish breast cancer patients used in this study who were recorded as sporadic cases. A larger number of Irish patients would be required to consolidate these findings and be representative of the Irish breast cancer population.     

Presence of Alcohol and Drugs in Hispanic Versus Non-Hispanic Youth Suicide Victims in Miami-Dade County,Florida

This study examines the association between the presence of drugs and alcohol at time of suicide in Hispanic versus non-Hispanic youth suicide victims in Miami-Dade County, Florida. The Medical Examiner’s records of 435 persons aged 24 years or younger classified as suicides in Miami-Dade County, Florida, from 1990 to 2011 were reviewed. Hispanic youth in Miami-Dade County, Florida were 1.62 times more likely than non-Hispanic youth to have used drugs and alcohol at time of suicide (OR 1.62; 95 % CI 1.07–2.04; p = 0.049). Firearm use was significantly associated with drug and alcohol use at time of death. Use of drugs and alcohol at the time of death are important risk factors for suicide in Hispanic youth.     

Autoerythrocyte sensitization syndrome (Gardner–Diamond syndrome): review of the literature**

A review of the literature concerning psychogenic purpura is presented. The diagnosis is usually based on typical anamnestic data, clinical presentation (painful inflammatory skin lesions, which progressed to ecchymoses during the next 24 h) and positive diagnostic tests with intracutaneous injections of 80% solution of washed autologous erythrocytes. No pathological findings of blood coagulation parameters are usually detected. Histopathological evaluations of lesional biopsies revealed non-specific changes. Taking into account the high frequency of psychic disorders and stress dependence of skin symptoms, therapy with psychotropic drugs (according to indications) and psychotherapy are pathogenetically grounded methods of treatment in psychogenic purpura, and should be provided together with symptomatic therapy.     

Novel Thogotovirus Associated with Febrile Illness and Death,United States, 2014

A previously healthy man from eastern Kansas, USA, sought medical care in late spring because of a history of tick bite, fever, and fatigue. The patient had thrombocytopenia and leukopenia and was given doxycycline for a presumed tickborne illness. His condition did not improve. Multiorgan failure developed, and he died 11 days after illness onset from cardiopulmonary arrest. Molecular and serologic testing results for known tickborne pathogens were negative. However, testing of a specimen for antibodies against Heartland virus by using plaque reduction neutralization indicated the presence of another virus. Next-generation sequencing and phylogenetic analysis identified the virus as a novel member of the genus Thogotovirus.     

Removal of Species Constraints in Antibody Detection

Serum antibodies from myriad species, particularly birds, can provide key information regarding the transmission and the expansion of the territory of emerging pathogens. Expedient antibody analysis is constrained by a lack of species-specific reagents, a deficiency potentially highlighted by the recent swine-origin influenza A virus (H1N1) outbreak. Available methodologies present difficulties that discourage thorough serologic monitoring of potential disease vectors or hosts. Rapid high-throughput procedures that combined serum amine labeling via biotinylation, contaminant removal, and microsphere-based immunoassays for antibodies to three arboviruses were developed. Agent-specific adaptations of this simple format should facilitate expanded surveillance and diagnostic capabilities regarding pathogens of human and veterinary importance.Serologic analysis of samples obtained from nondomestic animals, birds in particular, can provide key information regarding the transmission and the expansion of the territory of emerging pathogens (1). Unfortunately, species-specific reagents such as antispecies capture antibodies and detection conjugates, necessary for most rapid diagnostic methods, are frequently unavailable due to a lack of commercial interest. Traditional methods for circumventing species constraints often use live pathogens, are technically challenging, or are so time-consuming that large-scale testing becomes impractical (2). Methods that utilize protein G (4) are able to capture and detect mammalian IgG but cannot be used when the antibodies of interest are IgM and IgY, the former being the first of the Igs to be generated after infection and the latter being the avian and reptilian equivalent of IgG. The results of blocking enzyme-linked immunosorbent assay (ELISAs) (3) are sometimes inconsistent, and test sensitivities are dependent on the relative affinities of the competing monoclonal and serum antibodies to the antigens. Disease surveillance that involves the analysis of antibodies in nondomestic species is thus limited.The ideal method for the detection of antibodies in a range of species would be rapid, be capable of high throughput, provide a positive signal (as opposed to a signal reduction via competition), and require a small sample volume. Total antibody measurement would be advantageous, because surveillance is usually conducted without knowledge of the timing of infection. Biotin (vitamin H) is well-known to react with free amine groups on proteins (18). We determined that virus-specific serum antibodies independent of the species of origin could be biotinylated and directly detected in microsphere immunoassays (biotin-MIAs) that were modified from established protocols (11). Here we describe the development of two species-independent antibody detection methods for use with arboviruses, which involve animals as vectors or hosts. The first is a duplex procedure for the detection of antibodies to West Nile (WN) and St. Louis encephalitis (SLE) viruses, and the second is a procedure for the identification of anti-eastern equine encephalitis (anti-EEE) virus antibodies.