Cortical-evoked potentials reflect speech-in-noise perception in children

Children are known to be particularly vulnerable to the effects of noise on speech perception, and it is commonly acknowledged that failure of central auditory processes can lead to these difficulties with speech-in-noise (SIN) perception. However, little is known about the mechanistic relationship between central processes and the perception of SIN. Our aims were twofold: to examine the effects of noise on the central encoding of speech through measurement of cortical event-related potentials and to examine the relationship between cortical processing and behavioral indices of SIN perception. We recorded cortical responses to the speech syllable [da] in quiet and multi-talker babble noise in 32 children with a broad range of SIN perception. Outcomes suggest inordinate effects of noise on auditory function in the bottom SIN perceivers compared with the top perceivers. The cortical amplitudes in the top SIN group remained stable between conditions, whereas amplitudes increased significantly in the bottom SIN group, suggesting a developmental central processing impairment in the bottom perceivers that may contribute to difficulties in encoding and perceiving speech in challenging listening environments.     

Prevalence of Medication Nonadherence to Co-medication Compared to Immunosuppressants in Heart Transplant Recipients: Findings From the International Cross-sectional BRIGHT Study

Purpose

To assess and compare the prevalence of medication nonadherence (MNA) (implementation and persistence) to immunosuppressants and co-medications in heart transplant recipients.

HTLV-1 propels untransformed CD4 lymphocytes into the cell cycle while protecting CD8 cells from death

Human T cell leukemia virus type 1 (HTLV-1) infects both CD4⁺ and CD8⁺ lymphocytes, yet it induces adult T cell leukemia/lymphoma (ATLL) that is regularly of the CD4⁺ phenotype. Here we show that in vivo infected CD4⁺ and CD8⁺ T cells displayed similar patterns of clonal expansion in carriers without malignancy. Cloned infected cells from individuals without malignancy had a dramatic increase in spontaneous proliferation, which predominated in CD8⁺ lymphocytes and depended on the amount of tax mRNA. In fact, the clonal expansion of HTLV-1–positive CD8⁺ and CD4⁺ lymphocytes relied on 2 distinct mechanisms — infection prevented cell death in the former while recruiting the latter into the cell cycle. Cell cycling, but not apoptosis, depended on the level of viral-encoded tax expression. Infected tax-expressing CD4⁺ lymphocytes accumulated cellular defects characteristic of genetic instability. Therefore, HTLV-1 infection establishes a preleukemic phenotype that is restricted to CD4⁺ infected clones.     

Radiolabeling of trastuzumab with 177Lu via DOTA,a new radiopharmaceutical for radioimmunotherapy of breast cancer

AimTrastuzumab is a monoclonal antibody that is used in treating breast cancer. We labeled this monoclonal antibody with lutetium-177 and performed in vitro quality control tests as a first step in the production of a new radiopharmaceutical.Material and MethodsTrastuzumab was labeled with lutetium-177 using DOTA as chelator. Radiochemical purity and stability in buffer and human blood serum were determined using thin layer chromatography. Immunoreactivity and toxicity of the complex were tested on MCF7 breast cancer cell line.ResultsThe radiochemical purity of the complex was 96±0.9%. The stabilities in phosphate buffer and in human blood serum at 96 h postpreparation were 93±1.2% and 85±3.5%, respectively. The immunoreactivity of the complex was 89±1.4%. At a concentration of 1 nM, the complex killed 70±3% of MCF7 cells. At 1.9 nM, 90±5% of the cells were killed.ConclusionsThe results showed that the new complex could be considered for further evaluation in animals and possibly in humans as a new radiopharmaceutical for use in radioimmunotherapy against breast cancer.     

From the Cover: A strategy for blood biomarker amplification and localization using ultrasound

Blood biomarkers have significant potential applications in early detection and management of various diseases, including cancer. Most biomarkers are present in low concentrations in blood and are difficult to discriminate from noise. Furthermore, blood measurements of a biomarker do not provide information about the location(s) where it is produced. We hypothesize a previously undescribed strategy to increase the concentration of biomarkers in blood as well as localize the source of biomarker signal using ultrasound energy directly applied to tumor cells. We test and validate our hypothesis in cell culture experiments and mouse tumor xenograft models using the human colon cancer cell line LS174T, while measuring the biomarker carcinoembryonic antigen (CEA) before and after the use of ultrasound to liberate the biomarker from the tumor cells. The results demonstrate that the application of low-frequency ultrasound to tumor cells causes a significant release of tumor biomarker, which can be measured in the blood. Furthermore, we establish that this release is specific to the direct application of the ultrasound to the tumor, enabling a method for localization of biomarker production. This work shows that it is possible to use ultrasound to amplify and localize the source of CEA levels in blood of tumor-bearing mice and will allow for a previously undescribed way to determine the presence and localization of disease more accurately using a relatively simple and noninvasive strategy.