Prevalence of valvular heart disease in cardiac amyloidosis and impact on survival.

Background: Limited data exists on the prognostic impact of valvular heart disease in cardiac amyloidosis (CA). We therefore sought to define the prevalence of valvular disease in patients with CA and assess the effects of significant valve disease on survival.

Methods: This multi-center retrospective cohort study included consecutive patients with confirmed transthyretin (TTR) or light chain (AL) amyloidosis.

Impact of Tafamidis on Survival in a Real-World Community-Based Cohort.

Tafamidis is the only therapy shown to improve survival in transthyretin cardiac amyloidosis (ATTR) based on randomized controlled trial data. We sought to evaluate the impact of tafamidis on survival in a real-world community-based cohort. This was a prospective observational cohort study that included consecutive patients with confirmed ATTR based on biopsy or TcPYP imaging.

Cell biology: Short stop is a team player in intercellular transport.

A new study reveals a role for the spectraplakin Short stop in bridging actin fibers and microtubules, thereby organizing a stable microtubule track for dynein-based transport through intercellular bridges during fruit fly egg development.

Treatment of Rotator Cuff Tears with platelet rich plasma: a prospective study with 2 year follow-up.

Background: Surgical treatment of full-thickness rotator cuff (RC) tears is associated with generally good results. There is no consensus regarding treatment of partial thickness tears that fail conservative treatment. The purpose of this study was to look at the efficacy and confirm the safety of dual injection PRP into the shoulder of patients with rotator cuff pathology who have failed conservative treatment with followup to two years.

Using biodosimetry to enhance the public health response to a nuclear incident.

Radiation Biodosimetry is a continually developing clinical diagnostic field, which focuses on biological markers that proportionally change in relationship to the amount of ionizing radiation absorbed. Examples of host marker response include changes in white cell count, specific proteins in circulation, RNAs in white blood cells, or chromosome fidelity in affected lymphocytes. Measurements of radiation biomarkers correlate with the approximate radiation dose absorbed and indirectly provide an assessment of the likelihood of developing acute radiation syndrome.

Medical countermeasures for radiation induced health effects: report of an Interagency Panel Session held at the NASA Human Research Program Investigator's Workshop, 26 January 2017.

An Interagency Panel Session organized by the NASA Human Research Program (HRP) Space Radiation Program Element (SRPE) was held during the NASA HRP Investigator's Workshop (IWS) in Galveston, Texas on 26 January 2017 to identify complementary research areas that will advance the testing and development of medical countermeasures (MCMs) in support of radioprotection and radiation mitigation on the ground and in space. There were several areas of common interest identified among the various participating agencies. This report provides a summary of the topics discussed by each agency along with potential areas of intersection for mutual collaboration opportunities.

Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) Science and the CBRNE Science Medical Operations Science Support Expert (CMOSSE).

A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery.

Hematological Effects of Non-Homogenous Ionizing Radiation Exposure in a Non-Human Primate Model.

Detonation of a radiological or nuclear device in a major urban area will result in heterogenous radiation exposure, given to the significant shielding of the exposed population due to surrounding structures. Development of biodosimetry assays for triage and treatment requires knowledge of the radiation dose-volume effect for the bone marrow (BM). This proof-of-concept study was designed to quantify BM damage in the non-human primate (NHP) after exposure to one of four radiation patterns likely to occur in a radiological/nuclear attack with varying levels of BM sparing.

UNITED STATES DEPARTMENT OF HEALTH AND HUMAN SERVICES BIODOSIMETRY AND RADIOLOGICAL/NUCLEAR MEDICAL COUNTERMEASURE PROGRAMS.

The United States Department of Health and Human Services (HHS) is fully committed to the development of medical countermeasures to address national security threats from chemical, biological, radiological, and nuclear agents. Through the Public Health Emergency Medical Countermeasures Enterprise, HHS has launched and managed a multi-agency, comprehensive effort to develop and operationalize medical countermeasures. Within HHS, development of medical countermeasures includes the National Institutes of Health (NIH), (led by the National Institute of Allergy and Infectious Diseases), the Office of the Assistant Secretary of Preparedness and Response/Biomedical Advanced Research and Development Authority (BARDA); with the Division of Medical Countermeasure Strategy and Requirements, the Centers for Disease Control and Prevention, and the Food and Drug Administration as primary partners in this endeavor.

Assessment of biodosimetry methods for a mass-casualty radiological incident: medical response and management considerations.

Following a mass-casualty nuclear disaster, effective medical triage has the potential to save tens of thousands of lives. In order to best use the available scarce resources, there is an urgent need for biodosimetry tools to determine an individual's radiation dose. Initial triage for radiation exposure will include location during the incident, symptoms, and physical examination.

Chemical interplay in the mechanism of partial agonist activation in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, one subtype in the family of ionotropic glutamate receptors, are the main receptors responsible for excitatory signaling in the mammalian central nervous system. Previous studies utilitizing the isolated ligand binding domain of these receptors have provided insight into the role of specific ligand-protein interactions in mediating receptor activation. However, these studies relied heavily on the partial agonist kainate, in which the alpha-amine group is constrained in a pyrrolidine ring.

Validation of the Health-Related Productivity Questionnaire Diary (HRPQ-D) on a sample of patients with infectious mononucleosis: results from a phase 1 multicenter clinical trial.

The objective of this work was to assess the performance of the newly developed Health-Related Productivity Questionniare-Diary (HRPQ-D). Patients completed the HRPQ-D daily for 1-week periods during weeks 1, 2, 4, and 8 of a clinical trial for infectious mononucleosis. Productivity data were collected on a daily basis in terms of absenteeism, presenteeism, and combined lost productivity for three work venues (work outside home, housework, and classes/homework).

Phase I study of atevirdine mesylate (U-87201E) monotherapy in HIV-1-infected patients.

The safety, tolerability, and antiviral activity of atevirdine (ATV), a nonnucleoside reverse transcriptase inhibitor, were studied in a phase I/II clinical trial (ACTG 187) of patients with CD4 counts < or =500/mm3. In all, 34 HIV-1-infected patients were randomized to receive ATV for 12 weeks in doses chosen to achieve one of three serum trough levels: 5 to 13 microM, 14 to 22 microM, or 23 to 31 microM. Rash was the most common adverse event, with a grade 3 or 4 rash occurring in 4 patients.

Effects of reverse transcriptase inhibitor therapy on the HIV-1 viral burden in semen.

HIV-1 infection continues to spread worldwide, primarily through sexual intercourse. Because semen is a major vehicle for transmission of HIV-1, we evaluated the effects of reverse transcriptase inhibitor therapy on the amount of HIV-1 in semen. The semen and blood of 11 HIV-1-infected men (i.

Randomized, controlled phase I/II, trial of combination therapy with delavirdine (U-90152S) and conventional nucleosides in human immunodeficiency virus type 1-infected patients.

Delavirdine mesylate (DLV) is a potent nonnucleoside reverse transcriptase inhibitor with activity specific for human immunodeficiency virus type 1. In the present phase I/II study we evaluated the safety, toxicity, pharmacokinetics, and antiretroviral activities of two-drug and three-drug combinations of DLV and conventional doses of nucleoside analogs compared with those of both DLV monotherapy and two-drug nucleoside analog therapy. A total of 85 human immunodeficiency virus type 1 infected patients with CD4 counts of 100 to 300 cells per mm3 were enrolled in two periods: in the first period patients were randomized to receive either zidovudine (ZDV) plus didanosine (group 1) or ZDV plus didanosine plus escalating doses (400 to 1,200 mg/day) of DLV (group 2).

Validation of a quantitative RNA PCR assay for HIV-1 in human plasma.

A quantitative human immunodeficiency virus type 1 (HIV-1) RNA polymerase chain reaction assay has been validated analytically and clinically in > 13,000 samples. The assay is highly reproducible with intra- and inter-assay precision of 16% and 19%, respectively. In 1,542 of 1,548 subjects with CD4+ counts of 0-500 cells per mm3, viral RNA levels were quantifiable and ranged from approximately 3,000-52,200,000 copies per milliliter.

Use of recombinant soluble CD4 Pseudomonas exotoxin, a novel immunotoxin, for treatment of persons infected with human immunodeficiency virus.

Single and multiple doses of sCD4-PE40, a soluble recombinant fusion toxin selectively toxic to gp120-expressing cells, were evaluated in persons infected with human immunodeficiency virus type 1 (HIV-1). Seventeen of 24 patients who completed a single-dose safety trial were given either 1, 5, 10, or 15 micrograms/kg of sCD4-PE40 by intravenous bolus once a month for 2 months, then weekly for 6 weeks. The weekly maximally tolerated dose was 10 micrograms/kg.

Validation of an immunoradiometric assay to measure plasma levels of active renin.

An immunoradiometric assay (IRMA) for active renin in human plasma was analytically and clinically validated. Analytical validation established 1) precision, 2) recovery, 3) linearity, 4) cross-reactivity, 5) sample stability, and 6) the validity and specificity of the 125I-labeled anti-renin monoclonal in the Diagnostics Pasteur immunoradiometric renin kit. Clinical validation included 1) establishing normal reference range for renin, 2) comparing plasma renin activity (PRA) results to immunoreactive renin levels in subjects on Upjohn research protocols, and 3) comparing the renin responsiveness of sodium replete subjects to that of sodium deplete subjects prior to, during, and after infusion with Upjohn renin inhibitory peptide, ditekiren.

A chicken sex-limited protein that crossreacts with the fourth component of complement.

Plasma samples from more than 300 inbred chickens were screened by using an immunofixation technique with antibody against the fourth component of complement (C4) from humans. Precipitation patterns of plasma from adult male and sexually immature birds, either male or female, were identical. Plasma from egg-laying hens demonstrated a distinctly different precipitation pattern compared with plasma of other birds, with one additional band appearing 14 to 9 days before production of the first egg.

Characterization and mapping of a nonessential pseudorabies virus glycoprotein.

Antigenic variants of pseudorabies virus (PRV) containing mutations in a viral glycoprotein with a molecular weight of 82,000 (gIII) were isolated by selecting for resistance to a complement-dependent neutralizing monoclonal antibody (MCA82-2) directed against gIII. These mutants were completely resistant to neutralization with MCA82-2 in the presence of complement. Two mutants selected for further studies either did not express gIII or expressed an improperly processed form of the glycoprotein.

Production and characterization of monoclonal antibodies directed against pseudorabies virus.

Hybridoma cell lines producing monoclonal antibodies to pseudorabies virus (PRV) were established. The monoclonal antibodies were characterized with respect to their antigenic specifications and biological activities. Two monoclonal antibodies immunoprecipitated the 50 kDa PRV glycoprotein (gp50) and two immunoprecipitated the 82 kDa glycoprotein (gp82).