Understanding preferences for receiving health communications and information about clinical trials: a cross-sectional study among US adults.

OBJECTIVE: Effective health communication is critical for understanding and acting on health information. This cross-sectional study explored participants' understanding of their health condition, their preferences for receiving health communications, and their interest in receiving clinical trial results across several therapeutic areas. METHODS: The study recruited participants via social media, email newsletters, and advocacy organizations. An online screener captured demographic information (health conditions, age, race/ethnicity, gender, and education). Eligible participants were emailed an online survey assessing preferred sources and formats for receiving health information, interest in learning about topics related to the results of clinical trials, and health literacy levels. RESULTS: In total, 449 participants (median age, 35 years [range, 18-76]; White, 53%; higher education, 65%; mean (range) health literacy score, 1.9 [0.4-3.0]) from 45 US states completed the survey representing 12 disease indications (bipolar, blood and solid tumor cancers, irritable bowel syndrome, inflammatory bowel disease, major depressive disorder, migraine, Parkinson's, psoriasis/atopic dermatitis, retinal vein occlusion/macular degeneration, rheumatoid arthritis, and spasticity). Healthcare providers were the preferred source of health information (59%), followed by Internet searches (11%). Least preferred sources were social media (5%), friends/family (3%), and email newsletters (2%). Participants preferred multiple formats and ranked reading materials online as most preferred (33%), along with videos (28%) and infographics (27%). Printed materials (14%) and audio podcasts (9%) were the least preferred formats. A majority of the participants reported that the health information they found was hard to understand (57%) and confusing (62%). Most participants (85%) were somewhat/very interested in learning about clinical trial results, with the highest interest in short summaries of safety (78%) and efficacy (74%) results. CONCLUSION: Effective health communication may be achieved via multiple formats shared directly by healthcare providers.

Researchers wanted to learn how people preferred to receive health-related communications, including information about the results of clinical trials. They surveyed 449 people from 45 US states with 12 different health conditions. The survey questions asked people about their preferred sources and ways of getting health information. It also asked about their interest in learning about clinical trials related to their health condition. The results showed that most people preferred to get health information from their healthcare providers (59%). The Internet was the second most popular choice (11%) for getting health information. People did not like getting health information from social media, friends or family, or email newsletters as much. When it came to how health information was shared, people liked reading materials online (33%), watching videos (28%), and looking at infographics (27%). They did not like printed materials and audio podcasts as much. Most people (85%) were interested in learning about the results of clinical trials in short summaries. They wanted to know about the safety (78%) and how well the treatments worked (74%) in the short summaries. In conclusion, people liked getting health information from healthcare providers like doctors, nurses, and others in different formats. Sharing information in different formats through healthcare providers may improve communication for patients with different health conditions.

An Analysis of the Effects of Spaceflight and Vaccination on Antibody Repertoire Diversity.

Ab repertoire diversity plays a critical role in the host's ability to fight pathogens. CDR3 is partially responsible for Ab-Ag binding and is a significant source of diversity in the repertoire. CDR3 diversity is generated during VDJ rearrangement because of gene segment selection, gene segment trimming and splicing, and the addition of nucleotides. We analyzed the Ab repertoire diversity across multiple experiments examining the effects of spaceflight on the Ab repertoire after vaccination. Five datasets from four experiments were analyzed using rank-abundance curves and Shannon indices as measures of diversity. We discovered a trend toward lower diversity as a result of spaceflight but did not find the same decrease in our physiological model of microgravity in either the spleen or bone marrow. However, the bone marrow repertoire showed a reduction in diversity after vaccination. We also detected differences in Shannon indices between experiments and tissues. We did not detect a pattern of CDR3 usage across the experiments. Overall, we were able to find differences in the Ab repertoire diversity across experimental groups and tissues.

Effects of skeletal unloading on the bone marrow antibody repertoire of tetanus toxoid and/or CpG treated C57BL/6J mice.

Spaceflight is known to impact the immune system in multiple ways. However, its effect on the antibody repertoire, especially in response to challenge, has not been well characterized. The development of the repertoire has multiple steps that could be affected by spaceflight, including V-(D-)J-gene segment rearrangement and the selection of complementarity determining regions (CDRs); specifically, CDR3, responsible for much of the diversity in the repertoire. We used skeletal unloading with the antiorthostatic suspension (AOS) model to simulate some of the physiological effects associated with spaceflight. Animals ± AOS were challenged with tetanus toxoid (TT) and/or CpG, an adjuvant. Two weeks after challenge, bone marrow was collected and sequenced using the Illumina MiSeq 2 × 300 platform. The resulting antibody repertoire was characterized, including V-, D- (heavy only), and J-gene segment usage, constant region usage, CDR3 length, and V(D)J combinations. We detected changes in gene-segment usage in response to AOS, TT, and CpG treatment in both the heavy and light chains. Additionally, changes were seen in the class-switched VH-gene repertoire. Alterations were also detected in V/J pairing for both the heavy and light chains, and changes in CDR3 length. We also detected lower levels of CDR3 AA overlap than detected in the splenic repertoire. These results demonstrate that AOS, TT, and CpG alter the bone marrow antibody repertoire however, it is still unclear from the data whether there is a loss of host antigen-specific responsiveness because of the change in gene use.

A comparison of unamplified and massively multiplexed PCR amplification for murine antibody repertoire sequencing.

Sequencing antibody repertoires has steadily become cheaper and easier. Sequencing methods usually rely on some form of amplification, often a massively multiplexed PCR prior to sequencing. To eliminate potential biases and create a data set that could be used for other studies, our lab compared unamplified sequencing results from the splenic heavy-chain repertoire in the mouse to those processed through two commercial applications. We also compared the use of mRNA vs total RNA, reverse transcriptase, and primer usage for cDNA synthesis and submission. The use of mRNA for cDNA synthesis resulted in higher read counts but reverse transcriptase and primer usage had no statistical effects on read count. Although most of the amplified data sets contained more antibody reads than the unamplified data set, we detected more unique V-gene segments in the unamplified data set. Although unique CDR3 detection was much lower in the unamplified data set, RNASeq detected 98% of the high frequency CDR3s. We have shown that unamplified profiling of the antibody repertoire is possible, detects more V-gene segments, and detects high frequency clones in the repertoire.

Effects of skeletal unloading on the antibody repertoire of tetanus toxoid and/or CpG treated C57BL/6J mice.

Spaceflight affects the immune system, but the effects on the antibody repertoire, responsible for humoral immunity, has not been well explored. In particular, the complex gene assembly and expression process; including mutations, might make this process vulnerable. Complementarity determining region 3 (CDR3), composed of parts of the V-(D-)J-gene segments, is very important for antigen binding and can be used as an important measure of variability. Skeletal unloading, and the physiological effects of it, parallel many impacts of space flight. Therefore, we explored the impact of skeletal unloading using the antiorthostatic suspension (AOS) model. Animals were experimentally challenged with tetanus toxoid (TT) and/or the adjuvant CpG. Blood was analyzed for anti-TT antibody and corticosterone concentrations. Whole spleen tissue was prepared for repertoire characterization. AOS animals showed higher levels of corticosterone levels, but AOS alone did not affect anti-TT serum antibody levels. Administration of CpG significantly increased the circulating anti-TT antibody concentrations. AOS did alter constant gene usage resulting in higher levels of IgM and lower levels of IgG. CpG also altered constant gene region usage increasing usage of IgA. Significant changes could be detected in multiple V-, D-, and J-gene segments in both the heavy and light chains in response to AOS, TT, and CpG treatments. Analysis of class-switched only transcripts revealed a different pattern of V-gene segment usage than detected in the whole repertoire and also showed significant alterations in gene segment usage after challenge. Alterations in V/J pairing were also detected in response to challenge. CDR3 amino acid sequence overlaps were similar among treatment groups, though the addition of CpG lowered overlap in the heavy chain. We isolated 3,045 whole repertoire and 98 potentially TT-specific CDR3 sequences for the heavy chain and 569 for the light chain. Our results demonstrate that AOS alters the repertoire response to challenge with TT and/or CpG.

A comparison of unamplified and massively multiplexed PCR amplification for murine antibody repertoire sequencing.

Sequencing antibody repertoires has steadily become cheaper and easier. Sequencing methods usually rely on some form of amplification, often a massively multiplexed PCR prior to sequencing. To eliminate potential biases and create a data set that could be used for other studies, our laboratory compared unamplified sequencing results from the splenic heavy-chain repertoire in the mouse to those processed through two commercial applications. We also compared the use of mRNA vs total RNA, reverse transcriptase, and primer usage for cDNA synthesis and submission. The use of mRNA for cDNA synthesis resulted in higher read counts but reverse transcriptase and primer usage had no statistical effects on read count. Although most of the amplified data sets contained more antibody reads than the unamplified data set, we detected more unique variable (V)-gene segments in the unamplified data set. Although unique CDR3 detection was much lower in the unamplified data set, RNASeq detected 98% of the high-frequency CDR3s. We have shown that unamplified profiling of the antibody repertoire is possible, detects more V-gene segments, and detects high-frequency clones in the repertoire.

Effects of spaceflight on the immunoglobulin repertoire of unimmunized C57BL/6 mice.

Spaceflight has been shown to suppress the adaptive immune response, altering the distribution and function of lymphocyte populations. B lymphocytes express highly specific and highly diversified receptors, known as immunoglobulins (Ig), that directly bind and neutralize pathogens. Ig diversity is achieved through the enzymatic splicing of gene segments within the genomic DNA of each B cell in a host. The collection of Ig specificities within a host, or Ig repertoire, has been increasingly characterized in both basic research and clinical settings using high-throughput sequencing technology (HTS). We utilized HTS to test the hypothesis that spaceflight affects the B-cell repertoire. To test this hypothesis, we characterized the impact of spaceflight on the unimmunized Ig repertoire of C57BL/6 mice that were flown aboard the International Space Station (ISS) during the Rodent Research One validation flight in comparison to ground controls. Individual gene segment usage was similar between ground control and flight animals, however, gene segment combinations and the junctions in which gene segments combine was varied among animals within and between treatment groups. We also found that spontaneous somatic mutations in the IgH and Igκ gene loci were not increased. These data suggest that space flight did not affect the B cell repertoire of mice flown and housed on the ISS over a short period of time.

Characterization of the naive murine antibody repertoire using unamplified high-throughput sequencing.

Antibody specificity and diversity are generated through the enzymatic splicing of genomic gene segments within each B cell. Antibodies are heterodimers of heavy- and light-chains encoded on separate loci. We studied the antibody repertoire from pooled, splenic tissue of unimmunized, adult female C57BL/6J mice, using high-throughput sequencing (HTS) without amplification of antibody transcripts. We recovered over 90,000 heavy-chain and over 135,000 light-chain immunoglobulin sequences. Individual V-, D-, and J-gene segment usage was uniform among the three mouse pools, particularly in highly abundant gene segments, with low frequency V-gene segments not being detected in all pools. Despite the similar usage of individual gene segments, the repertoire of individual B-cell CDR3 amino acid sequences in each mouse pool was highly varied, affirming the combinatorial diversity in the B-cell pool that has been previously demonstrated. There also was some skewing in the V-gene segments that were detected depending on chromosomal location. This study presents a unique, non-primer biased glimpse of the conventionally housed, unimmunized antibody repertoire of the C57BL6/J mouse.

Validation of Methods to Assess the Immunoglobulin Gene Repertoire in Tissues Obtained from Mice on the International Space Station.

Spaceflight is known to affect immune cell populations. In particular, splenic B cell numbers decrease during spaceflight and in ground-based physiological models. Although antibody isotype changes have been assessed during and after space flight, an extensive characterization of the impact of spaceflight on antibody composition has not been conducted in mice. Next Generation Sequencing and bioinformatic tools are now available to assess antibody repertoires. We can now identify immunoglobulin gene- segment usage, junctional regions, and modifications that contribute to specificity and diversity. Due to limitations on the International Space Station, alternate sample collection and storage methods must be employed. Our group compared Illumina MiSeq sequencing data from multiple sample preparation methods in normal C57Bl/6J mice to validate that sample preparation and storage would not bias the outcome of antibody repertoire characterization. In this report, we also compared sequencing techniques and a bioinformatic workflow on the data output when we assessed the IgH and Igκ variable gene usage. This included assessments of our bioinformatic workflow on Illumina HiSeq and MiSeq datasets and is specifically designed to reduce bias, capture the most information from Ig sequences, and produce a data set that provides other data mining options. We validated our workflow by comparing our normal mouse MiSeq data to existing murine antibody repertoire studies validating it for future antibody repertoire studies.

Evasion and interactions of the humoral innate immune response in pathogen invasion, autoimmune disease, and cancer.

The humoral innate immune system is composed of three major branches, complement, coagulation, and natural antibodies. To persist in the host, pathogens, such as bacteria, viruses, and cancers must evade parts of the innate humoral immune system. Disruptions in the humoral innate immune system also play a role in the development of autoimmune diseases. This review will examine how Gram positive bacteria, viruses, cancer, and the autoimmune conditions systemic lupus erythematosus and anti-phospholipid syndrome, interact with these immune system components. Through examining evasion techniques it becomes clear that an interplay between these three systems exists. By exploring the interplay and the evasion/disruption of the humoral innate immune system, we can develop a better understanding of pathogenic infections, cancer, and autoimmune disease development.