Community Engagement of Adolescents in the Development of a Patient-Centered Outcomes Tool for Adolescents with a History of Hypospadias Repair

Introduction Hypospadias may lead to long-term issues with urination, sexual function and psychosocial well-being. Limited evidence exists regarding the healthcare communication preferences of male adolescents regarding sensitive topics. Objective The purpose of this qualitative study was to explore the healthcare communication preferences of male adolescents regarding sensitive topics (e.g. urinary and sexual issues) and engage them in in the initial stages of development a patient-centered outcomes tool for adolescents with a history of hypospadias repair. Study Design A multi-disciplinary team with communication design expertise, pediatric urology experts, and health services researchers developed a self-reported toolkit for adolescent patients who had hypospadias repair as children. The toolkit featured short writing/diagramming exercises and scales to facilitate participant reflections about genital appearance, urination, sexual function and psychosocial well-being. We recruited students from two local high schools for two focus groups to obtain feedback about the usability/acceptability of the toolkit’s appearance/content. We inquired about language preferences and preferred format and/or setting for sharing sensitive information with researchers. The focus groups were audio recorded, professionally transcribed, checked for accuracy and analyzed by two coders using qualitative content analysis. Major themes and subthemes were identified and representative quotes were selected. Results We conducted two focus groups in January 2018 with 33 participants, ages 14-18. Participants preferred language that would make patients feel comfortable as well as serious, clinical language rather than slang terms/sexual humor (Extended Summary Table). They recommended avoidance of statements implying that something is wrong with a patient or statements that would pressure the patient into providing answers. They suggested fill-in-the-blank and open-ended responses to encourage freedom of expression and colorful graphics to de-emphasize the test-like appearance of the toolkit. Most participants preferred a toolkit format to a one-on-one interview to discuss sensitive topics such as urinary or sexual issues. Participants would prefer either a male interviewer or would like to have a choice of interviewer gender for individual qualitative interviews, and they recommended a focus group leader with a history of hypospadias repair. Discussion This study provides a rich description of a group of male high school students’ experiences with healthcare providers and researchers. Its qualitative design limits generalizability and our findings may not be similar to adolescents with a history of hypospadias repair. Conclusion We used focus group feedback on the toolkit prototype to refine the tool for use in a future study of adolescents with history of hypospadias repair

User-centered development of a hypospadias decision aid prototype

Introduction: Many parents who choose hypospadias repair for their sons experience decisional conflict (DC) and decisional regret (DR). We previously found that parental decision-making about hypospadias surgery is a complex process characterized by cyclic information-seeking to alleviate anxiety and confusion. Objective: The objective of this study was to engage parents of hypospadias patients and pediatric providers in the co-design of a decision aid (DA) prototype to facilitate shared decision-making about hypospadias surgery and address DC and DR. Methods: From August 2018 to January 2019, we conducted three co-design workshops with parents of hypospadias patients, pediatric urology and general pediatric providers to discuss their recommendations for a DA prototype. Activities were audio recorded and professionally transcribed. Transcripts and worksheets were analyzed by six coders using qualitative analysis to identify key aspects of a hypospadias DA desired by stakeholders. We conducted a collaborative design and prototyping session to establish key features and requirements, created a content map visualizing this work, and then developed a DA prototype. Results: Parent participants included 6 mothers and 4 fathers: 8 Caucasian, 2 African-American; median age 31 years. Providers included pediatric urology (n = 7) and general pediatric providers (n = 10): median age 47.5 years, 83.3% Caucasian, 58.3% male, 58.3% MD's and 41.7% nurse practitioners. Participants created user-friendly, interactive DA prototypes with "24/7" availability that had three key functions: 1) provide accurate, customizable, educational content, 2) connect parents with each other, and 3) engage them in a decision-making activity. The prototype consisted of five modules (Extended Summary Figure). "Hypospadias Basics" includes epidemiology and a hypospadias severity scale. "Surgery Basics" includes goals, illustrated steps, and pros/cons of surgery. "Testimonials" includes videos of parents and adolescents discussing their experiences. "Help me Decide" includes a decisional conflict scale and a decision-making activity (i.e. values clarification method). "Frequently Asked Questions" covers general hypospadias information, perioperative expectations and a review of postoperative care. Discussion: To our knowledge, this is the first DA prototype developed for a pediatric urology condition using a human-centered design approach to engage many key stakeholders in the development process. One limitation of this study is the small population sampled, which limits generalizability and means that our findings may not reflect the views of all parents or pediatric providers involved in hypospadias decision-making. Conclusions: We created a parent-centered hypospadias DA prototype that provides decision support in an online, interactive format. Future directions include further testing with usability experts, providers and parents

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Indirect effects of parasites in invasions

1. Introduced species disrupt native communities and biodiversity worldwide. Parasitic infections (and at times, their absence) are thought to be a key component in the success and impact of biological invasions by plants and animals. They can facilitate or limit invasions, and positively or negatively impact native species. 2. Parasites have not only direct effects on their hosts, but also indirect effects on the species with which their hosts interact. Indirect effects include density-mediated effects (resulting from parasite-induced reduction in host reproduction and survival) as well as trait-mediated indirect effects (resulting from parasite-induced changes in host phenotype, behavior or life history). These effects are not mutually exclusive but often interact. 3. The importance of these indirect interactions for invasion success, and the extent to which these effects ramify throughout communities and influence ecosystems undergoing biological invasion provide the focus of our review. Examples from the animal and plant literature illustrate the importance of parasites in mediating both competitive and consumer–resource interactions between native and invasive species. 4. Parasites are involved in indirect interactions at all trophic levels. Furthermore, the indirect effects of parasitic infection are important at a range of biological scales from within a host to the whole ecosystem in determining invasion success and impact. 5. To understand the importance of parasitic infection in invasion success and in the outcomes for invaded communities requires an interdisciplinary approach by ecologists and parasitologists, across animal and plant systems. Future research should develop a framework integrating community ecology, evolution and immunology to better understand and manage the spread of invasive species and their diseases

The cytotoxic and growth inhibitory effects of CDIM9 in MD-MB231 and BT549 cells

<p><b>Copyright information:</b></p><p>Taken from "1,1-Bis(3'-indolyl)-1-(-biphenyl)methane inhibits basal-like breast cancer growth in athymic nude mice"</p><p>http://breast-cancer-research.com/content/9/4/R56</p><p>Breast cancer research : BCR 2007;9(4):R56-R56.</p><p>Published online 31 Aug 2007</p><p>PMCID:PMC2206732.</p><p></p> MDA-MB231 cells, SKMCs, BT549 cells, and HSMMs were treated with serial diluted CDIM9 at between 1 × 10and 1.9 × 10mol/l for 48 hours. The ECvalues were determined using GraphPad Prism software. Cell growth inhibition assay. MD-MB231 and BT549 cells were treated with 1 to 10 μmol/l CDIM9 for 6 days, and cell numbers were determined as described in Materials and methods. Results are expressed as means ± standard error for three separate determinations at each time point. CDIM9, 1,1-bis (3'-indolyl)-1-(p-biphenyl) methane; EC, concentration producing 50% of the maximum possible response; HSMM, human muscle myoblast; SKMC, human skeletal muscle cell

Prevalence and significance of clonal hematopoiesis of indeterminate potential in lung transplant recipients

Abstract Background Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition of somatic mutations that leads to an expanded blood cell clone, has been associated with development of a pro-inflammatory state. An enhanced or dysregulated inflammatory response may contribute to rejection after lung transplantation, however the prevalence of CHIP in lung recipients and influence of CHIP on allograft outcomes is unknown. Methods We analyzed whole-exome sequencing data in 279 lung recipients to detect CHIP, defined by pre-specified somatic mutations in 74 genes known to promote clonal expansion of hematopoietic stem cells. We compared the burden of acute rejection (AR) over the first post-transplant year in lung recipients with vs. without CHIP using multivariable ordinal regression. Multivariate Cox proportional hazards models were used to assess the association between CHIP and CLAD-free survival. An exploratory analysis evaluated the association between the number of CHIP-associated variants and chronic lung allograft dysfunction (CLAD)-free survival. Results We detected 64 CHIP-associated mutations in 45 individuals (15.7%), most commonly in TET2 (10.8%), DNMT3A (9.2%), and U2AF1 (9.2%). Patients with CHIP tended to be older but did not significantly differ from patients without CHIP in terms of race or native lung disease. Patients with CHIP did not have a higher incidence of AR over the first post-transplant year (p = 0.45) or a significantly increased risk of death or CLAD (adjusted HR 1.25, 95% CI 0.88–1.78). We did observe a significant association between the number of CHIP variants and CLAD-free survival, specifically patients with 2 or more CHIP-associated variants had an increased risk for death or CLAD (adjusted HR 3.79, 95% CI 1.98–7.27). Conclusions Lung recipients have a higher prevalence of CHIP and a larger variety of genes with CHIP-associated mutations compared with previous reports for the general population. CHIP did not increase the risk of AR, CLAD, or death in lung recipients