Design and Methods of the Validating Injury to the Renal Transplant Using Urinary Signatures (VIRTUUS) Study in Children.

Lack of noninvasive diagnostic and prognostic biomarkers to reliably detect early allograft injury poses a major hindrance to long-term allograft survival in pediatric kidney transplant recipients. METHODS: Validating Injury to the Renal Transplant Using Urinary Signatures Children's Study, a North American multicenter prospective cohort study of pediatric kidney transplant recipients, aims to validate urinary cell mRNA and metabolite profiles that were diagnostic and prognostic of acute cellular rejection (ACR) and BK virus nephropathy (BKVN) in adult kidney transplant recipients in Clinical Trials in Organ Transplantation-4. Specifically, we are investigating: (1) whether a urinary cell mRNA 3-gene signature (18S-normalized CD3ε, CXCL10 mRNA, and 18S ribosomal RNA) discriminates biopsies with versus without ACR, (2) whether a combined metabolite profile with the 3-gene signature increases sensitivity and specificity of diagnosis and prognostication of ACR, and (3) whether BKV-VP1 mRNA levels in urinary cells are diagnostic of BKVN and prognostic for allograft failure. RESULTS: To date, 204 subjects are enrolled, with 1405 urine samples, including 144 biopsy-associated samples. Among 424 urine samples processed for mRNA, the median A260:280 ratio (RNA purity) was 1.91, comparable with Clinical Trials in Organ Transplantation-4 (median 1.82). The quality control failure rate was 10%. Preliminary results from urine supernatant showed that our metabolomics platform successfully captured a broad array of metabolites. Clustering of pool samples and overlay of samples from various batches demonstrated platform robustness. No study site effect was noted. CONCLUSIONS: Multicenter efforts to ascertain urinary biomarkers in pediatric kidney transplant recipients are feasible with high-quality control. Further study will inform whether these signatures are discriminatory and predictive for rejection and infection.

Stakeholder conceptualisation of multi-level HIV and AIDS determinants in a Black epicentre.

HIV has reached epidemic proportions among African Americans in the USA but certain urban contexts appear to experience a disproportionate disease burden. Geographic information systems mapping in Philadelphia indicates increased HIV incidence and prevalence in predominantly Black census tracts, with major differences across adjacent communities. What factors shape these geographic HIV disparities among Black Philadelphians? This descriptive study was designed to refine and validate a conceptual model developed to better understand multi-level determinants of HIV-related risk among Black Philadelphians. We used an expanded ecological approach to elicit reflective perceptions from administrators, direct service providers and community members about individual, social and structural factors that interact to protect against or increase the risk for acquiring HIV within their community. Gender equity, social capital and positive cultural mores (e.g., monogamy, abstinence) were seen as the main protective factors. Historical negative contributory influences of racial residential segregation, poverty and incarceration were among the most salient risk factors. This study was a critical next step toward initiating theory-based, multi-level community-based HIV prevention initiatives.

Addressing Unmet Sexual Health Needs among Black Adolescents with Mental Illnesses.

Despite advances in HIV epidemiologic and prevention research, adolescents with mental illnesses remain a historically underserved group with respect to human immunodeficiency virus (HIV)/sexually transmitted infection (STI) prevention resources. Black adolescents with mental illnesses in particular are a relatively underserved, hidden population in the field of sexual health. Strategies and guidelines are needed to account for underlying psychopathology among Black adolescents with mental illnesses in ways that current models have yet to address. In this paper, we propose several actionable mechanisms to better integrate HIV/STI and mental health related services and activities for sexual health promotion.

Multilevel drivers of human immunodeficiency virus/acquired immune deficiency syndrome among Black Philadelphians: exploration using community ethnography and geographic information systems.

BACKGROUND: Unequal human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) distribution is influenced by certain social and structural contexts that facilitate HIV transmission and concentrate HIV in disease epicenters. Thus, one of the first steps in designing effective community-level HIV/AIDS initiatives is to disentangle the influence of individual, social, and structural factors on HIV risk. Combining ethnographic methodology with geographic information systems mapping can allow for a complex exploration of multilevel factors within communities that facilitate HIV transmission in highly affected areas. OBJECTIVES: We present the formative comparative community-based case study findings of an investigation of individual-, social-, and structural-level factors that contribute to the HIV/AIDS epidemic among Black Philadelphians. METHODS: Communities were defined using census tracts. The methodology included ethnographic and geographic information systems mapping, observation, informal conversations with residents and business owners, and secondary analyses of census tract-level data in four Philadelphia neighborhoods. RESULTS: Factors such as overcrowding, disadvantage, permeability in community boundaries, and availability and accessibility of health-related resources varied significantly. Furthermore, HIV/AIDS trended with social and structural inequities above and beyond the community's racial composition. DISCUSSION: This study was a first step to disentangle relationships between community-level factors and potential risk for HIV in an HIV epicenter. The findings also highlight stark sociodemographic differences within and across racial groups and further substantiate the need for comprehensive, community-level HIV prevention interventions. These findings from targeted U.S. urban communities have potential applicability for examining the distribution of HIV/AIDS in broader national and international geosocial contexts.