A multiinstitutional, multidisciplinary model for developing and teaching translational research in health disparities

Health disparities may affect any person in any community in the world, resulting from a multitude of factors including socioeconomic status, race, ethnicity, environment, and genetics. The impact of health disparities is felt by affected individuals, their families, communities, and the greater health care system. There is a critical need to increase health disparities research activities. This may be achieved by expanding and strengthening the training, education and career development of motivated clinicians, physicians and basic scientists, engaging them in clinical and translational research. Translational research relies on collaboration across disciplines, facilitating the dissemination and transfer of knowledge to populations for the overall improvement of health while decreasing the economic burden of health care. The University of Puerto Rico Medical Sciences Campus (UPR-MSC), Schools of Health Professions and Medicine joint initiatives, Clinical Research Education and Career Development (CRECD) and Hispanics in Research Capability (HiREC) programs, convened health disparities experts, faculty and scholars from multiple disciplines, cultural backgrounds and institutions. Together, they created a model for teaching translational research in health disparities that spans disciplines without boundaries.     

Body image in men with HIV

OBJECTIVE: To determine body image among HIV-infected men and to determine the relationship of lipodystrophy on body image. METHODOLOGY: Self-report questionnaires on body image were distributed to HIV-infected men at the university-based HIV clinic. Two previously validated instruments, the Body Image Quality of Life (BIQLI) scale and the Situational Inventory of Body Image Dysphoria Short Form (SIBID-S) were used to measure body image effects. The presence of lipodystrophy was determined by both self-report and physician examination. Demographic characteristics, disease stage, health status, and quality of life were also ascertained. Analysis of responses was performed via both group comparisons and linear regression analyses. RESULTS: One hundred ten men responded. Seventy-one percent identified their sexual orientation as men having sex with men (MSM). Forty-eight reported the presence of lipodystrophic characteristics; 62 reported no lipodystrophic changes. Agreement regarding the presence of lipodystrophy between physician and subject was 0.80 as measured by the kappa coefficient of agreement. Compared to HIV-infected men who denied lipodystrophy, HIV-infected men with self-reported lipodystrophy demonstrated poor body image as measured by BIQLI (p < 0.0001) and SIBID-S scales (p = 0.0001). Similarly, physician rated lipodystrophy was significantly associated with both body image subscale scores. CONCLUSIONS: We demonstrate that lipodystrophy among HIV-infected men is associated with poor body image.     

A cost comparison of off-pump CABG versus on-pump CABG at one-year: The Canadian off-pump CABG registry

BACKGROUND: Evidence suggests that off-pump coronary artery bypass graft surgery (CABG) is as safe and effective as on-pump CABG, and the cost of initial hospitalization for off-pump CABG is less expensive than on-pump CABG. However, it is uncertain whether the cost savings are sustained over a longer period of time. OBJECTIVE: To assess in-hospital and one-year direct medical costs of off-pump CABG versus on-pump CABG in the context of the Canadian health care system. METHODS AND RESULTS: From March 2001 to December 2002, 1657 consecutive patients enrolled in the Canadian Off-Pump CABG Registry were compared with 1693 consecutive on-pump patients from Hamilton Health Sciences CABG database. At one year, patients of both groups were followed by telephone interview. An economic analysis was conducted from the perspective of the Ontario Ministry of Health and Long-Term Care, and the data analysis was based on propensity score-matched registry patients (1233 pairs) to ensure the comparability of the two study groups. Clinical event and resource use information was collected from all patients. Unit costs from the Hamilton Health Sciences case-costing system were used to estimate hospital costs; all costs were reported in 2003 Canadian dollars. Sensitivity analyses were performed to account for uncertainties. The cost of initial hospitalization for off-pump CABG was significantly less than on-pump CABG (11,744 dollars versus 13,720 dollars, P < 0.001). Although follow-up costs were similar between the groups, the one-year total cost per patient for off-pump CABG remained significantly less than on-pump CABG (12,063 dollars versus 14,141 dollars, P < 0.001). CONCLUSION: Off-pump CABG offers significant savings during initial hospitalization that are also sustained after one year.     

Incomplete penetrance of susceptibility genes for MHC-determined immunoglobulin deficiencies in monozygotic twins discordant for type 1 diabetes

Incomplete intrinsic penetrance is the failure of some genetically susceptible individuals (e.g., monozygotic twins of those who have a trait) to exhibit that trait. For the first time, we examine penetrance of susceptibility genes for multiple MHC gene-determined traits in the same subjects. Serum levels of IgA, IgD, IgG3, but not IgG4, in 50 pairs of monozygotic twins discordant for type 1 diabetes (T1D) correlated more closely in the twins than in random paired controls. The frequencies of subjects deficient in IgA (6%), IgD (33%) and IgG4 (12%), but not in IgG3, were higher in the twins than in controls. We postulate that this was because the MHC haplotypes (and possible non-MHC genes) that predispose to T1D also carry susceptibility genes for certain immunoglobulin deficiencies. Immunoglobulin deficiencies were not associated with T1D. Pairwise concordance for the deficiencies in the twins was 50% for IgA, 57% for IgD and 50% for IgG4. There were no significant associations among the specific immunoglobulin deficiencies except that all IgA-deficient subjects had IgD deficiency. Thus, intrinsic penetrance is a random process independently affecting different MHC susceptibility genes. Because multiple different external triggers would be required to explain the results, differential environmental determinants appear unlikely.     

Murine epidermal Langerhans cells and keratinocytes express functional P2X7 receptors

Please cite this paper as: Murine epidermal Langerhans cells and keratinocytes express functional P2X₇ receptors. Experimental Dermatology 2010; 19 : e151–e157. Abstract: Extracellular ATP via the activation of purinergic P2 receptors has an emerging role in cutaneous biology; however, the distribution of these receptors in mouse skin is poorly defined. This study investigated whether murine epidermal cell subpopulations express functional purinergic P2X₇ receptors. P2X₇ expression was examined by immunoblotting and immunofluorescence staining of epidermal cells from C57Bl/6 mice. P2X₇ function was evaluated by nucleotide‐induced ethidium⁺ uptake measurements in epidermal cells from C57Bl/6 mice, and from P2X₇ deficient mice and wild‐type littermate controls. P2X₇ was detected in whole epidermal cell preparations, and specifically on Langerhans cells (LCs) and keratinocytes (KCs). ATP induced ethidium⁺ uptake into LCs and KCs, with EC₅₀ values of 503 and 482 μm, respectively. BzATP, and to a lesser extent ATPγS and ADP, also induced ethidium⁺ uptake; while UTP, αβ‐meth‐ATP and NAD were ineffective. ATP‐induced ethidium⁺ uptake was impaired by Na⁺ and Mg²⁺, and the P2X₇ antagonist, A‐438079 and was absent in LCs and KCs from P2X₇ deficient mice. These results demonstrate that murine LCs and KCs express functional P2X₇, and support a role for this receptor in cutaneous biology.     

Child-rearing practices of primary caregivers of HIV-infected children: An integrative review of the literature

The number of human immunodeficiency virus (HIV)-infected children has increased because of the HIV and acquired immunodeficiency syndrome epidemic. Yet little is known about the child-rearing practices of these children's primary caregivers. The purpose of this article is to describe what is known about the child-rearing practices of primary caregivers of HIV-infected children. The review covers a 10-year period from 1990 to 2000. Three electronic bibliographic databases (MEDLINE, CINAHL, and AIDSLINE) were explored. Key words used were HIV-positive children, caregivers, and child-rearing. A total of 50 papers were examined. Using the Matrix Method, each paper was evaluated according to five frames of reference: journal, purpose, sample, method, and findings. Content analysis was used to identity salient themes. Themes that emerged were: caregiver, child, and interactions or child-rearing practices. These findings affirm the parent-child interaction model generated by Kathryn E. Barnard and support this framework as a tool for investigating the relationships between these children and their caregivers.     

Familial recurrence of SOX2 anophthalmia syndrome: phenotypically normal mother with two affected daughters

The SOX2 anophthalmia syndrome is emerging as a clinically recognizable disorder that has been identified in 10-15% of individuals with bilateral anophthalmia. Extra-ocular anomalies are common. The majority of SOX2 mutations identified appear to arise de novo in probands ascertained through the presence of anophthalmia or microphthalmia. In this report, we describe two sisters with bilateral anophthalmia/microphthalmia, brain anomalies and a novel heterozygous SOX2 gene single-base pair nucleotide deletion, c.551delC, which predicts p.Pro184ArgfsX19. The hypothetical protein product is predicted to lead to haploinsufficient SOX2 function. Mosaicism for this mutation in the SOX2 gene was also identified in their clinically unaffected mother in peripheral blood DNA. Thus it cannot be assumed that all SOX2 mutations in individuals with anophthalmia/microphthalmia are de novo. Testing of parents is indicated when a SOX2 mutation is identified in a proband.