Partial dearterialization of the liver allograft

The clinical course of five patients with partial dearterialization of their hepatic allografts is described. One patient died and three others suffered serious morbidity as a direct or indirect result of this complication. Partial dearterialization of the liver allograft is a serious and potentially life-threatening complication for which preservation of the complete hepatic arterial supply is important, even if this requires reconstruction of the aberrant vessels. © 1990 Springer-Verlag

How a universal health system reduces inequalities: lessons from England

Background: Provision of universal coverage is essential for achieving equity in healthcare, but inequalities still exist in universal healthcare systems. Between 2004/5 and 2011/12 the English NHS, which has provided universal coverage since 1948, made sustained efforts to reduce health inequalities by strengthening primary care. We provide the first comprehensive assessment of trends in socioeconomic inequalities of primary care access, quality and outcomes during this period. Methods: Whole-population small area longitudinal study, based on 32,482 neighbourhoods of approximately 1,500 people in England from 2004/5 to 2011/12. We measured slope indices of inequality in four indicators: (i) patients per family doctor (ii) primary care quality (iii) preventable emergency hospital admissions and (iv) mortality from conditions considered amenable to healthcare. Results: Between 2004/5 and 2011/12 there were larger absolute improvements on all indicators in more deprived neighbourhoods. The modelled gap between the most and least deprived neighbourhoods in England decreased by: 193 patients per family doctor (95% confidence interval 173 to 213), 3.29 percentage points of primary care quality (3.13 to 3.45), 0.42 preventable hospitalisations per 1,000 people (0.29 to 0.55) and 0.23 amenable deaths per 1,000 people (0.15 to 0.31). By 2011/12 inequalities in primary care supply and quality were almost eliminated but socio-economic inequality was still associated with 158,396 preventable hospitalisations and 37,983 deaths amenable to healthcare. Conclusions: Between 2004/5 and 2011/12 the NHS succeeded in substantially reducing socioeconomic inequalities in primary care access and quality but made only modest reductions in healthcare outcome inequalities

Temporal Trends in Vertebral Size and Shape from Medieval to Modern-Day

Human lumbar vertebrae support the weight of the upper body. Loads lifted and carried by the upper extremities cause significant loading stress to the vertebral bodies. It is well established that trauma-induced vertebral fractures are common especially among elderly people. The aim of this study was to investigate the morphological factors that could have affected the prevalence of trauma-related vertebral fractures from medieval times to the present day. To determine if morphological differences existed in the size and shape of the vertebral body between medieval times and the present day, the vertebral body size and shape was measured from the 4th lumbar vertebra using magnetic resonance imaging (MRI) and standard osteometric calipers. The modern samples consisted of modern Finns and the medieval samples were from archaeological collections in Sweden and Britain. The results show that the shape and size of the 4th lumbar vertebra has changed significantly from medieval times in a way that markedly affects the biomechanical characteristics of the lumbar vertebral column. These changes may have influenced the incidence of trauma- induced spinal fractures in modern populations

A miR-200b/200c/429-Binding Site Polymorphism in the 3′ Untranslated Region of the AP-2α Gene Is Associated with Cisplatin Resistance

The transcription factor AP-2α functions as a tumor suppressor by regulating various genes that are involved in cell proliferation and apoptosis. Chemotherapeutic drugs including cisplatin induce post-transcriptionally endogenous AP-2α, which contributes to chemosensitivity by enhancing therapy-induced apoptosis. microRNAs (miRNAs) miR-200b, miR-200c and miR-429 (miR-200b/200c/429) are up-regulated in endometrial and esophageal cancers, and their overexpression correlates with resistance to cisplatin treatment. Using computational programs, we predicted that the 3′ untranslated region (UTR) of AP-2α gene contains a potential miRNA response element (MRE) for the miR-200b/200c/429 family, and the single nucleotide polymorphism (SNP) site rs1045385 (A or C allele) resided within the predicted MRE. Luciferase assays and Western blot analysis demonstrated that the miR-200b/200c/429 family recognized the MRE in the 3′ UTR of AP-2α gene and negatively regulated the expression of endogenous AP-2α proteins. SNP rs1045385 A>C variation enhanced AP-2α expression by disrupting the binding of the miR-200b/200c/429 family to the 3′ UTR of AP-2α. The effects of the two polymorphic variants on cisplatin sensitivity were determined by clonogenic assay. The overexpression of AP-2α with mutant 3′ UTR (C allele) in the endometrial cancer cell line HEC-1A, which has high levels of endogenous miR-200b/200c/429 and low levels of AP-2α protein, significantly increased cisplatin sensitivity, but overexpression of A allele of AP-2α has no significant effects, compared with mock transfection. We concluded that miR-200b/200c/429 induced cisplatin resistance by repressing AP-2α expression in endometrial cancer cells. The SNP (rs1045385) A>C variation decreased the binding of miR-200b/200c/429 to the 3′ UTR of AP-2α, which upregulated AP-2α protein expression and increased cisplatin sensitivity. Our results suggest that SNP (rs1045385) may be a potential prognostic marker for cisplatin treatment

MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens

The PITX3 bicoid-type homeodomain transcription factor plays an important role in lens development in vertebrates. PITX3 deficiency results in a spectrum of phenotypes from isolated cataracts to microphthalmia in humans, and lens degeneration in mice and zebrafish. While identification of downstream targets of PITX3 is vital for understanding the mechanisms of normal ocular development and human disease, these targets remain largely unknown. To isolate genes that are directly regulated by PITX3, we performed a search for genomic sequences that contain evolutionarily conserved bicoid/PITX3 binding sites and are located in the proximity of known genes. Two bicoid sites that are conserved from zebrafish to human were identified within the human promoter of the major intrinsic protein of lens fiber, MIP/AQP0. MIP/AQP0 deficiency was previously shown to be associated with lens defects in humans and mice. We demonstrate by both chromatin immunoprecipitation and electrophoretic mobility shift assay that PITX3 binds to MIP/AQP0 promoter region in vivo and is able to interact with both bicoid sites in vitro. In addition, we show that wild-type PITX3 is able to activate the MIP/AQP0 promoter via interaction with the proximal bicoid site in cotransfection experiments and that the introduction of mutations disrupting binding to this site abolishes this activation. Furthermore, mutant forms of PITX3 fail to produce the same levels of transactivation as wild-type when cotransfected with the MIP/AQP0 reporter. Finally, knockdown of pitx3 in zebrafish affects formation of a DNA-protein complex associated with mip1 promoter sequences; and examination of expression in pitx3 morphant and control zebrafish revealed a delay in and reduction of mip1 expression in pitx3-deficient embryos. Therefore, our data suggest that PITX3 is involved in direct regulation of MIP/AQP0 expression and that the alteration of MIP/AQP0 expression is likely to contribute to the lens phenotype in cataract patients with PITX3 mutations

A Model for Interprofessional Health Disparities Education: Student-Led Curriculum on Chronic Hepatitis B Infection

Although health disparities are commonly addressed in preclinical didactic curricula, direct patient care activities with affected communities are more limited. To address this problem, health professional students designed a preclinical service-learning curriculum on hepatitis B viral (HBV) infection, a major health disparity affecting the Asian/Pacific Islander (API) population, integrating lectures, skills training, and direct patient care at student-run clinics. An urban health professions campus. Medical and other health professional students at University of California, San Francisco, organized a preclinical didactic and experiential elective, and established two monthly clinics offering HBV screening, vaccination, and education to the community. Between 2004 and 2009, 477 students enrolled in the student-led HBV curriculum. Since the clinics’ inception in 2007, 804 patients have been screened for chronic HBV; 87% were API immigrants, 63% had limited English proficiency, and 46% were uninsured. Serologically, 10% were found to be chronic HBV carriers, 44% were susceptible to HBV, and 46% were immune. Our student-led didactic and experiential elective can serve as an interprofessional curricular model for learning about specific health disparities while providing important services to the local community

Transition to the new race/ethnicity data collection standards in the Department of Veterans Affairs

BACKGROUND: Patient race in the Department of Veterans Affairs (VA) information system was previously recorded based on an administrative or clinical employee's observation. Since 2003, the VA started to collect self-reported race in compliance with a new federal guideline. We investigated the implications of this transition for using race/ethnicity data in multi-year trends in the VA and in other healthcare data systems that make the transition. METHODS: All unique users of VA healthcare services with self-reported race/ethnicity data in 2004 were compared with their prior observer-recorded race/ethnicity data from 1997 – 2002 (N = 988,277). RESULTS: In 2004, only about 39% of all VA healthcare users reported race/ethnicity values other than "unknown" or "declined." Females reported race/ethnicity at a lower rate than males (27% vs. 40%; p < 0.001). Over 95% of observer-recorded data agreed with self-reported data. Compared with the patient self-reported data, the observer-recorded White and African American races were accurate for 98% (kappa = 0.89) and 94% (kappa = 0.93) individuals, respectively. Accuracy of observer-recorded races was much worse for other minority groups with kappa coefficients ranging between 0.38 for American Indian or Alaskan Natives and 0.79 for Hispanic Whites. When observer-recorded race/ethnicity values were reclassified into non-African American groups, they agreed with the self-reported data for 98% of all individuals (kappa = 0.93). CONCLUSION: For overall VA healthcare users, the agreement between observer-recorded and self-reported race/ethnicity was excellent and observer-recorded and self-reported data can be used together for multi-year trends without creating serious bias. However, this study also showed that observation was not a reliable method of race/ethnicity data collection for non-African American minorities and racial disparity might be underestimated if observer-recorded data are used due to systematic patterns of inaccurate race/ethnicity assignments

Systematic Neighborhood Observations at High Spatial Resolution: Methodology and Assessment of Potential Benefits

There is a growing body of public health research documenting how characteristics of neighborhoods are associated with differences in the health status of residents. However, little is known about how the spatial resolution of neighborhood observational data or community audits affects the identification of neighborhood differences in health. We developed a systematic neighborhood observation instrument for collecting data at very high spatial resolution (we observe each parcel independently) and used it to collect data in a low-income minority neighborhood in Dallas, TX. In addition, we collected data on the health status of individuals residing in this neighborhood. We then assessed the inter-rater reliability of the instrument and compared the costs and benefits of using data at this high spatial resolution. Our instrument provides a reliable and cost-effect method for collecting neighborhood observational data at high spatial resolution, which then allows researchers to explore the impact of varying geographic aggregations. Furthermore, these data facilitate a demonstration of the predictive accuracy of self-reported health status. We find that ordered logit models of health status using observational data at different spatial resolution produce different results. This implies a need to analyze the variation in correlative relationships at different geographic resolutions when there is no solid theoretical rational for choosing a particular resolution. We argue that neighborhood data at high spatial resolution greatly facilitates the evaluation of alternative geographic specifications in studies of neighborhood and health

Drivers and barriers to acceptance of human-papillomavirus vaccination among young women: a qualitative and quantitative study

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) is a necessary cause of cervical dysplasia and cancer, and of genital warts. Few studies have examined attitudes to HPV vaccination since the introduction of HPV vaccines. We aimed to investigate the reasons for young women's acceptance or rejection of the quadrivalent HPV vaccine after its general availability in Denmark.</p> <p>Method</p> <p>A literature review assessed attitudes towards HPV vaccination and the information was used to identify relevant questions for telephone and focus group interviews with women aged 16-26 who had decided to receive or reject HPV vaccination. 435 women across Denmark were interviewed by telephone. Qualitative interviews were undertaken in focus groups with 33 women living in Odense who had completed the telephone survey. Four focus groups were set up according to age (16-20 and 21-26 years of age) and acceptance/rejection of the vaccine.</p> <p>Results</p> <p>Of 839 women initially contacted by telephone, 794 were included, 411 (49%) said they accepted vaccination but only 201 (24%) had actually received the vaccine and these latter were interviewed. 242 women said they refused vaccination of which 234 were interviewed. Women who were undecided were excluded from the study. Prevention of cervical cancer was the main driver for acceptance of the vaccine, followed by parental encouragement and financial support, personal experience of someone with cancer and recommendation by health-care professionals. The greatest barrier to vaccination was its cost. A lack of information about the benefits of vaccination for sexually active women was also an important barrier and the older participants in particular considered that they were too old to be vaccinated. Knowledge about HPV and its role in the development of cervical cancer and genital warts was poor.</p> <p>Conclusions</p> <p>The difference between intention to be vaccinated and starting vaccination was considerable, and a large proportion of women aged 16-26 did not wish to be vaccinated. If the most important barriers to vaccination were addressed (cost and a lack of information about vaccination benefits), it is likely that the uptake of vaccination in Denmark would increase substantially.</p

Regulatory T cells and their role in rheumatic diseases: a potential target for novel therapeutic development

Regulatory T cells have an important role in limiting immune reactions and are essential regulators of self-tolerance. Among them, CD4+CD25high regulatory T cells are the best-described subset. In this article, we summarize current knowledge on the phenotype, function, and development of CD4+CD25high regulatory T cells. We also review the literature on the role of these T cells in rheumatic diseases and discuss the potential for their use in immunotherapy