Epigenetics of renal cell carcinoma: the path towards new diagnostics and therapeutics

Aberrant DNA methylation, in particular promoter hypermethylation and transcriptional silencing of tumor suppressor genes, has an important role in the development of many human cancers, including renal cell carcinoma (RCC). Indeed, apart from mutations in the well studied von Hippel-Lindau gene (VHL), the mutation frequency rates of known tumor suppressor genes in RCC are generally low, but the number of genes found to show frequent inactivation by promoter methylation in RCC continues to grow. Here, we review the genes identified as epigenetically silenced in RCC and their relationship to pathways of tumor development. Increased understanding of RCC epigenetics provides new insights into the molecular pathogenesis of RCC and opportunities for developing novel strategies for the diagnosis, prognosis and management of RCC

Interrogating the prevention approach of the Housing (Wales) Act 2014 for people with mental health needs who are homeless

Rates of homelessness and poor mental health present significant challenges across the globe. In this article, we explore how these intersecting issues have been addressed in Wales through Part 2 of the Housing (Wales) Act 2014 through a paradigm shift towards a prevention model. This article reports findings from a study (conducted between 2016 and 2018) which evaluated the processes and impacts of the Act against the backdrop of welfare reform and systemic changes taking place in Wales and the UK. Using new evidence, we offer a critical examination of how homelessness prevention policy operates in practice and how social values and power affect policy implementation. We offer new evidence of the translation of policy into practice through the experiences of two stakeholder groups: people with mental health needs and service providers. In doing so, we offer a critique of how policy and practice could be modified to improve outcomes for homeless people with implications for prevention policy in Wales and in other contexts and different welfare regimes

A Project to Produce Calves from Selected Historical Angus Bulls

As part of the 50th anniversary of the McNay Research Farm, cows were inseminated with semen from Angus bulls of the 1950s and the 1970/1980s. The goal was to produce calves from Angus bulls that were popular 50 years ago and 25 years ago for viewing at the McNay Research Farm’s 50th Anniversary celebration in September 2006

ISU Angus Cow 98398: A Model of Longevity

ISU purebred Angus cow 98398 is a story of longevity and productivity. As the oldest cow in the ISU McNay herd, she is 16 years old, born April 19, 1998 at the former ISU Rhodes Farm, Rhodes, Iowa, Marshall County. She had her first calf in 2001 and has calved every year since, including twins in 2006 and 2008. She and the rest of the ISU research Angus beef herd moved to the ISU McNay Research Farm, Chariton, Iowa, in 2004. She is due with her 16th calf this fall (a heifer), which will make 16 calves in 14 years of calving. With the 2014 calf, she will have had eight bulls and eight heifers averaging 82.5 lb at birth (Table 1). The average adjusted weaning weight of her calves is 515.4 lb (Table1)

Expression of HIV receptors, alternate receptors and co-receptors on tonsillar epithelium: implications for HIV binding and primary oral infection

BACKGROUND: Primary HIV infection can develop from exposure to HIV in the oral cavity. In previous studies, we have documented rapid and extensive binding of HIV virions in seminal plasma to intact mucosal surfaces of the palatine tonsil and also found that virions readily penetrated beneath the tissue surfaces. As one approach to understand the molecular interactions that support HIV virion binding to human mucosal surfaces, we have examined the distribution of the primary HIV receptor CD4, the alternate HIV receptors heparan sulfate proteoglycan (HS) and galactosyl ceramide (GalCer) and the co-receptors CXCR4 and CCR5 in palatine tonsil. RESULTS: Only HS was widely expressed on the surface of stratified squamous epithelium. In contrast, HS, GalCer, CXCR4 and CCR5 were all expressed on the reticulated epithelium lining the tonsillar crypts. We have observed extensive variability, both across tissue sections from any tonsil and between tonsils, in the distribution of epithelial cells expressing either CXCR4 or CCR5 in the basal and suprabasal layers of stratified epithelium. The general expression patterns of CXCR4, CCR5 and HS were similar in palatine tonsil from children and adults (age range 3–20). We have also noted the presence of small clusters of lymphocytes, including CD4(+ )T cells within stratified epithelium and located precisely at the mucosal surfaces. CD4(+ )T cells in these locations would be immediately accessible to HIV virions. CONCLUSION: In total, the likelihood of oral HIV transmission will be determined by macro and micro tissue architecture, cell surface expression patterns of key molecules that may bind HIV and the specific properties of the infectious inoculum

Developing the agenda for European Union collaboration on non-communicable diseases research in Sub-Saharan Africa

<p>Abstract</p> <p>Background</p> <p>Health research is increasing in Africa, but most resources are currently chanelled towards infectious diseases and health system development. While infectious diseases remain a heavy burden for some African countries, non-communicable diseases (NCDs) account for more than half of all deaths globally and WHO predicts 27% increase in NCDs in Africa over the next decade. We present findings of a European-Africa consultation on the research agenda for NCDs.</p> <p>Methods</p> <p>A workshop was held in Yaoundé, Cameroon, organized by the Network for the Coordination and Advancement of Sub-Saharan Africa-European Union Science and Technology Cooperation (CAAST-Net). Drawing on initial presentations, a small expert group from academic, clinical, public-health and administrative positions considered research needs in Africa for cardiovascular disease, cancer and diabetes.</p> <p>Results</p> <p>Research in Africa can draw from different environmental and genetic characteristics to understand the causes of the disease, while economic and social factors are important in developing relevant strategies for prevention and treatment. The suggested research needs include better methods for description and recording, clinical studies, understanding cultural impacts, prevention strategies, and the integrated organisation of care. Specific fields proposed for research are listed.</p> <p>Conclusions</p> <p>Our paper contributes to transparency in the process of priority-setting for health research in Africa. Although the European Union Seventh Framework Research Programme prioritises biomedical and clinical research, research for Africa should also address broader social and cultural research and intervention research for greatest impact. Research policy leaders in Africa must engage national governments and international agencies as well as service providers and research communities. None can act effectively alone. Bringing together the different stakeholders, and feeding the results through to the European Union research programme is a valuable contribution of CAAST-Net.</p

APCR, factor V gene known and novel SNPs and adverse pregnancy outcomes in an Irish cohort of pregnant women

<p>Abstract</p> <p>Background</p> <p>Activated Protein C Resistance (APCR), a poor anticoagulant response of APC in haemostasis, is the commonest heritable thrombophilia. Adverse outcomes during pregnancy have been linked to APCR. This study determined the frequency of APCR, factor V gene known and novel SNPs and adverse outcomes in a group of pregnant women.</p> <p>Methods</p> <p>Blood samples collected from 907 pregnant women were tested using the Coatest^®Classic and Modified functional haematological tests to establish the frequency of APCR. PCR-Restriction Enzyme Analysis (PCR-REA), PCR-DNA probe hybridisation analysis and DNA sequencing were used for molecular screening of known mutations in the factor V gene in subjects determined to have APCR based on the Coatest^®Classic and/or Modified functional haematological tests. Glycosylase Mediated Polymorphism Detection (GMPD), a SNP screening technique and DNA sequencing, were used to identify SNPs in the factor V gene of 5 APCR subjects.</p> <p>Results</p> <p>Sixteen percent of the study group had an APCR phenotype. Factor V Leiden (FVL), FV Cambridge, and haplotype (H) R2 alleles were identified in this group. Thirty-three SNPs; 9 silent SNPs and 24 missense SNPs, of which 20 SNPs were novel, were identified in the 5 APCR subjects. Adverse pregnancy outcomes were found at a frequency of 35% in the group with APCR based on Classic Coatest^®test only and at 45% in the group with APCR based on the Modified Coatest^®test. Forty-eight percent of subjects with FVL had adverse outcomes while in the group of subjects with no FVL, adverse outcomes occurred at a frequency of 37%.</p> <p>Conclusions</p> <p>Known mutations and novel SNPs in the factor V gene were identified in the study cohort determined to have APCR in pregnancy. Further studies are required to investigate the contribution of these novel SNPs to the APCR phenotype. Adverse outcomes including early pregnancy loss (EPL), preeclampsia (PET) and intrauterine growth restriction (IGUR) were not significantly more frequent in subjects with APCR compared to normal pregnant women however Pregnancy induced hypertension (PIH) was found to be associated with FVL in our study group.</p

The HIV-associated tuberculosis epidemic--when will we act?

Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in affected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensified tuberculosis case finding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be effective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past