Allelic variants of KLK2 gene predict presence of prostate cancer at biopsy

Objective: Several single nucleotide polymorphisms associated with prostate cancer risk have been reported in recent years. We evaluated polymorphisms in the human glandular kallikrein 2 (KLK2) genes because the protein product of this gene is known to be increased in prostate cancer. Materials and methods: Blood samples were collected from sixty patients who underwent prostate biopsy sectioning, and from their genomic DNA the SNPs in KLK2 gene were investigated by direct DNA sequencing. Another 138 archived prostate tissue sections were also evaluated using the TaqMan SNP genotyping assay. Results: Eighteen known SNPs were identified in the KLK2 gene. The SNPs were located in introns, coding exons and untranslated regions of the gene. Further analysis showed that two of the SNPs were associated with prostate disease. The T/T allele of rs198977 was significantly predictive of the presence of prostate cancer at biopsy and was also associated with high tumour grade. The A/A allele of rs2664155 was also significantly associated with the presence of benign hyperplasia at biopsy. Conclusion: Our results support previous reports of association of the rs198977 SNP with prostate cancer risk and also indicated a link with the disease phenotype. However, the second SNP (rs2664155) was more associated with benign hyperplasia than prostate cancer risk. The method of TaqMan SNP genotyping could be clinically useful in genetic screening and risk stratification of patients for prostate diseases

From scientist to academic developer: A story

When I started in Higher Education [HE] as a Lecturer in Biomedicine in 2002, I thought a good teacher was someone who could present their subject in an interesting manner in a PowerPoint presentation for an hour. My approach to assessment was based on the academic essays and examinations I had struggled with as a student. Through the parallel processes of being a Course Director and taking a Postgraduate Certificate [PGCert] in HE, I realised that this approach was not only far from true, but the tip of a very complex iceberg. The way I thought about students, their development, their assessment, and the support they needed to reach their potential was transformed through an inspiring developer and conversations with my peers. Collectively, we were passionate about making a difference to students at our University, and although the size of the iceberg was daunting, we were determined to chip away at it and make a difference

Health baseline comparisons and quality of life in people with cancer

This programme of research involved the development of a new health psychology concept: health baseline comparisons (HBCs). This is defined as the comparative baselines used to assess subjective health status. The following broad research questions were tested: Which HBCs are adopted by individuals with cancer?; What are the implications of different HBCs for quality of life (QoL) and other types of well-being?; How stable are HBCs throughout a course of treatment? A mixed-methodology approach was adopted to address the research questions. Five studies were conducted, all but the initial pilot study involving a clinical sample of people with cancer. A questionnaire to measure the use of different HBCs was developed and pilot tested, before being used to examine HBCs in people with breast and prostate cancer. On further refining the HBC construct, the questionnaire was re-validated and used to explore HBCs in women undergoing chemotherapy for breast cancer. The extent to which HBCs predicted QoL and psychological well-being was also examined in these studies. The stability of HBCs was sought from the same women two-months post-chemotherapy, focusing on associations with QoL and emotional well-being. The cross-sectional and longitudinal findings obtained in the first four studies were supplemented by a series of semi-structured interviews with a purposive sample of women from the longitudinal study. Interview transcripts were analysed via interpretative phenomenological analysis. Five categories of health baselines emerged from this programme of research: social; social comparison; biological; illness-specific; and turning to others. Some evidence was found that HBCs can change over time or be affected by illness and its treatment. Some HBCs, particularly social comparison and illness-specific baselines, were found to be significant predictors of QoL and psychological well-being, but the variance accounted for in these outcomes was generally small. Although the HBC questionnaire had acceptable internal consistency and reflected the experiences of people during cancer treatment and in the survivorship period, evidence was also found that the type and pattern of HBCs are subject to individual differences. This indicates that assessment of the construct also requires a qualitative and personalised component. The implications of the findings for the development of interventions are discussed and ideas for future research explored.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Prevalence of visual impairment and severity of diabetic retinopathy in various ethnic groups in the UK

Diabetic Retinopathy (DR) is a leading cause of visual impairment (VI) in the working population. Minor ethnic groups are at increased risk of diabetes. Diabetic Retinopathy In Various Ethnic groups in the United Kingdom (DRIVE UK) is a cross-sectional study to estimate the prevalence of DR, VI and associated risk factors for sight threatening diabetic retinopathy (STDR) in Afro-Caribbeans (AC) and South Asians (SA) compared to Caucasians. People with diabetes in two regions in the United Kingdom who were screened and/or treated for DR from September 2008 to September 2009 were included in this study. VI and severe visual impairment (SVI) were defined as Snellen visual acuity of ≤ 6/18 and ≤ 6/60 respectively. DR was graded according to National Screening Committee (NSC) for diabetes guidelines UK. There were 57,144 people on the diabetic register, of which retinopathy data was available from 50,285 (88.1%) subjects (type 1 n=3,323, type 2 n=46,962). In type 1 and type 2 diabetes, any DR was detected in 53.1%, 39.5%, diabetic maculopathy in 13.1%, 8.4% and STDR in 9.91%, 4.0% of people respectively. STDR was significantly more prevalent in the SA (10.3%) and AC (11.5%) populations compared to Caucasians (5.5%). Overall VI was significantly higher in the ethnic minority population. A total of 7.5% (95% CI 7.3, 7.8) people with diabetes were not eligible for driving based on their visual acuity, 3.4% (95% CI 3.2, 3.5) were classified as VI and 0.4% (95% CI 0.33, 0.44) as SVI. Risk factors for STDR were found to include longer duration of diabetes and higher mean HbA1c. This study provides information that could be used to help develop future service frameworks and guidelines for local health bodies responsible for delivery of end userservices. The study also supports the need to explore the role of inflammatory, genetic and epigenetic factors as markers for ethnic differences in DR and potential treatment avenues for diabetic retinopathy.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A systematic review protocol to identify the key benefits and associated program characteristics of community gardening for vulnerable populations

Gardening has long been a popular pastime. There is a growing evidence base for the health and well-being benefits of gardening. Community gardening brings a social aspect to gardening, thereby increasing the potential benefits to include addressing social inclusion and poor community health through sharing of values, support of others, and building networks. This systematic review protocol aims to determine the characteristics of community gardening that could lead to beneficial outcomes such as connection with the community and development of new skills. Thirteen academic databases will be searched for studies looking at the benefits of community gardening, with a focus on vulnerable populations. Data will be extracted from all studies meeting the inclusion criteria and summarized to provide an overview of the current literature. This systematic review aims to provide a comprehensive investigation into community gardening, its benefits, and how they are achieved for the target population. By gathering and synthesizing this information, the review should allow policy makers and practitioners to work more effectively to address health and social inequities, by highlighting areas of need and enabling optimization of future interventions

Identifying key benefits and characteristics of community gardening for vulnerable populations : a systematic review

Vulnerable communities (including people from refugee, Indigenous, culturally and linguistically diverse, and low socioeconomic backgrounds) represent the most at-risk populations facing inequities and negative health, economic, and social outcomes. Te recent COVID-19 pandemic both highlighted and fuelled these disparities. Community gardening has emerged as a communitybased solution to address these inequities, yet the research literature has largely considered outcomes for the general population rather than those with the most need. Tis paper represents the frst systematic review to summarise the evidence on the broad impact of community gardening on outcomes for vulnerable populations. A systematic search of 13 databases (PubMed, Medline, Scopus, ScienceDirect, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Web of Science, Academic Search Complete, Education Source, Education Resources Information Center, Psychology and Behavioral Science Collection, SocINDEX, and Allied Health and Complementary Medicine Database) for English language articles from 1985 to 2022 was conducted. Tere were 33 studies identifed where females were substantially overrepresented in the studies compared to males, and the main criteria for vulnerability included low socioeconomic-status and culturally diverse populations. Findings revealed that community gardening provides a wide range of benefts for vulnerable populations, with social connection, health, education, and nutrition being the more commonly cited. A relative emphasis on benefts of social connections, education, and nutrition is apparent for vulnerable populations in comparison to reviews considering the general population. Te quality of studies was evaluated as moderate with little information provided about program characteristics. Tese shortcomings reduce the understanding of what characteristics are most likely to result in improvements and limit the capacity of practitioners to translate research into policy and practice for vulnerable communities

Molecular basis for maize as a risk factor for oesophageal cancer in a South African population

Throughout the world squamous cell carcinoma of the oesophagus seems to be an increasing problem. There is a huge variation in prevalence globally; locations such as Japan, Iran, China and Finland can have ten times the prevalence compared to other western countries. One place that is hugely affected is Transkei, a 16,000 square mile area of South Africa. Some of the factors proposed to be implicated with squamous cell carcinoma in this region include tobacco smoking, alcohol consumption, bacterial infections and fungal infection of common food crops. In addition, the ‘Sammon theory’ links carcinogenesis in Transkei to the high consumption of maize by the population. Through a chain of reactions it is postulated that a component of maize inhibits the breakdown of growth factors, which have already been implicated in cancer. This study investigates the Transkei population and updates the Sammon theory with current research to predict a theory at a molecular level. This theory is then tested with novel research to show PGE2, shown here in high concentrations in gastric fluid samples, directly increases the proliferation of oesophageal cell lines. Gastric fluid samples from the Transkei population are then shown to have a mitogenic effect on oesophageal cells, supporting a theory that gastric fluid regurgitation commonly found in this population predisposes them to cancer. Further experimentation on the expression of related proteins shows how high PGE2 may increase its own production by increasing COX 2 expression, leading to a positive feedback loop causing constant proliferative stimulation of the oesophageal squamous tissue in the presence of the COX 2 substrate, aracadonic acid. Therefore this thesis suggests that a high maize diet provides the correct conditions for regurgitation of increased concentrations of PGE2 into the oesophagus leading to squamous hyper-proliferation over long periods of time through self stimulated production, which would normally have ceased over a much shorter time if only localised PGE2 was produced through natural restitution.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Investigations of a possible link between age-related macular degeneration and atherosclerosis

Increasing epidemiological evidence suggests a link between atherosclerosis and age-related macular degeneration (AMD). There are two main hypotheses that explain the link. One hypothesis is that AMD and atherosclerosis are tissue responses to injury. The ‘Response to Injury’ hypothesis defined as ‘abnormal reparative response to chronic, recurrent injurious stimuli’ speculates that AMD and atherosclerosis may be cellular effects of chronic or repetitive risk factors. The second hypothesis suggests that AMD is secondary to vascular insufficiency caused by atherosclerosis. The research in this thesis is an attempt to test these hypotheses to better understand the correlation of AMD and atherosclerosis. Both basic and clinical science approaches are employed. Part one focuses on the role of extracellular matrix (ECM) proteins in the pathogenesis of AMD. Both serum elastin derived peptides (S-EDP) and matrix metalloproteinases (MMP-2 and MMP-9) are raised in subjects with atherosclerosis. The circulating levels of these matrix components were tested in patients with varying degree of severity of AMD and compared to age-matched controls. Both S-EDP and MMP-9 were found to be significantly raised in patients with AMD, while MMP-2 did not correlate with it. S-EDP is elevated in abdominal aortic aneurysm (AAA), a manifestation of atherosclerosis. Since S-EDP correlates with size of both AAA and severity of AMD, this research looked at a possible association between the two diseases but found no significant correlation. The second part of this thesis investigates whether chronic inflammation may explain the co-existence of the two diseases. With the recent finding that Complement Factor H (CFH) is related to AMD, this study focused on the role of complement activation in AMD, speculating that the final common pathway of both diseases may be chronic inflammation. Increased systemic complement activation was found in neovascular AMD, as assessed by the measurement of C3a des Arg. Part three of this thesis tested the second hypothesis that AMD is secondary to the vascular insufficiency caused by atherosclerosis. Both the choroidal blood flow and retinal vessel calibre in patients with asymmetric AMD were studied and no significant changes in ocular haemodynamics were noted. In conclusion, this research favours the concept that atherosclerosis and AMD are parallel responses to chronic, recurrent injurious stimuli, with extracellular matrix remodelling and probably inflammatory response being the common cellular responses. This research did not find any significant ocular haemodynamic changes in subjects with asymmetric AMD.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

An investigation into minichromosomal maintenance proteins (MCMs) for the diagnosis of prostate cancer, as a possible alternative to prostate specific antigen (PSA)

The current strategy for the diagnosis of prostate cancer includes serum prostate specific antigen (PSA) measurement. There is however debate into its specificity and sensitivity, so new diagnostic markers are under investigation. Minichromosomal maintenance proteins (MCMs) are potential markers for the diagnosis of neoplasia, as they are involved in cellular replication. The aim of this study is to assess MCM2, 5 and 7 as new diagnostic markers for prostate cancer, to compare the clinical usefulness of PSA and to develop a less invasive technique for diagnosis. PSA specificity was investigated in several human cellular lines, and a clinical study was performed to assess expression in prostatic tissue and blood serum. MCM2, 5 and 7 was investigated by translational and transcriptional means in two prostate cell lines PNT1A and PC-3. In addition, a clinical study was performed to assess the expression of MCM2, 5 and 7 in prostate tissue, urine and blood The results suggest that PSA is not prostate specific, as it is synthesised and secreted by several non-prostatic cell lines. In addition PSA testing does not conclusively indicate neoplastic tissue and serum testing only has 63% sensitivity and 60% specificity in accurately identifying prostate cancer. The in vitro results suggest that the PC-3 cells express less MCM2, 5 and 7 on both the protein and mRNA level compared to the PNT1A cells, suggesting that MCM2, 5 and 7 maybe performing a bigger role than just replication of DNA. The tissue results indicate that there is an increase in MCM2, 5 and 7 epithelial nuclei staining for neoplastic condition compared to BPH. While the clinical study on urine sediment indicates increased MCM2, 5 and 7 staining in prostatic neoplasia compared to BPH and the transcriptional study on MCM5 can identify neoplastic tissue from BPH as 11/12 cancerous patients expressed MCM5 compared to only 3/23 BPH patients. Finally the transcriptional study on the blood samples is inconclusive and need to be repeated These results suggest that serum PSA testing is not ideal for the diagnosis of prostate cancer, that MCM2, 5 and 7 appear to have potential as new diagnostic markers and may aid the histopathologist to allocate Gleason score. Also the MCMs may have potential in the development of a less invasive technique through the use of urine sediment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Medical Students and Pandemic Influenza

To assess knowledge of pandemic influenza, we administered a questionnaire to all medical students at the University of Alberta; 354 (69%) of 510 students responded. Data from questionnaires such as this could help determine the role of medical students during a public health emergency