The emerging roles of DNA methylation in the clinical management of prostate cancer

Aberrant DNA methylation is one of the hallmarks of carcinogenesis and has been recognized in cancer cells for more than 20 years. The role of DNA methylation in malignant transformation of the prostate has been intensely studied, from its contribution to the early stages of tumour development to the advanced stages of androgen independence. The most significant advances have involved the discovery of numerous targets such as GSTP1, Ras-association domain family 1A (RASSF1A) and retinoic acid receptor beta2 (RARbeta2) that become inactivated through promoter hypermethylation during the course of disease initiation and progression. This has provided the basis for translational research into methylation biomarkers for early detection and prognosis of prostate cancer. Investigations into the causes of these methylation events have yielded little definitive data. Aberrant hypomethylation and how it impacts upon prostate cancer has been less well studied. Herein we discuss the major developments in the fields of prostate cancer and DNA methylation, and how this epigenetic modification can be harnessed to address some of the key issues impeding the successful clinical management of prostate cancer.

Workplace accommodation for older teachers in Japan and Germany: The role of the institutional context in supporting late career options for teachers with ill-health

Due to population ageing, Japan and Germany have to extend individuals´ working lives. However, disability increases with old-age. Workplace accommodation is a means to enable disabled individuals to remain productively employed. Drawing on qualitative interview data, this paper explores how School Authorities in these countries use workplace accommodation to support ill teachers, a white-collar profession strongly affected by (mental) ill-health. It furthermore explores how such measures influence older teachers´ career expectations and outcomes. It finds that even though the institutional contexts are similar, career options and expectations vary, though with similar (negative) outcomes for national strategies to extend working lives.

Strategies to improve the accuracy of vision measurement by teachers in rural Chinese secondary schoolchildren: Xichang Pediatric Refractive Error Study (X-PRES) report no. 6.

OBJECTIVE: To assess and improve the accuracy of lay screeners compared with vision professionals in detecting visual impairment in secondary schoolchildren in rural China. METHODS: After brief training, 32 teachers and a team of vision professionals independently measured vision in 1892 children in Xichang. The children also underwent vision measurement by health technicians in a concurrent government screening program. RESULTS: Of 32 teachers, 28 (87.5%) believed that teacher screening was worthwhile. Sensitivity (93.5%) and specificity (91.2%) of teachers detecting uncorrected presenting visual acuity of 20/40 or less were better than for presenting visual acuity (sensitivity, 85.2%; specificity, 84.8%). Failure of teachers to identify children owning but not wearing glasses and teacher bias toward better vision in children wearing glasses explain the worse results for initial vision. Wearing glasses was the student factor most strongly predictive of inaccurate teacher screening (P < .001). The sensitivity and specificity of the government screening program detecting low presenting visual acuity were 86.7% and 28.7%, respectively. CONCLUSIONS: Teacher vision screening after brief training can achieve accurate results in this setting, and there is support among teachers for screening. Screening of uncorrected rather than presenting visual acuity is recommended in settings with a high prevalence of corrected and uncorrected refractive error. Low specificity in the government program renders it ineffective.

Attitudes of students, parents, and teachers toward glasses use in rural China.

OBJECTIVE:

To use focus groups to understand barriers to glasses use among children in rural China.

METHODS:

Separate focus groups were conducted between December 17, 2007, and August 5, 2008, for the following 3 groups at each of 3 schools in rural China: children aged 14 to 18 years with myopia of less than -0.5 diopters in both eyes, those children's parents, and those children's teachers. Participants were also asked to rank their responses to questions about glasses use. The focus group transcripts were coded independently by 2 investigators using qualitative data management software.

RESULTS:

Respondents of all 3 types indicated that glasses purchase and wear should be delayed in children with early myopia and might be harmful to the eyes. Parents and students reported being uncertain about children's actual myopia status and whether glasses should be worn. Parents ranked their most common reason for not buying glasses as being "too busy with work," whereas "too expensive" ranked low. Inconvenience was ranked as an important reason for not wearing glasses among all 3 student groups. "Accuracy of lens power" was the first-ranked requirement for glasses among all student groups, whereas "new and attractive styles" was ranked last by all. All 3 types of respondents believed that wearing glasses or failing to wear them might worsen myopia.

CONCLUSIONS:

Educational programs are needed to address significant knowledge gaps in families and schools about glasses use in rural China. Cost and the need for attractive styles may not be significant barriers to use in this setting, raising the possibility of paying for such programs through cost recovery.

Exogenous RNA interference exposes contrasting roles for sugar exudation in host-finding by plant pathogens

Plant parasitic nematodes (PPN) locate host plants by following concentration gradients of root exudate chemicals in the soil. We present a simple method for RNA interference (RNAi)-induced knockdown of genes in tomato seedling roots, facilitating the study of root exudate composition, and PPN responses. Knockdown of sugar transporter genes, STP1 and STP2, in tomato seedlings triggered corresponding reductions of glucose and fructose, but not xylose, in collected root exudate. This corresponded directly with reduced infectivity and stylet thrusting of the promiscuous PPN Meloidogyne incognita, however we observed no impact on the infectivity or stylet thrusting of the selective Solanaceae PPN Globodera pallida. This approach can underpin future efforts to understand the early stages of plant-pathogen interactions in tomato and potentially other crop plants.

Sequence and expression of complement factor H gene cluster variants and their roles in age-related macular degeneration risk

Purpose: To investigate how potentially functional genetic variants are coinherited on each of four common complement factor H (CFH) and CFH-related gene haplotypes and to measure expression of these genes in eye and liver tissues.

Methods: We sequenced the CFH region in four individuals (one homozygote for each of four common CFH region haplotypes) to identify all genetic variants. We studied associations between the haplotypes and AMD phenotypes in 2157 cases and 1150 controls. We examined RNA-seq profiles in macular and peripheral retina and retinal pigment epithelium/choroid/sclera (RCS) from eight eye donors and three liver samples.

Results: The haplotypic coinheritance of potentially functional variants (including missense variants, novel splice sites, and the CFHR3–CFHR1 deletion) was described for the four common haplotypes. Expression of the short and long CFH transcripts differed markedly between the retina and liver. We found no expression of any of the five CFH-related genes in the retina or RCS, in contrast to the liver, which is the main source of the circulating proteins.

Conclusions: We identified all genetic variants on common CFH region haplotypes and described their coinheritance. Understanding their functional effects will be key to developing and stratifying AMD therapies. The small scale of our expression study prevented us from investigating the relationships between CFH region haplotypes and their expression, and it will take time and collaboration to develop epidemiologic-scale studies. However, the striking difference between systemic and ocular expression of complement regulators shown in this study suggests important implications for the development of intraocular and systemic treatments.

Applied behaviour analysis: What do teachers of students with autism spectrum disorder know

With rising numbers of school-aged children with autism educated in mainstream classrooms and applied behaviour analysis (ABA) considered the basis of best practice, teachers’ knowledge in this field has become a key concern for inclusion. Self-reported knowledge of ABA of special needs teachers (n=165) was measured and compared to their actual knowledge of ABA demonstrated in accurate responses to a multiple-choice test. Findings reported here show that teachers’ self-perceived knowledge exceeded actual knowledge and that actual knowledge of ABA was not related to training received by government agency. Implications for teacher training are discussed.

How do clinicians become teachers? A communities of practice perspective.

There is widespread acceptance that clinical educators should be trained to teach, but faculty development for clinicians is undermined by poor attendance and inadequate learning transfer. As a result there has been growing interest in situating teacher development initiatives in clinical workplaces. The relationship between becoming a teacher and clinical workplace contexts is under theorised. In response, this qualitative research set out to explore how clinicians become teachers in relation to clinical communities and institutions. Using communities of practice (CoP) as a conceptual framework this research employed the sensitising concepts of regimes of competence and vertical (managerial) and horizontal (professional) planes of accountability to elucidate structural influences on teacher development. Fourteen hospital physicians completed developmental timelines and underwent semi-structured interviews, exploring their development as teachers. Despite having very different developmental pathways, participants’ descriptions of their teacher identities and practice that were remarkably congruent. Two types of CoP occupied the horizontal plane of accountability i.e. clinical teams (Firms) and communities of junior doctors (Fraternities). Participants reproduced teacher identities and practice that were congruent with CoPs’ regimes of competence in order to gain recognition and legitimacy. Participants also constructed their teacher identities in relation to institutions in the vertical plane of accountability (i.e. hospitals and medical schools). Institutions that valued teaching supported the development of teacher identities along institutionally defined lines. Where teaching was less valued, clinicians adapted their teacher identities and practices to suit institutional norms. Becoming a clinical educator entails continually negotiating one’s identity and practice between two potentially conflicting planes of accountability. Clinical CoPs are largely conservative and reproductive of teaching practice whereas accountability to institutions is potentially disruptive of teacher identity and practice.