DNA methylotype analysis in colorectal cancer

The methylation status of a gene promoter is considered to be an important mechanism for the development of many tumors, including colorectal cancer. Recent studies have shown that specific patterns of DNA methylation across multiple CpG loci in some human tumors are more informative than the detection of one single CpG locus in tumor genomes. In the present study, multiple CpG methylations of three genes (CDKN2A, DPYD and MLH1) were detected in DNA samples from patients with colorectal cancer using Pyrosequencing(®) technology. The bisulfite-converted DNA was amplified with a nested PCR and five or six CpG loci of each gene were assessed to determine DNA methylotype. Our data showed that 10/49 (20.4%), 6/48 (12.5%) and 14/49 (28.6%) of tumors were methylated with a DNA methylation level >0.2 in CDKN2A, DPYD and MLH1, respectively. Our study indicated a similar DNA methylation level across the multiple CpG loci for all three genes in the methylated tumor DNA samples, demonstrating a dichotomous trait in DNA methylation. The tumor DNA samples had unique DNA methylation patterns, which were high-degree and multiple-site methylation, but the normal DNA samples had no or a low-degree and dispersed single-site methylation. In addition, an inverse correlation in those methylated tumors was observed between DNA methylation and RNA expression for MLH1 (R(S)=−0.62, P=0.003), but not for CDKN2A and DPYD. In conclusion, distinctive DNA methylotypes exist in colorectal cancer and may depict a distinct biology in apparently homogeneous tumors

Uptake of hepatitis C specialist services and treatment following diagnosis by dried blood spot in Scotland

Background: Dried blood spot (DBS) testing for hepatitis C (HCV) was introduced to Scotland in 2009. This minimally invasive specimen provides an alternative to venipuncture and can overcome barriers to testing in people who inject drugs (PWID). Objectives: The objective of this study was to determine rates and predictors of: exposure to HCV, attendance at specialist clinics and anti-viral treatment initiation among the DBS tested population in Scotland. Study design: DBS testing records were deterministically linked to the Scottish HCV Clinical database prior to logistic regression analysis. Results: In the first two years of usage in Scotland, 1322 individuals were tested by DBS of which 476 were found to have an active HCV infection. Linkage analysis showed that 32% had attended a specialist clinic within 12 months of their specimen collection date and 18% had begun anti-viral therapy within 18 months of their specimen collection date. A significantly reduced likelihood of attendance at a specialist clinic was evident amongst younger individuals (<35 years), those of unknown ethnic origin and those not reporting injecting drug use as a risk factor. Conclusion: We conclude that DBS testing in non-clinical settings has the potential to increase diagnosis and, with sufficient support, treatment of HCV infection among PWID

Employability initiatives in undergraduate education and application to human nutrition: A scoping review

Human nutrition is a growing field with an increasing job market and high demand for university study, yet graduates report feeling underprepared for and unaware of potential job opportunities. This scoping review aimed to identify employment initiatives used in undergraduate programs to support an evidence-based approach to the development of future initiatives for human nutrition courses. The scoping review following PRISMA-ScR criteria was initially conducted in October 2018 and updated in April 2020. Search terms were selected to identify studies that reported on employability or work-readiness embedded within the course curriculum for undergraduate students. Fourteen papers met the eligibility criteria. Papers included were from Australia (9), United Kingdom (2), United States (1), New Zealand (1) and Germany (1). Papers described initiatives fitting broad categories of placements, project-based industry collaboration, practice-based eLearning, mentoring and building graduate attributes. Placements were the most common type of initiative and project-based industry collaboration demonstrated the highest levels of student and employer satisfaction. The success of initiatives was often attributed to incorporating diverse approaches to real-world, problem-solving skills. Mentoring and eLearning were used to promote employability soft skills, while industry-based placements provided students with practical experience. Placement in specific workplace settings should be representative of the diverse job options for nutrition graduates. Human nutrition degrees should consider incorporating strategies that develop soft skills and project-based skills while exposing students to diverse workplace settings within industry

An exploratory study of industry perspectives to inform undergraduate nutrition employability initiatives

Aim The aim of this study was to explore nutrition professionals' perspectives of nutrition graduates' employability skills, and knowledge and skills required in the industry to understand gaps in undergraduate nutrition curriculum. Methods Nutrition professionals (n = 26) across Australia were approached to participate in semi-structured interviews via telephone in 2018. Interviews were transcribed verbatim, data analysed using thematic analysis, and results interpreted and discussed. Results Nine participants across six work environments completed interviews. Common work roles were identified in their diverse areas of practice: nutrition educators, food developers, team members, and business leaders. Nutrition professionals identified that, in addition to evidence-based discipline knowledge, key skills and knowledge needed for their roles were interpersonal communication, including writing and listening. Participants highlighted the need for employability skills to be embedded within curriculum with emphasis on professional skills, business skills and discipline-specific skills in communicating complex science messages to a range of audiences. Networking, and formal and informal work-integrated learning were viewed as important vehicles for developing required skills. Participants expected that universities develop curriculum to address gaps; however, reflection by the academic researchers suggested this should be a joint role. Conclusions Early career planning, professional skill development, work experience and networking opportunities should enhance graduate employability

The prevalence of hepatitis C virus among people of South Asian origin in Glasgow: results from a community based survey and laboratory surveillance

Background South Asians often present late with HCV or HBV related liver disease which could have been avoided with early diagnosis and subsequent treatment; however the prevalence of HCV/HBV among South Asians in Glasgow is not known. Accordingly, to inform the need for case finding among this group we aimed to examine the prevalence of Hepatitis C virus (HCV) among South Asians living in Glasgow. Methods A community-based survey recruited individuals at six mosques and four community centres serving the South Asian community during 2009-2010; participants had predominantly never been HCV tested. Laboratory surveillance data involving all individuals tested for HCV during 1993-2009 were examined and South Asians were identified using Nam Pehchan software. Results In the community-based survey, 2.6% of 1288 participants tested HCV-antibody positive; the prevalence ranged from 0.6% among those born in the UK to 3.1% among those born in Pakistan. The odds of testing HCV-antibody positive were significantly raised among those who had surgery in South Asia (aOR: 5.0, 95% CI: 2.0-12.3) and had either medical/dental treatment or an injection in South Asia (aOR: 2.2, 95% CI: 1.0-5.0). Of 6404 South Asians identified from laboratory surveillance data, 9.3% tested HCV positive. An estimated 38% (330/870) of HCV-infected South Asians living in Glasgow remain undiagnosed. Conclusions South Asians living in Glasgow, particularly those born outside the UK are at greater risk of HCV infection than the general population. Efforts to increase awareness and testing in this population are warranted.</p

A Phase II Study of Irinotecan and Carboplatin in Advanced Non-small Cell Lung Cancer with Pharmacogenomic Analysis: Final Report

PurposeWe conducted a phase II study of carboplatin and irinotecan in patients with advanced non-small cell lung cancer (NSCLC). In addition, we studied the correlation between certain genotypes of enzymes involved in irinotecan metabolism with efficacy and toxicity.Patients and MethodsPatients with stage IIIB, IV, or recurrent NSCLC received a combination of irinotecan and carboplatin every 3 weeks at a dose of 200 mg/m2 and area under the curve of 5. Pharmacogenomic analysis was performed on several genes of interest (ABCB1, CYP3A4*1B, ERCC2, GSTP1, UGT1A1*28, and XRCC1).ResultsForty-two patients enrolled between December 2001 and January 2004. Six patients achieved partial responses (14%), and 19 (45%) had stable disease. The median progression-free survival was 6.9 months. The median overall survival was 11.7 months, with 1-year overall survival of 42%. The most common toxicities were hematologic; grade 3 or 4 neutropenia was experienced by 26 patients (62%) during treatment, and 15 patients (36%) experienced grade 3 or 4 thrombocytopenia. The homozygous UGT1A1*28 (7/7) genotype was associated with grade 4 neutropenia in three of four patients (75%), but only eight out of 30 (27%) with 6/6 or 6/7 genotypes experienced grade 4 neutropenia (p = 0.09). None of the 14 patients with the GSTP1 I105V A/A genotype had a partial response, as opposed to five out of 19 (26%) of those with the G/A or G/G genotypes (p = 0.057).ConclusionThe combination of carboplatin and irinotecan is an active combination in NSCLC, with response rates comparable with other platinum-containing doublets. Further studies with irinotecan should incorporate prospective pharmacogenomic analysis to identify markers for response and toxicity