Pre-Adolescent Cardio-Metabolic Associations and Correlates: PACMAC methodology and study protocol

Introduction: Although cardiovascular disease is typically associated with middle or old age, the atherosclerotic process often initiates early in childhood. The process of atherosclerosis appears to be occurring at an increasing rate, even in pre-adolescents, and has been linked to the childhood obesity epidemic. This study will investigate the relationships between obesity, lifestyle behaviours and cardiometabolic health in pre-pubescent children aged 8–10 years, and investigates whether there are differences in the correlates of cardiometabolic health between Māori and Caucasian children. Details of the methodological aspects of recruitment, inclusion/exclusion criteria, assessments, statistical analyses, dissemination of findings and anticipated impact are described. Methods and analysis Phase 1: a cross-sectional study design will be used to investigate relationships between obesity, lifestyle behaviours (nutrition, physical activity/fitness, sleep behaviour, psychosocial influences) and cardiometabolic health in a sample of 400 pre-pubescent (8–10 years old) children. Phase 2: in a subgroup (50 Caucasian, 50 Māori children), additional measurements of cardiometabolic health and lifestyle behaviours will be obtained to provide objective and detailed data. General linear models and logistic regression will be used to investigate the strongest correlate of (1) fatness; (2) physical activity; (3) nutritional behaviours and (4) cardiometabolic health. Ethics and dissemination Ethical approval will be obtained from the New Zealand Health and Disabilities Ethics Committee. The findings from this study will elucidate targets for decreasing obesity and improving cardiometabolic health among preadolescent children in New Zealand. The aim is to ensure an immediate impact by disseminating these findings in an applicable manner via popular media and traditional academic forums. Most importantly, results from the study will be disseminated to participating schools and relevant Māori health entities

Epigenetics: Its Understanding Is Crucial to a Sustainable Healthcare System

Understanding the molecular impact of lifestyle factors has never been so important; a period in time where there are so many adults above retirement age has been previously unknown. As a species, our life expectancy is increasing yet the period of our lives where we enjoy good health is not expanding proportionately. Over the next 50 years we will need to almost double the percentage of GDP spent on health care, largely due to the increasing incidence of obesity related chronic diseases. A greater understanding and implementation of an integrated approach to health is required. Research exploring the impact of nutritional and exercise intervention on the epigenetically flexible genome is up front in terms of addressing healthy aging. Alongside this, we need a greater understanding of the interaction with our immune and nervous systems in preserving and maintaining health and cognition

De novo transcriptome assembly, functional annotation and differential gene expression analysis of juvenile and adult E. fetida, a model oligochaete used in ecotoxicological studies

Abstract Background Earthworms are sensitive to toxic chemicals present in the soil and so are useful indicator organisms for soil health. Eisenia fetida are commonly used in ecotoxicological studies; therefore the assembly of a baseline transcriptome is important for subsequent analyses exploring the impact of toxin exposure on genome wide gene expression. Results This paper reports on the de novo transcriptome assembly of E. fetida using Trinity, a freely available software tool. Trinotate was used to carry out functional annotation of the Trinity generated transcriptome file and the transdecoder generated peptide sequence file along with BLASTX, BLASTP and HMMER searches and were loaded into a Sqlite3 database. To identify differentially expressed transcripts; each of the original sequence files were aligned to the de novo assembled transcriptome using Bowtie and then RSEM was used to estimate expression values based on the alignment. EdgeR was used to calculate differential expression between the two conditions, with an FDR corrected P value cut off of 0.001, this returned six significantly differentially expressed genes. Initial BLASTX hits of these putative genes included hits with annelid ferritin and lysozyme proteins, as well as fungal NADH cytochrome b5 reductase and senescence associated proteins. At a cut off of P = 0.01 there were a further 26 differentially expressed genes. Conclusion These data have been made publicly available, and to our knowledge represent the most comprehensive available transcriptome for E. fetida assembled from RNA sequencing data. This provides important groundwork for subsequent ecotoxicogenomic studies exploring the impact of the environment on global gene expression in E. fetida and other earthworm species

Using NGS-methylation profiling to understand the molecular pathogenesis of young MI patients who have subsequent cardiac events

Globally, ischaemic heart disease is a major contributor to premature morbidity and mortality. A significant number of young Myocardial Infarction (MI) patients (aged <55 y) have subsequent cardiac events within a year of their index event. This study used Next Generation Sequencing (NGS) methylation to understand the pathogenesis in this subset of young MI patients, comparing them to a cohort of patients without recurrent events. Cases and controls were matched for age, gender, ethnicity, and comorbidities. Differential methylation analyses were performed on Reduced Representation Bisulphite Sequencing (RRBS) data. Across the group and within case–control pairs’ variation were analysed. Pairwise comparisons across each matched case–control pair resulted in a list of genes that were consistently significantly differentially methylated between all 16 matched pairs. This gene list was input into pathway analysis databases. Of particular relevance to cardiac pathology the following pathways were identified as over-represented in the patients with recurrent events; cell adhesion, transcription regulation and cardiac electrical conduction, specifically relating to calcium channel activity. This study looked at methylation differences between two populations of young MI patients. There were significantly different methylation profiles between the two groups studied; key pathways were identified as specifically affected in the patients with recurrent cardiac events. Matched pairwise comparisons and detailed interpretations of DNA methylation data may help to elucidate complex pathogeneses within and between clinical subtypes. Further analysis will determine whether these epigenomic differences can be useful as predictive biomarkers of clinical progression

Granular necrosis: a distinctive form of cell death in malignant tumours

Foci of necrosis are frequently seen in malignant tumours and may be due to a variety of causes. Different types of necrosis are given various names based upon their morphological features and presumed pathogenesis, such as coagulative, liquefactive and fibrinoid necrosis. Here, we propose the term 'granular necrosis' (GN) for a specific form of tumour necrosis characterised by the presence of well-defined necrotic foci being sharply demarcated from adjacent viable tumour. A constant feature is loss of architecture resulting in an amorphous necrotic mass containing granular nuclear and cytoplasmic debris, without an associated neutrophilic infiltrate. There is usually extensive karyorrhexis, which in larger tumours is more prominent at the periphery. These foci are often microscopic but may range up to several millimetres or larger in size. This distinctive form of necrosis has been erroneously given a variety of names in the literature including coagulative necrosis and microscopic necrosis, which on the basis of the aforementioned gross and microscopic findings is inappropriate. It is apparent that this is a specific form of necrosis, hence the descriptive term 'granular necrosis' that differentiates this form of necrosis from other types. The presence of GN is recognised as occurring in a variety of tumour types, being commonly seen in renal cell carcinoma, where it has been shown to have independent prognostic significance. In some epithelial and stromal tumours of the uterus, the presence of GN also has prognostic significance and is a defining feature for the differentiation of uterine leiomyoma and leiomyosarcoma. The pathogenesis of GN is unresolved. It does not show the features of apoptosis and in recent studies has been shown to have some of the molecular changes associated with necroptosis

Intraductal carcinoma of the prostate is an aggressive form of invasive carcinoma and should be graded

Infiltration of the prostatic ducts by prostatic adenocarcinoma occurs relatively frequently, being most commonly associated with high grade disease. It is now recognised that intraductal carcinoma of the prostate (IDCP) has an associated poor prognosis and this is reflected in its histological, molecular and immunohistochemical features. The current recommendation of the World Health Organization is that IDCP not be taken into consideration when grading prostate adenocarcinoma. It is apparent that Gleason did not differentiate between IDCP and stromal invasive carcinoma when developing and validating his grading system, and recent studies suggest that the incorporation of IDCP grading into the overall grading of the specimen provides additional prognostic information