Towards accurate and precise T1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions

Mapping of the longitudinal relaxation time (T1) and extracellular volume (ECV) offers a means of identifying pathological changes in myocardial tissue, including diffuse changes that may be invisible to existing T1-weighted methods. This technique has recently shown strong clinical utility for pathologies such as Anderson- Fabry disease and amyloidosis and has generated clinical interest as a possible means of detecting small changes in diffuse fibrosis; however, scatter in T1 and ECV estimates offers challenges for detecting these changes, and bias limits comparisons between sites and vendors. There are several technical and physiological pitfalls that influence the accuracy (bias) and precision (repeatability) of T1 and ECV mapping methods. The goal of this review is to describe the most significant of these, and detail current solutions, in order to aid scientists and clinicians to maximise the utility of T1 mapping in their clinical or research setting. A detailed summary of technical and physiological factors, issues relating to contrast agents, and specific disease-related issues is provided, along with some considerations on the future directions of the field. Towards accurate and precise T1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions. Available from: https://www.researchgate.net/publication/317548806_Towards_accurate_and_precise_T1_and_extracellular_volume_mapping_in_the_myocardium_a_guide_to_current_pitfalls_and_their_solutions [accessed Jun 13, 2017]

Transcriptional Profiling of Human Liver Identifies Sex-Biased Genes Associated with Polygenic Dyslipidemia and Coronary Artery Disease

Sex-differences in human liver gene expression were characterized on a genome-wide scale using a large liver sample collection, allowing for detection of small expression differences with high statistical power. 1,249 sex-biased genes were identified, 70% showing higher expression in females. Chromosomal bias was apparent, with female-biased genes enriched on chrX and male-biased genes enriched on chrY and chr19, where 11 male-biased zinc-finger KRAB-repressor domain genes are distributed in six clusters. Top biological functions and diseases significantly enriched in sex-biased genes include transcription, chromatin organization and modification, sexual reproduction, lipid metabolism and cardiovascular disease. Notably, sex-biased genes are enriched at loci associated with polygenic dyslipidemia and coronary artery disease in genome-wide association studies. Moreover, of the 8 sex-biased genes at these loci, 4 have been directly linked to monogenic disorders of lipid metabolism and show an expression profile in females (elevated expression of ABCA1, APOA5 and LDLR; reduced expression of LIPC) that is consistent with the lower female risk of coronary artery disease. Female-biased expression was also observed for CYP7A1, which is activated by drugs used to treat hypercholesterolemia. Several sex-biased drug-metabolizing enzyme genes were identified, including members of the CYP, UGT, GPX and ALDH families. Half of 879 mouse orthologs, including many genes of lipid metabolism and homeostasis, show growth hormone-regulated sex-biased expression in mouse liver, suggesting growth hormone might play a similar regulatory role in human liver. Finally, the evolutionary rate of protein coding regions for human-mouse orthologs, revealed by dN/dS ratio, is significantly higher for genes showing the same sex-bias in both species than for non-sex-biased genes. These findings establish that human hepatic sex differences are widespread and affect diverse cell metabolic processes, and may help explain sex differences in lipid profiles associated with sex differential risk of coronary artery disease

How Important is the Timing of Radioiodine Ablation in Differentiated Thyroidal Carcinomas: A Referral Centre Experience.

INTRODUCTION: It's difficult to make a scientific, evidence-based approach about the timing of radioiodine remnant ablation (RRA) in patients with differentiated thyroid carcinomas (DTCs). Primary aim of the study was to reveal whether timing of RRA relates to achievement of non- structurally incomplete response (non-SIR) in low/intermediate and high-risk patients. Another aim was to reveal the correlation of timing with non-SIR status in reproductive-age women. MATERIALS AND METHODS: Records of 279 low, intermediate, and high-risk patients were analysed, retrospectively. Number of days between surgery and RRA is referred to as timing. Low/intermediate-risk patients, high-risk patients, and low/intermediate-risk reproductive-age women were divided into non-SIR and SIR groups, according to 2015 American Thyroid Association guidelines for therapy response. The relationship between timing and therapy response was analysed statistically. RESULTS: We could not find any significant relationship in patients with low/intermediate risk between timing and non-SIR, including women between 18-49 years of age (p >0.1). For high-risk patients, we found a statistically significant relationship between timing and non-SIR response. According to ROC analysis, RRA ≤58 days was found as a cut-off value. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated as 83.3%, 70.0%, 2.78, and 0.24, respectively. CONCLUSION: RRA must be initiated within 58 days after surgery in patients with high-risk DTCs. Under this approach, risk of SIR and associated mortality risk may be reduced. RRA timing for women in reproductive ages with low/intermediate risk groups may be planned according to their pregnancy/breastfeeding intent. For other low/intermediate risk groups, they can safely proceed according to the capacity of the medical facility and related logistical considerations