Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women’s Heart Health Study

Aims/hypothesis  

Type 2 diabetes is associated with greater relative risk of CHD in women than in men, which is not fully explained by conventional cardiovascular risk factors. We assessed whether cardiovascular risk factors including more novel factors such as markers of insulin resistance, inflammation, activated coagulation and endothelial dysfunction differ more between diabetic and non-diabetic women than between diabetic and non-diabetic men, and the role of insulin resistance.     

Knockdown of leptin A expression dramatically alters zebrafish development

Using morpholino antisense oligonucleotide (MO) technology, we blocked leptin A or leptin receptor expression in embryonic zebrafish, and analyzed consequences of leptin A knock-down on fish development. Embryos injected with leptin A or leptin receptor MOs (leptin A or leptin receptor morphants) had smaller bodies and eyes, undeveloped inner ear, enlarged pericardial cavity, curved body and/or tail and larger yolk compared to control embryos of the same stages. The defects persisted in 6-9days old larvae. We found that blocking leptin A function had little effect on the development of early brain (1day old), but differentiation of both the morphant dorsal brain and retinal cells was severely disrupted in older (2days old) embryos. Despite the enlarged pericardial cavity, differentiation of cardiac cells appeared to be similar to control embryos. Formation of the morphants' inner ear is also severely disrupted, which corroborates existing reports of leptin receptor expression in inner ear of both zebrafish and mammals. Co-injection of leptin A MO and recombinant leptin results in partial rescue of the wild-type phenotype. Our results suggest that leptin A plays distinct roles in zebrafish development.     

The Korean version of the University of Washington Quality of Life Questionnaire for Patients with Head and Neck Cancer, and its use in an initial validation study of 56 patients

The University of Washington Quality of Life (UW-QOL) questionnaire is often used to assess health-related quality of life (HRQOL) of head and neck cancer patients. The aim of this study was to translate the UW-QOL version 4 into the Korean language and to carry out an initial validation study. A recognized methodology for translation of questionnaires was used. The validation study used the final Korean version between March and September 2009. Adult patients were recruited, with a confirmed diagnosis of head and neck cancer, therapy completed and disease-free for at least 1 year. The UW-QOL was successfully translated into Korean. 56 patients completed Korean versions of UW-QOL, the Beck Depression Inventory and the World Health Organization Quality of Life-BREF and various expected correlations were confirmed first between the two UW-QOL subscales (Spearman 0.54 p<0.001) and then of these subscales with the other concurrent measures. Lower (worse) UW-QOL scores were seen for later stage patients in all 12 domains. The Korean version of UW-QOL is ready for use in the assessment of HRQOL for Korean patients. Validation work needs to be continued to further establish psychometric properties of the questionnaire for use in this population.     

CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development

The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation, and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the hematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other hematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that depends on CLEC-2 and Syk. These studies found that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behavior in vitro.