Overweight and obesity on the island of Ireland: an estimation of costs

Objectives The increasing prevalence of overweight and obesity worldwide continues to compromise population health and creates a wider societal cost in terms of productivity loss and premature mortality. Despite extensive international literature on the cost of overweight and obesity, findings are inconsistent between Europe and the USA, and particularly within Europe. Studies vary on issues of focus, specific costs and methods. This study aims to estimate the healthcare and productivity costs of overweight and obesity for the island of Ireland in 2009, using both top-down and bottom-up approaches.

Methods Costs were estimated across four categories: healthcare utilisation, drug costs, work absenteeism and premature mortality. Healthcare costs were estimated using Population Attributable Fractions (PAFs). PAFs were applied to national cost data for hospital care and drug prescribing. PAFs were also applied to social welfare and national mortality data to estimate productivity costs due to absenteeism and premature mortality.

Results The healthcare costs of overweight and obesity in 2009 were estimated at €437 million for the Republic of Ireland (ROI) and €127.41 million for NI. Productivity loss due to overweight and obesity was up to €865 million for ROI and €362 million for NI. The main drivers of healthcare costs are cardiovascular disease, type II diabetes, colon cancer, stroke and gallbladder disease. In terms of absenteeism, low back pain is the main driver in both jurisdictions, and for productivity loss due to premature mortality the primary driver of cost is coronary heart disease.

Conclusions The costs are substantial, and urgent public health action is required in Ireland to address the problem of increasing prevalence of overweight and obesity, which if left unchecked will lead to unsustainable cost escalation within the health service and unacceptable societal costs.

A genomic island linked to ecotype divergence in Atlantic cod

The genomic architecture underlying ecological divergence and ecological speciation with gene flow is still largely unknown for most organisms. One central question is whether divergence is genome-wide or localized in 'genomic mosaics' during early stages when gene flow is still pronounced. Empirical work has so far been limited, and the relative impacts of gene flow and natural selection on genomic patterns have not been fully explored. Here, we use ecotypes of Atlantic cod to investigate genomic patterns of diversity and population differentiation in a natural system characterized by high gene flow and large effective population sizes, properties which theoretically could restrict divergence in local genomic regions. We identify a genomic region of strong population differentiation, extending over approximately 20 cM, between pairs of migratory and stationary ecotypes examined at two different localities. Furthermore, the region is characterized by markedly reduced levels of genetic diversity in migratory ecotype samples. The results highlight the genomic region, or 'genomic island', as potentially associated with ecological divergence and suggest the involvement of a selective sweep. Finally, we also confirm earlier findings of localized genomic differentiation in three other linkage groups associated with divergence among eastern Atlantic populations. Thus, although the underlying mechanisms are still unknown, the results suggest that 'genomic mosaics' of differentiation may even be found under high levels of gene flow and that marine fishes may provide insightful model systems for studying and identifying initial targets of selection during ecological divergence.

The role of societal norms in portion size related behaviour in Denmark and on the Island of Ireland

Purpose:
Social norms influence eating behavior, but little is known about their role in portion size-related behavior. This study
explored the role of social eating norms in Denmark (DK) and the Island of Ireland (IOI) in relation to portion size-related
behavior.

Methods:
In a survey DK (n=1063) and IOI (n=1012) respondents rated social eating norms (11 items) and portion size-related behavior
(3 items) on a 7-point scale (1=strongly disagree to 7=strongly agree). The 3 items relate to: 1) anticipating how
much will be eaten at the beginning of a meal, 2) clearing the plate, and 3) clearing the plate even when full. Sociodemographics
and eating attitudes (e.g. cognitive restraint) were measured as background variables

Results:
Two social eating factors were identified: The ‘limit intake’ norm (6 items) and the ‘plate cleaning’ norm (3 items). The
DK participants reported stronger ‘limit intake’ norms and weaker ‘plate cleaning’ norms than IOI. In both countries
females reported stronger ‘limit intake’ norms while males reported stronger ‘plate cleaning’ norms. In DK, age was
positively correlated with both social eating norm factors. The ‘limit intake’ norm had stronger association with anticipating
how much will be eaten at the beginning of a meal, but the ‘plate cleaning’ norm had stronger association with
clearing the plate. Only the ‘plate cleaning’ norm was associated with clearing the plate even when full.

Conclusions:
The social eating norms vary significantly between countries and genders. The ‘limit intake’ and ‘plate cleaning’ norms
play a role in consumers’ reported portion size-related behavior.

POU2F1 activity regulates HOXD10 and HOXD11 promoting a proliferative and invasive phenotype in head and neck cancer

HOX genes are master regulators of organ morphogenesis and cell differentiation during embryonic development, and continue to be expressed throughout post-natal life. To test the hypothesis that HOX genes are dysregulated in head and neck squamous cell carcinoma (HNSCC) we defined their expression profile, and investigated the function, transcriptional regulation and clinical relevance of a subset of highly expressed HOXD genes. Two HOXD genes, D10 and D11, showed strikingly high levels in HNSCC cell lines, patient tumor samples and publicly available datasets. Knockdown of HOXD10 in HNSCC cells caused decreased proliferation and invasion, whereas knockdown of HOXD11 reduced only invasion. POU2F1 consensus sequences were identified in the 5' DNA of HOXD10 and D11. Knockdown of POU2F1 significantly reduced expression of HOXD10 and D11 and inhibited HNSCC proliferation. Luciferase reporter constructs of the HOXD10 and D11 promoters confirmed that POU2F1 consensus binding sites are required for optimal promoter activity. Utilizing patient tumor samples a significant association was found between immunohistochemical staining of HOXD10 and both the overall and the disease-specific survival, adding further support that HOXD10 is dysregulated in head and neck cancer. Additional studies are now warranted to fully evaluate HOXD10 as a prognostic tool in head and neck cancers.

Potential impacts of climate change on agriculture and food safety within the island of Ireland

Climate and other environmental change presents a number of challenges for effective food safety. Food production, distribution and consumption takes place within functioning ecosystems but this backdrop is often ignored or treated as static and unchanging. The risks presented by environmental change include novel pests and diseases, often caused by problem species expanding their spatial distributions as they track changing conditions, toxin generation in crops, direct effects on crop and animal production, consequences for trade networks driven by shifting economic viability of production methods in changing environments and finally, wholesale transformation of ecosystems as they respond to novel climatic regimes.

Vitamin D3 suppresses morphological evolution of the cribriform cancerous phenotype

Development of cribriform morphology (CM) heralds malignant change in human colon but lack of mechanistic understanding hampers preventive therapy. This study investigated CM pathobiology in three-dimensional (3D) Caco-2 culture models of colorectal glandular architecture, assessed translational relevance and tested effects of 1,25(OH)2D3, the active form of vitamin D. CM evolution was driven by oncogenic perturbation of the apical polarity (AP) complex comprising PTEN, CDC42 and PRKCZ (phosphatase and tensin homolog, cell division cycle 42 and protein kinase C zeta). Suppression of AP genes initiated a spatiotemporal cascade of mitotic spindle misorientation, apical membrane misalignment and aberrant epithelial configuration. Collectively, these events promoted “Swiss cheese-like” cribriform morphology (CM) comprising multiple abnormal “back to back” lumens surrounded by atypical stratified epithelium, in 3D colorectal gland models. Intestinal cancer driven purely by PTEN-deficiency in transgenic mice developed CM and in human CRC, CM associated with PTEN and PRKCZ readouts. Treatment of PTEN-deficient 3D cultures with 1,25(OH)2D3 upregulated PTEN, rapidly activated CDC42 and PRKCZ, corrected mitotic spindle alignment and suppressed CM development. Conversely, mutationally-activated KRAS blocked 1,25(OH)2D3 rescue of glandular architecture. We conclude that 1,25(OH)2D3 upregulates AP signalling to reverse CM in a KRAS wild type (wt), clinically predictive CRC model system. Vitamin D could be developed as therapy to suppress inception or progression of a subset of colorectal tumors.

Phenotype-Based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Regulator of Ocular Angiogenesis

Retinal angiogenesis is tightly regulated to meet oxygenation and nutritional requirements. In diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, uncontrolled angiogenesis can lead to blindness. Our goal is to better understand the molecular processes controlling retinal angiogenesis and discover novel drugs that inhibit retinal neovascularization. Phenotype-based chemical screens were performed using the ChemBridge Diverset^TM library and inhibition of hyaloid vessel angiogenesis in Tg(fli1:EGFP) zebrafish. 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol, (quininib) robustly inhibits developmental angiogenesis at 4–10 μM in zebrafish and significantly inhibits angiogenic tubule formation in HMEC-1 cells, angiogenic sprouting in aortic ring explants, and retinal revascularization in oxygen-induced retinopathy mice. Quininib is well tolerated in zebrafish, human cell lines, and murine eyes. Profiling screens of 153 angiogenic and inflammatory targets revealed that quininib does not directly target VEGF receptors but antagonizes cysteinyl leukotriene receptors 1 and 2 (CysLT_1–2) at micromolar IC₅₀ values. In summary, quininib is a novel anti-angiogenic small-molecule CysLT receptor antagonist. Quininib inhibits angiogenesis in a range of cell and tissue systems, revealing novel physiological roles for CysLT signaling. Quininib has potential as a novel therapeutic agent to treat ocular neovascular pathologies and may complement current anti-VEGF biological agents.