Genetic and Functional Assessment of the Role of the rs13431652-A and rs573225-A Alleles in the G6PC2 Promoter That Are Strongly Associated With Elevated Fasting Glucose Levels

OBJECTIVE Genome-wide association studies have identified a single nucleotide polymorphism (SNP), rs560887, located in a G6PC2 intron that is highly correlated with variations in fasting plasma glucose (FPG). G6PC2 encodes an islet-specific glucose-6-phosphatase catalytic subunit. This study examines the contribution of two G6PC2 promoter SNPs, rs13431652 and rs573225, to the association signal. RESEARCH DESIGN AND METHODS We genotyped 9,532 normal FPG participants (FPG <6.1 mmol/l) for three G6PC2 SNPs, rs13431652 (distal promoter), rs573225 (proximal promoter), rs560887 (3rd intron). We used regression analyses adjusted for age, sex, and BMI to assess the association with FPG and haplotype analyses to assess comparative SNP contributions. Fusion gene and gel retardation analyses characterized the effect of rs13431652 and rs573225 on G6PC2 promoter activity and transcription factor binding. RESULTS Genetic analyses provide evidence for a strong contribution of the promoter SNPs to FPG variability at the G6PC2 locus (rs13431652: β = 0.075, P = 3.6 × 10−35; rs573225 β = 0.073 P = 3.6 × 10−34), in addition to rs560887 (β = 0.071, P = 1.2 × 10−31). The rs13431652-A and rs573225-A alleles promote increased NF-Y and Foxa2 binding, respectively. The rs13431652-A allele is associated with increased FPG and elevated promoter activity, consistent with the function of G6PC2 in pancreatic islets. In contrast, the rs573225-A allele is associated with elevated FPG but reduced promoter activity. CONCLUSIONS Genetic and in situ functional data support a potential role for rs13431652, but not rs573225, as a causative SNP linking G6PC2 to variations in FPG, though a causative role for rs573225 in vivo cannot be ruled out

Imaging of bronchial pathology in antibody deficiency: Data from the European Chest CT Group

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.</p

Painting the Body: Feminist Musings on Visual Autographies

In this paper I look at autographical depictions of the body in the work of Mato Ioannidou, a Greek woman artist, who participated in a wider narrative-based project on visual and textual entanglements between life and art. The paper unfolds in three parts: first, I give an overview of Ioannidou’s artwork, making connections with significant events in her life; then I discuss feminist theorizations of embodiment and visual auto/biography; and finally I draw on insights from Spinozist feminist philosophers to discuss the artist’s portrayal of women’s bodies in three cycles of her work. What I argue is that the body becomes a centerpiece in the attempt to perceive connections between life and art through expressionism rather than representation

Effects of multiple stressors on cyanobacteria abundance vary with lake type

Blooms of cyanobacteria are a current threat to global water security that is expected to increase in the future because of increasing nutrient enrichment, increasing temperature and extreme precipitation in combination with prolonged drought. However, the responses to multiple stressors, such as those above, are often complex and there is contradictory evidence as to how they may interact. Here we used broad scale data from 494 lakes in central and northern Europe, to assess how cyanobacteria respond to nutrients (phosphorus), temperature and water retention time in different types of lakes. Eight lake types were examined based on factorial combinations of major factors that determine phytoplankton composition and sensitivity to nutrients: alkalinity (low and medium‐high), colour (clear and humic) and mixing intensity (polymictic and stratified). In line with expectations, cyanobacteria increased with temperature and retention time in five of the eight lake types. Temperature effects were greatest in lake types situated at higher latitudes, suggesting that lakes currently not at risk could be affected by warming in the future. However, the sensitivity of cyanobacteria to temperature, retention time and phosphorus varied among lake types highlighting the complex responses of lakes to multiple stressors. For example, in polymictic, medium‐high alkalinity, humic lakes cyanobacteria biovolume was positively explained by retention time and a synergy between TP and temperature while in polymictic, medium‐high alkalinity, clear lakes only retention time was identified as an explanatory variable. These results show that, although climate change will need to be accounted for when managing the risk of cyanobacteria in lakes, a ‘one‐size fits‐all’ approach is not appropriate. When forecasting the response of cyanobacteria to future environmental change, including changes caused by climate and local management, it will be important to take this differential sensitivity of lakes into account

The Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICA)

To explore the various couplings across space and time and between ecosystems in a consistent manner, atmospheric modeling is moving away from the fractured limited-scale modeling strategy of the past toward a unification of the range of scales inherent in the Earth system. This paper describes the forward-looking Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICA), which is intended to become the next-generation community infrastructure for research involving atmospheric chemistry and aerosols. MUSICA will be developed collaboratively by the National Center for Atmospheric Research (NCAR) and university and government researchers, with the goal of serving the international research and applications communities. The capability of unifying various spatiotemporal scales, coupling to other Earth system components, and process-level modularization will allow advances in both fundamental and applied research in atmospheric composition, air quality, and climate and is also envisioned to become a platform that addresses the needs of policy makers and stakeholders

Emotions and Emotion Regulation in Breast Cancer Survivorship

Emotional distress in cancer patients is an important outcome; however, emotional experience does not begin and end with emotion generation. Attempts to regulate emotions may lessen their potentially negative effects on physical and psychological well-being. Researchers have called for the study of emotion regulation (ER) in health psychology and psycho-oncology. Thus, this review has three aims. First, we discuss current understandings of emotion and ER across the cancer trajectory, including the principles of ER and methods for its assessment. Second, we present a model for examining the mediating effects of ER on psychosocial outcomes. Third, we “round out” the discussion with an example: new data on the role of ER in recurrent breast cancer. Taken together, these aims illustrate the impact of affective regulatory processes on cancer patients’ long-term outcomes. As survival rates increase, long-term follow-up studies are needed to characterize the dynamic, reciprocal effects of emotion and ER for cancer survivors. Further research on ER may help women with breast cancer better manage the challenges associated with diagnosis and treatment

Multiple approaches to enhancing cancer communication in the next decade: translating research into practice and policy

Communicating risk and other health information in a clear, understandable, and actionable manner is critical for the prevention and control of cancer, as well as the care of affected individuals and their family members. However, the swift pace of development in communication technologies has dramatically changed the health communication landscape. This digital era presents new opportunities and challenges for cancer communication research and its impact on practice and policy. In this article, we examine the science of health communication focused on cancer and highlight important areas of research for the coming decade. Specifically, we discuss three domains in which cancer communication may occur: (a) among patients and their healthcare providers; (b) within and among families and social networks; and (c) across communities, populations, and the public more broadly. We underscore findings from the prior decade of cancer communication research, provide illustrative examples of future directions for cancer communication science, and conclude with considerations for diverse populations. Health informatics studies will be necessary to fully understand the growing and complex communication settings related to cancer: such works have the potential to change the face of information exchanges about cancer and elevate our collective discourse about this area as newer clinical and public health priorities emerge. Researchers from a wide array of specialties are interested in examining and improving cancer communication. These interdisciplinary perspectives can rapidly advance and help translate findings of cancer communication in the field of behavioral medicine

Health Literacy in Surgical Oncology Patients: An Observational Study at a Comprehensive Cancer Center.

BACKGROUND: Low health literacy is associated with increased resource use and poorer outcomes in medical and surgical patients with various diseases. This observational study was designed to determine (1) the prevalence of low health literacy among surgical patients with cancer at an NCI-designated Comprehensive Cancer Center (CCC), and (2) associations between health literacy and clinical outcomes. METHODS: Patients receiving surgery (N=218) for gastrointestinal (60%) or genitourinary cancers (22%) or sarcomas (18%) were recruited during their postsurgical hospitalization. Patients self-reported health literacy using the Brief Health Literacy Screening Tool (BRIEF). Clinical data (length of stay [LoS], postacute care needs, and unplanned presentation for care within 30 days) were abstracted from the electronic medical records 90 days after surgery. Multivariate linear and logistic regressions were used to examine the relationship between health literacy and clinical outcomes, adjusting for potential confounding variables. RESULTS: Of 218 participants, 31 (14%) showed low health literacy (BRIEF score ≤12). In regression analyses including 212 patients with complete data, low health literacy significantly predicted LoS (β = -1.82; 95% CI, -3.00 to -0.66; P=.002) and postacute care needs (odds ratio [OR], 0.25; 95% CI, 0.07-0.91). However, health literacy was not significantly associated with unplanned presentation for care in the 30 days after surgery (OR, 0.51; 95% CI, 0.20-1.29). CONCLUSIONS: This study demonstrates the prevalence of low health literacy in a surgical cancer population at a high-volume NCI-designated CCC and its association with important clinical outcomes, including hospital LoS and postacute care needs. Universal screening and patient navigation may be 2 approaches to mitigate the impact of low health literacy on postsurgical outcomes