Patient-reported burden of intensified surveillance and surgery in high-risk individuals under pancreatic cancer surveillance

In high-risk individuals participating in a pancreatic cancer surveillance program, worrisome features warrant for intensified surveillance or, occasionally, surgery. Our objectives were to determine the patient-reported burden of intensified surveillance and/or surgery, and to assess post-operative quality of life and opinion of surgery. Participants in our pancreatic cancer surveillance program completed questionnaires including the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). For individuals who underwent intensified surveillance, questionnaires before, during, and ≥ 3 weeks after were analyzed. In addition, subjects who underwent intensified surveillance in the past 3 years or underwent surgery at any time, were invited for an interview, that included the Short-Form 12 (SF-12). A total of 31 high-risk individuals were studied. During the intensified surveillance period, median CWS scores were higher (14, IQR 7), as compared to before (12, IQR 9, P = 0.007) and after (11, IQR 7, P = 0.014), but eventually returned back to baseline (P = 0.823). Median HADS scores were low: 5 (IQR 6) for anxiety and 3 (IQR 5) for depression, and they were unaff

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW ($\textit{P}$  < 5 × 10$^{-8}$). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$  = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$  = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$  = 6.5 × 10$^{-9}$). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions ($\textit{P}$ = 1.9 × 10$^{-4}$). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.For a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust

Mechanisms Regulating Grain Contamination with Trichothecenes Trans located from the Stem Base of Wheat (Triticum aestivum) Infected with Fusarium culmorum

Factors limiting trichothecene contamination of mature wheat grains after Fusarium infection are of major interest in crop production. In addition to ear infection, systemic translocation of deoxynivalenol (DON) may contribute to mycotoxin levels in grains after stem base infection with toxigenic Fusarium spp. However, the exact and potential mechanisms regulating DON translocation into wheat grains from the plant base are still unknown. We analyzed two wheat cultivars differing in susceptibility to Fusarium head blight (FHB), which were infected at the stem base with Fusarium culmorum in climate chamber experiments. Fungal DNA was found only in the infected stem base tissue, whereas DON and its derivative, DON-3-glucoside (D3G), were detected in upper plant parts. Although infected stem bases contained more than 10,000 mu g kg(-1) dry weight (DW) of DON and mean levels of DON after translocation in the ear and husks reached 1,900 mu g kg(-1) DW, no DON or D3G was detectable in mature grains. D3G quantification revealed that DON detoxification took mainly place in the stem basis, where &lt;= 50% of DON was metabolized into D3G. Enhanced expression of a gene putatively encoding a uridine diphosphate-glycosyltransferase (GenBank accession number FG985273) was observed in the stein base after infection with F. culmorum. Resistance to F. culmorum stem base infection, DON glycosylation in the stem base, and mycotoxin translocation were unrelated to cultivar resistance to FHB. Histological studies demonstrated that the vascular transport of DON labeled with fluorescein as a tracer from the peduncle to the grain was interrupted by a barrier zone at the interface between grain and rachilla, formerly described as "xylem discontinuity". This is the first study to demonstrate the effective control of influx of systemically translocated fungal mycotoxins into grains at the rachilla-seed interface by the xylem discontinuity tissue in wheat ears.Agency for Renewable Resources (FNR