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Hemochromatosis gene (HFE)-associated hereditary hemochromatosis (HH) is a genetic predisposition to iron overload and subsequent signs and symptoms of disease that potentially affects approximately 80,000 persons in Australia and almost 1 million persons in the United States. Most clinical cases are homozygous for the Cys282Tyr (C282Y) mutation in the HFE gene, with serum ferritin (SF) concentration >1000 lg/L as the strongest predictor of cirrhosis. The optimal treatment regimen for those with SF concentrations above the normal range but <1000 lg/L is unknown. We assessed HFE mutations in a prospective cohort of 31,192 participants of northern European descent, aged 40-69 years. An HFE-stratified random sample of 1438 participants including all C282Y homozygotes with iron studies 12 years apart were examined by physicians blinded to participants' HFE genotype. All previously undiagnosed C282Y homozygotes (35 male, 67 female) and all HFE wild-types (131 male, 160 female) with baseline and follow-up SF concentrations <1000 lg/L were assessed for HH-associated signs and symptoms including abnormal second/third metacarpophalangeal joints (MCP2/3), raised liver enzymes, hepatomegaly, and self-reported liver disease, fatigue, diabetes mellitus, and use of arthritis medication. The prevalence of HH-associated signs and symptoms was similar for C282Y homozygotes and HFE wild-types for both normal and moderately elevated SF concentrations. The maximum prevalence difference between HFE genotype groups with moderately elevated SF was 11% (MCP2/3, 95% confidence interval 5 26%, 29%; P 5 0.22) and for normal SF was 6% (arthritis medicine use, 95% confidence interval 5 23%, 16%; P 5 0.11). Conclusion: Previously undiagnosed C282Y homozygotes with SF concentrations that remain below 1000 lg/L are at low risk of developing HH-associated signs and symptoms at an age when disease would be expected to have developed. These observations have implications for the management of C282Y homozygotes. (HEPATOLOGY 2010;52:925-933)

Maternal thyrotoxicosis, predominantly secondary to Graves' disease, affects 0.2% of all pregnancies. The Endocrine Society guidelines recommend the use of propylthiouracil as a first-line drug for thyrotoxicosis in pregnancy because of associations between carbimazole or methimazole and congenital anomalies. However, recent studies have highlighted the risk of severe liver injury with propylthiouracil. Here, we report another case with multiple congenital anomalies following in utero exposure to carbimazole and review the literature to consider the risks and benefits of available pharmacological treatments for thyrotoxicosis in pregnancy.

Environmental DNA reveals links between abundance and composition of airborne grass pollen and respiratory health Highlights d Airborne grass pollen assemblages are quantitatively structured in space and time d The respiratory health impacts of grass pollen may vary according to grass species

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describes a series of discussion panels held at the University of Illinois at Urbana-Champaign that helped the campus community learn more about the varied experiences of the student veterans in their midst and supported the student veterans in having a positive voice on campus.

Growth of pancreatic cancer is stimulated by gastrin in both a paracrine and an autocrine fashion. Traditional therapies have not significantly improved survival, and recently pancreatic cancer has been deemed a “cold” tumor due to its poor response to immunotherapy. Strategies to improve survival of pancreatic cancer are desperately needed. In the current investigation, we studied the effects of an anti-gastrin cancer vaccine, polyclonal antibody stimulator (PAS; formerly called G17DT and Gastrimmune), used alone or in combination with a programmed cell death receptor (PD)-1 immune checkpoint antibody on pancreatic cancer growth, metastases, and the tumor microenvironment (TME). Immune-competent female C57BL/6 mice bearing syngeneic orthotopic murine pancreatic cancer treated with PAS had significantly smaller tumors and fewer metastases. Examination of the TME demonstrated decreased fibrosis with fewer M2 and more M1 tumor-associated macrophages. Expression of the E-cadherin gene was significantly increased and expression of the TGFβR2 gene was decreased compared with controls. Mice treated with PAS or the combination of PAS and PD-1 antibody exhibited significantly less tumor expression of phospho-paxillin, the focal adhesion protein β-catenin, and matrix metalloproteinase-7. This study suggests that inhibition of the cancer-promoting effects of gastrin in pancreatic cancer can decrease metastases by altering the TME and decreasing pathways that activate the epithelial mesenchymal transition. The PAS vaccine appears to change the TME, making it more susceptible to therapy with an immune checkpoint antibody. This novel combination of two immunotherapies may improve survival of pancreatic cancer by decreasing both tumor growth and metastasis formation. NEW & NOTEWORTHY Survival from advanced pancreatic cancer is poor, in part due to dense fibrosis of the tumor microenvironment, increased number of M2-polarized macrophages that promote angiogenesis and invasion, and lack of “target-specific” therapy. Herein, we report that a tumor vaccine that selectively targets gastrin decreases pancreatic cancer growth and metastases. Furthermore, the gastrin vaccine polyclonal antibody stimulator alters the tumor microenvironment rendering it more responsive to immunotherapy with a programmed cell death receptor-1 immune checkpoint antibody.

32Grass pollen is the world's most harmful outdoor aeroallergen and sensitivity varies between 33 species. Different species of grass flower at different times, but it is not known how airborne 34 communities of grass pollen change in time and space. Persistence and high mobility of grass 35 pollen could result in increasingly diverse seasonal pollen communities. Conversely, if grass 36 pollen does not persist for an extended time in the air, shifting pollen communities would be 37 predicted throughout the summer months. Here, using targeted high throughput sequencing, 38we tracked the seasonal progression of airborne Poaceae pollen biodiversity across Britain, 39 throughout the grass allergy season. All grass genera displayed discrete, temporally restricted 40 peaks of pollen incidence which varied with latitude, revealing that the taxonomic composition 41 of grass pollen exposure changes substantially across the allergy season. By developing more 42 refined aeroallergen profiling, we predict that our findings will facilitate the exploration of links 43 between taxon-specific exposure of harmful grass pollen and disease, with concomitant socio-44 economic benefits. 45 46 47