Description: Background: Patients with chronic hepatitis B virus infection (CHB) usually mount a modest T cell response against HBV epitopes. In order to determine immunogenic epitopes of HBV recognized by HBV-specific T cells, previous studies focused on previously confirmed HBV epitopes and assessed the T cell response by the number of HBV-specific T cells by IFN-γ ELISPOT. Methods: We studied T cell functionality by combined in silico methods predicting HBV-specific epitopes and experimental investigations on the recognition of these epitopes. 30 chronic CHB patients and 10 patients with resolved HBV (RHB) were included in the study. We identified epitopes from the literature and by in silico analysis. These were evaluated for immunogenicity by use of synthetic peptides representing the epitopes through exposure to PBMCs from patients with CHB or RHB by IFN-γ ELISPOT. The number of IFN-γ producing cells (SFC), mean spot size (MSS) and stimulation index (SI) were recorded. Results: The frequency of HBV-specific T cells producing IFN-γ after stimulation with HBV epitopes was similar in CHB and RHB patients. CHB patients had a higher MSS SI than RHB patients. Patients not carrying the HLA-A2 genotype had higher SFC SI and MSS SI. Patients with HLA-A11 had higher MSS SI compared to non- HLA-A11 allele patients. HBeAg-positive patients had a lower MSS SI, and none of the HBeAg positive patients had the HLA-A11 genotype. We found 3 immunogenic epitopes not described previously. Conclusion: IFN-γ ELISPOT-determined MSS is an efficient marker for T cell recognition of epitopes. This experimental measure showed the in silico analysis for epitope prediction to be a valuable tool in future studies on HLA genotypes and HBV epitopes. This way our study now points to previously unappreciated consequences of carrying the HLA-A11 allele in terms of stronger immunity to HBV.

Description: Article Comprehensive elucidation of metal-support interactions is important for controlling and improving their performances in a range of pertinent technologies. Here, the authors reveal how subsurface defects influence the adhesion and wetting of a metal on the surface of a metal oxide. Nature Communications doi: 10.1038/ncomms9845 Authors: Igor Beinik, Matti Hellström, Thomas N. Jensen, Peter Broqvist, Jeppe V. Lauritsen

Description: A restored riparian zone was characterized to understand the effects of flooding on subsurface hydrological flow paths and nitrate removal in groundwater. Field and laboratory investigations were combined with numerical modeling of dynamic flow and reactive nitrate transport. Flooding enhances nitrate removal in groundwater primarily by two mechanisms. First, by creating a stagnant flow zone beneath the flooded area thereby increasing the residence time and leaving more time for nitrate removal. Secondly, nitrate removal is increased by enhancing upward flow into the highly reactive organic-rich top layers. Flooding therefore contributes to nitrate removal in “hot spots”, where nitrate is transported to the peat and during “hot moments”, when flow is stagnant. The permeability of the capping peat layer relative to the aquifer is important as it controls both mechanisms. The model shows that the deep-seated nitrate removal is greater than projected from the laboratory nitrate reduction experiments. This article is protected by copyright. All rights reserved.

Description: ABSTRACT Mycotoxins are fungi-born metabolites that can contaminate foods through mould-infected crops. They are a significant food/feed-safety issue across the globe and represent a substantial financial burden for the world economy. Moreover, with a changing climate and fungal biota, there is now much discussion about emerging mycotoxins that are measurable at significant levels in crops world-wide. Unfortunately, we still know very little about the bioavailability and toxic potentials of many of these less characterized mycotoxins, including the large family of enniatins. In this study, we present new occurrence data for enniatin A, A1, B, B1 and beauvericin in four Danish crops: oat, wheat, and barley from the 2010 harvest, and rye from 2011 harvest. The occurrence of the four enniatins were B 〉 B1 〉 A1 〉 A. Enniatin B was detected in 100% of tested samples regardless of crop type. In addition to occurrence data, we report a proof-of-concept study using a human-relevant high-content hepatotoxicity, or “quadroprobe,” assay to screen mycotoxins for their cytotoxic potential. The assay was sensitive for most cytotoxic compounds in the 0.009–100 µM range. Among eight tested mycotoxins (enniatin B, beauvericin, altenariol, deoxynivalenol, aflatoxin B1, andrastin A, citrinin, and penicillic acid), enniatin B and beauvericin showed significant cytotoxicity at a concentration lower than that for aflatoxin B1, which is the archetypal acute hepatotoxic and liver-carcinogenic mycotoxin. Hence, the quadroprobe hepatotoxicity assay may become a valuable assessment tool for toxicity assessment of mycotoxins in the future. © 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016.

Description: Cancer survival rates are lower in Denmark than in comparable European countries. This may partly be attributable to subgroups of cancer patients who seek medical attention at late disease stages. It is unknown if differences in usual (i.e. customary) consultation frequency in general practice are associated with cancer prognosis. We aimed to estimate the cancer prognosis of cancer patients stratified by their usual consultation frequency in general practice. We performed a population-based cohort study including 123,943 incident cancer patients aged 50-89 years diagnosed in Denmark in 2009-2013. We estimated associations between the patient's usual general practitioner (GP) consultation frequency 19-36 months before the cancer diagnosis and all-cause mortality by using hazard ratios (HR), estimated by Cox proportional hazards regression. We also estimated the associations between the patient's usual GP consultation frequency and tumour stage, by using logistic regression estimates of odds ratios (ORs). Patients who usually did not see their GP (non-consulters) had higher all-cause mortality (HR=1.39 (95% CI: 1.33-1.44)) compared to patients who usually saw their GP three to five times during an 18 months period (average consulters). Non-consulters had higher odds of having distant tumour stage (OR=1.46 (95% CI: 1.38-1.57)) than average consulters. Similar, yet less strong, patterns were seen among patients with low usual GP consultation frequency, yet not statistically significant for all cancer types. In conclusion, the association between usual GP non-consultation and cancer prognosis is a combination of at least two things: a mechanism through more advanced tumour stage and other independent factors. This article is protected by copyright. All rights reserved.

Description: Nature Reviews Urology 14, 523 (2017). doi:10.1038/nrurol.2017.98 Authors: Christian Fuglesang S. Jensen, Peter Østergren, James M. Dupree, Dana A. Ohl, Jens Sønksen & Mikkel Fode The link between varicoceles and male infertility has been a matter of debate for more than half a century. Varicocele is considered the most common correctable cause of male infertility, but some men with varicoceles are able to father children, even without intervention. In addition,

Description: Coupling picolinic acid (pyridine-2-carboxylic acid) and pyridine-2,6-dicarboxylic acid with N-alkylanilines affords a range of mono- and bis-amides in good to moderate yields. These amides are of interest for potential applications in catalysis, coordination chemistry and molecular devices. The reaction of picolinic acid with thionyl chloride to generate the acid chloride in situ leads not only to the N-alkyl-N-phenylpicolinamides as expected but also the corresponding 4-chloro-N-alkyl-N-phenylpicolinamides in the one pot. The two products are readily separated by column chromatography. Chlorinated products are not observed from the corresponding reactions of pyridine-2,6-dicarboxylic acid. X-Ray crystal structures for six of these compounds are described. These structures reveal a general preference for cis amide geometry in which the aromatic groups (N-phenyl and pyridyl) are cis to each other and the pyridine nitrogen anti to the carbonyl oxygen. Variable temperature 1H NMR experiments provide a window on amide bond isomerisation in solution. Scientific Reports 5 doi: 10.1038/srep09950

Description: Background: Lung cancer stage at diagnosis predicts possible curative treatment. In Denmark and the UK, lung cancer patients have lower survival rates than citizens in most other European countries, which may partly be explained by a comparatively longer diagnostic interval in these two countries. In Denmark, a pathway was introduced in 2008 allowing general practitioners (GPs) to refer patients suspected of having lung cancer directly to fast-track diagnostics. However, symptom presentation of lung cancer in general practice is known to be diverse and complex, and systematic knowledge of the routes to diagnosis is needed to enable earlier lung cancer diagnosis in Denmark. This study aims to describe the routes to diagnosis, the diagnostic activity preceding diagnosis and the diagnostic intervals for lung cancer in the Danish setting. Methods: We conducted a national registry-based cohort study on 971 consecutive incident lung cancer patients in 2010 using data from national registries and GP questionnaires. Results: GPs were involved in 68.3% of cancer patients’ diagnostic pathways, and 27.4% of lung cancer patients were referred from the GP to fast-track diagnostic work-up. A minimum of one X-ray was performed in 85.6% of all cases before diagnosis. Patients referred through a fast-track route more often had diagnostic X-rays (66.0%) than patients who did not go through fast-track (49.4%). Overall, 33.6% of all patients had two or more X-rays performed during the 90 days before diagnosis. Patients whose symptoms were interpreted as non-alarm symptoms or who were not referred to fast-track were more likely to experience a long diagnostic interval than patients whose symptoms were interpreted as alarm symptoms or who were referred to fast-track. Conclusions: Lung cancer patients followed several diagnostic pathways. The existing fast-track pathway must be supplemented to ensure earlier detection of lung cancer. The high incidence of multiple X-rays warrants a continued effort to develop more accurate lung cancer tests for use in primary care.

Description: Prior to 2008 and the discovery of several important hawksbill turtle ( Eretmochelys imbricata ) nesting colonies in the EP (Eastern Pacific), the species was considered virtually absent from the region. Research since that time has yielded new insights into EP hawksbills, salient among them being the use of mangrove estuaries for nesting. These recent revelations have raised interest in the genetic characterization of hawksbills in the EP, studies of which have remained lacking to date. Between 2008 and 2014, we collected tissue samples from 269 nesting hawksbills at nine rookeries across the EP and used mitochondrial DNA sequences (766 bp) to generate the first genetic characterization of rookeries in the region. Our results inform genetic diversity, population differentiation, and phylogeography of the species. Hawksbills in the EP demonstrate low genetic diversity: We identified a total of only seven haplotypes across the region, including five new and two previously identified nesting haplotypes (pooled frequencies of 58.4% and 41.6%, respectively), the former only evident in Central American rookeries. Despite low genetic diversity, we found strong stock structure between the four principal rookeries, suggesting the existence of multiple populations and warranting their recognition as distinct management units. Furthermore, haplotypes EiIP106 and EiIP108 are unique to hawksbills that nest in mangrove estuaries, a behavior found only in hawksbills along Pacific Central America. The detected genetic differentiation supports the existence of a novel mangrove estuary “reproductive ecotype” that may warrant additional conservation attention. From a phylogeographic perspective, our research indicates hawksbills colonized the EP via the Indo-Pacific, and do not represent relict populations isolated from the Atlantic by the rising of the Panama Isthmus. Low overall genetic diversity in the EP is likely the combined result of few rookeries, extremely small reproductive populations and evolutionarily recent colonization events. Additional research with larger sample sizes and variable markers will help further genetic understanding of hawksbill turtles in the EP. This study represents the first genetic characterization of critically endangered hawksbill turtle rookeries in the eastern Pacific Ocean. Despite low genetic diversity in the region, we found strong stock structuring among four rookeries. Phylogenetic analysis revealed that hawksbills colonized the eastern Pacific via the Indo-Pacific, rather than representing a relict population isolated from the Atlantic by the rising of the Panama Isthmus. We found haplotypes unique to hawksbills nesting in mangrove estuaries and this behavior is exclusive to hawksbills along Pacific Central America, indicating the existence of a novel mangrove estuary reproductive ecotype.