Late effects of cancer treatment:shared care

Many adverse effects of cancer treatment develop years after treatment completion. Late effects such as cardiotoxicity, metabolic syndrome, and osteoporosis can sometimes be prevented or reduced if they are detected early. This makes it important to continue to monitor patients after they have been discharged from secondary care. Shared care means that patients, general practitioners, and oncologists are jointly involved in the management of these late effects. To this end, a personalized care plan should be prepared that clearly describes each person's role and which provides recommendations for screening and, if necessary, interventions. It would seem logical that general practitioners have a pivotal role in this because of their broad background and experience with multimorbidity and chronic illnesses. A precondition for successful shared care is the availability of better and more consistent aftercare protocols for various types of cancer treatment and better scientific support for the relevance of screening for late effects

Genome-wide association study of cardiovascular disease in testicular cancer patients treated with platinum-based chemotherapy

Genetic variation may mediate the increased risk of cardiovascular disease (CVD) in chemotherapy-treated testicular cancer (TC) patients compared to the general population. Involved single nucleotide polymorphisms (SNPs) might differ from known CVD-associated SNPs in the general population. We performed an explorative genome-wide association study (GWAS) in TC patients. TC patients treated with platinum-based chemotherapy between 1977 and 2011, age ≤55 years at diagnosis, and ≥3 years relapse-free follow-up were genotyped. Association between SNPs and CVD occurrence during treatment or follow-up was analyzed. Data-driven Expression Prioritized Integration for Complex Trait (DEPICT) provided insight into enriched gene sets, i.e., biological themes. During a median follow-up of 11 years (range 3-37), CVD occurred in 53 (14%) of 375 genotyped patients. Based on 179 SNPs associated at p ≤ 0.001, 141 independent genomic loci associated with CVD occurrence. Subsequent, DEPICT found ten biological themes, with the RAC2/RAC3 network (linked to endothelial activation) as the most prominent theme. Biology of this network was illustrated in a TC cohort (n = 60) by increased circulating endothelial cells during chemotherapy. In conclusion, the ten observed biological themes highlight possible pathways involved in CVD in chemotherapy-treated TC patients. Insight in the genetic susceptibility to CVD in TC patients can aid future intervention strategies

Isolation of ‘Candidatus Nitrosocosmicus franklandus’, a novel ureolytic soil archaeal ammonia oxidiser with tolerance to high ammonia concentration

Acknowledgements The authors would like to thank Mr Kevin Mackenzie and Mrs Gillian Milne (University of Aberdeen) for technical support with scanning electron microscopy, and Dr Robin Walker for access to the Woodlands Field experimental plots at the SRUC,Craibstone Estate, Aberdeen. Funding This work was financially supported by Natural Environmental Research Council (standard grants NE/I027835/1 and NE/L006286/1 and fellowship NE/J019151/1), EC Marie Curie ITN NORA, Grant Agreement No. 316472, the AXA Research Fund and the Centre for Genome Enabled Biology and Medicine, University of Aberdeen.Peer reviewedPublisher PD

Ammonia oxidation: Ecology, physiology, biochemistry and why they must all come together

Ammonia oxidation is a fundamental core process in the global biogeochemical nitrogen cycle. Oxidation of ammonia (NH3) to nitrite (NO2 −) is the first and rate-limiting step in nitrification and is carried out by distinct groups of microorganisms. Ammonia oxidation is essential for nutrient turnover in most terrestrial, aquatic and engineered ecosystems and plays a major role, both directly and indirectly, in greenhouse gas production and environmental damage. Although ammonia oxidation has been studied for over a century, this research field has been galvanised in the past decade by the surprising discoveries of novel ammonia oxidising microorganisms. This review reflects on the ammonia oxidation research to date and discusses the major gaps remaining in our knowledge of the biology of ammonia oxidation

The pH dependency of N-converting enzymatic processes, pathways and microbes: effect on net N₂O production

Nitrous oxide (N2O) is emitted during microbiological nitrogen (N) conversion processes, when N2O production exceeds N2O consumption. The magnitude of N2O production vs. consumption varies with pH and controlling net N2O production might be feasible by choice of system pH. This article reviews how pH affects enzymes, pathways and microorganisms that are involved in N-conversions in water engineering applications. At a molecular level, pH affects activity of cofactors and structural elements of relevant enzymes by protonation or deprotonation of amino acid residues or solvent ligands, thus causing steric changes in catalytic sites or proton/electron transfer routes that alter the enzymes' overall activity. Augmenting molecular information with, e.g., nitritation or denitrification rates yields explanations of changes in net N2O production with pH. Ammonia oxidizing bacteria are of highest relevance for N2O production, while heterotrophic denitrifiers are relevant for N2O consumption at pH > 7.5. Net N2O production in N-cycling water engineering systems is predicted to display a ‘bell-shaped’ curve in the range of pH 6.0–9.0 with a maximum at pH 7.0–7.5. Net N2O production at acidic pH is dominated by N2O production, whereas N2O consumption can outweigh production at alkaline pH. Thus, pH 8.0 may be a favourable pH set-point for water treatment applications regarding net N2O production

Growth Differentiation Factor 15 (GDF-15) Plasma Levels Increase during Bleomycin- and Cisplatin-Based Treatment of Testicular Cancer Patients and Relate to Endothelial Damage

Introduction Chemotherapy-related endothelial damage contributes to the early development of cardiovascular morbidity in testicular cancer patients. We aimed to identify relevant mechanisms of and search for candidate biomarkers for this endothelial damage. Methods Human micro-vascular endothelial cells (HMEC-1) were exposed to bleomycin or cisplatin with untreated samples as control. 18k cDNA microarrays were used. Gene expression differences were analysed at single gene level and in gene sets clustered in biological pathways and validated by qRT-PCR. Protein levels of a candidate biomarker were measured in testicular cancer patient plasma before, during and after bleomycin-etoposide-cisplatin chemotherapy, and related to endothelial damage biomarkers (von Willebrand Factor (vWF), high-sensitivity C-Reactive Protein (hsCRP)). Results Microarray data identified several genes with highly differential expression; e.g. Growth Differentiation Factor 15 (GDF-15), Activating Transcription Factor 3 (ATF3) and Amphiregulin (AREG). Pathway analysis revealed strong associations with 'p53' and 'Diabetes Mellitus' gene sets. Based on known function, we measured GDF-15 protein levels in 41 testicular patients during clinical follow-up. Pre-chemotherapy GDF-15 levels equalled controls. Throughout chemotherapy GDF-15, vWF and hsCRP levels increased, and were correlated at different time-points. Conclusion An unbiased approach in a preclinical model revealed genes related to chemotherapy-induced endothelial damage, like GDF-15. The increases in plasma GDF-15 levels in testicular cancer patients during chemotherapy and its association with vWF and hsCRP suggest that GDF-15 is a potentially useful biomarker related to endothelial damage

Influence of Pregnancy on Aortic Diameter in Women With the Turner Syndrome

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