Browsing by Subject "Europe"
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Item Genetically-regulated transcriptomics & copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry(BioMed Central Ltd., 2020-10-02) Pathak, Gita A.; Polimanti, Renato; Silzer, Talisa K.; Wendt, Frank R.; Chakraborty, Ranajit; Phillips, Nicole R.BACKGROUND: Proctitis is an inflammation of the rectum and may be induced by radiation treatment for cancer. The genetic heritability of developing radiotoxicity and prior role of genetic variants as being associated with side-effects of radiotherapy necessitates further investigation for underlying molecular mechanisms. In this study, we investigated gene expression regulated by genetic variants, and copy number variation in prostate cancer survivors with radiotoxicity. METHODS: We investigated proctitis as a radiotoxic endpoint in prostate cancer patients who received radiotherapy (n = 222). We analyzed the copy number variation and genetically regulated gene expression profiles of whole-blood and prostate tissue associated with proctitis. The SNP and copy number data were genotyped on Affymetrix(R) Genome-wide Human SNP Array 6.0. Following QC measures, the genotypes were used to obtain gene expression by leveraging GTEx, a reference dataset for gene expression association based on genotype and RNA-seq information for prostate (n = 132) and whole-blood tissue (n = 369). RESULTS: In prostate tissue, 62 genes were significantly associated with proctitis, and 98 genes in whole-blood tissue. Six genes - CABLES2, ATP6AP1L, IFIT5, ATRIP, TELO2, and PARD6G were common to both tissues. The copy number analysis identified seven regions associated with proctitis, one of which (ALG1L2) was also associated with proctitis based on transcriptomic profiles in the whole-blood tissue. The genes identified via transcriptomics and copy number variation association were further investigated for enriched pathways and gene ontology. Some of the enriched processes were DNA repair, mitochondrial apoptosis regulation, cell-to-cell signaling interaction processes for renal and urological system, and organismal injury. CONCLUSIONS: We report gene expression changes based on genetic polymorphisms. Integrating gene-network information identified these genes to relate to canonical DNA repair genes and processes. This investigation highlights genes involved in DNA repair processes and mitochondrial malfunction possibly via inflammation. Therefore, it is suggested that larger studies will provide more power to infer the extent of underlying genetic contribution for an individual's susceptibility to developing radiotoxicity.Item Risk of psychological ill health and methods of organisational downsizing: a cross-sectional survey in four European countries(BioMed Central Ltd., 2017-09-29) Andreeva, Elena; Brenner, M. Harvey; Theorell, Töres; Goldberg, MarcelThe manner in which organizational downsizing is implemented can make a substantial difference as to whether the exposed workers will suffer from psychological ill health. Surprisingly, little research has directly investigated this issue. We examined the likelihood of psychological ill health associated with strategic and reactive downsizing.|A cross-sectional survey included 1456 respondents from France, Sweden, Hungary and the United Kingdom: 681 employees in stable workplaces (reference group) and 775 workers from downsized companies. Reactive downsizing was exemplified by the exposures to compulsory redundancies of medium to large scale resulting in job loss or surviving a layoff while staying employed in downsized organizations. The workforce exposed to strategic downsizing was represented by surplus employees who were internally redeployed and supported through their career change process within a policy context of "no compulsory redundancy". Symptoms of anxiety, depression and emotional exhaustion were assessed in telephone interviews with brief subscales from Hospital Anxiety Scale (HADS-A), Hopkins Symptom Checklist (SCL-CD|We observed no increased risk of psychological ill health in the case of strategic downsizing. The number of significant associations with psychological ill health was the largest for the large-scale reactive downsizing: surviving a layoff was consistently associated with all three outcome measures; returning to work after the job loss experience was related to anxiety and depression, while persons still unemployed at interview had elevated odds of anxiety. After reactive medium-scale downsizing, unemployment at interview was the only exposure associated with anxiety and depression.|The manner in which organizational downsizing is implemented can be important for the psychological wellbeing of workers. If downsizing is unavoidable, it should be achieved strategically. Greater attention is needed to employment and health policies supporting the workers after reactive downsizing.