BackgroundWe previously reported the in vitro spontaneous transformation of human mesenchymal stem cells (MSC) generating a population with tumorigenic potential, that we termed transformed mesenchymal cells (TMC).Methodology/Principal FindingsHere we have characterized the molecular changes associated with TMC generation. Using microarrays techniques we identified a set of altered pathways and a greater number of downregulated than upregulated genes during MSC transformation, in part due to the expression of many untranslated RNAs in MSC. Microarray results were validated by qRT-PCR and protein detection.Conclusions/SignificanceIn our model, the transformation process takes place through two sequential steps; first MSC bypass senescence by upregulating c-myc and repressing p16 levels. The cells then bypass cell crisis with acquisition of telomerase activity, Ink4a/Arf locus deletion and Rb hyperphosphorylation. Other transformation-associated changes include modulation of mitochondrial metabolism, DNA damage-repair proteins and cell cycle regulators. In this work we have characterized the molecular mechanisms implicated in TMC generation and we propose a two-stage model by which a human MSC becomes a tumor cell.

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These results show that detection of mRNA based on the qRT-PCR of the telomerase hTERT(N) gene in plasma clearly differentiates between healthy and colorectal cancer patients and that hTERT(N) can be detected and quantified in plasma. This opens up a new field as a noninvasive blood test for colorectal cancer diagnosis.

BackgroundShort and long term sickness absence (SA) are due to different causes, therefore require different approaches to intervention. In research on SA, incidence had usually been analysed separately from the duration of episodes.ObjectiveDescribe the usefulness of the analysis of SA incidence by segmentation of duration of episodes versus non-segmented analysis.MethodsWe compared overall incidence of non-work related SA and incidence of SA segmented by duration (short duration (≤ 15 days), medium (16–30, 31–90) and long (> 90)). We used data from a health insurance company (“mutua”) in Spain during 2011 (230,332 episodes, 752,906 workers). The incidence rate was calculated according to age groups (<25, 25–34, 35–44, 45–54, ≥55). We computed rate ratios, with their 95% confidence interval (95% CI), to quantify linear trend (RR-T) and association (RR) of SA between age groups.ResultsThe overall incidence of SA showed a steady decline with age (RR-T = 0.92, 95% CI = 0.91–0.92) with an incidence of 36.4% in <25 years versus 29.3% in ≥55 years (RR = 1.24, 95% CI = 1.22–1.27). The overall excess incidence observed in young is produced by short duration (RR-T = 0.82, 95% CI = 0.82–0 82; RR = 1.98, 95% CI = 1.93–2.03). In addition, the incidence of long term SA changed this pattern (RR-T = 1.32, 95% CI = 1.30–1.33), being more frequent in ≥55 years relative to the youngest (5.5% versus 2.1%, RTI = 3.19, 95% CI = 2.97–3.43).ConclusionsThe analysis of indicators of SA segmented by duration of episodes provides more precise image than that obtained from global data. Information on the type of episodes of IT according to duration provides valuable information for SA intervention.

Background One way used to measure the absenteeism is the analysis of incidence of non-work related sickness absence (NWSA). Study of incidence by segments duration and its evolution allow identifying typology of incidence of NWSA, being useful in the sickness absence management.ObjectiveDescribe evolution of incidence of NWSA by segments duration between 2009 and 2015 in Spain.Methods We computed the overall incidence of NWSA and by segments duration. The data used for this study comes from a health insurance company in Spain from 2009 to 2015. The analysis was stratified by age (18–24, 25–34, 35–44, 45–54 and 55–64 years) and sex. Segments were defined by periods (days) short (≤15), medium (16–30, 31–90) and long (>90) term. The Annual Percentage Change (APC) was calculated using the Poisson Model with an inflection point in 2013.Results The overall evolution of incidence of NWSA showed a decreasing trend in 2009–2013 (APC −8%, 95% CI: −12%; − 5%), and an increasing in 2013–2015 (APC 5%, 95% CI: −3%; 13%). The drop of the APC had similar incidence of NWSA in all duration segments being the short processes the ones with a major contribution. Incidence of NWSA (overall and segments) presented an APC more pronounced in workers under 25 years. In 2009 the incidence of short processes in younger workers were 2.4 times higher than in older, while from 2013 to 2015, this difference was reduced to 1.5. In both sexes, the evolution of INWSA was similar, with higher values in women.Conclusions Changes in the evolution of incidence of NWSA occurred in all segments of duration, being the short duration segments those with more influence. The declension was more noticeable in younger workers. The ascension showed that the differences by age decreased as a result of the short duration processes.

BackgroundDifferent countries have shown an inverse relationship between unemployment rates and indicators of sickness absence during periods of economic recession. To our knowledge there is no study which has investigated the relationship between unemployment and absenteeism in Spain.ObjectivesEvaluate the relationship between indicators of absenteeism and unemployment in Spain during 2009-2014.MethodsWe obtained incidence (IR) and absenteeism rates (AR) of non-work related sickness absence (NWSA). Data was obtained from the population protected by a health insurance company (“mutua”) collected by the Social Security. Data on unemployment rates (UR) was provided by the National Statistics Institute in Spain. The relationship between indicators of NWSA and unemployment in the period 2009 to 2014 was graphically described using time trend plots. Scatter plots of NWSA indicators were also made against unemployment. Finally, we fitted statistical regression models using absenteeism indicators as dependent variables and unemployment rates as an explanatory variable.ResultsIncidence and absenteeism rates of NWSA showed downward trends in 2009–2014 (IR 2009 = 28.1% and IR 2014 = 20.8%; AR 2009 = 2.5% and AR 2014 = 2.0%). On the other hand, the unemployment rate had an upward trend in the study period (UR 2009 = 17.9% and UR 2014 = 24.4%). An inverse relationship between unemployment rates and absenteeism indicators was observed (incidence rates: Beta unemployment = −0.93 (p < 0.01) and R-Squared = 95.2%; absenteeism rates: Beta unemployment = −0.08 (p < 0.01) and R-Squared = 99.0%).ConclusionsAs in previous international studies, an inverse relationship between unemployment and absenteeism was observed in Spain. Specific studies are needed to evaluate explanatory hypotheses such as those associated with the theory of discipline and changes in the workforce.