Global gene expression analyses of hematopoietic stem cell-like cell lines with inducible Lhx2 expression

BACKGROUND: Expression of the LIM-homeobox gene Lhx2 in murine hematopoietic cells allows for the generation of hematopoietic stem cell (HSC)-like cell lines. To address the molecular basis of Lhx2 function, we generated HSC-like cell lines where Lhx2 expression is regulated by a tet-on system and hence dependent on the presence of doxycyclin (dox). These cell lines efficiently down-regulate Lhx2 expression upon dox withdrawal leading to a rapid differentiation into various myeloid cell types. RESULTS: Global gene expression of these cell lines cultured in dox was compared to different time points after dox withdrawal using microarray technology. We identified 267 differentially expressed genes. The majority of the genes overlapping with HSC-specific databases were those down-regulated after turning off Lhx2 expression and a majority of the genes overlapping with those defined as late progenitor-specific genes were the up-regulated genes, suggesting that these cell lines represent a relevant model system for normal HSCs also at the level of global gene expression. Moreover, in situ hybridisations of several genes down-regulated after dox withdrawal showed overlapping expression patterns with Lhx2 in various tissues during embryonic development. CONCLUSION: Global gene expression analysis of HSC-like cell lines with inducible Lhx2 expression has identified genes putatively linked to self-renewal / differentiation of HSCs, and function of Lhx2 in organ development and stem / progenitor cells of non-hematopoietic origin

Heart failure in Finland: clinical characteristics, mortality, and healthcare resource use

AimsThe aims of this study were to describe patient characteristics of the adult chronic heart failure (HF) population and to estimate the prevalence, incidence, healthcare resource utilization (HCRU), and mortality associated with HF in Southwest Finland.Methods and resultsThis was a retrospective biobank and clinical registry study. Adult patients with an HF diagnosis (International Statistical Classification of Diseases and Related Health Problems (ICD) code I50) during 2004–2013 in secondary care were included in the study and compared with age‐matched and gender‐matched control patients without an I50 diagnosis. HF patients were stratified in groups by left ventricular ejection fraction (LVEF) as follows: LVEF ConclusionsThe high mortality rate and HCRU among the studied HF patients highlight the severity of the disease and the economic and social burden on both patients and society. This calls for improved methods of care for this large patient population.</p

Altered Methylation of IGF2 Locus 20 Years after Preterm Birth at Very Low Birth Weight

Peer reviewe

BigDataAtHeart_HFDataCatalogue_Final.xlsx

We have developed the methodology and platform for “Comprehensive and systematic review of contemporary data sources”, by focusing on data sources for heart failure (HF). We have queried established search engines of published biomedical literature (e.g. EMBASE, MEDLINE) and have targeted clinical and non-clinical journals and conferences. We comprehensively characterized data sources on the basis of: data type, design, region, country and type of CV disease, with an initial emphasis on HF. This has resulted in a comprehensive data catalogue of over 300 data sources included in non-interventional studies of HF and disseminated in the public domain

Health economic modeling of the potential cost saving effects of Neurally Adjusted Ventilator Assist

Objectives: Asynchrony between patient and ventilator breaths is associated with increased duration of mechanical ventilation (MV). Neurally Adjusted Ventilatory Assist (NAVA) controls MV through an esophageal reading of diaphragm electrical activity via a nasogastric tube mounted with electrode rings. NAVA has been shown to decrease asynchrony in comparison to pressure support ventilation (PSV). The objective of this study was to conduct a health economic evaluation of NAVA compared with PSV. Methods: We developed a model based on an indirect link between improved synchrony with NAVA versus PSV and fewer days spent on MV in synchronous patients. Unit costs for MV were obtained from the Swedish intensive care unit register, and used in the model along with NAVA-specific costs. The importance of each parameter (proportion of asynchronous patients, costs, and average MV duration) for the overall results was evaluated through sensitivity analyses. Results: Base case results showed that 21% of patients ventilated with NAVA were asynchronous versus 52% of patients receiving PSV. This equals an absolute difference of 31% and an average of 1.7 days less on MV and a total cost saving of US$7886 (including NAVA catheter costs). A breakeven analysis suggested that NAVA was cost effective compared with PSV given an absolute difference in the proportion of asynchronous patients greater than 2.5% (49.5% versus 52% asynchronous patients with NAVA and PSV, respectively). The base case results were stable to changes in parameters, such as difference in asynchrony, duration of ventilation and daily intensive care unit costs. Conclusion: This study showed economically favorable results for NAVA versus PSV. Our results show that only a minor decrease in the proportion of asynchronous patients with NAVA is needed for investments to pay off and generate savings. Future studies need to confirm this result by directly relating improved synchrony to the number of days on MV

Metabolic Effects of Basal or Premixed Insulin Treatment in 5077 Insulin-Naïve Type 2 Diabetes Patients: Registry-Based Observational Study in Clinical Practice

To investigate the clinical effects associated with premixed insulin (PM) and basal insulin [insulin NPH (NPH), insulin glargine (IG), insulin detemir (ID)], in insulin-na\uefve patients with type 2 diabetes in routine clinical care

Epidemiology of heart failure and trends in diagnostic work-up : a retrospective, population-based cohort study in Sweden

Purpose: The purpose of this study was to examine the trends in heart failure (HF) epidemiology and diagnostic work-up in Sweden. Methods: Adults with incident HF (&gt;= 2 ICD-10 diagnostic codes) were identified from linked national health registers (cohort 1, 2005-2013) and electronic medical records (cohort 2, 2010-2015; primary/secondary care patients from Uppsala and Vasterbotten). Trends in annual HF incidence rate and prevalence, risk of all-cause and cardiovascular disease (CVD)-related 1-year mortality and use of diagnostic tests 6 months before and after first HF diagnosis (cohort 2) were assessed. Results: Baseline demographic and clinical characteristics were similar for cohort 1 (N=174,537) and 2 (N=8,702), with mean ages of 77.4 and 76.6 years, respectively; almost 30% of patients were aged &gt;= 85 years. From 2010 to 2014, age-adjusted annual incidence rate of HF/1,000 inhabitants decreased (from 3.20 to 2.91, cohort 1; from 4.34 to 3.33, cohort 2), while age-adjusted prevalence increased (from 1.61% to 1.72% and from 2.15% to 2.18%, respectively). Age-adjusted 1-year all-cause and CVD-related mortality was higher in men than in women among patients in cohort 1 (all-cause mortality hazard ratio [HR] men vs women 1.07 [95% CI 1.06-1.09] and CVD-related mortality subdistribution HR for men vs women 1.04 [95% CI 1.02-1.07], respectively). While 83.5% of patients underwent N-terminal pro-B-type natriuretic peptide testing, only 36.4% of patients had an echocardiogram at the time of diagnosis, although this increased overtime. In the national prevalent HF population (patients with a diagnosis in 1997-2004 who survived into the analysis period; N=273,999), death from ischemic heart disease and myocardial infarction declined between 2005 and 2013, while death from HF and atrial fibrillation/flutter increased (P&lt;0.0001 for trends over time). Conclusion: The annual incidence rate of HF declined over time, while prevalence of HF has increased, suggesting that patients with HF were surviving longer over time. Our study confirms that previously reported epidemiological trends persist and remain to ensure proper diagnostic evaluation and management of patients with HF

Global gene expression analyses of hematopoietic stem cell-like cell lines with inducible expression-2

<p><b>Copyright information:</b></p><p>Taken from "Global gene expression analyses of hematopoietic stem cell-like cell lines with inducible expression"</p><p>BMC Genomics 2006;7():75-75.</p><p>Published online 6 Apr 2006</p><p>PMCID:PMC1459142.</p><p>Copyright © 2006 Richter et al; licensee BioMed Central Ltd.</p> off (upper panel) and 10 genes with up-regulated expression when expression is turned off (lower panel). Relative expression of each gene is set as 1 when is expressed (Day 0) and is compared to the expression at day 3 after dox withdrawal