BACKGROUND: To analyze the incidence and clinical-microbiological characteristics of osteomyelitis (OM) in a tertiary Spanish hospital. METHODS: All cases diagnosed with OM between January 2007 and December 2010 were retrospectively reviewed. The variables examined include epidemiological characteristics, risk factors, affected bone, radiographic changes, histology, microbiological culture results, antibiotic treatment, and the need for surgery. RESULTS: Sixty-three cases of OM were diagnosed. Twenty-six patients (41.3%) had acute OM whereas 37 patients (58.7%) were classified as chronic OM. OM may result from haematogenous or contiguous microbial seeding. In this group, 49 patients (77.8%) presented with OM secondary to a contiguous source of infection and 14 patients had hematogenous OM (22.2%). Staphylococcus aureus was the most commonly found microorganism. CONCLUSIONS: OM mainly affected patients with risk factors related to the presence of vascular diseases. Antibiotic treatment must be guided by susceptibility patterns of individual microorganisms, although it must be performed together with surgery in most of the cases.
Acute Disease ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Child ; Child, Preschool ; Chronic Disease ; Female ; Humans ; Infant ; Male ; Middle Aged ; *Osteomyelitis/drug therapy/epidemiology/microbiology ; Retrospective Studies ; Risk Factors ; Spain/epidemiology ; Staphylococcal Infections ; Staphylococcus aureus/isolation & purification ; Tertiary Care Centers ; Young Adult

The generation of functional retinal pigment epithelium (RPE) is of great therapeutic interest to the field of regenerative medicine and may provide possible cures for retinal degenerative diseases, including age-related macular degeneration (AMD). Although RPE cells can be produced from either embryonic stem cells or induced pluripotent stem cells, direct cell reprogramming driven by lineage-determining transcription factors provides an immediate route to their generation. By monitoring a human RPE specific Best1::GFP reporter, we report the conversion of human fibroblasts into RPE lineage using defined sets of transcription factors. We found that Best1::GFP positive cells formed colonies and exhibited morphological and molecular features of early stage RPE cells. Moreover, they were able to obtain pigmentation upon activation of Retinoic acid (RA) and Sonic Hedgehog (SHH) signaling pathways. Our study not only established an ideal platform to investigate the transcriptional network regulating the RPE cell fate determination, but also provided an alternative strategy to generate functional RPE cells that complement the use of pluripotent stem cells for disease modeling, drug screening, and cell therapy of retinal degeneration.
Animals ; Bestrophins ; Cell Differentiation ; Cell Line ; Cell Lineage ; Chloride Channels ; genetics ; metabolism ; Embryonic Stem Cells ; cytology ; metabolism ; Eye Proteins ; genetics ; metabolism ; Fibroblasts ; cytology ; metabolism ; Genes, Reporter ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Mice ; Pigmentation ; Retinal Pigment Epithelium ; cytology ; metabolism ; Transcription Factors ; metabolism

With defined culture protocol, human embryonic stem cells (hESCs) are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for cardiac disease therapies. In this study, we successfully generated a highly pure population of human cardiomyocytes (hCMs) (>95% cTnT(+)) from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA methylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene functions and disease mechanisms. Moreover, we show that cardiac-structural genes and cardiac-transcription factors have distinct epigenetic mechanisms to regulate their gene expression, providing a better understanding of how the epigenetic machinery coordinates to regulate gene expression in different cell types.
Cell Differentiation ; Cell Line ; DNA Methylation ; Embryonic Stem Cells ; cytology ; metabolism ; Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Myocytes, Cardiac ; cytology ; metabolism ; Transcription, Genetic

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cell Culture Techniques ; methods ; Child ; Female ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Male ; Middle Aged

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2 foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2 cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.