ABSTRACT
Clostridium difficile has rapidly emerged as the leading cause of antibiotic-associated diarrheal disease, with the transcontinental spread of various PCR ribotypes, including 001, 017, 027 and 078. However, the genetic basis for the emergence of C. difficile as a human pathogen is unclear. Whole genome sequencing was used to analyze genetic variation and virulence of a diverse collection of thirty C. difficile isolates, to determine both macro and microevolution of the species. Horizontal gene transfer and large-scale recombination of core genes has shaped the C. difficile genome over both short and long time scales. Phylogenetic analysis demonstrates C. difficile is a genetically diverse species, which has evolved within the last 1.1-85 million years. By contrast, the disease-causing isolates have arisen from multiple lineages, suggesting that virulence evolved independently in the highly epidemic lineages.
Subject(s)
Clostridioides difficile/genetics , Evolution, Molecular , Computational Biology , Gene Expression Regulation, Bacterial , Gene Transfer Techniques , Genome, Bacterial , Molecular Sequence Data , Phylogeny , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Recombination, Genetic , Sequence Analysis, DNA , Species Specificity , Time Factors , VirulenceABSTRACT
The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.
Subject(s)
Chromosomes, Human, X/genetics , Evolution, Molecular , Genomics , Sequence Analysis, DNA , Animals , Antigens, Neoplasm/genetics , Centromere/genetics , Chromosomes, Human, Y/genetics , Contig Mapping , Crossing Over, Genetic/genetics , Dosage Compensation, Genetic , Female , Genetic Linkage/genetics , Genetics, Medical , Humans , Male , Polymorphism, Single Nucleotide/genetics , RNA/genetics , Repetitive Sequences, Nucleic Acid/genetics , Sequence Homology, Nucleic Acid , Testis/metabolismABSTRACT
OBJECTIVE: Study impact of health literacy on educational intervention for patients "Living with Coronary Artery Disease." METHODS: 187 patients were randomized to: VHS/DVD plus printed booklet; or booklet alone prior to scheduled visit. Main outcome measures included CAD knowledge assessment, clinical outcomes (weigh and blood pressure) and health behaviors (diet, exercise, and smoking); while functional health literacy was assessed as a possible predictor variable. RESULTS: Knowledge scores and health behaviors improved following both interventions. Those receiving the booklet and video also had a significant improvement in exercise, and weight loss. There was a trend (p=0.07) towards greater improvement in test scores among those receiving the booklet plus video. Patients with lower health literacy benefited as much as higher literacy patients. CONCLUSIONS: Incorporation of an educational program into clinical visits for patients with chronic disease improved disease-specific knowledge and prompted patients to become activated and involved in their care, improving health behaviors and outcomes. Lower health literacy was not a barrier to this beneficial effect. PRACTICE IMPLICATIONS: Patients with lower health literacy may also benefit from educational, shared decision-making interventions.