Younger adult type 2 diabetic patients have poorer glycaemic control: A cross-sectional study in a primary care setting in Singapore

10.1186/1472-6823-13-18BMC Endocrine Disorders13-BEDM

Regulatory (pan-)genome of an obligate intracellular pathogen in the PVC superphylum.

Like other obligate intracellular bacteria, the Chlamydiae feature a compact regulatory genome that remains uncharted owing to poor genetic tractability. Exploiting the reduced number of transcription factors (TFs) encoded in the chlamydial (pan-)genome as a model for TF control supporting the intracellular lifestyle, we determined the conserved landscape of TF specificities by ChIP-Seq (chromatin immunoprecipitation-sequencing) in the chlamydial pathogen Waddlia chondrophila. Among 10 conserved TFs, Euo emerged as a master TF targeting >100 promoters through conserved residues in a DNA excisionase-like winged helix-turn-helix-like (wHTH) fold. Minimal target (Euo) boxes were found in conserved developmentally-regulated genes governing vertical genome transmission (cytokinesis and DNA replication) and genome plasticity (transposases). Our ChIP-Seq analysis with intracellular bacteria not only reveals that global TF regulation is maintained in the reduced regulatory genomes of Chlamydiae, but also predicts that master TFs interpret genomic information in the obligate intracellular α-proteobacteria, including the rickettsiae, from which modern day mitochondria evolved

The Waddlia Genome: A Window into Chlamydial Biology

Growing evidence suggests that a novel member of the Chlamydiales order, Waddlia chondrophila, is a potential agent of miscarriage in humans and abortion in ruminants. Due to the lack of genetic tools to manipulate chlamydia, genomic analysis is proving to be the most incisive tool in stimulating investigations into the biology of these obligate intracellular bacteria. 454/Roche and Solexa/Illumina technologies were thus used to sequence and assemble de novo the full genome of the first representative of the Waddliaceae family, W. chondrophila. The bacteria possesses a 2′116′312bp chromosome and a 15′593 bp low-copy number plasmid that might integrate into the bacterial chromosome. The Waddlia genome displays numerous repeated sequences indicating different genome dynamics from classical chlamydia which almost completely lack repetitive elements. Moreover, W. chondrophila exhibits many virulence factors also present in classical chlamydia, including a functional type III secretion system, but also a large complement of specific factors for resistance to host or environmental stresses. Large families of outer membrane proteins were identified indicating that these highly immunogenic proteins are not Chlamydiaceae specific and might have been present in their last common ancestor. Enhanced metabolic capability for the synthesis of nucleotides, amino acids, lipids and other co-factors suggests that the common ancestor of the modern Chlamydiales may have been less dependent on their eukaryotic host. The fine-detailed analysis of biosynthetic pathways brings us closer to possibly developing a synthetic medium to grow W. chondrophila, a critical step in the development of genetic tools. As a whole, the availability of the W. chondrophila genome opens new possibilities in Chlamydiales research, providing new insights into the evolution of members of the order Chlamydiales and the biology of the Waddliaceae

Investigating the Geochemical Model for Molybdenum Mineralization in the JEB Tailings Management Facility at McClean Lake, Saskatchewan: An X‑ray Absorption Spectroscopy Study

The geochemical model for Mo mineralization in the JEB Tailings Management Facility (JEB TMF), operated by AREVA Resources Canada at McClean Lake, Saskatchewan, was investigated using X-ray Absorption Near-Edge Spectroscopy (XANES), an elemental-specific technique that is sensitive to low elemental concentrations. Twenty five samples collected during the 2013 sampling campaign from various locations and depths in the TMF were analyzed by XANES. Mo K-edge XANES analysis indicated that the tailings consisted primarily of Mo⁶⁺ species: powellite (CaMoO₄), ferrimolybdite (Fe₂(MoO₄)₃·8H₂O), and molybdate adsorbed on ferrihydrite (Fe­(OH)₃ – MoO₄). A minor concentration of a Mo⁴⁺ species in the form of molybdenite (MoS₂) was also present. Changes in the Mo mineralization over time were inferred by comparing the relative amounts of the Mo species in the tailings to the independently measured aqueous Mo pore water concentration. It was found that ferrimolybdite and molybdate adsorbed on ferrihydrite initially dissolves in the TMF and precipitates as powellite

Analysis of the Mo Speciation in the JEB Tailings Management Facility at McClean Lake, Saskatchewan

The JEB Tailings Management Facility (TMF) is central to reducing the environmental impact of the uranium ore processing operation located at the McClean Lake facility and operated by AREVA Resources Canada (AREVA). The geochemical controls of this facility are largely designed around the idea that elements of concern, such as Mo, will be controlled in the very long term through equilibrium with supporting minerals. However, these systems are far from equilibrium when the tailings are first placed in the TMF, and it can take years, decades, or centuries to reach equilibrium. Therefore, it is necessary to understand how these reactions evolve toward an equilibrium state to understand the very long-term behavior of the TMF and to ensure that the elements of concern will be adequately contained. To this end, the Mo speciation in a series of samples taken from the JEB TMF during the 2008 sampling campaign has been analyzed. This analysis was performed using powder X-ray diffraction (XRD), X-ray fluorescence mapping (μ-XRF), and X-ray absorption near-edge spectroscopy (XANES). These results show that only XANES was effective in speciating Mo in the tailings samples, because it was both element-specific and sensitive enough to detect the low concentrations of Mo present. These results show that the predominant Mo-bearing phases present in the TMF are powellite, ferrimolybdite, and molybdate adsorbed on ferrihydrite

Developing a Quality Measure for Clinical Inertia in Diabetes Care

OBJECTIVE: To develop a valid quality measure that captures clinical inertia, the failure to initiate or intensify therapy in response to medical need, in diabetes care and to link this process measure with outcomes of glycemic control. DATA SOURCES: Existing databases from 13 Department of Veterans Affairs hospitals between 1997 and 1999. STUDY DESIGN: Laboratory results, medications, and diagnoses were collected on 23,291 patients with diabetes. We modeled the decision to increase antiglycemic medications at individual visits. We then aggregated all visits for individual patients and calculated a treatment intensity score by comparing the observed number of increases to that expected based on our model. The association between treatment intensity and two measures of glycemic control, change in HbA1c during the observation period, and whether the outcome glycosylated hemoglobin (HbA1c) was greater than 8 percent, was then examined. PRINCIPAL FINDINGS: Increases in antiglycemic medications occured at only 9.8percent of visits despite 39percent of patients having an initial HbA1c level greater than 8 percent. A clinically credible model predicting increase in therapy was developed with the principal predictor being a recent HbA1c greater than 8 percent. There were considerable differences in the intensity of therapy received by patients. Those patients receiving more intensive therapy had greater improvements in control (p<.001). CONCLUSIONS: Clinical inertia can be measured in diabetes care and this process measure is linked to patient outcomes of glycemic control. This measure may be useful in efforts to improve clinicians management of patients with diabetes