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Objectives Literature from stroke and cardiac hospital admissions demonstrate a higher prevalence of undiagnosed type 2 diabetes compared with the general population. Fewer diabetes screening studies exist in the general medicine population, none of which have been based in Canada. Our primary objective in this study was to determine the prevalence of probable undiagnosed diabetes (glycated hemoglobin [A1C]≥6.5%) in hospitalized medicine patients. Secondary objectives were to identify the prevalence of undiagnosed dysglycemia (A1C≥6.0%) and the subsequent management of emergent cases. Methods In this prospective cohort study, adult patients admitted to internal medicine at a tertiary hospital in Ontario were screened for diabetes using an A1C test over a 3-month period. Baseline demographics and outcomes were compared using t tests, chi-square tests and Fisher’s exact tests for normoglycemia, undiagnosed dysglycemia and probable undiagnosed diabetes. A regression analysis was performed to identify any relationships between various cardiovascular-related risk factors and A1C. Results A total of 53 adult patients were enrolled. The prevalence of probable undiagnosed diabetes and undiagnosed dysglycemia was 7.5% (n=4) and 30.2% (n=16), respectively. Implementation of diabetes management strategies and/or documentation of the finding occurred in 4 of 16 patients. Regression analysis showed no relationship between either cardiovascular-related risk factors or admission glucose with A1C. Conclusions A broader screening approach may capture previously undiagnosed cases of diabetes that do not belong to traditionally at-risk populations. Future studies should focus on identifying risk factors for undiagnosed dysglycemia in hospitalized patients, including ethnicity and barriers to community access, so that appropriate screening programs can be developed.

Nuclease colicins are antibacterial proteins produced by certain strains of E. coli to reduce competition from rival strains. These colicins are generally organized with an N-terminal transport (T)-domain, a central receptor binding (R)-domain, and a C-terminal cytotoxic nuclease domain. These colicins are always produced in complex with an inhibitory immunity protein, which dissociates prior entrance of the cytotoxic domain in the target cell. How exactly colicins traverse the cell envelope is not understood, yet this knowledge is important for the design of new antibacterial therapies. In this report, we find that the cytotoxic rRNAse domain of colicin E3, lacking both T- and R-domains, is sufficient to inhibit cell growth provided the immunity protein Im3 has been removed. Thus, while the T-domain is needed for dissociation of Im3, the rRNAse alone can associate to the cell surface without R-domain. Accordingly, we find a high affinity interaction (Kd ~1-2μM) between the rRNAse domain and lipopolysaccharides (LPS). Furthermore, we show that binding of ColE3 to LPS destabilizes the secondary structure of the toxin, which is expectedly crucial for transport through the narrow pore of the porin OmpF. The effect of LPS on binding and unfolding of ColE3 may be indicative of a broader role of LPS for transport of colicins in general.

TonB-dependent transporters are β-barrel outer membrane proteins occluded by a plug domain. Upon ligand binding, these transporters extend a periplasmic motif termed the TonB box. The TonB box permits the recruitment of the inner membrane protein complex TonB-ExbB-ExbD, which drives import of ligands in the cell periplasm. It is unknown precisely how the plug domain is moved aside during transport nor have the intermediate states between TonB recruitment and plug domain movement been characterized biochemically. Here we employ nanodiscs, native gel electrophoresis, and scintillation proximity assays to determine the binding kinetics of vitamin B12 to BtuB. The results show that ligand-bound BtuB recruits a monomer of TonB (TonB∆1-31), which in turn increases retention of vitamin B12 within the transporter. The TonB box and the extracellular residue valine 90 that forms part of the vitamin B12 binding site are essential for this event. These results identify a novel step in the TonB-dependent transport process. They show that TonB binding to BtuB trap the ligand, possibly until the ExbB-ExbD complex is activated or recruited to ensure subsequent transport.

TonB-dependent membrane receptors from bacteria have been analyzed in detergent-containing solution, an environment that may influence the role of ligand in inducing downstream interactions. We report reconstitution of FhuA into a membrane mimetic: nanodiscs. In contrast to previous results in detergent, we show that binding of TonB to FhuA in nanodiscs depends strongly on ferricrocin. The stoichiometry of interaction is 1:1 and the binding constant KD is ~200nM; an equilibrium affinity that is ten-fold lower than reported in detergent. FhuA in nanodiscs also forms a high-affinity binding site for colicin M (KD ~3.5nM), while ferricrocin renders FhuA refractory to colicin binding. Together, these results demonstrate the importance of the ligand in regulating receptor interactions and the advantages of nanodiscs to study β-barrel membrane proteins in a membrane-like environment.

Contributing editor Alan Mills reports from October's LED 2005 conference in San Diego, California, where delegates heard how the recently achieved record LED flux levels have opened up a large portion of the general lighting market to LED penetration, at least on the basis of cost of ownership.

Abstract 4773 Background: Venous thromboembolism (VTE) prophylaxis has been recommended in clinical guidelines as an appropriate strategy for hospitalized cancer patients based on evidence of reduced VTE events and reduced mortality. However, current guidelines do not specify the appropriate length of VTE prophylaxis in this population. Real world data is needed to understand the prevalence of symptomatic and confirmed VTE for this patient population to help clinicians determine strategies regarding the appropriate duration of treatment. Objective: To document the incidence of symptomatic late VTE events in hospitalized patients who have active cancer. Methods: Charts from 1134 consecutive medical patients age > 60 years who were hospitalized in the Calgary region and discharged between January and February 2008 were abstracted using standardized case record forms. All hospitals in the region use a common unique patient identifier number, thus enabling the tracking of subsequent patient visits to the emergency room, inpatient admissions or outpatient visits occurring anywhere in the region's acute care system. Any identified patient was followed for a subsequent visit related to VTE. Active cancer patients were defined as those who have a cancer diagnosis at hospital admission and have a planned cancer surgery or receiving cancer treatment or were receiving palliative treatment or whose cancer treatment was not specified. Records were excluded if the patient was admitted for VTE or to rule out VTE, receiving chronic anticoagulation, experiencing acute coronary syndromes, had a hospital stay ≤ 3 days, had a remote cancer history, was a surgical or orthopedic patient, or pregnant. Data was collected on the timing of VTE related events for up to 100 days post discharge. Results: A total of 358 patients met criteria over the review period. Seventy-three percent (261/358) of all active cancer patients received mechanical or pharmacological prophylaxis in hospital. Twenty-three percent of these patients were identified as requiring medical care for symptoms associated with VTE. Confirmation of VTE by diagnostic testing occurred in 4.8% (95% CI, 2.6% to 7%) while the other 18% (95% CI, 14.0% to 22%) had diagnostic tests that were negative or inconclusive. The mean length of time to confirmed first VTE event was 38.2 days post admission. Conclusion: This study demonstrates that in a real life setting 23% of active cancer patients would develop symptoms of VTE requiring a health professional's attention with 4.8% having VTE confirmed by diagnostic testing. These events occurred despite thromboprophylaxis in hospital and suggest that the risk of symptomatic VTE could be higher in real life compared to that reported in randomized clinical trials where patients are screened for asymptomatic VTE. These findings show that the prevalence of VTE warrants consideration of extended thromboprophylaxis in active cancer patients, as the benefits of extended prophylactic therapy may outweigh the risks in this population. Disclosures: Hull: sanofi-aventis: Consultancy; LEO Pharma: Consultancy; Pfizer: Consultancy; Portola: Consultancy; Merck: Consultancy; Bayer: Consultancy; Johnson & Johnson: Consultancy. Merali:sanofi-aventis: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; BMS: Consultancy; Abbott: Consultancy; Boehringer Ingelheim: Consultancy; Genzyme: Consultancy; LEO Pharma: Consultancy; Nycomed: Consultancy; Otsuka: Consultancy. Mills:Pfizer: Consultancy; sanofi-aventis: Research Funding. Komari:sanofi-aventis: Employment.

The Allende meteorite has been examined with a view to applying thermoluminescence (TL) to the study of a meteorite's passage through the atmosphere. At least three kinds of TL-bearing minerals are present. A strong peak at 140°C is due to forsterite, and one at 200°C is probably caused by cordierite. By far the most intense TL comes from an alteration product associated with gehlenite. In the 4-cm diameter meteorite examined the 200°C TL varied in intensity across the stone, showing it to be produced by fragmentation. Temperature gradients induced by atmospheric heating can also be derived, and indicate the orientation of the meteorite. Together with fusion crust measurements these results enable the final phase of the meteorite's passage through the atmosphere to be delineated.

Chondrules were extracted from the Bjurbole and Chainpur chondritic meteorites by gentle crushing and hand-picking. Individual chondrules were examined with apparatus incorporating two orthogonal binocular microscopes, and their three major axes measured. Various statistical methods were used to analyse size distribution and shape. These parameters were found to be very similar in chondrules from both meteorites. Maximum chondrule diameters ranged from 0.4 to 2.4 mm, with prominent peaks in distribution at about 1.00 mm. No chondrules with maximum diameters less than 0.4 mm were observed, even after assiduous search. The chondrules departed from sphericity by only small amounts and in a random fashion. These results are discussed in relation to proposed theories for the origin of chondrules and suggest to the authors that the melting of nebula dust-ball agglomerates by some high-energy event was the most probable chondrule-forming process.

The orientation of chondrule long-axes has been examined in relatively friable (Allegan, Bjurbole, Chainpur) and more compacted (Allende, Kediri, Knyahinya, Parnallee) meteorites. Preferential chondrule orientations were detected in the more compacted specimens but were found to be much less well developed in the frible meteorites. We conclude therefore that the chondrule petrofabric was imposed during compaction in the meteorite parent bodies.