Key predictors and burden of meticillin-resistant Staphylococcus aureus infection in comparison with meticillin-susceptible S. aureus infection in an Australian hospital setting.

BACKGROUND: Staphylococcus aureus is associated with significant mortality and increased burden on the healthcare system. Relatively few reliable estimates are available regarding the impact of meticillin-resistant S. aureus (MRSA) infection compared with meticillin-susceptible S. aureus (MSSA) infection. AIMS: To compare patients with MRSA infection and MSSA infection to identify differences in inpatient mortality, length of stay and costs of hospital services, and identify predictors of MRSA as a cause of S. aureus infection. METHODS: An analytical, retrospective, longitudinal study using non-identifiable linked data on adults admitted to hospitals of a health district in Australia with a diagnosis of S. aureus infection over a 10-year period. The main outcome measure was 30-day inpatient mortality. Secondary endpoints included total overnight stays, all-cause inpatient mortality, and hospitalization costs within 1 year of index admission. FINDINGS: Inpatient mortality at 30, 100 and 365 days was estimated to be significantly greater for patients with MRSA infection. The mean additional cost of MRSA infection when controlling for additional factors was $5988 and 4 nights of additional hospital stay per patient within 1 year of index admission. Key predictors of MRSA infection were: date of index admission; higher comorbidity score; greater socio-economic disadvantage; admission to hospital other than via the emergency department; older age; and prior admission to hospital within 28 days of index admission. CONCLUSIONS: MRSA infection is associated with increased inpatient mortality, costs and hospital length of stay compared with MSSA infection. Efforts are required to alleviate the additional burden of MRSA infection on patients and healthcare systems.

Major adverse cardiovascular events in older emergency department patients presenting with non-cardiac medical complaints.

OBJECTIVE: The risk of major adverse cardiovascular events (MACE) for older emergency department (ED) patients presenting with non-cardiac medical complaints is unknown. To apply preventive measures timely, early identification of high-risk patients is incredibly important. We aimed at investigating the incidence of MACE within one year after their ED visit and the predictive value of high-sensitivity cardiac troponin T (hs-cTnT) and N­terminal pro-B-type natriuretic peptide (NT-proBNP) for subsequent MACE. METHODS: This is a substudy of a Dutch prospective cohort study (RISE UP study) in older (≥ 65 years) medical ED patients who presented with non-cardiac complaints. Biomarkers were measured upon ED arrival. Cox-regression analysis was used to determine the predictive value of the biomarkers, when corrected for other possible predictors of MACE, and area under the curves (AUCs) were calculated. RESULTS: Of 431 patients with a median age of 79 years, 86 (20.0%) developed MACE within 1 year. Both hs-cTnT and NT-proBNP were predictive of MACE with an AUC of 0.74 (95% CI 0.68-0.80) for both, and a hazard ratio (HR) of 2.00 (95% CI 1.68-2.39) and 1.82 (95% CI 1.57-2.11) respectively. Multivariate analysis correcting for other possible predictors of MACE revealed NT-proBNP as an independent predictor of MACE. CONCLUSION: Older medical ED patients are at high risk of subsequent MACE within 1 year after their ED visit. While both hs-cTnT and NT-proBNP are predictive, only NT-proBNP is an independent predictor of MACE. It is likely that early identification of those at risk offers a window of opportunity for prevention.

DNA replication at the single-molecule level.

A cell can be thought of as a highly sophisticated micro factory: in a pool of billions of molecules - metabolites, structural proteins, enzymes, oligonucleotides - multi-subunit complexes assemble to perform a large number of basic cellular tasks, such as DNA replication, RNA/protein synthesis or intracellular transport. By purifying single components and using them to reconstitute molecular processes in a test tube, researchers have gathered crucial knowledge about mechanistic, dynamic and structural properties of biochemical pathways. However, to sort this information into an accurate cellular road map, we need to understand reactions in their relevant context within the cellular hierarchy, which is at the individual molecule level within a crowded, cellular environment. Reactions occur in a stochastic fashion, have short-lived and not necessarily well-defined intermediates, and dynamically form functional entities. With the use of single-molecule techniques these steps can be followed and detailed kinetic information that otherwise would be hidden in ensemble averaging can be obtained. One of the first complex cellular tasks that have been studied at the single-molecule level is the replication of DNA. The replisome, the multi-protein machinery responsible for copying DNA, is built from a large number of proteins that function together in an intricate and efficient fashion allowing the complex to tolerate DNA damage, roadblocks or fluctuations in subunit concentration. In this review, we summarize advances in single-molecule studies, both in vitro and in vivo, that have contributed to our current knowledge of the mechanistic principles underlying DNA replication.

Spectroscopy on the B850 band of individual light-harvesting 2 complexes of Rhodopseudomonas acidophila. I. Experiments and Monte Carlo simulations.

The electronic structure of the circular aggregate of 18 bacteriochlorophyll a (BChl a) molecules responsible for the B850 absorption band of the light-harvesting 2 (LH2) complex of the photosynthetic purple bacterium Rhodopseudomonas acidophila has been studied by measuring fluorescence-excitation spectra of individual complexes at 1.2 K. The spectra reveal several well-resolved bands that are obscured in the single, broad B850 band observed in conventional absorption measurements on bulk samples. They are interpreted consistently in terms of the exciton model for the circular aggregate of BChl a molecules. From the energy separation between the different exciton transitions a reliable value of the intermolecular interaction is obtained. The spectra of the individual complexes allow for a distinction between the intra- and the intercomplex disorder. In addition to the random disorder, a regular modulation of the interaction has to be assumed to account for all the features of the observed spectra. This modulation has a C(2) symmetry, which strongly suggests a structural deformation of the ring into an ellipse.

Spectroscopy on the B850 band of individual light-harvesting 2 complexes of Rhodopseudomonas acidophila. II. Exciton states of an elliptically deformed ring aggregate.

Spectroscopy of individual light-harvesting 2 complexes from purple photosynthetic bacteria revealed a deformation of the circular complex into C(2) symmetry. The present work relates the geometry of the deformed aggregate to its spectroscopic properties. Different models of elliptical deformation are discussed and compared with the experimental findings. It is shown that the model with smaller interpigment distances, where the curvature of the ellipse is small, provides the best agreement with fluorescence excitation spectra of individual complexes.

Spectroscopy of individual light-harvesting 2 complexes of Rhodopseudomonas acidophila: diagonal disorder, intercomplex heterogeneity, spectral diffusion, and energy transfer in the B800 band.

This paper reports a detailed spectroscopic study of the B800 absorption band of individual light-harvesting 2 (LH2) complexes of the photosynthetic purple bacterium Rhodopseudomonas acidophila at 1. 2 K. By applying single-molecule detection techniques to this system, details and properties can be revealed that remain obscured in conventional ensemble experiments. For instance, from fluorescence-excitation spectra of the individual complexes a more direct measure of the diagonal disorder could be obtained. Further spectral diffusion phenomena and homogeneous linewidths of individual bacteriochlorophyll a (BChl a) molecules are observed, revealing valuable information on excited-state dynamics. This work demonstrates that it is possible to obtain detailed spectral information on individual pigment-protein complexes, providing direct insight into their electronic structure and into the mechanisms underlying the highly efficient energy transfer processes in these systems.