Intramacrophage survival of uropathogenic Escherichia coli : differences between diverse clinical isolates and between mouse and human macrophages

Uropathogenic E. coli (UPEC) are the primary cause of urinary tract infections. Recent studies have demonstrated that UPEC can invade and replicate within epithelial cells, suggesting that this bacterial pathogen may occupy an intracellular niche within the host. Given that many intracellular pathogens target macrophages, we assessed the interactions between UPEC and macrophages. Colonization of the mouse bladder by UPEC strain CFT073 resulted in increased expression of myeloid-restricted genes, consistent with the recruitment of inflammatory macrophages to the site of infection. In in vitro assays, CFT073 was able to survive within primary mouse bone marrow-derived macrophages (BMM) up to 24 h post-infection. Three additional well-characterized clinical UPEC isolates associated with distinct UTI symptomatologies displayed variable long-term survival within BMM. UPEC strains UTI89 and VR50, originally isolated from patients with cystitis and asymptomatic bacteriuria respectively, showed elevated bacterial loads in BMM at 24 h post-infection as compared to CFT073 and the asymptomatic bacteriuria strain 83972. These differences did not correlate with differential effects on macrophage survival or initial uptake of bacteria. E. coli UTI89 localized to a Lamp1+ vesicular compartment within BMM. In contrast to survival within mouse BMM, intracellular bacterial loads of VR50 were low in both human monocyte-derived macrophages (HMDM) and in human T24 bladder epithelial cells. Collectively, these data suggest that some UPEC isolates may subvert macrophage anti-microbial pathways, and that host species differences may impact on intracellular UPEC survival.

Clinical and economic outcomes of nutrition interventions across the continuum of care

Optimal nutrition across the continuum of care plays a key role in the short- and long-term clinical and economic outcomes of patients. Worldwide, an estimated one-quarter to one-half of patients admitted to hospitals each year are malnourished. Malnutrition can increase healthcare costs by delaying patient recovery and rehabilitation and increasing the risk of medical complications. Nutrition interventions have the potential to provide cost-effective preventive care and treatment measures. However, limited data exist on the economics and impact evaluations of these interventions. In this report, nutrition and health system researchers, clinicians, economists, and policymakers discuss emerging global research on nutrition health economics, the role of nutrition interventions across the continuum of care, and how nutrition can affect healthcare costs in the context of hospital malnutrition.

Exploring Australian intensive care physicians clinical judgement during donation after cardiac death : an exploratory qualitative study

BACKGROUND: Donation after Cardiac Death (DCD) is one possible solution to the world wide organ shortage. Intensive care physicians are central to DCD becoming successful since they are responsible for making the clinical judgements and decisions associated with DCD. Yet international evidence shows health care professionals have not embraced DCD and are often reluctant to consider it as an option for patients. PURPOSE: To explore intensive care physicians' clinical judgements when selecting a suitable DCD candidate. METHODS: Using interpretative exploratory methods six intensive care physicians were interviewed from three hospital sites in Australia. Following verbatim transcription, data was subjected to thematic analysis. FINDINGS: Three distinct themes emerged. Reducing harm and increasing benefit was a major focus of intensive care physicians during determination of DCD. There was an acceptance of DCD if there was clear evidence that donation was what the patient and family wanted. Characteristics of a defensible decision reflected the characteristics of sequencing, separation and isolation, timing, consensus and collaboration, trust and communication to ensure that judgements were robust and defensible. The final theme revealed the importance of minimising uncertainty and discomfort when predicting length of survival following withdrawal of life-sustaining treatment. CONCLUSION: DCD decisions are made within an environment of uncertainty due to the imprecision associated with predicting time of death. Lack of certainty contributed to the cautious and collaborative strategies used by intensive care physicians when dealing with patients, family members and colleagues around end-of-life decisions, initiation of withdrawal of life-sustaining treatment and the discussion about DCD. This study recommends that nationally consistent policies are urgently needed to increase the degree of certainty for intensive care staff concerning the DCD processes.

NT-ProBNP levels in saliva and its clinical relevance to heart failure

Background: Current blood based diagnostic assays to detect heart failure (HF) have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body's health and well being and similar to 20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels. Methods: Saliva samples were collected from healthy volunteers (n = 40) who had no underlying heart conditions and HF patients (n = 45) at rest. Samples were stored at -80 degrees C until analysis. A customised homogeneous sandwich AlphaLISA((R)) immunoassay was used to quantify NT-proBNP levels in saliva. Results: Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37) and the correlation was r(2) = 0.78 (p<0.01, y = 1.705 x +1910.8). The median salivary NT-proBNP levels in the healthy and HF participants were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay showed a clinical sensitivity of 82.2% and specificity of 100%, positive predictive value of 100% and negative predictive value of 83.3%, with an overall diagnostic accuracy of 90.6%. Conclusion: We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations.

Saliva as an emerging biofluid for clinical diagnosis and applications of MEMS/NEMS in salivary diagnostics

Saliva as a biological fluid is gaining wider acceptance for diagnosing diseases. The growing interest in saliva as a biological fluid is due to its noninvasiveness, ease of use, cost-effectiveness, and multiple sample collection possibilities as well as minimal risk to health care professionals of contracting infectious organisms such as HIV and Hep B. However, the clinical translation of saliva is hampered by our lack of understanding of the biomolecular transportation from blood into saliva, the diurnal variations of biomolecules present in saliva, and relatively low levels of analytes (100th to a 1000th fold less than in blood). We provide information on the current status of salivary research, salivary diagnostics empowered by nanotechnology, and future prospects in this emerging field of saliva diagnostics.