Cytotoxic rhamnolipid micelles drive acute virulence in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic human pathogen that has developed multi- or even pan-drug resistance toward most frontline and last resort antibiotics, leading to increasing frequency of infections and deaths among hospitalized patients, especially those with compromised immune systems. Further complicating treatment, P. aeruginosa produces numerous virulence factors that contribute to host tissue damage and immune evasion, promoting bacterial colonization and pathogenesis. In this study, we demonstrate the importance of rhamnolipid production in host-pathogen interactions. Secreted rhamnolipids form micelles that exhibited highly acute toxicity toward murine macrophages, rupturing the plasma membrane and causing organellar membrane damage within minutes of exposure. While rhamnolipid micelles (RMs) were particularly toxic to macrophages, they also caused membrane damage in human lung epithelial cells, red blood cells, Gram-positive bacteria, and even noncellular models like giant plasma membrane vesicles. Most importantly, rhamnolipid production strongly correlated with P. aeruginosa virulence against murine macrophages in various panels of clinical isolates. Altogether, our findings suggest that rhamnolipid micelles are highly cytotoxic virulence factors that drive acute cellular damage and immune evasion during P. aeruginosa infections.

Cytotoxic rhamnolipid micelles drive acute virulence in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic human pathogen that has developed multi- or even pan-drug resistance towards most frontline and last resort antibiotics, leading to increasing infections and deaths among hospitalized patients, especially those with compromised immune systems. Further complicating treatment, P. aeruginosa produces numerous virulence factors that contribute to host tissue damage and immune evasion, promoting bacterial colonization and pathogenesis. In this study, we demonstrate the importance of rhamnolipid production in host-pathogen interactions. Secreted rhamnolipids form micelles that exhibited highly acute toxicity towards murine macrophages, rupturing the plasma membrane and causing organellar membrane damage within minutes of exposure. While rhamnolipid micelles (RMs) were particularly toxic to macrophages, they also caused membrane damage in human lung epithelial cells, red blood cells, Gram-positive bacteria, and even non-cellular models like giant plasma membrane vesicles. Most importantly, rhamnolipid production strongly correlated to P. aeruginosa virulence against murine macrophages in various panels of clinical isolates. Altogether, our findings suggest that rhamnolipid micelles are highly cytotoxic virulence factors that drive acute cellular damage and immune evasion during P. aeruginosa infections.

Unprecedented Dual Light-Switching Response of a Metal Dipyridophenazine Complex toward Amyloid-ß Aggregation.

Probes for monitoring protein aggregation with a variety of photophysical properties are of importance for the fundamental understanding of the aggregation process as well as for drug discovery. In this manuscript we report the photoluminescence response of the metal dipyridophenazine complex [Re(CO)3(dppz)(Py)](+) in the presence of aggregated Aß. [Re(CO)3(dppz)(Py)](+) shows an instantaneous increase in photoluminescence with fibrillar Aß (primary light-switching), and an unprecedented further increase in photoluminescence upon light irradiation at 362 nm (secondary light switching). The total increase in photoluminescence amounts to 105-fold, which we show can be used to monitor Aß aggregation in real time.

Effect of left atrial and ventricular abnormalities on renal transplant recipient outcome-a single-center study.

BACKGROUND: Premature cardiovascular (CV) death is the commonest cause of death in renal transplant recipients. Abnormalities of left ventricular (LV) structure (collectively termed uremic cardiomyopathy) and left atrial (LA) dilation, a marker of fluid status and diastolic function, are risk factors for reduced survival in patients with end stage renal disease (ESRD). In the present analysis, we studied the impact of pre-transplant LA and LV abnormalities on survival after successful renal transplantation (RT). METHODS: One hundred nineteen renal transplant recipients (first transplant, deceased donors) underwent cardiovascular MRI (CMR) as part of CV screening prior to inclusion on the waiting list. Data regarding transplant function and patient survival after transplantation were collected. RESULTS: Median post-transplant follow-up was 4.3 years (interquartile range (IQR) 1.9, 6.2). During the post-transplant period, 13 patients returned to dialysis after graft failure and 23 patients died with a functioning graft. Survival analyses, censoring for patients returning to dialysis, showed that pre-transplant LV hypertrophy and elevated LA volume were significantly associated with reduced survival after transplantation. Multivariate Cox regression analyses demonstrated that longer waiting time, poorer transplant function, presence of LV hypertrophy and higher LA volume on screening CMR and female sex were independent predictors of death in patients with a functioning transplant. CONCLUSIONS: Presence of LVH and higher LA volume are significant, independent predictors of death in patients who are wait-listed and proceed with renal transplantation.

Human parvovirus 4 infection, Cameroon.

In a post hoc analysis of samples collected in 2009, we determined seroprevalence of parvovirus 4 (PARV4) among elderly Cameroonians. PARV4 seropositivity was associated with receipt of intravenous antimalarial drugs, intramuscular streptomycin, or an intramuscular contraceptive, but not hepatitis C virus seropositivity. Findings suggest parenteral acquisition of some PARV4 infections.

Stable isotope labeling method targeting terminal tyrosine for relative peptide quantitation using mass spectrometry.

Many neuropeptides lack suitable amino acid residues for modification by existing selective isotope labeling methods and use in relative quantitation by mass spectrometry. To address this issue, a new stable isotope labeling method that targets tyrosine residues by coupling with light cysteine (d(0)) or heavy cysteine (d(2)) in the presence of tyrosinase was developed. Optimal derivatization conditions for 1microM leucine-enkephalin were achieved when 10mM cysteine and 200U/ml tyrosinase at pH 6.8 to 7.2 were used for a 60-min incubation period at room temperature. Under these conditions, leucine-enkephalin present at concentrations as low as 125nM was successfully labeled. When comparisons between the lightly labeled (d(0)) and heavily labeled (d(2)) forms were made, a discrepancy between the actual concentration ratio and the raw peak intensity ratio was observed; this is due to the overlap of an isotopic peak of the d(0) with the monoisotopic peak of d(2). Fortunately, this discrepancy can be corrected by one of two simple computational approaches described. The quantitative labeling of this method to neuropeptides with the terminal tyrosine was confirmed and provides an alternative when other selective isotope-coded affinity tagging methods are not suitable.

Moving targets: the effect of animation on identification of action word representations.

This study examined the conditions under which action representations - presented in both static and dynamic formats - were most readily identified. Preschoolers without disabilities selected graphics corresponding to a spoken word from a computerized four-choice array. Although pre-tests confirmed that the children had all of the stimulus words in their lexical repertoires, their demonstration of that knowledge when the stimuli were presented in graphical form was less robust. The children were generally more challenged by the static representations than the dynamic ones, and their performances were most accurate with the most realistic dynamic representations. A developmental effect was noted, as children's symbol identification became more accurate across the range of representational forms as they got older.

Nutritional supplementation of very old people at hospital discharge increases muscle strength: a randomised controlled trial.

BACKGROUND: Undernutrition is common in older people admitted to hospital, but little is known about how nutritional state changes after discharge. OBJECTIVE: This randomised controlled trial was designed to examine the effect of oral nutritional supplementation of undernourished very old people prepared to take supplements after hospital discharge following acute illness. METHODS: Participants aged>or=75 years with a BMIor=5% during an acute hospital stay were allocated at random to either oral nutritional supplementation for 8 weeks from hospital discharge or to usual care. Primary outcome was change in weight, secondary outcomes were handgrip strength and anthropometry. RESULTS: Of 198 patients eligible to participate, 136 patients (mean age 85 years) were randomised and 76/136 (56%) completed the study. Twenty percent (13/66) of the intervention group withdrew after only 2 weeks, citing intolerance of the supplements. Using intention-to-treat analysis, body weight increased by a mean of 1.6 and 2.2% in the control and intervention groups, respectively, but this between-group difference was not significant (p = 0.188). However, handgrip strength increased more (p=0.055) in the intervention group (13.9%) than in the control group (7.2%). CONCLUSIONS: Oral nutritional supplementation was associated with a greater increase in handgrip strength than in non-supplemented controls and this observation merits further study.

To PEG or not to PEG.

Patients with adequate intestinal function who are unable to eat may benefit from enteral tube feeding. Percutaneous endoscopic gastrostomy (PEG) is preferred when prolonged treatment is envisaged. PEG feeding will reduce morbidity and mortality in many such patients by reversing malnutrition. The increasing numbers of elderly patients with chronic diseases have resulted in an increased demand for PEG placement that has stretched resources. Many patients who are referred for PEGs are frail and the procedure is associated with complications. Careful management and support for the carers in the community are essential. Not all patients benefit from PEG feeding. The aim must be an improvement in the quality of life, not a prolongation of terminal disease.

Nutritional status of elective gastrointestinal surgery patients pre- and post-operatively.

BACKGROUND AND AIMS: Studies have indicated that undernutrition is common on admission to hospital but there is limited data on change in nutritional parameters during the hospital stay. We assessed the nutritional status of elective gastrointestinal surgery patients on admission and documented change in nutritional indices during hospitalisation. METHODS: Two hundred patients aged 18-80 years undergoing elective open gastrointestinal surgery were nutritionally assessed on admission and 150 were reassessed on commencement of oral diet post-surgery. Data were collected on height, weight, upper arm anthropometry and hand-grip dynamometry. RESULTS: On admission BMI <20, 20-24.9 and >25, respectively, were found in 9%, 34% and 57% of patients. Post-surgery, 34% of patients experienced a clinically significant weight loss. Males lost significantly more weight (3.7% vs 1.6%, P<0.001) and tended to lose muscle mass while females preferentially lost subcutaneous fat. CONCLUSIONS: The incidence of undernutrition on admission appears to be lower than previously reported. However, clinically significant weight loss was common and this study highlighted gender differences in the changes in nutritional parameters experienced by gastrointestinal surgery patients. This differential influence of gender warrants further investigation and may have implications for the nutritional management of such patients.