Psl trails guide exploration and microcolony formation in Pseudomonas aeruginosa biofilms.

Bacterial biofilms are surface-associated, multicellular, morphologically complex microbial communities. Biofilm-forming bacteria such as the opportunistic pathogen Pseudomonas aeruginosa are phenotypically distinct from their free-swimming, planktonic counterparts. Much work has focused on factors affecting surface adhesion, and it is known that P. aeruginosa secretes the Psl exopolysaccharide, which promotes surface attachment by acting as 'molecular glue'. However, how individual surface-attached bacteria self-organize into microcolonies, the first step in communal biofilm organization, is not well understood. Here we identify a new role for Psl in early biofilm development using a massively parallel cell-tracking algorithm to extract the motility history of every cell on a newly colonized surface. By combining this technique with fluorescent Psl staining and computer simulations, we show that P. aeruginosa deposits a trail of Psl as it moves on a surface, which influences the surface motility of subsequent cells that encounter these trails and thus generates positive feedback. Both experiments and simulations indicate that the web of secreted Psl controls the distribution of surface visit frequencies, which can be approximated by a power law. This Pareto-type behaviour indicates that the bacterial community self-organizes in a manner analogous to a capitalist economic system, a 'rich-get-richer' mechanism of Psl accumulation that results in a small number of 'elite' cells becoming extremely enriched in communally produced Psl. Using engineered strains with inducible Psl production, we show that local Psl concentrations determine post-division cell fates and that high local Psl concentrations ultimately allow elite cells to serve as the founding population for initial microcolony development.

Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential.

Antiviral compounds that increase the resistance of host tissues represent an attractive class of therapeutic. Here, we show that squalamine, a compound previously isolated from the tissues of the dogfish shark (Squalus acanthias) and the sea lamprey (Petromyzon marinus), exhibits broad-spectrum antiviral activity against human pathogens, which were studied in vitro as well as in vivo. Both RNA- and DNA-enveloped viruses are shown to be susceptible. The proposed mechanism involves the capacity of squalamine, a cationic amphipathic sterol, to neutralize the negative electrostatic surface charge of intracellular membranes in a way that renders the cell less effective in supporting viral replication. Because squalamine can be readily synthesized and has a known safety profile in man, we believe its potential as a broad-spectrum human antiviral agent should be explored.

Nutmeg overdose: Spice not so nice.

BACKGROUND: Nutmeg is a spice common to many kitchens around the world and is being used for many other reasons, such as an aphrodisiac, antimicrobial, antioxidant and analgesic, yet little is known about the toxic effects of nutmeg. CASE REPORT: A case is presented of a young male who took an overdose of nutmeg and presented via ambulance to the Emergency Department with multiple psychiatric and neurological symptoms. The case is described in detail, especially in regard to the prehospital and Emergency Department presentation. Emergency personnel should be aware of nutmeg toxicity due to its ability to mimic many other neurological, cardiac and psychiatric conditions. Therefore, increased awareness of this issue can help minimize the risk of misdiagnosis. The importance of communication between the Emergency personnel and the pre-hospital team is stressed. A discussion is included concerning the pathophysiology of nutmeg toxicity, its history, symptomatology, differential diagnosis and treatment.

A 69-year-old presenting with musculoskeletal low back pain: a case of lumbosacral chordoma.

OBJECTIVE: The purpose of this case report is to describe the presentation of a patient with lumbosacral chordoma characterized by somatic chronic low back pain and intermittent sacral nerve impingement. CASE REPORT: A 69-year-old male presenting to an emergency department (ED) with low back pain was provided analgesics and muscle relaxants then referred for a series of chiropractic treatments. Chiropractic treatment included manipulation, physical therapy, and rehabilitation. After 3 times per week for a total of 4 weeks, re-examination showed little relief of his symptoms. His pain symptoms worsened and he presented to the ED for the second time. Magnetic resonance imaging was performed and revealed a high intensity mass. INTERVENTION AND OUTCOME: The soft tissue mass identified on magnetic resonance imaging was surgically removed. Shortly after the surgery, the patient developed post-operative bleeding and was returned to surgery. During the second procedure, he developed a post-operative hemorrhage related to the development of disseminated intravascular coagulation and subsequently died during the second procedure. A malignant lumbosacral chordoma was diagnosed on pathologic examination. CONCLUSION: This case report describes the presentation of a patient with lumbosacral chordoma presenting with musculoskeletal low back pain. Chordomas are rare with few prominent manifestations. An early diagnosis can potentially make a difference in morbidity and mortality. Due to its insidious nature, it is a difficult diagnosis and one that is often delayed.

Presence of other allergic disease modifies the effect of early childhood traffic-related air pollution exposure on asthma prevalence.

Nitrogen dioxide (NO2), a surrogate measure of traffic-related air pollution (TRAP), has been associated with incident childhood asthma. Timing of exposure and atopic status may be important effect modifiers. We collected cross-sectional data on asthma outcomes from Toronto school children aged 5-9years in 2006. Lifetime home, school and daycare addresses were obtained to derive birth and cumulative NO2 exposures for a nested case-control subset of 1497 children. Presence of other allergic disease (a proxy for atopy) was defined as self-report of one or more of doctor-diagnosed rhinitis, eczema, or food allergy. Generalized estimating equations were used to adjust for potential confounders, and examine hypothesized effect modifiers while accounting for clustering by school. In children with other allergic disease, birth, cumulative and 2006 NO2 were associated with lifetime asthma (OR 1.46, 95% CI 1.08-1.98; 1.37, 95% CI 1.00-1.86; and 1.60, 95% CI 1.09-2.36 respectively per interquartile range increase) and wheeze (OR 1.44, 95% CI 1.10-1.89; 1.31, 95% CI 1.02-1.67; and 1.60, 95% CI 1.16-2.21). No or weaker effects were seen in those without allergic disease, and effect modification was amplified when a more restrictive algorithm was used to define other allergic disease (at least 2 of doctor diagnosed allergic rhinitis, eczema or food allergy). The effects of modest NO2 levels on childhood asthma were modified by the presence of other allergic disease, suggesting a probable role for allergic sensitization in the pathogenesis of TRAP initiated asthma.