Staphylococcal toxic shock syndrome 2000-2006: epidemiology, clinical features, and molecular characteristics

Introduction

Circulating strains of Staphylococcus aureus (SA) have changed in the last 30 years including the emergence of community-associated methicillin-resistant SA (MRSA). A report suggested staphylococcal toxic shock syndrome (TSS) was increasing over 2000–2003. The last population-based assessment of TSS was 1986.

Methods

Population-based active surveillance for TSS meeting the CDC definition using ICD-9 codes was conducted in the Minneapolis-St. Paul area (population 2,642,056) from 2000–2006. Medical records of potential cases were reviewed for case criteria, antimicrobial susceptibility, risk factors, and outcome. Superantigen PCR testing and PFGE were performed on available isolates from probable and confirmed cases.

Results

Of 7,491 hospitalizations that received one of the ICD-9 study codes, 61 TSS cases (33 menstrual, 28 non-menstrual) were identified. The average annual incidence per 100,000 of all, menstrual, and non-menstrual TSS was 0.52 (95% CI, 0.32–0.77), 0.69 (0.39–1.16), and 0.32 (0.12–0.67), respectively. Women 13–24 years had the highest incidence at 1.41 (0.63–2.61). No increase in incidence was observed from 2000–2006. MRSA was isolated in 1 menstrual and 3 non-menstrual cases (7% of TSS cases); 1 isolate was USA400. The superantigen gene tst-1 was identified in 20 (80%) of isolates and was more common in menstrual compared to non-menstrual isolates (89% vs. 50%, p = 0.07). Superantigen genes sea, seb and sec were found more frequently among non-menstrual compared to menstrual isolates [100% vs 25% (p = 0.4), 60% vs 0% (p<0.01), and 25% vs 13% (p = 0.5), respectively].

Discussion

TSS incidence remained stable across our surveillance period of 2000–2006 and compared to past population-based estimates in the 1980s. MRSA accounted for a small percentage of TSS cases. tst-1 continues to be the superantigen associated with the majority of menstrual cases. The CDC case definition identifies the most severe cases and has been consistently used but likely results in a substantial underestimation of the total TSS disease burden.     

The Tiam1 PDZ Domain Couples to Syndecan1 and Promotes Cell-Matrix Adhesion

The T-cell lymphoma invasion and metastasis gene 1 (Tiam1) is a guanine exchange factor (GEF) for the Rho-family GTPase Rac1 that is crucial for the integrity of adherens junctions, tight junctions, and cell-matrix interactions. This GEF contains several protein-protein interaction domains, including a PDZ domain. Earlier studies identified a consensus PDZ-binding motif and a synthetic peptide capable of binding to the Tiam1 PDZ domain, but little is known about its ligand specificity and physiological role in cells. Here, we investigated the structure, specificity, and function of the Tiam1 PDZ domain. We determined the crystal structures of the Tiam1 PDZ domain free and in complex with a “model” peptide, which revealed the structural basis for ligand specificity. Protein database searches using the consensus PDZ-binding motif identified two eukaryotic cell adhesion proteins, Syndecan1 and Caspr4, as potential Tiam1 PDZ domain binding proteins. Equilibrium binding experiments confirmed that C-terminal peptides derived from Syndecan1 and Caspr4 bound the Tiam1 PDZ domain. NMR chemical shift perturbation experiments indicated that the Tiam1 PDZ/Syndecan1 and PDZ/Caspr4 complexes were structurally distinct and identified key residues likely to be responsible for ligand selectivity. Moreover, cell biological analysis established that Syndecan1 is a physiological binding partner of Tiam1 and that the PDZ domain has a function in cell-matrix adhesion and cell migration. Collectively, our data provide insight into the structure, specificity, and function of the Tiam1 PDZ domain. Importantly, our data report on a physiological role for the Tiam1 PDZ domain and establish a novel link between two previously unrelated signal transduction pathways, both of which are implicated in cancer.     

Why inter‐country loans will not help sumatra's elephants

Asian elephants (Elephas maximus) in western zoos are likely to become extinct unless elephants are regrouped into breeding units or additional elephants are imported from range States. There have been proposals for the export of elephants from elephant camps in Sumatra, Indonesia. In exchange, zoos would be expected to provide funds or support ‘in kind’ for the camps or for the conservation of wild elephants. Most of the elephants in the Sumatran camps were captured because of crop‐raiding problems around protected areas or because elephant habitat has been and continues to be lost to development schemes and illegal conversion of protected areas to agriculture. Capture‐related mortality rates are high and conditions in the camps are poor, with low standards of veterinary care and husbandry. This is partly due to over‐crowding and inadequate budgets. It might seem, therefore, that the loan of elephants to western zoos would improve the lot of these elephants and reduce the pressures on the camps. However, we show that both total and annual demand for Asian elephants, and particularly Sumatran elephants (E. m. sumatranus), by western zoos are low, and consequently the resources generated by any loan scheme would be limited. Elephant loan schemes are unlikely to have significant beneficial impact on either the conservation or welfare of elephants in Sumatra. More importantly, a credible loan scheme would require a permanent moratorium on the capture of wild elephants in Sumatra. Such a moratorium is needed to prevent illicit captures for sale or loan. At present, wild elephants are caught to replace those that die at the camps or are moved to other facilities. Without a moratorium, the loan of elephants to overseas zoos would contribute directly to reductions in wild elephant populations in Sumatra. However, a moratorium is likely to prove impossible to enforce, and this alone should call into question the desirability of any loan scheme. Zoo Biol 25:235–246, 2006. © 2006 Wiley‐Liss, Inc.     

Morphological and kinematic basis of the hummingbird flight stroke: scaling of flight muscle transmission ratio

Hummingbirds (Trochilidae) are widely known for their insect-like flight strokes characterized by high wing beat frequency, small muscle strains and a highly supinated wing orientation during upstroke that allows for lift production in both halves of the stroke cycle. Here, we show that hummingbirds achieve these functional traits within the limits imposed by a vertebrate endoskeleton and muscle physiology by accentuating a wing inversion mechanism found in other birds and using long-axis rotational movement of the humerus. In hummingbirds, long-axis rotation of the humerus creates additional wing translational movement, supplementing that produced by the humeral elevation and depression movements of a typical avian flight stroke. This adaptation increases the wing-to-muscle-transmission ratio, and is emblematic of a widespread scaling trend among flying animals whereby wing-to-muscle-transmission ratio varies inversely with mass, allowing animals of vastly different sizes to accommodate aerodynamic, biomechanical and physiological constraints on muscle-powered flapping flight.     

High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma

In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2-3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED), 3 times/week, 10-weeks). The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome), and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th), cytolytic (CTL), and regulatory (Treg) T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF) by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden), increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression), lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity), and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis). These results suggest that the deleterious effects of high trait anxiety could be: exacerbated by life-stressors, accentuated by the stress of cancer diagnosis/treatment, and mediate increased tumor progression and/or metastasis. Therefore, it may be beneficial to investigate the use of chemotherapy-compatible anxiolytic treatments immediately following cancer diagnosis, and during cancer treatment/survivorship.     

Lipoteichoic acid is an important microbe-associated molecular pattern of Lactobacillus rhamnosus GG

Background

Receptors with a single transmembrane (TM) domain are essential for the signal transduction across the cell membrane. NMR spectroscopy is a powerful tool to study structure of the single TM domain. The expression and purification of a TM domain in Escherichia coli (E.coli) is challenging due to its small molecular weight. Although ketosteroid isomerase (KSI) is a commonly used affinity tag for expression and purification of short peptides, KSI tag needs to be removed with the toxic reagent cyanogen bromide (CNBr).

Result

The purification of the TM domain of p75 neurotrophin receptor using a KSI tag with the introduction of a thrombin cleavage site is described herein. The recombinant fusion protein was refolded into micelles and was cleaved with thrombin. Studies showed that purified protein could be used for structural study using NMR spectroscopy.

Conclusions

These results provide another strategy for obtaining a single TM domain for structural studies without using toxic chemical digestion or acid to remove the fusion tag. The purified TM domain of p75 neurotrophin receptor will be useful for structural studies.     

Effects of synthetic cohesin-containing scaffold protein architecture on binding dockerin-enzyme fusions on the surface of Lactococcus lactis

Background

In the last years, the biotechnological production of platform chemicals for fuel components has become a major focus of interest. Although ligno-cellulosic material is considered as suitable feedstock, the almost inevitable pretreatment of this recalcitrant material may interfere with the subsequent fermentation steps. In this study, the fungus Ustilago maydis was used to produce itaconic acid as platform chemical for the synthesis of potential biofuels such as 3-methyltetrahydrofuran. No studies, however, have investigated how pretreatment of ligno-cellulosic biomass precisely influences the subsequent fermentation by U. maydis. Thus, this current study aims to first characterize U. maydis in shake flasks and then to evaluate the influence of three exemplary pretreatment methods on the cultivation and itaconic acid production of this fungus. Cellulose enzymatically hydrolysed in seawater and salt-assisted organic-acid catalysed cellulose were investigated as substrates. Lastly, hydrolysed hemicellulose from fractionated beech wood was applied as substrate.

Results

U. maydis was characterized on shake flask level regarding its itaconic acid production on glucose. Nitrogen limitation was shown to be a crucial condition for the production of itaconic acid. For itaconic acid concentrations above 25 g/L, a significant product inhibition was observed. Performing experiments that simulated influences of possible pretreatment methods, U. maydis was only slightly affected by high osmolarities up to 3.5 osmol/L as well as of 0.1 M oxalic acid. The production of itaconic acid was achieved on pretreated cellulose in seawater and on the hydrolysed hemicellulosic fraction of pretreated beech wood.

Conclusion

The fungus U. maydis is a promising producer of itaconic acid, since it grows as single cells (yeast-like) in submerged cultivations and it is extremely robust in high osmotic media and real seawater. Moreover, U. maydis can grow on the hemicellulosic fraction of pretreated beech wood. Thereby, this fungus combines important advantages of yeasts and filamentous fungi. Nevertheless, the biomass pretreatment does indeed affect the subsequent itaconic acid production. Although U. maydis is insusceptible to most possible impurities from pretreatment, high amounts of salts or residues of organic acids can slow microbial growth and decrease the production. Consequently, the pretreatment step needs to fit the prerequisites defined by the actual microorganisms applied for fermentation.     

Using the Functional Movement Screen™ to evaluate the effectiveness of training

The Functional Movement Screen? (FMS) has demonstrated some efficacy in the prediction of injuries and is thus used by many practitioners to make recommendations for exercise. However, questions remain regarding its utility as a means to evaluate the effectiveness of training. Sixty firefighters volunteered to participate, and their FMS scores were examined before and after 12 weeks of training. Individuals were graded on how they chose to perform rather than how they could perform. The participants were assigned to 1 of 3 groups: intervention 1, intervention 2, or control. The 2 intervention groups received three 1.5-hour training sessions each week and differed in the emphasis that was placed on movement quality. Sagittal and frontal plane videos were used to grade the FMS with 3 methods: the standard 0-3 scale, a 100-point scale that weighted specific compensations (research standard), and a modified 100-point scale whereby grades were assigned based on the total number of compensations present. There were no significant differences in the total FMS scores for any group posttraining. However, the scores of 85% of the firefighters who did not receive training did change. The 100-point scale methods resulted in more FMS score changes posttraining, but the between-group interactions were identical to those found with the standard scoring method. The control group's scores were not consistent pretraining and posttraining; thus, the influence of each intervention could not be evaluated. Currently, the FMS might provide a momentary impression of general movement quality, although further efforts would likely assist in the development of better ways to implement the test, interpret the results, and generate reliable scores.