Trimeric autotransporter adhesins: variable structure, common function.

Trimeric autotransporter adhesins (TAAs) are important virulence factors in gram-negative pathogens. Despite the variety of hosts ranging from plants to mammals and the specialized regulation of TAAs, their molecular organization follows surprisingly simple rules: they form trimeric surface structures with a head-stalk-anchor architecture. The head and stalk are composed of a small set of domains, building blocks that are frequently arranged repetitively. We propose that this repetitive arrangement facilitates recombination of domains to modulate the specificity of the common function: adhesion to the host

Prevention

Rare but regularly recurring complications are leading to ongoing regulation of the commercial, non-medical whole-body electromyostimulation (WB-EMS) market. In addition to the revised German Radiation Protection Statutes (NiSV), the Deutsche Industrie Norm (DIN) 33961-5 was recently published with safety policies for WB-EMS application, anchoring both relative and absolute contraindications for WB-EMS for the first time. The purpose of this article is to justify the rationale of contraindications in a commercial setting and to support their consistent application.While the relative contraindicationsappear plausible and uncritical, absolute contraindications for WB-EMS are much more debatable. In fact, some absolute contraindications (e.g. diabetes mellitus) could be safely addressed by WB-EMS at least after careful medical anamnesis and competent, close supervision. However, this requires sound knowledge of WB-EMS on the part of physicians and instructors, low user-trainer ratios and prompt medical care in an emergency.However, considering the multitude of different settings of commercial WB-EMS, in extreme cases with hardly supervised, only video-guided WB-EMS sessions, the necessary accurateness and expertise for safe WB-EMS is not always guaranteed. That there is no mandatory licensing of WB-EMS instructors, the key players in WB-EMS, underscores the concern. Whilst acknowledging the multitude of high-quality suppliers, it is advised thatthe commercial, non-medical WB-EMS sector as a whole to be wary of indications with significantly increased complication potential. Lastly, the mandatory acceptance of the contraindications listed in DIN 33961-5 might be considered as an inevitable step towards preventing overregulation by official authorities.KEY WORDS: Whole-Body Electromyostimulation, DIN 33961-5, Commercial Application, Guidelin

Obligatory role of gamma interferon for host survival in a murine model of infection with Burkholderia pseudomallei.

Burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative bacterium capable of causing either acute lethal sepsis or chronic but eventually fatal disease in infected individuals. However, despite the clinical importance of this infection in areas where it is endemic, there is essentially no information on the mechanisms of protective immunity to the bacterium. We describe here a murine model of either acute or chronic infection with B. pseudomallei in Taylor Outbred (TO) mice which mimics many features of the human pathology. Intraperitoneal infection of TO mice at doses of >10(6) CFU resulted in acute septic shock and death within 2 days. In contrast, at lower doses mice were able to clear the inoculum from the liver and spleen over a 3- to 4-week period, but persistence of the organism at other sites resulted in a chronic infection of between 2 and 16 months duration which was eventually lethal in all of the animals tested. Resistance to acute infection with B. pseudomallei was absolutely dependent upon the production of gamma interferon (IFN-gamma) in vivo. Administration of neutralizing monoclonal antibody against IFN-gamma lowered the 50% lethal dose from >5 x 10(5) to ca. 2 CFU and was associated with 8,500- and 4,400-fold increases in the bacterial burdens in the liver and spleen, respectively, together with extensive destruction of lymphoid architecture in the latter organ within 48 h. Neutralization of either tumor necrosis factor alpha or interleukin-12 but not granulocyte-macrophage colony-stimulating factor, also increased susceptibility to infection in vivo. Together, these results provide the first evidence of a host protective mechanism against B. pseudomallei. The rapid production of IFN-gamma within the first day of infection determines whether the infection proceeds to an acute lethal outcome or becomes chronic