Peer-based intervention for acute stress reaction: adaptations by five militaries.

Military service members need to be able to operate under conditions of extreme stress to ensure the success of their team's mission; however, an acute stress reaction (ASR) can compromise team safety and effectiveness by rendering an individual unable to function. Building on an intervention originally developed by the Israel Defense Forces, several countries have developed, tested, and disseminated a peer-based intervention to help service members manage acute stress in others. This paper reviews how five countries (Canada, Germany, Norway, the UK and the USA) adjusted the protocol to fit their organisational culture while retaining essential elements of the original procedure, suggesting there can be interoperability and mutual intelligibility in the management of ASR by military allies. Future research should examine the parameters of effectiveness for this intervention, the impact of intervention on long-term trajectories, and individual differences in managing ASR.

Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer.

Herein, we describe a novel approach in the search for prostate cancer biomarkers, which relies on the transcriptome within tumour exosomes. As a proof-of-concept, we show the presence of two known prostate cancer biomarkers, PCA-3 and TMPRSS2:ERG the in exosomes isolated from urine of patients, showing the potential for diagnosis and monitoring cancer patients status.

Delayed invasion of the kidney and brain by Borrelia crocidurae in plasminogen-deficient mice.

Borrelia crocidurae is an etiologic agent of relapsing fever in Africa and is transmitted to humans by the bite of soft ticks of the genus Ornithodoros. The role of the plasminogen (Plg) activation system for the pathogenicity of B. crocidurae was investigated by infection of Plg-deficient (plg(-/-)) and Plg wild-type (plg(+/+)) mice. No differences in spirochetemia were observed between the plg(-/-) and plg(+/+) mice. However, signs indicative of brain invasion, such as neurological symptoms and/or histopathological changes, were more common in plg(+/+) mice. Quantitative immunohistochemical analysis demonstrated infection of spirochetes in kidney interstitium and brain as soon as 2 days postinoculation. Lower numbers of extravascular spirochetes in plg(-/-) mice during the first days of infection suggested a less efficient invasion mechanism in these mice than in the plg(+/+) mice. The invasion of the kidneys in plg(-/-) mice produced no significant inflammation, as seen by quantitative immunohistochemistry of the CD45 common leukocyte marker. However, significant kidney inflammation was observed with infection in the plg(+/+) mice. In brain, inflammation was more severe in plg(+/+) mice than in plg(-/-) mice, and the numbers of CD45(+) cells increased significantly with duration of infection in the plg(+/+) mice. The results show that invasion of brain and kidney occurs as early as 2 days after inoculation. Also, Plg is not required for establishment of spirochetemia by the organism, whereas it is involved in the invasion of organs.

Allele substitution of the streptokinase gene reduces the nephritogenic capacity of group A streptococcal strain NZ131.

To investigate the role of allelic variants of streptokinase in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), site-specific integration plasmids were constructed, which contained either the non-nephritis-associated streptokinase gene (skc5) from the group C streptococcal strain Streptococcus equisimilis H46A or the nephritis-associated streptokinase gene (ska1) from the group A streptococcal nephritogenic strain NZ131. The plasmids were introduced by electroporation and homologous recombination into the chromosome of an isogenic derivative of strain NZ131, in which the streptokinase gene had been deleted and which had thereby lost its nephritogenic capacity in a mouse model of APSGN. The introduction of a non-nephritis-associated allelic variant of streptokinase did not rescue the nephritogenic capacity of the strain. The mutant and the wild-type strains produced equivalent amounts of streptokinase. Complementation of the ska deletion derivative with the original ska allele reconstituted the nephritogenicity of wild-type NZ131. The findings support the hypothesis that the role of streptokinase in the pathogenesis of APSGN is related to the allelic variant of the protein.

Borrelia pathogenesis research in the post-genomic and post-vaccine era.

In the two years after publication of the genome sequence of Borrelia burgdorferi and reports on human field trials of a vaccine against Lyme borreliosis, there has been further progress in understanding of host-parasite interactions during Lyme borreliosis and relapsing fever. Some mechanisms that Borrelia spirochetes use to avoid elimination and to persist in the host are novel. In addition, the recent discovery of antigenic variation in the Lyme disease agent B. burgdorferi adds to the complexity of the possible virulence properties of this human pathogen.

Pathogenic mechanism of acute post-streptococcal glomerulonephritis.

Considerable knowledge has been accumulated regarding the characteristics of acute post-streptococcal glomerulonephritis (APSGN), and many attempts have been made to identify a streptococcal factor or factors responsible for triggering this disease. However, the pathogenic mechanism behind APSGN remains largely unknown. As glomerular deposition of C3 is generally demonstrated before that of IgG in the disease process, it is likely that the inflammatory response is initiated by renal deposition of a streptococcal product, rather than by deposition of antibodies or pre-formed immune complexes. During recent years, a number of streptococcal products have been suggested to be involved in the pathogenic process. In this review, possible roles of these factors are discussed in the context of the clinical and renal findings most often demonstrated in patients with APSGN. Streptokinase was observed to be required in order to induce signs of APSGN in mice, and a number of findings suggest that the initiation of the disease may occur as a result of renal binding by certain nephritis-associated variants of this protein. However, additional factors may be required for the development of the disease.

Streptokinase as a mediator of acute post-streptococcal glomerulonephritis in an experimental mouse model.

Group A streptococcal infections are sometimes followed by the inflammatory kidney disease acute post-streptococcal glomerulonephritis (APSGN). To test the importance of streptokinase in the pathogenesis of this disease, isogenic strains of the nephritis isolate NZ131, differing only in the ability to produce streptokinase of the nephritis-associated ska1 genotype, were used for infection in a mouse tissue cage model for APSGN. Streptokinase production was found to be a prerequisite for the capacity of the strain to induce APSGN in mice. In addition, streptokinase was demonstrated in the kidneys of mice infected with the nephritogenic NZ131 and EF514 strains. After infection with the nonnephritogenic strain S84, neither streptokinase nor C3 deposition were observed. Deposition of streptokinase in the glomeruli was detected as soon as 4 days after infection. These findings provide support for the hypothesis that streptokinase initiates the nephritis process by glomerular deposition, which leads to local activation of the complement cascade. Detection of streptokinase in kidney tissue increased with the degree of glomerular hypercellularity. Thus, the severity of the pathological process may be a reflection of the degree of streptokinase deposition.

An experimental model for acute poststreptococcal glomerulonephritis in mice.

A number of factors have been implicated in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN). The lack of a reliable animal model has made it difficult to further examine the role of these factors in the pathogenetic process. In this report, we present a tissue cage model in mice for the study of APSGN. Morphological and immunohistological changes in the kidney, resembling those of APSGN in man, were induced at high frequency in the experimental model after infection with group A streptococcal nephritis isolates. Nephritis-associated strain induced hypercellularity, occlusion of capillaries, and C3 deposition at high frequencies compared to the changes induced in animals infected with a non-nephritis-associated strain and non-infected controls. In animals infected with a nephritis isolate, hematuria and proteinuria were also detected. If penicillin treatment was initiated on the third day of infection, the development of the nephritis process was prevented. Streptokinase, as well as preabsorbing antigen and streptococcal pyrogenic exotoxin B (SpeB), have been implicated in the pathogenesis of APSGN. These proteins, as well as SpeA and SpeF, were detected in the fluids of the infectious focus, regardless of the origin of the strains and whether or not glomerulonephritis was seen. Antibodies to streptokinase were evoked in the majority of the infected animals. This immune response did not correlate with the nephritic process since hypercellularity was also seen in animals which lacked detectable streptokinase antibodies. The results show that the mouse tissue cage model can be used to study APSGN and to evaluate factors involved in the pathogenesis of the disease.

Streptokinase gene polymorphism in group A streptococci isolated from Ethiopian children with various disease manifestations.

Certain variants of streptokinase from group A streptococci have been associated with acute post-streptococcal glomerulonephritis (APSGN). The streptokinase gene (ska) has previously been grouped into nine different polymorphic genotypes of which ska1, ska2, ska6, and ska9 were identified in group A streptococci associated with clinical and experimental APSGN. A total of 53 group A streptococci isolated from Ethiopian children: five from acute rheumatic fever, 18 from APSGN, ten each from tonsillitis, impetigo and healthy carriers, were analyzed for ska gene polymorphism using polymerase chain reaction (PCR) and restriction enzyme analysis. The frequency of the nephritis-associated streptokinase genotypes was 83% among the APSGN isolates and 74% in the non-ASPGN isolates. ska2 was the most commonly found genotype with a frequency of 64% among all isolates, 66% among the APSGN isolates, and 63% among the non-APSGN isolates. ska1 was identified in 13% among all isolates and 17% among the APSGN isolates. Seventeen non-APSGN isolates from Scandinavian countries were studied for comparison and all carried either ska1 or ska2. The other nephritis-associated ska6 and ska9 were not detected among the 53 Ethiopian isolates. ska1 was exclusively associated with serum opacity reaction (SOR) producers. ska2 was evenly distributed among SOR-positive and SOR-negative isolates. The other genotypes were detected only among SOR-negative strains. The findings of the present study showed an even distribution of the nephritis-associated streptokinase gene among group A streptococcal isolates with no correlation to disease pattern. Thus additional factors must also be operative in the pathogenesis of APSGN.

Bacterial contamination of organic dusts: effects on pulmonary cell reactions.

The influence of water extracts from different organic dusts on the number of free lung cells was studied in short-term exposure experiments. A large increase in the number of leukocytes was found 24 hours after exposure to extracts from cotton and hay. The number of macrophages was not affected. The increase was greater when the dusts were incubated at 37 C and 100% relative humidity prior to the preparation of the extract. This procedure caused an increase in the number of bacteria. When different bacterial species were studied endotoxin-producing strains were found to cause the largest effect.