A new human challenge model for testing heat-stable toxin-based vaccine candidates for enterotoxigenic Escherichia coli diarrhea - dose optimization, clinical outcomes, and CD4+T cell responses

Enterotoxigenic Escherichia coli (ETEC) are a common cause of diarrheal illness in young children and travelers. There is yet no licensed broadly protective vaccine against ETEC. One promising vaccine development strategy is to target strains expressing the heat-stable toxin (ST), particularly the human ST (STh), since infections with these strains are among the leading causes of diarrhea in children in low-and-middle income countries. A human challenge model based on an STh-only ETEC strain will be useful to evaluate the protective efficacy of new ST-based vaccine candidates. To develop this model, we experimentally infected 21 healthy adult volunteers with the epidemiologically relevant STh-only ETEC strain TW10722, identified a suitable dose, assessed safety, and characterized clinical outcomes and immune responses caused by the infection. Doses of 1x10(10) colony-forming units (CFU) of TW10722 gave a suitable attack risk of 67% for moderate or severe diarrhea and an overall diarrhea attack risk of 78%. Non-diarrheal symptoms were mostly mild or moderate, and there were no serious adverse events. During the first month after ingesting the challenge strain, we measured significant increases in both activated CD4+ T cells and levels of serum IgG and IgA antibodies targeting coli surface antigen 5 (CS5) and 6 (CS6), as well as the E. coli mucinase YghJ. The CS5-specific CD4+ T cell and antibody responses were still significantly elevated one year after experimental infection. In conclusion, we have developed a safe STh-only ETEC-based human challenge model which can be efficiently used in Phase 2B trials to evaluate the protective efficacy of new ST-based vaccine candidates

“Es fundamental que la información que se transmita sea confiable”

El flamante Doctor Honoris Causa de la UNLP, Emilio Luque Fadón, de la Universidad Autónoma de Barcelona, fue uno de los conferencistas de CACIC 2017. Durante su estadía por la ciudad de La Plata, el español habló acerca de las nuevas tecnologías, su tolerancia a los fallos y el consumo energético.Facultad de Informátic

Genre as tool in the transmission of practice over time and across professional boundaries

In this article, we are concerned with the processes through which a central activity in the natural sciencesclassificationis instantiated in the writing practices of psychotherapists. We examined several psychotherapists\u27 grammatical, lexical, and rhetorical strategies for writing their initial evaluations of their clients\u27 problems. Using membership categorization device analysis from ethnomethodology, we examined several therapists\u27 written initial evaluations for their use of microlevel categories and categorizations derived both from clients\u27 own (oral) representations and the therapists\u27 professional repertoire. The resulting analysis suggests that clients\u27 emic, contextually grounded expressions are absorbed into a monological account reflecting the therapist\u27 s professional interpretive framework. The therapist thus translates the client\u27 s concerns into a set of meanings compatible with the classifications of psychopathology of the American Psychiatric Association\u27s (1994) Diagnostic and Statistical Manual of Mental Disorders (4th ed.). The resulting written account supports a billable diagnosis thereby fulfilling its institutional purpose. It fails, however, to serve another important purpose to many therapists, which is helping the therapist to guide the therapy process by providing a record of the client\u27s perspective of his or her lifeworld. Copyright © 1997, Regents of the University of California on behalf of the Laboratory of Comparative Human Cognition

Dihomo-γ-linolenic acid inhibits tumour necrosis factor-α production by human leucocytes independently of cyclooxygenase activity

Dietary oils (such as borage oil), which are rich in γ-linolenic acid (GLA), have been shown to be beneficial under inflammatory conditions. Dihomo-GLA (DGLA) is synthesized directly from GLA and forms a substrate for cyclooxygenase (COX) enzymes, resulting in the synthesis of lipid mediators (eicosanoids). In the present study, the immunomodulatory effects of DGLA were investigated and compared with those of other relevant fatty acids. Freshly isolated human peripheral blood mononuclear cells (PBMC) were cultured in fatty acid (100 µm)-enriched medium for 48 hr. Subsequently, cells were stimulated with lipopolysaccharide (LPS) for 20 hr and the cytokine levels were measured, in supernatants, by enzyme-linked immunosorbent assay (ELISA). Phospholipids were analysed by gas chromatography. Fatty acids were readily taken up, metabolized and incorporated into cellular phospholipids. Compared with the other fatty acids tested, DGLA exerted pronounced modulatory effects on cytokine production. Tumour necrosis factor-α (TNF-α) and interleukin (IL)-10 levels were reduced to 60% of control levels, whereas IL-6 levels were not affected by DGLA. Kinetic studies showed that peak levels of TNF-α, occurring early after LPS addition, were inhibited strongly, whereas IL-10 levels were not affected until 15 hr after stimulation. Both the reduction of cytokine levels and the decrease in arachidonic acid levels in these cells, induced by DGLA, were dose dependent, suggesting a shift in eicosanoid-subtype synthesis. However, although some DGLA-derived eicosanoids similarly reduced TNF-α levels, the effects of DGLA were probably not mediated by COX products, as the addition of indomethacin did not alter the effects of DGLA. In conclusion, these results suggest that DGLA affects cytokine production by human PBMC independently of COX activation