Multicenter, International Study of MIC/ MEC Distributions for definition of epidemiological cutoff values for sporothrix species identified by molecular methods

Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrix schenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 /ml; itraconazole, 2 and 2 μg/ml; posaconazole, 2 and 2 μg/ml; and voriconazole, 64 and 32 μg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 μg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana. These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.A. Espinel-Ingroff, D. P. B. Abreu, R. Almeida-Paes, R. S. N. Brilhante, A. Chakrabarti, A. Chowdhary, F. Hagen, S. Córdoba, G. M. Gonzalez, N. P. Govender, J. Guarro, E. M. Johnson, S. E. Kidd, S. A. Pereira, A. M. Rodrigues, S. Rozental, M. W. Szeszs, R. Ballesté Alaniz, A. Bonifaz, L. X. Bonfietti, L. P. Borba-Santos, J. Capilla, A. L. Colombo, M. Dolande, M. G. Isla, M. S. C. Melhem, A. C. Mesa-Arango, M. M. E. Oliveira, M. M. Panizo, Z. Pires de Camargo, R. M. Zancope-Oliveira, J. F. Meis, J. Turnidge

A Novel Redox Method for Rapid Production of Functional Bi-Specific Antibodies For Use in Early Pilot Studies

We demonstrate here a rapid alternative method for the production of functional bi-specific antibodies using the mild reducing agent 2-mercaptoethanesulfonic acid sodium salt (MESNA). Following reduction of a mixture of two monoclonal antibodies with MESNA to break inter heavy chain bonds, this solution is dialysed under oxidising conditions and antibodies are allowed to reform. During this reaction a mixture of antibodies is formed, including parental antibodies and bi-specific antibody. Bi-specific antibodies are purified over two sequential affinity columns. Following purification, bi-specificity of antibodies is determined in enzyme-linked immunosorbent assays and by flow cytometry. Using this redox method we have been successful in producing hybrid and same-species bi-specific antibodies in a time frame of 6–10 working days, making this production method a time saving alternative to the time-consuming traditional heterohybridoma technology for the production of bi-specific antibodies for use in early pilot studies. The use of both rat and mouse IgG antibodies forming a rat/mouse bi-specific antibody as well as producing a pure mouse bi-specific antibody and a pure rat bi-specific antibody demonstrates the flexibility of this production method

Energia solar disponible en la ciudad de México

CIES2020 - XVII Congresso Ibérico e XIII Congresso Ibero-americano de Energia SolarRESUMEN: En el año 2014, con recursos del Instituto de Ciencia y Tecnología del Distrito Federal (PINVII-7), se instalaron 10 piranómetros en las estaciones de la Red Automática de Monitoreo Atmosférico (RAMA), de la Secretaría del Medio Ambiente de la Ciudad de México. Estos instrumentos se encuentran conectados al sistema de adquisición de datos de la RAMA por lo que existe una medición cada minuto. Los instrumentos fueron calibrados por el Servicio Solarimétrico Mexicano y referenciados a la Escala Radiométrica Mundial, garantizando que la calibración de las mediciones. Con la información solarimétrica de esta red, durante sus primeros cuatro años, se elaboraron mapas de Irradiación Solar Global en superficie, así como la Base de Datos correspondiente. Toda la información y los mapas, se encuentra disponible en la página de Internet del Servicio Solarimétrico Mexicano y puede ser consultada libremente (http://areas.geofisica.unam.mx/solarimetrico/). Este proyecto no tiene fecha para concluir, por lo que cada año se incrementará la base de datos y los mapas se volverán a elaborar anualmente para aumentar su certidumbre.ABSTRACT: In 2014, with funds of the Institute of Science and Technology of Mexico City (PINVII-7), 10 pyranometers were installed in stations from the Automatic Network of Atmospheric Monitoring (RAMA), of the Secretariat of the Environment of México City. These instruments are connected to the data acquisition system of the RAMA, sampled every minute. The instruments were calibrated by the Mexican Solarimetric Service and referenced to the Global Radiometric Scale, so the information generated is considered reliable. With the first four years information of this network, Global Solar Irradiation maps were prepared on the surface, as well as the corresponding Data Base. All information and maps are available on the website of the Solarimetric Mexican Service http://areas.geofisica.unam.mx/solarimetrico/ and can be consulted freely. This project does not have an ending date, so the database will be increased each year and the maps will be re-prepared annually to increase their certainty.info:eu-repo/semantics/publishedVersio

Chromoblastomycosis after a leech bite complicated by myiasis: a case report

Background Chromoblastomycosis is a chronic mycotic infection, most common in the tropics and subtropics, following traumatic fungal implantation. Case presentation A 72 year-old farmer was admitted to Luang Namtha Provincial Hospital, northern Laos, with a growth on the left lower leg which began 1 week after a forefoot leech bite 10 years previously. He presented with a cauliflower-like mass and plaque-like lesions on his lower leg/foot and cellulitis with a purulent tender swelling of his left heel. Twenty-two Chrysomya bezziana larvae were extracted from his heel. PCR of a biopsy of a left lower leg nodule demonstrated Fonsecaea pedrosoi, monophora, or F. nubica. He was successfully treated with long term terbinafin plus itraconazole pulse-therapy and local debridement. Conclusions Chromoblastomycosis is reported for the first time from Laos. It carries the danger of bacterial and myiasis superinfection. Leech bites may facilitate infection.This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

A Novel Modular Antigen Delivery System for Immuno Targeting of Human 6-sulfo LacNAc-Positive Blood Dendritic Cells (SlanDCs)

Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Schäkel et al. (2006) Immunity 24, 767-777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells.Single chain fragment variables were prepared from presently available decavalent monoclonal anti-slan IgM antibodies but failed to bind to slanDCs. Therefore, a novel multivalent anti-slanDC scaffold was developed which consists of two components: (i) a single chain bispecific recombinant diabody (scBsDb) that is directed on the one hand to the slan epitope and on the other hand to a novel peptide epitope tag, and (ii) modular (antigen-containing) linker peptides that are flanked at both their termini with at least one peptide epitope tag. Delivery of a Tetanus Toxin-derived antigen to slanDCs via such a scBsDb/antigen scaffold allowed us to recall autologous Tetanus-specific memory T cells.In summary our data show that (i) the slan epitope can be used for delivery of antigens to this class of human-specific DCs, and (ii) antigens bound to the slan epitope can be taken up by slanDCs, processed and presented to T cells. Consequently, our novel modular scaffold system may be useful for the development of human vaccines

Exploiting the Role of Endogenous Lymphoid-Resident Dendritic Cells in the Priming of NKT Cells and CD8+ T Cells to Dendritic Cell-Based Vaccines

Transfer of antigen between antigen-presenting cells (APCs) is potentially a physiologically relevant mechanism to spread antigen to cells with specialized stimulatory functions. Here we show that specific CD8+ T cell responses induced in response to intravenous administration of antigen-loaded bone marrow-derived dendritic cells (BM-DCs), were ablated in mice selectively depleted of endogenous lymphoid-resident langerin+ CD8α+ dendritic cells (DCs), suggesting that the antigen is transferred from the injected cells to resident APCs. In contrast, antigen-specific CD4+ T cells were primed predominantly by the injected BM-DCs, with only very weak contribution of resident APCs. Crucially, resident langerin+ CD8α+ DCs only contributed to the priming of CD8+ T cells in the presence of maturation stimuli such as intravenous injection of TLR ligands, or by loading the BM-DCs with the glycolipid α-galactosylceramide (α-GalCer) to recruit the adjuvant activity of activated invariant natural killer-like T (iNKT) cells. In fact, injection of α-GalCer-loaded CD1d−/− BM-DCs resulted in potent iNKT cell activation, suggesting that this glycolipid antigen can also be transferred to resident CD1d+ APCs. While iNKT cell activation per se was independent of langerin+ CD8α+ DCs, some iNKT cell-mediated activities were reduced, notably release of IL-12p70 and transactivation of NK cells. We conclude that both protein and glycolipid antigens can be exchanged between distinct DC species. These data suggest that the efficacy of DC-based vaccination strategies may be improved by the incorporation of a systemic maturation signal aimed to engage resident APCs in CD8+ T cell priming, and α-GalCer may be particularly well suited to this purpose

A dynamic T cell–limited checkpoint regulates affinity-dependent B cell entry into the germinal center

Entry into the germinal center requires antigen-bearing B cells to compete for cognate T cell help at the T–B border

Epidemiology of Invasive Fungal Infections in Latin America

The pathogenic role of invasive fungal infections (IFIs) has increased during the past two decades in Latin America and worldwide, and the number of patients at risk has risen dramatically. Working habits and leisure activities have also been a focus of attention by public health officials, as endemic mycoses have provoked a number of outbreaks. An extensive search of medical literature from Latin America suggests that the incidence of IFIs from both endemic and opportunistic fungi has increased. The increase in endemic mycoses is probably related to population changes (migration, tourism, and increased population growth), whereas the increase in opportunistic mycoses may be associated with the greater number of people at risk. In both cases, the early and appropriate use of diagnostic procedures has improved diagnosis and outcome

The Nontoxic Cholera B Subunit Is a Potent Adjuvant for Intradermal DC-Targeted Vaccination

CD4+ T cells are major players in the immune response against several diseases; including AIDS, leishmaniasis, tuberculosis, influenza and cancer. Their activation has been successfully achieved by administering antigen coupled with antibodies, against DC-specific receptors in combination with adjuvants. Unfortunately, most of the adjuvants used so far in experimental models are unsuitable for human use. Therefore, human DC-targeted vaccination awaits the description of potent, yet nontoxic adjuvants. The nontoxic cholera B subunit (CTB) can be safely used in humans and it has the potential to activate CD4+ T cell responses. However, it remains unclear whether CTB can promote DC activation and can act as an adjuvant for DC-targeted antigens. Here, we evaluated the CTB's capacity to activate DCs and CD4+ T cell responses, and to generate long-lasting protective immunity. Intradermal (i.d.) administration of CTB promoted late and prolonged activation and accumulation of skin and lymphoid-resident DCs. When CTB was co-administered with anti-DEC205-OVA, it promoted CD4+ T cell expansion, differentiation, and infiltration to peripheral nonlymphoid tissues, i.e., the skin, lungs and intestine. Indeed, CTB promoted a polyfunctional CD4+ T cell response, including the priming of Th1 and Th17 cells, as well as resident memory T (RM) cell differentiation in peripheral nonlymphoid tissues. It is worth noting that CTB together with a DC-targeted antigen promoted local and systemic protection against experimental melanoma and murine rotavirus. We conclude that CTB administered i.d. can be used as an adjuvant to DC-targeted antigens for the induction of broad CD4+ T cell responses as well as for promoting long-lasting protective immunity