A spatiotemporal epidemiological investigation of the impact of environmental change on the transmission dynamics of Echinococcus spp. in Ningxia Hui Autonomous Region, China

Background: Human echinococcoses are zoonotic parasitic diseases of major public health importance globally. According to recent estimates, the geographical distribution of echinococcosis is expanding and becoming an emerging and re-emerging problem in several regions of the world. Echinococcosis endemicity is geographically heterogeneous and might be affected by global environmental change over time. The aims of my research were: 1) to assess and quantify the spatiotemporal variation in land cover and climate change in Ningxia Hui Autonomous Region (NHAR); 2) to identify highly endemic areas for human echinococcoses in NHAR, and to determine the environmental covariates that have shaped the local geographical distribution of the disease; 3) to develop spatial statistical models that explain and predict the spatiotemporal variation of human exposure to Echinococcus spp. in a highly endemic county of NHAR; and 4) to analyse associations between the environment and the spatiotemporal variation of human exposure to the parasites and dog infections with Echinococcus granulosus and Echinococcus multilocularis in four echinococcosis-endemic counties of NHAR. Methods: Data on echinococcosis infections and human exposure to E. granulosus and E. multilocularis were obtained from different sources: 1) A hospital-based retrospective survey of human echinococcosis cases in NHAR between 1992 and 2013; 2) three cross-sectional surveys of school children conducted in Xiji County in 2002–2003, 2006–2007 and 2012–2013; and 3) A cross-sectional survey of human exposure and dog infections with E. granulosus and E. multilocularis conducted in Xiji, Haiyuan, Guyuan and Tongxin Counties. Environmental data were derived from high-resolution (30 m) imagery from Landsat 4/5-TM and 8-OLI and meteorological reports provided by the Chinese Academy of Sciences. Image analysis techniques and a Bayesian statistical framework were used to conduct a land cover change detection analyses and to develop regression models that described and quantified climate trends and the environmental factors associated with echinococcosis risk at different spatial scales. Results: The land cover changes observed in NHAR from 1991 to 2015 concurred with the main goals of a national policy on payments for ecosystem services, implemented in the Autonomous Region, in increasing forest and herbaceous vegetation coverages and in regenerating bareland. Statistically significant positive trends were observed in annual, summer and winter temperatures in most of the region, and a small magnitude change was found in annual precipitation, in the same 25-year period. The south of NHAR was identified as a highly endemic area for cystic echinococcosis (CE; caused by E. granulosus) and alveolar echinococcosis (AE; caused by E. multilocularis). Selected environmental covariates explained most of the spatial variation in AE risk, while the risk of CE appeared to be less spatially variable at the township level. The risk of exposure to E. granulosus expanded across Xiji County from 2002–2013, while the risk of exposure to E. multilocularis became more confined in communities located in the south of this highly endemic area. In 2012–2013, the predicted seroprevalences of human exposure to E. granulosus and dog infection with this parasite were characterised by similar geographical patterns across Xiji, Haiyuan, Guyuan and Tongxin Counties. By contrast, the predicted high seroprevalence areas for human exposure and dog infection with E. multilocularis did not coincide spatially. Climate, land cover and landscape fragmentation played a key role in explaining some of the observed spatial variation in the risk of infection with Echinococcus spp. among schoolchildren and dogs in the south of NHAR at the village level. Conclusions: The findings of this research defined populations at a high risk of human exposure to E. granulosus and E. multilocularis in NHAR. The research provides evidence on the potential effects of landscape regeneration projects on the incidence of human echinococcoses due to the associations found between the infections and regenerated land. This information will be essential to track future requirements for scaling up and targeting the control strategies proposed by the National Action Plan for Echinococcosis Control in China and may facilitate the design of future ecosystem management and protection policies and a more effective response to emerging local environmental risks. The predictive models developed as part of this research can also be used to monitor echinococcosis infections and the emergence in Echinococcus spp. transmission in the most affected areas

Valor predictivo de las pruebas serologicas para el diagnostico y seguimiento de la paracoccidoidomycosis

Con el objeto de determinar el valor predictivo de las pruebas serológicas (F¡jación de Complemento, FC, e Inmunodifusión en Gel de Agar, IDGA), utilizadas regularmente en nuestro laboratorio para el diagnóstico y el seguimiento de la paracoccidioidomicosis, se analizaron los datos provenientes de 43 pacientes con la enfermedad. Tales pacientes fueron tratados en forma identica (Ketoconazol, 200 mg/dia por 6 meses); además ambas pruebas serológicas utilizaron un mismo lote de antigeno, eliminando asi posibles variables. Fuera de los sueros provenientes de los 43 pacientes con paracoccidioidomicosis (A), se estudiaron 50 sueros de pacientes con otras micosis profundas (B) y 92 sueros de personas sanas (C). Empleamos las fórmulas dadas por GALEN y GAMBINO6 y hallamos que la sensibilidad de ambas pruebas serológicas era comparable, sin diferencia estadísticamente significativa entre ellas (FC = 93%, IDGA - 88.4%). Dicha sesibilidad tendia a disminuir con el tratamiento, siendo más marcada su baja durante las observaciones post-terapia. Al analizar la especificidad se encontró que la IDGA era totalmente específica, no encontrandose falsos positivos en las poblaciones controles estudiadâs (B y C). La FC mostró un 96.7% de especificidad frente a la población C y un 82% frente a la B, siendo estadistisarnente significativa la diferencia entre ambas. Basados en los datos ariteriores, se buscó et valor predictivo, hallaridose que la IDGA da seguridad completa para el diagnóstiso en cualquiera de los períodos evaluados no asi la FC, la que mostró disminución de tales valores durante la terapia y la post-terapia. La curva respectiva mostró como a medida que pasaba el tiempo, disminuía la posibiildad de diferenciar la paracoccidioidomicosis (A) de otras micosis (B), manteniendose, sinembargo, la diferencia con los controles normales (C).A serologic study was undertaken in a group of 43 patients with active paracoccidioidomycosis who were treated in the same form (ketoconazole), for identical periods of time (6 months), and folio wed-up for various periods posttherapy. The tests employed were agar gel immunodiffusion (AGID) and complement fixation (FC). Also studied were 50 sera from patients with proven histoplasmosis and pulmonary aspergilloma, 30 patients with culturaly proven tuberculosis as well as 92 specimens from healthy individuals, residents in the endemic area for paracoccidioidomycosis. A single lot of yeast filtrate antigen was used throughout the study. The value of each test was measured according to GALEN and GAMBINO6. Both tests were highly sensitive, 89 and 93% respectively. Regarding their specificity, the AGID was totally specific while the CF exhibited 96.6% and 97% specificity in front of tuberculosis patients and healthy individuals respectively and 82% in comparison with patients with other mycoses. The concept of predictive value, that is, the certainty one has in accepting a positive test as diagnostic of paracoccidioidomycosis, favored the AGID procedure (100%) over the CF test. The latter could sort out with 93% certainty a patient with paracoccidioidomycosis among a group of healthy individuals and with 97.5% in the case of TB patients; when the group in question was composed by individuals with other deep mycoses, such certainty was lower (81%). The above results indicate that both the AGID and the CF tests furnish results of high confidence; one should not relay, however, in the CF alone as a means to establish the specific diagnosis of paracoccidioidomycosis

Papel do ferro no mecanismo fungicida mediado pelo óxido nítrico de macrófagos murinos ativados com IFN-gama contra conídias do Paracoccidioides brasiliensis

Iron is an essential growth element of virtually all microorganisms and its restriction is one of the mechanisms used by macrophages to control microbial multiplication. Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis, an important systemic mycosis in Latin America, is inhibited in its conidia-to-yeast conversion in the absence of iron. We studied the participation of iron in the nitric oxide (NO)-mediated fungicidal mechanism against conidia. Peritoneal murine macrophages activated with 50U/mL of IFN-gamma or treated with 35 µM Deferoxamine (DEX) and infected with P. brasiliensis conidia, were co-cultured and incubated for 96 h in the presence of different concentrations of holotransferrin (HOLO) and FeS0(4). The supernatants were withdrawn in order to assess NO2 production by the Griess method. The monolayers were fixed, stained and observed microscopically. The percentage of the conidia-to-yeast transition was estimated by counting 200 intracellular propagules. IFN-gamma-activated or DEX-treated Mthetas presented marked inhibition of the conidia-to-yeast conversion (19 and 56%, respectively) in comparison with non-activated or untreated Mthetas (80%). IFN-gamma-activated macrophages produced high NO levels in comparison with the controls. Additionally, when the activated or treated-macrophages were supplemented with iron donors (HOLO or FeSO4), the inhibitory action was reversed, although NO production remained intact. These results suggest that the NO-mediated fungicidal mechanism exerted by IFN-gamma-activated macrophages against P. brasiliensis conidia, is dependent of an iron interaction.O ferro é elemento essencial para o crescimento de microrganismos e sua limitação é um dos mecanismos usados por macrófagos para controlar a multiplicação microbiana. Paracoccidioides brasiliensis, o agente da paracoccidioidomicose, uma das micoses sistêmicas mais importantes na América Latina, é inibido em sua conversão de conídia-à-levedura na ausência do ferro. Estudamos a participação do ferro no mecanismo fungicida mediado pelo óxido nítrico (NO) na sua interação com as conídias do fungo. Macrófagos peritoneais murinos ativados com 50U/mL de IFN-gama ou tratados com 35 µM Deferoxamina (DEX) e infectados com conídias do P. brasiliensis foram co-cultivados e incubados por 96 h na presença de concentrações diferentes de holotransferrina (HOLO) e FeS0(4). Os sobrenadantes foram retirados a fim de avaliar a produção de NO2 pelo método de Griess. Os macrófagos eram fixados, corados e observados ao microscópio. A porcentagem da transição de conídia-à-levedura foi estimada contando 200 propágulos intracelulares. Os macrófagos ativados com citocina ou tratados com DEX apresentaram inibição marcada da conversão de conídia-à-levedura (19 e 56%, respectivamente) em comparação com macrófagos controle (80%). Os macrófagos ativados com IFN-gama produziram elevação nos níveis de NO em comparação com macrófagos não-tratados ou não-activados. Adicionalmente, quando as monocapas ativadas ou tratadas foram suplementadas com doadores do ferro (HOLO ou FeSO4), a ação inibitória foi revertida embora a produção de NO permanecesse intacto. Estes resultados sugerem que o mecanismo fungicida mediado pelo NO exercido por macrófagos ativados com IFN-gama contra conídias do P. brasiliensis é dependente de uma interação do ferro

Formulación del plan de manejo de residuos sólidos peligrosos de la Empresa Coats Cadena S.A.

La formulación del proyecto plan de gestión de residuos sólidos peligrosos generados en Coats Cadena S.A. se hace necesario para dar continuidad al manejo que la empresa da al aspecto ambiental y sus impactos en recursos naturales y a su vez, dar cumplimiento a los lineamientos ambientales vigentes. Un aspecto positivo de la mpresa Coats Cadena S.A. es que cuenta con un Programa de Gestión y Manejo Integral de Residuos Sólidos (PGIRS) elaborado en el año 1998, el cual constituye la herramienta base en el manejo de sus Residuos. Debido a la entrada en vigencia del Decreto 4741 de 2005 por el cual se reglamenta la prevención y manejo de residuos o desechos peligrosos, se hace necesario la actualización de dicho programa con los nuevos lineamientos exigidos. Dentro de la política de Medio Ambiente de Coats Cadena S.A. en el numeral 1 enuncia; “Asegurar que sus operaciones cumplan con todas las legislaciones existentes y los estándares ambientales definidos por el grupo”. Teniendo en cuenta lo anterior y el Decreto 4741, este proyecto incluirá lineamientos para: • Elaborar un plan de manejo de los residuos o desechos peligrosos que se generan en los diferentes procesos productivos. • Identificar las características de peligrosidad de cada uno de los residuos o desechos peligrosos que se generen. • Garantizar que el envasado o empacado, embalado y etiquetado de sus residuos o desechos peligrosos, se realice conforme a la normatividad vigente. NTC 1692. (Art. 10 Decreto 4741 de 2005). • Dar cumplimiento a lo establecido en el decreto 1609 de 2002 y suministrar al transportista de los residuos o desechos peligrosos las respectivas hojas de seguridad. • Atender cualquier accidente o eventualidad que se presente mediante un plan de emergencia. • Exigir y conservar la documentación de ley a cada uno de los receptores. • Garantizar la correcta contratación de servicios de almacenamiento, aprovechamiento, tratamiento y disposición final de los residuos y desechos generados, de conformidad con la normatividad ambiental vigente. Este proyecto se presenta en la modalidad de monografía de compilación de tipo investigativo

El trabajo colectivo en torno a recursos en el MOOC eFAN maths

En este artículo presentamos el MOOC eFAN maths, dispositivo virtual de formación de profesores de matemáticas sobre la utilización de herramientas tecnológicas en la clase de matemáticas. A partir de la interacción generada en los grupos, analizamos el trabajo colectivo de los profesores de matemáticas durante el desarrollo de su proyecto, los recursos que compartieron y que produjeron, y cómo contribuyeron estos al desarrollo de los proyectos

Tratamento com posaconazol de casos de cromoblastomicose e micetoma maduromicótico resistentes a outros antifúngicos

Eumycetoma and chromoblastomycosis are chronic, disfiguring fungal infections of the subcutaneous tissue that rarely resolve spontaneously. Most patients do not achieve sustained long-term benefits from available treatments; therefore, new therapeutic options are needed. We evaluated the efficacy of posaconazole, a new extended-spectrum triazole antifungal agent, in 12 patients with eumycetoma or chromoblastomycosis refractory to existing antifungal therapies. Posaconazole 800 mg/d was given in divided doses for a maximum of 34 months. Complete or partial clinical response was considered a success; stable disease or failure was considered a nonsuccess. All 12 patients had proven infections refractory to standard therapy. Clinical success was reported for five of six patients with eumycetoma and five of six patients with chromoblastomycosis. Two patients were reported to have stable disease. As part of a treatment-use extension protocol, two patients with eumycetoma who initially had successful outcome were successfully retreated with posaconazole after a treatment hiatus of >; 10 months. Posaconazole was well tolerated during long-term administration (up to 1015 d). Posaconazole therapy resulted in successful outcome in most patients with eumycetoma or chromoblastomycosis refractory to standard therapies, suggesting that posaconazole may be an important treatment option for these diseases.Eumicetoma e cromoblastomicose são infecções fúngicas crônicas do tecido subcutâneo que evoluem com aspecto desfigurado, raramente involuindo espontaneamente. A maioria dos pacientes não apresenta melhora sustentada por longo tempo com os tratamentos disponíveis, sendo de grande importância as novas opções terapêuticas. A eficácia do posaconazol, um novo agente antifúngico de amplo espectro do grupo dos triazóis, foi estudada em 12 pacientes com eumicetoma ou cromoblastomicose refratária às terapêuticas antifúngicas disponíveis. Os pacientes receberam por no máximo 34 meses, doses divididas de 800 mg/dia de posaconazol. Resposta clínica parcial ou completa foi considerada como sucesso; doença estável ou falha terapêutica foi considerada como insucesso. Todos os 12 pacientes tinham infecções comprovadas ou prováveis, refratárias à terapêutica padrão preconizada. Sucesso clínico foi registrado em cinco de seis pacientes com eumicetoma e cinco de seis pacientes com cromoblastomicose. Em dois pacientes observou-se doença estável. Como parte do protocolo de extensão do tratamento, dois pacientes com eumicetoma que inicialmente tinham tido sucesso terapêutico e que após um intervalo maior de 10 meses apresentaram recidiva da micose, foram retratados com sucesso com posaconazol. Posaconazol foi bem tolerado durante o longo período de administração (até 1015 dias). A terapêutica com posaconazol foi seguida de sucesso na maioria dos pacientes com eumicetoma ou cromoblastomicose refratária à terapêutica padrão, sugerindo que tal droga possa ser uma importante opção no tratamento de tais doenças

Virtual Collaborative Learning Environments with the Telepresence Platform Supported by the Teaching for Understanding Pedagogical Framework: Experiences in Higher Educational Process in Colombia

Virtual collaborative learning environments with the Telepresence Platform supported by the Teaching for Understanding pedagogical framework: experiences in Higher Educational process in Colombi

Lysozyme plays a dual role against the dimorphic fungus Paracoccidioides brasiliensis

In order to determine the role of lysozyme, an antimicrobial peptide belonging to the innate immune system, against the dimorphic fungus Paracoccidioides brasiliensis, co-cultures of the MH-S murine alveolar macrophages cell line with P. brasiliensis conidia were done; assays to evaluate the effect of physiological and inflammatory concentrations of lysozyme directly on the fungus life cycle were also undertaken. We observed that TNF-&#945;-activated macrophages significantly inhibited the conidia to yeast transition (p = 0.0043) and exerted an important fungicidal effect (p = 0.0044), killing 27% more fungal propagules in comparison with controls. Nonetheless, after adding a selective inhibitor of lysozyme, the fungicidal effect was reverted. When P. brasiliensis propagules were exposed directly to different concentrations of lysozyme, a dual effect was observed. Physiologic concentrations of the enzyme facilitated the conidia-to-yeast transition process (p < 0.05). On the contrary, inflammatory concentrations impaired the normal temperature-dependant fungal transition (p < 0.0001). When yeast cells were exposed to lysozyme, irrespective of concentration, the multiple-budding ability was badly impaired (p < 0.0001). In addition, ultra-structural changes such as subcellular degradation, fusion of lipid vacuoles, lamellar structures and interruption of the fibrilar layer were observed in lysozyme exposed conidia. These results suggest that lysozyme appears to exert a dual role as part of the anti-P. brasiliensis defense mechanisms.Com a finalidade de determinar o papel da lisozima, um peptídeo antimicrobiano que pertence ao sistema imune inato, contra o fungo dimórfico Paracoccidioides brasiliensis, foram feitas co-culturas de uma linha de macrófagos alveolares murinos (MH-S) com as conídias do fungo na presença ou não do TNF-&#945; e/ou um inibidor da lisozima; também foram feitos ensaios que avaliaram o efeito das concentrações fisiológicas e inflamatórias de lisozima diretamente sobre o ciclo de vida do fungo. Observamos que os macrófagos ativados com a citoquina tiveram um efeito significativo na inibição da transição conídia/levedura (p = 0,0043) e exerceram um efeito fungicida importante (p = 0,0044), matando mais de 27% das propágulas do fungo em comparação com os macrófagos não ativados. No entanto, após ser o inibidor seletivo da lisozima adicionado, o efeito fungicida foi revertido. Quando os propágulos do fungo foram expostos diretamente a diferentes concentrações da lisozima, um duplo efeito foi observado. Assim, as concentrações fisiológicas da enzima facilitaram o processo de transição conídia-levedura (p < 0,05). Contrariamente, as concentrações inflamatórias prejudicaram a transição fúngica (p < 0,0001). Quando as leveduras foram expostas a qualquer concentração de lisozima, sua capacidade de multi-brotação foi gravemente prejudicada (p < 0,0001). Além disso, mudanças ultra-estruturais, como a sub degradação, a fusão dos vacúolos dos lípidos, estruturas lamelares e interrupção da camada fibrilar foram observadas em conídios expostos à lisozima. Estes resultados sugerem que a lisozima poderia exercer um duplo papel no mecanismo antifúngico contra P. brasiliensis