Development of a stochastic agent-based model to evaluate surveillance strategies for detection of emergent porcine reproductive and respiratory syndrome strains.

BACKGROUND: The objective of the current study was to develop a stochastic agent-based model using empirical data from Ontario (Canada) swine sites in order to evaluate different surveillance strategies for detection of emerging porcine reproductive and respiratory syndrome virus (PRRSV) strains at the regional level. Four strategies were evaluated, including (i) random sampling of fixed numbers of swine sites monthly; (ii) risk-based sampling of fixed numbers, specifically of breeding sites (high-consequence sites); (iii) risk-based sampling of fixed numbers of low biosecurity sites (high-risk); and (iv) risk-based sampling of breeding sites that are characterized as low biosecurity sites (high-risk/high-consequence). The model simulated transmission of a hypothetical emerging PRRSV strain between swine sites through three important industry networks (production system, truck and feed networks) while considering sites' underlying immunity due to past or recent exposure to heterologous PRRSV strains, as well as demographic, geographic and biosecurity-related PRRS risk factors. Outcomes of interest included surveillance system sensitivity and time to detection of the three first cases over a period of approximately three years. RESULTS: Surveillance system sensitivities were low and time to detection of three first cases was long across all examined scenarios. CONCLUSION: Traditional modes of implementing high-risk and high-consequence risk-based surveillance based on site's static characteristics do not appear to substantially improve surveillance system sensitivity. Novel strategies need to be developed and considered for rapid detection of this and other emerging swine infectious diseases. None of the four strategies compared herein appeared optimal for early detection of an emerging PPRSV strain at the regional level considering model assumptions, the underlying population of interest, and absence of other forms of surveillance.

Randomized noninferiority clinical trial evaluating 3 commercial dry cow mastitis preparations: I. Quarter-level outcomes.

The study objective was to compare the efficacy of 3 commercial dry cow mastitis formulations regarding quarter-level prevalence of intramammary infections (IMI) postcalving, cure of preexisting infections over the dry period, prevention of new infections during the dry period, and risk for a clinical mastitis case between calving and 100d in milk (DIM). A total of 1,091 cows (4,364 quarters) from 6 commercial dairy herds in 4 different states (California, Iowa, Minnesota, and Wisconsin) were enrolled and randomized to 1 of the 3 treatments at dry-off: Quartermaster (QT; 1,000,000 IU of procaine penicillin G and 1 g of dihydrostreptomycin; Pfizer Animal Health, New York, NY), Spectramast DC (SP; 500 mg of ceftiofur hydrochloride; Pfizer Animal Health), or ToMorrow Dry Cow (TM; 300mg of cephapirin benzathine; Boehringer Ingelheim Vetmedica Inc., St. Joseph, MO). Quarter milk samples were collected for routine bacteriological culture before dry cow therapy treatment at dry-off, 0 to 6 DIM, and 7 to 13 DIM and an on-farm record-keeping system was used to retrieve data on clinical mastitis cases. Noninferiority analysis was used to evaluate the effect of treatment on the primary outcome, risk for a bacteriological cure during the dry period. Multivariable logistic regression techniques were used to describe the effect of treatment on risk for presence of IMI postcalving and risk of a new IMI during the dry period. Cox proportional hazards regression was used to describe the effect of treatment on the risk and time for quarters to experience an episode of clinical mastitis between calving and 100 DIM. The overall crude quarter-level prevalence of infection at dry-off was 19.2%. The most common pathogen isolated from milk samples at dry-off was coagulase-negative Staphylococcus, followed by Aerococcus spp. and other Streptococcus spp. Noninferiority analysis showed no effect of treatment on risk for a cure between dry-off and calving [least squares means (LSM): QT=93.3%, SP=92.6%, and TM=94.0%] and secondary analysis showed no effect of treatment on risk for presence of an IMI at 0 to 6 DIM (LSM: QT=16.5%, SP=14.1%, and TM=16.0%), risk for development of a new IMI between dry-off and 0 to 6 DIM (LSM: QT=14.8%, SP=12.3%, and TM=14.2%), or risk of experiencing a clinical mastitis event between calving and 100 DIM (LSM: QT=5.3%, SP=3.8%, and TM=4.1%). In conclusion, no difference was observed in efficacy among the 3 products evaluated when assessing the aforementioned quarter-level outcomes.

Randomized noninferiority clinical trial evaluating 3 commercial dry cow mastitis preparations: II. Cow health and performance in early lactation.

The objective of this randomized noninferiority clinical trial was to compare the effect of treatment with 3 different dry cow therapy formulations at dry-off on cow-level health and production parameters in the first 100 d in milk (DIM) in the subsequent lactation, including 305-d mature-equivalent (305 ME) milk production, linear score (LS), risk for the cow experiencing a clinical mastitis event, risk for culling or death, and risk for pregnancy by 100 DIM. A total of 1,091 cows from 6 commercial dairy herds in 4 states (California, Iowa, Minnesota, and Wisconsin) were randomly assigned at dry-off to receive treatment with 1 of 3 commercial products: Quartermaster (QT; Zoetis Animal Health, Madison, NJ), Spectramast DC (SP; Zoetis Animal Health) or ToMorrow Dry Cow (TM; Boehringer Ingelheim Vetmedica Inc., St Joseph, MO). All clinical mastitis, pregnancy, culling, and death events occurring in the first 100 DIM were recorded by farm staff using an on-farm electronic record-keeping system. Dairy Herd Improvement Association test-day records of milk production and milk component testing were retrieved electronically. Mixed linear regression analysis was used to describe the effect of treatment on 305ME milk production and LS recorded on the last Dairy Herd Improvement Association test day before 100 DIM. Cox proportional hazards regression analysis was used to describe the effect of treatment on risk for experiencing a case of clinical mastitis, risk for leaving the herd, and risk for pregnancy between calving and 100 DIM. Results showed no effect of treatment on adjusted mean 305 ME milk production (QT=11,759 kg, SP=11,574 kg, and TM=11,761 kg) or adjusted mean LS (QT=1.8, SP=1.9, and TM=1.6) on the last test day before 100 DIM. Similarly, no effect of treatment was observed on risk for a clinical mastitis event (QT=14.8%, SP=12.7%, and TM=15.0%), risk for leaving the herd (QT=7.5%, SP=9.2%, and TM=10.3%), or risk for pregnancy (QT=31.5%, SP=26.1%, and TM=26.9%) between calving and 100 DIM.

Salivary IL-21 and IgA responses to a competitive match in elite basketball players.

Athletes engaged in strenuous training might experience transient immune suppression that could lead to greater incidence of upper respiratory tract infections (URTI). Since interleukin 21 (IL-21) stimulates immunoglobulin A (IgA) secreting cells and a low level of this immunoglobulin is associated with increased incidence of URTI, the aim of the present study was to investigate the effect of a basketball match on salivary cortisol (sC), salivary IL-21 (sIL-21) and salivary IgA (sIgA) levels. Twenty male basketball players participated in an official game in two teams (10 players in each team). The saliva samples were collected before the warm-up and approximately 10-15 min after the end of the match and were analysed by ELISA methods. sC concentration increased significantly after the match while sIL-21 level was reduced (p < 0.05). In opposition to the study's hypothesis, sIgA level did not change in response to the match. The present findings suggest that a basketball match is sufficiently stressful to elevate sC concentration and attenuates the sIL-21 output without compromising the sIgA level. It is reasonable to speculate that the stability of sIgA acute responses to the match, despite the decrement in sIL-21, indicates that other mechanisms rather than IL-21 stimulating B cell proliferation/differentiation might modulate IgA concentration and secretion rate.

Session RPE and salivary immune-endocrine responses to simulated and official basketball matches in elite young male athletes.

The present study compared the ratings of perceived exertion (RPE) and immune-endocrine (IgA and cortisol) responses to simulated training matches (TM) and official matches (OM) in elite young male basketball players (N.=10). Saliva samples were collected from each player before and after three TM and two OM and subsequently tested for cortisol and IgA concentrations by immunoassay. The perceived intensity of each match was rated using a RPE scale (CR-10). The training match and official match data were pooled to provide an aggregate value for each setting. The session RPE scores from the OM were significantly (P<0.05) greater than the simulated TM. Pre- and postcortisol concentrations assessed during the OM were also found to be significantly higher than the TM (P<0.05). No significant changes in salivary IgA concentrations were observed across either the simulated or official match settings. In summary, the OM induced greater RPE and salivary cortisol responses than the simulated TM, probably due to the additional stressors associated with real competition. The data also suggests that acute changes in cortisol concentrations do not play a role in the regulation of salivary IgA under the current testing conditions.

Poultry Professionals' Perception of Participation in Voluntary Disease Mapping and Monitoring Programs in the United States: A Cluster Analysis.

The development and implementation of disease mapping and monitoring programs can be useful tools for rapid communication and control of endemic and epidemic infectious diseases affecting the food animal industry. Commercial livestock producers have traditionally been reluctant to share information related to animal health, challenging the large-scale implementation of such monitoring and mapping programs. The main objective of this study was to assess the perception of poultry professionals toward disease mapping and monitoring programs and to identify groups of poultry professionals with similar perceptions and attitudes toward these projects. We conducted a survey to identify the perceived risks and benefits to be able to properly address them and encourage industry participation in the future. An anonymous online survey was developed and distributed to poultry professionals through industry and professional associations. The participant's demographic information and perceptions of risk and benefits from participation on voluntary poultry disease mapping and monitoring programs were collected. Multiple correspondence analysis and hierarchical clustering on principal components were performed to identify groups of professionals with similar characteristics. A total of 63 participants from 21 states filled out the survey. The cluster analysis yielded two distinct groups of respondents, each including approximately 50% of respondents. Cluster 1 subjects could be characterized as optimistic, perceiving major benefits of sharing farm-level poultry disease information. However, they also had major concerns, mostly related to potential accidental data release and providing competitive advantages to rival companies. Cluster 2 subjects were characterized as perceiving a lesser degree of benefits from sharing farm-level poultry disease information. This second cluster mostly included production and service technicians. The roles and perceptions of risk and benefits of the participants contributed significantly to cluster assignment, while the represented commodity and geographic location in the United States did not. Successful development of voluntary poultry disease mapping and monitoring programs in the future will require that different sectors of poultry professionals be approached in different manners in order to highlight the benefits of the programs and to achieve maximum participation.

Artículo regular­Percepción de los profesionales avícolas sobre la participación en programas voluntarios de seguimiento y mapeo de enfermedades en los Estados Unidos: Análisis de conglomerados. El desarrollo y la implementación de programas de seguimiento y mapeo de enfermedades pueden ser herramientas útiles para la comunicación y el rápido control de las enfermedades infecciosas endémicas y epidémicas que afectan a la industria de los animales destinados a la producción de alimentos. Los productores de ganado comercial tradicionalmente se han mostrado renuentes a compartir información relacionada con la salud animal, desafiando la implementación a gran escala de tales programas de seguimiento y mapeo. El objetivo principal de este estudio fue evaluar la percepción de los profesionales avícolas hacia los programas de mapeo y seguimiento de enfermedades e identificar grupos de profesionales avícolas con percepciones y actitudes similares hacia los proyectos de mapeo y monitoreo. Se realizó una encuesta para identificar los riesgos y beneficios percibidos para poder abordarlos adecuadamente y fomentar la participación de la industria. Se desarrolló y distribuyó una encuesta anónima en línea entre profesionales avícolas a través de la industria y las asociaciones profesionales. Se recopiló la información demográfica de los participantes y las percepciones de los riesgos y beneficios de la participación en programas voluntarios de seguimiento y mapeo de las enfermedades avícolas. Se realizaron análisis de correspondencia múltiple y agrupamiento jerárquico de componentes principales para identificar grupos de profesionales con características similares. Un total de 63 participantes de 21 estados completaron la encuesta. El análisis de conglomerados arrojó dos grupos distintos de encuestados, cada uno con aproximadamente el 50% de los encuestados. Los sujetos del Grupo 1 podrían caracterizarse por ser optimistas y percibir los principales beneficios de compartir información sobre enfermedades de las aves de corral a nivel de granja. Sin embargo, también tenían preocupaciones importantes, principalmente relacionadas con la posible diseminación accidental de datos y la generación de ventajas de competencia para las empresas rivales. Los sujetos del Grupo 2 se caracterizaron por percibir un grado menor de beneficios al compartir información sobre enfermedades avícolas a nivel de granja. Este segundo grupo incluía principalmente a técnicos de producción y de servicio. Los roles y las percepciones de los riesgos y beneficios de los participantes contribuyeron significativamente a la asignación de grupos, mientras que el producto representado y la ubicación geográfica en los Estados Unidos no lo hicieron. Para el desarrollo exitoso de programas de seguimiento y mapeo de enfermedades de las aves comerciales en el futuro, es probable que sea necesario abordar a varios grupos de profesiones avícolas de diferentes maneras para lograr la máxima participación en el programa voluntario.

Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism.

Cisplatin is a widely used chemotherapeutic drug, but its side effects are a major limiting factor. Nephrotoxicity occurs in one third of patients undergoing cisplatin treatment. The acute tubular injury caused by cisplatin often leads to a defective repair process, which translates into chronic renal disorders. In this way, cisplatin affects tubular cells, and maladaptive tubules regeneration will ultimately result in tubulointerstitial fibrosis. Kinins are well known for being important peptides in the regulation of inflammatory stimuli, and kinin B1 receptor deficiency and antagonism have been shown to be beneficial against acute cisplatin nephrotoxicity. This study aimed to analyze the effects of kinin B1 receptor deletion and antagonism against repeated cisplatin-induced chronic renal dysfunction and fibrosis. Both the deletion and the antagonism of B1 receptor exacerbated cisplatin-induced chronic renal dysfunction. Moreover, the inhibition of B1 receptor increased tubular injury and tubulointerstitial fibrosis after repeated treatment with cisplatin. The balance between M1/M2 macrophage polarization plays an important role in renal fibrosis. Kinin B1 receptor antagonism had no impact on M1 markers when compared to cisplatin. However, YM1, an M2 marker and an important molecule for the wound healing process, was decreased in mice treated with kinin B1 receptor antagonist, compared to cisplatin alone. Endothelin-1 levels were also increased in mice with B1 receptor inhibition. This study showed that kinin B1 receptor inhibition exacerbated cisplatin-induced chronic renal dysfunction and fibrosis, associated with reduced YM1 M2 marker expression, thus possibly affecting the wound healing process.

Influence of an applied current on the vortex matter in a superconducting sample with structural defects.

We show how the inclusion of a structural defect of determined geometry controls the vortex state in a square superconducting sample in the presence of an external magnetic field and a dc current. We simulated the defects by using the deformation parameter τ ( x , y ) , solving the non-lineal time-dependent Ginzburg-Landau equations and using the link variable method, for four different geometries as possible options for the storage vortex, simulating the behavior of a capacitor. We found an exponential dependence of the current in which the first vortex penetrates the sample J → c as a function of the area of a square central defect in the sample. We also show the effect of the defects and the transport current on the magnetization, magnetic susceptibility, vorticity, and magnetic field at the first vortex entry into the sample H 1 and the density of the superconducting electrons.

Antimyotoxic Activity of Synthetic Peptides Derived from Bothrops atrox Snake Gamma Phospholipase A2 Inhibitor Selected by Virtual Screening.

BACKGROUND: Several studies have aimed to identify molecules that inhibit the toxic actions of snake venom phospholipases A2 (PLA2s). Studies carried out with PLA2 inhibitors (PLIs) have been shown to be efficient in this assignment. OBJECTIVE: This work aimed to analyze the interaction of peptides derived from Bothrops atrox PLIγ (atPLIγ) with a PLA2 and to evaluate the ability of these peptides to reduce phospholipase and myotoxic activities. METHODS: Peptides were subjected to molecular docking with a homologous Lys49 PLA2 from B. atrox venom modeled by homology. Phospholipase activity neutralization assay was performed with BthTX-II and different ratios of the peptides. A catalytically active and an inactive PLA2 were purified from the B. atrox venom and used together in the in vitro myotoxic activity neutralization experiments with the peptides. RESULTS: The peptides interacted with amino acids near the PLA2 hydrophobic channel and the loop that would be bound to calcium in Asp49 PLA2. They were able to reduce phospholipase activity and peptides DFCHNV and ATHEE reached the highest reduction levels, being these two peptides the best that also interacted in the in silico experiments. The peptides reduced the myotubes cell damage with a highlight for the DFCHNV peptide, which reduced by about 65%. It has been suggested that myotoxic activity reduction is related to the sites occupied in the PLA2 structure, which could corroborate the results observed in molecular docking. CONCLUSION: This study should contribute to the investigation of the potential of PLIs to inhibit the toxic effects of PLA2s.

Acute and subacute toxicity of the Carapa guianensis Aublet (Meliaceae) seed oil.

Carapa guianensis (Meliaceae), known as Andiroba in Brazil, has been used by Amazon Rainforest indigenous communities for treatment of coughs, convulsions, skin diseases, arthritis, rheumatism, ear infections, to heal wounds and bruises and as an insect repellent. Carapa guianensis seed oil (SO) was evaluated for its acute and subacute toxicity (30 days) by the oral route in Wistar rats. In the acute toxicity test, SO (0.625-5.0g/kg, n=5/sex) did not produce any hazardous symptoms or deaths. The subacute treatment with SO (0.375, 0.75 and 1.5g/kg, n=10/group) failed to change body weight gain, food and water consumption. Hematological analysis showed no significant differences in any of the parameters examined. However, in the biochemical parameters, there was an increase in the alanine aminotransferase (ALT) serum level (29%) in the group SO 1.5g/kg. In addition, absolute and relative liver weights were increased at the doses of 0.75g/kg (23.4 and 19.1%) and 1.5g/kg (18.7 and 33.1%). In conclusion, acute and subacute administration of Carapa guianensis seed oil did not produce toxic effects in male Wistar rats. However, the increase in the ALT serum level and in both absolute and relative liver weights may indicate a possible hepatic toxicity.

The investigation of DNA repair polymorphisms with histopathological characteristics and hormone receptors in a group of Brazilian women with breast cancer.

The association of tumor differentiation and estrogen receptor expression with the prognosis of breast cancer has been well established. Nevertheless, little is yet reported about the association of morphological characteristics of the tumor, estrogen receptor status and polymorphisms in low penetrance genes. The aim of the present study was to investigate a possible association between DNA repair gene polymorphisms (XRCC1, XPD, XRCC3, and RAD51) with histological type, grade and hormone receptor expression in a series of breast cancers. A cross-sectional study was carried out to evaluate 94 women with breast carcinoma, who had already been selected and included in a study on the association of DNA repair gene polymorphisms. For immunohistochemistry, formalin-fixed, paraffin-embedded tissue samples from breast tumors were consecutively retrieved from the histopathology files of our institution. DNA obtained from blood samples of the same patients was investigated for the presence of the following polymorphisms: Arg-399Gln located in the XRCC1 gene; 135C/G located in the RAD51 gene; Lys751Gln located in the XPD gene and Thr241Met located in the XRCC3 gene. Polymorphisms were considered to be independent variables and hormone receptor expression and the morphological characteristics of the tumors comprised the dependent variables. No statistically significant association was found between gene polymorphisms and hormone receptor status. The association between XRCC1-Arg399Gln polymorphism and ductal carcinoma was statistically significant (P = 0.02). The association of the XPD-Lys751Gln polymorphism with histological grade was also tatistically significant (p = 0.05). In conclusion, the XRCC1 genotype was found to be associated with ductal carcinoma histotypes and XPD genotype with low histological grade, which is the most frequent pattern of sporadic breast carcinomas.

Assessment of area spread of porcine reproductive and respiratory syndrome (PRRS) virus in three clusters of swine farms.

Despite decades of porcine reproductive and respiratory syndrome (PRRS) research, outbreaks with emerging and re-emerging PRRS virus (PRRSV) strains are not uncommon in North America. The role of area spread, commonly referred but not limited to airborne transmission, in originating such outbreaks is currently unknown. The main objective of this study was to explore the role of area spread on the occurrence of new PRRSV cases by combining information on genetic similarity among recovered PRRSV isolate's open-reading frame (ORF) 5 sequences and publicly available weather data. Three small regions were enrolled in the study for which high farm-level participation rate was achieved, and swine sites within those regions were readily sampled after reporting of an outbreak in a sow farm. Oral fluid PCR testing was used to determine PRRSV status of farms, and wind roses were generated for assessment of prevailing wind directions during 2-14 days preceding the outbreak. Under the conditions of this study, the data did not support the area spread theory as the main cause for these outbreaks. We suggest that for future studies, analysis of animal movement and other links between farms such as personnel, equipment and sharing of service providers should be incorporated for better insights on source of the virus. Furthermore, the development of rapid and easy diagnostic methods for ruling out resident PRRSV is urgently needed.

A toxicological evaluation of the effect of Carapa guianensis Aublet on pregnancy in Wistar rats.

The effects of the administration of Carapa guianensis Aublet (Meliaceae) seed oil were investigated during pregnancy in female Wistar rats. Five groups of pregnant rats (n=5-9 per group) were treated orally from the 7th to the 14th day of pregnancy (organogenic period), at doses of: 0, 0.375, 0.75, 1.5 and 3.0gkg(-1). On the 20th day of pregnancy, the animals were sacrificed and laparotomized to evaluate reproductive parameters. The results showed that there was no difference between the control and treated groups in terms of the number of live and dead fetuses, the dam-offspring relationship, the weight of the fetus, the weight of the placentae and ovaries, the number of implantation sites, the number of resorption sites, the number of corpora lutea in the ovaries, and the pre- and post-implantation loss rates. It is therefore concluded that administration of Carapa guianensis seed oil did not bring about any toxic effect on pregnancy in Wistar rats.

The use of large databases to inform the development of an intestinal scoring system for the poultry industry.

There is increasing interest among the poultry industry to develop a comprehensive index that can be used to evaluate overall intestinal health and impact on production performance. The Intestinal Integrity (I2) index is a quantitative measurement tool used to assess the intestinal health of flocks that use the Health Tracking System (HTSi), a global surveillance system developed by Elanco Animal Health that captures flock-level information on health and performance. To generate an I2 index score for a flock, the presence of 23 intestinal health conditions is assessed and recorded, then entered into a mathematical equation. The objective of this study was to use data from the HTSi dataset to investigate the association between health conditions contained within the I2 index and five performance outcomes: average daily gain (ADG), mortality during the first week, feed conversion ratio (FCR), European Production Efficiency Factor (EPEF), and percent livability. At the time of analysis, the HTSi dataset contained information from the years 2006-2015 on 921,646 individual bird necropsy records from over 153,576 flocks at 1,570 broiler production flows across 53 countries. Flock-level production data used for this study were available for a subset of this population, 33,212 total flocks representing 6 US and 4 UK production flows. A separate multivariable linear or logistic regression model, with farm as a random effect, was built for each of the five outcomes mentioned above. All models controlled for clustering of flocks within production flows. Significant associations were found between key performance indicators and ten intestinal conditions (gross E. acervulina, gross E. maxima, microscopic E. maxima, gizzard erosions, roundworms, excessive intestinal fluid, thin intestines, excessive intestinal mucus, feed passage, and necrotic enteritis) and two management parameters (production flow and down time). Results from this study demonstrate that large databases, such as the HTSi database, can be used to inform and evaluate changes that can optimize intestinal health, and hence welfare, productivity, and sustainability of the poultry industry. In addition, large databases can be used for monitoring and benchmarking intestinal health of poultry and informing the development of innovative indices such as the I2 index for scoring intestinal health and providing routine data for its calculation.

Investigation of the Occurrence of Porcine Reproductive and Respiratory Virus in Swine Herds Participating in an Area Regional Control and Elimination Project in Ontario, Canada.

The main goal of this study was to investigate the occurrence of porcine reproductive and respiratory syndrome virus (PRRSV)-specific genotypes in swine sites in Ontario (Canada) using molecular, spatial and network data from a porcine reproductive and respiratory syndrome (PRRS) regional control project. For each site, location, animal movement service provider (truck companies), PRRSV status and sequencing data of the open reading frame 5 (ORF5) were obtained. Three-kilometre buffers were created to evaluate neighbourhood characteristics for each site. Social network analysis was conducted on swine sites and trucking companies to assemble the network and define network components. Three different PRRSV genotypes were used as outcomes for statistical analysis based on the region's phylogenetic tree of the ORF5. Multivariable exact logistic regression was conducted to investigate the association between being positive for a specific genotype and two main exposures of interest: (i) having at least one neighbour within three km also positive for the same genotype outside the production system and (ii) having at least one positive site for the same genotype in the same truck network component outside the production system. Results showed that the importance of area spread and truck network on PRRSV occurrence differed according to genotype. Additionally, the Ontario PRRS database appears suitable for conducting regional disease investigations. Finally, the use of relatively new tools available for network, spatial and molecular analysis could be useful in investigation, control and prevention of endemic infectious diseases in animal populations.

CD123 target validation and preclinical evaluation of ADCC activity of anti-CD123 antibody CSL362 in combination with NKs from AML patients in remission.

Despite the heterogeneity of acute myeloid leukemia (AML), overexpression of the interleukin-3 receptor-α (CD123) on both the more differentiated leukemic blast and leukemic stem cells (LSCs) provides a therapeutic target for antibody treatment. Here we present data on the potential clinical activity of the monoclonal antibody CSL362, which binds to CD123 with high affinity. We first validated the expression of CD123 by 100% (52/52) of patient samples and the correlation of NPM1 and FLT3-ITD mutations with the high frequency of CD123 in AML. In vitro studies demonstrated that CSL362 potently induced antibody-dependent cell cytotoxicity (ADCC) of AML blasts including CD34+CD38-CD123+ LSCs by natural killer cells (NKs). Importantly, compared with healthy donor (HD) NKs, NKs drawn from AML patients in remission had a comparable ADCC activity against leukemic cells; of note, during remission, immature NKs were five times higher in AML patients than that in HDs. Significantly, we report a case where leukemic cells were resistant to autologous ADCC; however, the blasts were effectively lysed by CSL362 together with donor-derived NKs after allogeneic hematopoietic stem cell transplantation. These studies highlight CSL362 as a promising therapeutic option following chemotherapy and transplant so as to improve the outcome of AML patients.

Network, cluster and risk factor analyses for porcine reproductive and respiratory syndrome using data from swine sites participating in a disease control program.

The objectives of this study were to describe networks of Ontario swine sites and their service providers (including trucking, feed, semen, gilt and boar companies); to categorize swine sites into clusters based on site-level centrality measures, and to investigate risk factors for porcine reproductive and respiratory syndrome (PRRS) using information gathered from the above-mentioned analyses. All 816 sites included in the current study were enrolled in the PRRS area regional control and elimination projects in Ontario. Demographics, biosecurity and network data were collected using a standardized questionnaire and PRRS status was determined on the basis of available diagnostic tests and assessment by site veterinarians. Two-mode networks were transformed into one-mode dichotomized networks. Cluster and risk factor analyses were conducted separately for breeding and growing pig sites. In addition to the clusters obtained from cluster analyses, other explanatory variables of interest included: production type, type of animal flow, use of a shower facility, and number of neighboring swine sites within 3km. Unadjusted univariable analyses were followed by two types of adjusted models (adjusted for production systems): a generalizing estimation equation model (GEE) and a generalized linear mixed model (GLMM). Results showed that the gilt network was the most fragmented network, followed by the boar and truck networks. Considering all networks simultaneously, approximately 94% of all swine sites were indirectly connected. Unadjusted risk factor analyses showed significant associations between almost all predictors of interest and PRRS positivity, but these disappeared once production system was taken into consideration. Finally, the vast majority of the variation on PRRS status was explained by production system according to GLMM, which shows the highly correlated nature of the data, and raises the point that interventions at this level could potentially have high impact in PRRS status change and/or maintenance.

Evaluation of cytotoxicity and genotoxicity of Hancornia speciosa latex in Allium cepa root model.

The latex obtained from Hancornia speciosa Gomes (Mangabeira tree) is widely used in traditional medicine to treat a variety of diseases, including diarrhea, ulcer, gastritis, tuberculosis, acne and warts. In this study, the cytotoxicity and genotoxicity effects of H. speciosa latex on the root meristem cells of Allium cepa were examined. Onion bulbs were exposed to different concentrations of latex and then submitted to microscopic analysis using Giemsa stain. Water was used as a negative control and sodium azide as a positive control. The results showed that, under the testing conditions, the mitotic index (MI) of the onion roots submitted to latex treatment did not differ significantly from the negative control, which suggests that the latex is not cytotoxic. Low incidence of chromosome aberrations in the cells treated with H. speciosa latex was also observed, indicating that the latex does not have genotoxic effect either. The MI and the chromosome aberration frequency responded to the latex concentration, requiring more studies to evaluate the dosage effect on genotoxicity. The results indicate that in tested concentrations H. speciosa latex is probably not harmful to human health and may be potentially used in medicine.

Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism

Cisplatin is a widely used chemotherapeutic drug, but its side effects are a major limiting factor. Nephrotoxicity occurs in one third of patients undergoing cisplatin treatment. The acute tubular injury caused by cisplatin often leads to a defective repair process, which translates into chronic renal disorders. In this way, cisplatin affects tubular cells, and maladaptive tubules regeneration will ultimately result in tubulointerstitial fibrosis. Kinins are well known for being important peptides in the regulation of inflammatory stimuli, and kinin B1 receptor deficiency and antagonism have been shown to be beneficial against acute cisplatin nephrotoxicity. This study aimed to analyze the effects of kinin B1 receptor deletion and antagonism against repeated cisplatin-induced chronic renal dysfunction and fibrosis. Both the deletion and the antagonism of B1 receptor exacerbated cisplatin-induced chronic renal dysfunction. Moreover, the inhibition of B1 receptor increased tubular injury and tubulointerstitial fibrosis after repeated treatment with cisplatin. The balance between M1/M2 macrophage polarization plays an important role in renal fibrosis. Kinin B1 receptor antagonism had no impact on M1 markers when compared to cisplatin. However, YM1, an M2 marker and an important molecule for the wound healing process, was decreased in mice treated with kinin B1 receptor antagonist, compared to cisplatin alone. Endothelin-1 levels were also increased in mice with B1 receptor inhibition. This study showed that kinin B1 receptor inhibition exacerbated cisplatin-induced chronic renal dysfunction and fibrosis, associated with reduced YM1 M2 marker expression, thus possibly affecting the wound healing process.