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Prevention of infection with canine heartworm (Dirofilaria immitis) is based on the compliant administration of macrocyclic lactone (ML) drugs. Resistance to ML drugs is well documented in D. immitis; however, there remains a paucity of information on the spatial distribution and prevalence of resistant isolates. This project aims to improve understanding of ML-resistance by using a population genetic approach. We developed a large panel of microsatellite loci and identified 12 novel highly polymorphic markers. These 12, and five previously published markers were used to screen pools of microfilariae from 16 confirmed drug-susceptible, 25 confirmed drug-resistant, and from 10 suspected drug-resistant field isolates. In isolates where microfilarial suppression testing indicated resistance, Spatial Principal Component Analysis (sPCoA), Neighbor Joining Trees and Bayesian clustering all revealed high genetic similarity between pre- and post-treatment samples. Somewhat surprisingly, the Neighbor Joining tree and sPCoA generated using pairwise Nei's distances did not reveal clustering for resistant isolates, nor did it reveal state-level geographic clustering from samples collected in Georgia, Louisiana or Mississippi. In contrast, Discriminant Analysis of Principle Components was able to discriminate between susceptible, suspected-resistant and resistant samples. However, no resistance-associated markers were detected, and this clustering was driven by the combined effects of multiple alleles across multiple loci. Additionally, we measured unexpectedly large genetic distances between different passages of laboratory strains that originated from the same source infection. This finding strongly suggests that the genetic makeup of laboratory isolates can change substantially with each passage, likely due to genetic bottlenecking. Taken together, these data suggest greater than expected genetic variability in the resistant isolates, and in D. immitis overall. Our results also suggest that microsatellite genotyping lacks the sensitivity to detect a specific genetic signature for resistance. Future investigations using genomic analyses will be required to elucidate the genetic relationships of ML-resistant isolates., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The performance of tertiary moving bed biofilm reactors (MBBRs) was evaluated in terms of micropollutants (MPs) removal from secondary-treated municipal wastewater. After stepwise establishment of a mature biofilm, monitored by scanning electron and confocal microscopies, abiotic and biotic removals of MPs were deeply studied. Since no MPs reduction was observed by the both photodegradation and volatilization, abiotic removal of MPs was ascribed to the sorption onto the biomass. Target MPs i.e. Naproxen, Diclofenac, 17β-Estradiol and 4n-Nonylphenol, arranged in the ascending order of hydrophobicity, abiotically declined up to 2.8%, 4%, 9.5% and 15%, respectively. MPs sorption onto the suspended biomass was found around two times more than the biofilm, in line with MPs' higher sorption kinetic constants (k sor ) found for the suspended biomass. When comparing abiotic and biotic aspects, we found that biotic removal outperformed its counterpart for all compounds as Diclofenac, Naproxen, 17β-Estradiol and 4n-Nonylphenol were biodegraded by 72.8, 80.6, 84.7 and 84.4%, respectively. The effect of the changes in organic loading rates (OLRs) was investigated on the pseudo-first order degradation constants (k biol ), revealing the dominant biodegradation mechanism of co-metabolism for the removal of Diclofenac, Naproxen, and 4n-Nonylphenol, while 17β-Estradiol obeyed the biodegradation mechanism of competitive inhibition. Biotic removals and k biol values of all MPs were also seen higher in the biofilm as compared to the suspended biomass. To draw a conclusion, a quite high removal of recalcitrant MPs is achievable in tertiary MBBRs, making them a promising technology that supports both pathways of co-metabolism and competitive inhibition, next to the abiotic attenuation of MPs., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Visceral leishmaniasis is not endemic in West Africa. However, high seroprevalence of Leishmania infantum infection (one of the Leishmania species that cause visceral leishmaniasis) was detected in dogs and humans in the Mont Rolland community (close to Thiès, Senegal), despite the lack of reports concerning human clinical cases. Our aim was to genetically characterize this L. infantum population and identify its origin. We thus conducted seven field surveys in 25 villages of the Mont Rolland community between 2005 and 2009 and blood samples were collected from 205 dogs. Serological testing indicated that 92 dogs (44.9%) were positive for Leishmania infection. L. infantum was identified as the cause of infection. Analysis of 29 L. infantum isolates from these dogs by multilocus microsatellite typing and multilocus sequence typing indicated that this population had very limited genetic diversity, low level of heterozygosity and only seven different genotypes (79.3% of all isolates had the same genotype). Multilocus sequence typing showed that the Mont Rolland isolates clustered with strains from the Mediterranean basin and were separated from East African and Asian strains. Therefore, our data suggest a quite recent and unique introduction into Senegal of a L. infantum strain from the Mediterranean basin., (Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: Whether therapeutic drug monitoring of biologic therapy can predict the efficacy of adalimumab to prevent postoperative Crohn's disease recurrence is unknown., Aim: To investigate whether adalimumab trough levels and anti-adalimumab antibodies correlate with endoscopic and clinical outcomes in a series of patients treated with prophylactic adalimumab monotherapy after resective surgery., Methods: Post hoc analysis of a randomized, mesalamine-controlled trial. Adalimumab trough levels and antibodies were analysed every 8 weeks for 2 years using an homogeneous mobility shift assay., Results: At two years, 1/6 patient had clinical recurrence and 1/6 patient had endoscopic and clinical recurrence. At baseline (9.5 vs. 14.4 mcg/mL) and during follow-up [7.5 (4.4-9.8) vs. 13.9 (8.9-23.6)mcg/mL, p<0.01], median adalimumab trough levels in patients with clinical or endoscopic recurrence were lower than in those who maintained remission. Persistent antibodies-against-adalimumab were detected in the patient with both endoscopic and clinical recurrence., Conclusion: Measurement of adalimumab trough levels and anti-adalimumab antibodies after surgery could be useful to further reduce postoperative recurrence., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The present paper describes an analytical method for the determination of 2 widely administered anticancer drugs, ifosfamide and cyclophosphamide, contained in sewage sludge. The method relies on the extraction from the solid matrix by pressurized liquid extraction, sample purification by solid-phase extraction and analysis by ultra high performance liquid chromatography coupled with tandem mass spectrometry. The different parameters affecting the extraction efficiency were optimized using an experimental design. Solvent nature was the most decisive factor for the extraction but interactions between some parameters also appeared very influent. The method was applied to seven different types of sludge for validation. The performances of the analytical method displayed high variability between sludges with limits of detection spanning more than one order of magnitude and confirming the relevance of multi-sample validation. Matrix effect has been determined as the most limiting analytical step for quantification with different extent depending on analyte and sludge nature. For each analyte, the use of deuterated standard spiked at the very beginning ensured the complete compensation of losses regardless of the sample nature. The suitability of the method between freshly spiked and aged samples has also been verified. The optimized method was applied to different sludge samples to determine the environmental levels of anticancer drugs. The compounds were detected in some samples reaching 42.5μg/kgDM in ifosfamide for the most contaminated sample., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A methodology was developed to quantify the efficiency of yeast-based products for adsorption of three mycotoxins: zearalenone (ZEA), aflatoxin B(1) (AFB(1)), and ochratoxin A (OTA). Eight products were tested (yeast cell wall or inactivated yeast). The described experimental protocol based on in vitro tests provided reliable isotherms for each mycotoxin. The most suitable models were the Hill model for ZEA, the Langmuir model for AFB(1), and the Freundlich model for OTA. From these models, original mathematical affinity criteria were defined to quantify the product adsorption performances for each mycotoxin. The best yeast product, a yeast cell wall from baker's yeast, can adsorb up to 68% of ZEA, 29% of AFB(1), and 62% of OTA, depending on the mycotoxin concentrations. The adsorption capacity largely depended both on yeast composition and mycotoxin, but no direct correlation between yeast composition and adsorption capacity was found, confirming that adsorption of mycotoxin on yeast-based products involves complex phenomena. The results of this study are useful for comparing the adsorption efficiency of various yeast products and understanding the mechanisms involved in adsorption., (Copyright ©, International Association for Food Protection)

VEGFR-3 is essential for vascular development and maintenance of lymphatic vessel's integrity. Little is known about its cooperative effect with other receptors of the same family. Contrary to VEGFR-2, stimulation of VEGFR-3 by VEGF-C and -D failed to enhance its phosphorylation either in HEK293T or in PAE cells. These ligands were unable to induce angiogenesis of PAEC expressing VEGFR-3 alone. In the presence of VEGFR-2, VEGF-C and -D induced heterodimerization of VEGFR-3 with VEGFR-2. This heterodimerization was associated with enhanced VEGFR-3 phosphorylation and subsequent cellular responses as evidenced by the formation of capillary-like structures in PAE cells and proliferation of primary human endothelial cells expressing both receptors. Taken together, these results show for the first time that VEGFR-3 needs to be associated to VEGFR-2 to induce ligand-dependent cellular responses.