Resistance against macrocyclic lactones in Psoroptes ovis in cattle

Abstract Background Psoroptic mange is an important disease in beef cattle, and Belgian Blue cattle are particularly susceptible. Treatment failure of macrocyclic lactones against Psoroptes ovis has been reported, but clear evidence of in vivo resistance is still lacking. This study was conducted to investigate ML efficacy in 16 beef farms in Belgium and The Netherlands in vivo and in vitro.Methods On each farm a group of animals (n= 7-14) with clinical psoroptic mange was treated with two subcutaneous injections of a macrocyclic lactone with 7-10 days interval (15 farms) or a single injection with a long-acting macrocyclic lactone (1 farm). In vivo efficacy was assessed by the reduction in mite counts and clinical index (part of the body affected by lesions), the cure rate after the first treatment round and the number of treatment rounds needed to cure all animals. In vitro knock-down and mortality was evaluated in a contact test.Results Cure rates after the first treatment round varied from 0-80%. All farms needed two or more rounds of treatments to obtain full efficacy. Clinical index had a high variation and only started to reduce after the second treatment round. Only three farms were categorized as susceptible with a mean mite count reduction>95% and a lower limit of the uncertainty interval>90%. One farm had a mean reduction>95%, but its lower limit of the confidence interval was <90%. All other farms had mean reductions<95% and lower limits of their uncertainty intervals<90%. No correlation was found between in vitro lethal dose 50 and knock-down dose 50 values and any parameter of in vivo efficacy.Conclusion Unambiguous treatment failure was detected on 12/16 beef farms, confirming the presence of macrocyclic lactone resistance in Belgian Blue beef farms. In vitro parameters could not discriminate the farms based on their in vivo susceptibility. The mean reduction in mite counts and the lower limit of the confidence interval stood out as most useful parameter to identify acaricide resistance.

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Resistance against macrocyclic lactones in Psoroptes ovis in cattle

10.21203/rs.2.18981/v2 ◽

2020 ◽

Author(s):

Wouter van Mol ◽

Nathalie De Wilde ◽

Stijn Casaert ◽

Zhenzhen Chen ◽

Marieke Vanhecke ◽

...

Keyword(s):

Treatment Failure ◽

Lower Limit ◽

Macrocyclic Lactone ◽

Macrocyclic Lactones ◽

Psoroptes Ovis ◽

In Vivo Efficacy ◽

Knock Down ◽

Clinical Index

Abstract Background Psoroptic mange is an important disease in beef cattle, and Belgian Blue cattle are particularly susceptible. Treatment failure of macrocyclic lactones against Psoroptes ovis has been reported, but clear evidence of in vivo resistance is still lacking. This study was conducted to investigate the efficacy of macrocyclic lactone products in 16 beef farms in Belgium and The Netherlands in vivo and in vitro . Methods On each farm a group of animals (n= 7-14) with psoroptic mange was treated with two subcutaneous injections of a macrocyclic lactone product with 7-10 days interval (15 farms) or a single injection with a long-acting macrocyclic lactone (1 farm). In vivo efficacy was assessed by the reduction in mite counts and clinical index (estimated proportion of the body surface affected by lesions), the proportion of the animals with negative mite counts after the first treatment round and the number of treatment rounds needed to obtain zero mites counts in all animals. A mite population from a given farm was categorized as sensitive when the mite count reduction after the first treatment round >95% and the lower limit of the uncertainty interval >90%. Resistance was detected when both parameters were below the threshold. Resistance was suspected when only one was below its threshold. In vitro knock-down and mortality was evaluated in a contact test. Results The proportion of the animals with negative mite counts after the first treatment round varied from 0-80%. All farms needed two or more rounds of treatments to obtain zero mite counts on all animals. Clinical index had a high variation and only started to reduce after the second treatment round. Mite populations from three farms were categorized as sensitive, one as suspected resistant and the other 12 as resistant. No correlation was found between in vitro lethal dose 50 and knock-down dose 50 values and any parameter of in vivo efficacy. Conclusions Unambiguous treatment failure was detected on 12/16 beef farms, confirming the presence of macrocyclic lactone resistance on Belgian Blue beef farms. In vitro parameters could not discriminate the farms based on their in vivo sensitivity. The mean reduction in mite counts and the lower limit of the confidence interval are proposed as most useful parameters to identify acaricide resistance.

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Resistance against macrocyclic lactones in Psoroptes ovis in cattle

10.21203/rs.2.18981/v3 ◽

2020 ◽

Author(s):

Wouter van Mol ◽

Nathalie De Wilde ◽

Stijn Casaert ◽

Zhenzhen Chen ◽

Marieke Vanhecke ◽

...

Keyword(s):

Treatment Failure ◽

Lower Limit ◽

Macrocyclic Lactone ◽

The Body ◽

Macrocyclic Lactones ◽

Psoroptes Ovis ◽

In Vivo Efficacy ◽

Clinical Index

Abstract Background Psoroptic mange is an important disease in Belgian Blue cattle. Treatment failure of macrocyclic lactones against Psoroptes ovis has been reported, but clear evidence of in vivo resistance is lacking. This study assessed the efficacy of macrocyclic lactone products on 16 beef farms in Belgium and the Netherlands in vivo and in vitro . Methods On each farm a group of animals ( n = 7–14) with psoroptic mange was treated with two subcutaneous injections of a macrocyclic lactone product with 7–10 days interval (15 farms) or a single injection with a long-acting macrocyclic lactone (1 farm). In vivo efficacy was assessed by the reduction in mite counts, clinical index (proportion of the body surface affected by lesions), the proportion of the animals with negative mite counts after the first treatment round and the number of treatment rounds needed to obtain zero mites counts in all animals. A mite population was categorized as sensitive when the mite count reduction after the first treatment round > 95% and the lower limit of the uncertainty interval > 90%. Resistance was detected when both parameters were below their threshold and suspected when one parameter was too low. In vitro knockdown and mortality were evaluated in a contact test. Results The proportion of the animals with negative mite counts after the first treatment round varied from 0 to 80%. All farms needed two or more treatments rounds to obtain zero mite counts on all animals. Clinical index only started to reduce after the second treatment round. Mite populations from three farms were categorized as sensitive, one as suspected resistant and 12 as resistant. No correlation was found between in vitro lethal dose 50 and knockdown dose 50 values and in vivo efficacy parameters. Conclusions Unambiguous treatment failure was detected on 12 out of 16 farms, confirming the presence of macrocyclic lactone resistance on Belgian Blue beef farms. In vitro parameters could not discriminate the farms based on their in vivo sensitivity. The mean reduction in mite counts and the lower limit of the confidence interval are proposed as parameters to identify acaricide resistance.

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Knock down of HIF-1α in glioma cells reduces migration in vitro and invasion in vivo and impairs their ability to form tumor spheres

Molecular Cancer ◽

10.1186/1476-4598-9-133 ◽

2010 ◽

Vol 9 (1) ◽

pp. 133 ◽

Cited By ~ 131

Author(s):

Olga Méndez ◽

Jiri Zavadil ◽

Mine Esencay ◽

Yevgeniy Lukyanov ◽

Daniel Santovasi ◽

...

Keyword(s):

Glioma Cells ◽

Knock Down

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Diagnostic Validity of Digital Imaging Fiber-Optic Transillumination (DIFOTI) and Near-Infrared Light Transillumination (NILT) for Caries in Dentine

Journal of Clinical Medicine ◽

10.3390/jcm9020420 ◽

2020 ◽

Vol 9 (2) ◽

pp. 420

Author(s):

Ana Marmaneu-Menero ◽

José Enrique Iranzo-Cortés ◽

Teresa Almerich-Torres ◽

José Carmelo Ortolá-Síscar ◽

José María Montiel-Company ◽

...

Keyword(s):

Confidence Interval ◽

Qualitative Analysis ◽

Near Infrared ◽

Meta Analysis ◽

Infrared Light ◽

X Rays ◽

Carious Lesions ◽

Sensitivity Specificity

The objective of the study is to analyse the available evidence for the validity of the transillumination method in the diagnosis of interproximal caries. Bibliographic searches were carried out in three data bases (PubMed, Embase, Scopus) with the key words “Transillumination AND caries”. A total of 11 studies were selected for the qualitative analysis and meta-analysis. In the qualitative analysis, both in vivo and in vitro studies were included. The gold standards were tomography, digital radiography, and clinical visual diagnosis. The meta-analysis determined the sensitivity, specificity, and area below the ROC curve relative to the transillumination method in the diagnosis of caries in dentine. Meta-analysis results obtained for transillumination gave a sensitivity value of 0.69 (confidence interval: 0.54–0.81), a specificity value of 0.89 (confidence interval: 0.61–0.98), while giving an AUC value of 0.79 (confidence interval: 0.67–0.87). Transillumination is a method offering moderate validity in the diagnosis of carious lesions in dentine, there is no strong evidence that may enable us to affirm that transillumination may fully substitute X-rays in the complementary diagnosis of carious lesions

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YTHDF2 mediates the mRNA degradation of the tumor suppressors to induce AKT phosphorylation in N6-methyladenosine-dependent way in prostate cancer

Molecular Cancer ◽

10.1186/s12943-020-01267-6 ◽

2020 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Jiangfeng Li ◽

Haiyun Xie ◽

Yufan Ying ◽

Hong Chen ◽

Huaqing Yan ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Suppressors ◽

Mrna Degradation ◽

Akt Phosphorylation ◽

Knock Down ◽

Phosphorylated Akt ◽

And Migration ◽

Proliferation And Migration

Abstract Background N6-methyladenosine (m6A) is the most abundant modification in mRNA of humans. Emerging evidence has supported the fact that m6A is comprehensively involved in various diseases especially cancers. As a crucial reader, YTHDF2 usually mediates the degradation of m6A-modified mRNAs in m6A-dependent way. However, the function and mechanisms of m6A especially YTHDF2 in prostate cancer (PCa) still remain elusive. Methods To investigate the functions and mechanisms of YTHDF2 in PCa, in vitro, in vivo biofunctional assays and epigenetics experiments were performed. Endogenous expression silencing of YTHDF2 and METTL3 was established with lentivirus-based shRNA technique. Colony formation, flow cytometry and trans-well assays were performed for cell function identifications. Subcutaneous xenografts and metastatic mice models were combined with in vivo imaging system to investigate the phenotypes when knocking down YTHDF2 and METTL3. m6A RNA immunoprecipitation (MeRIP) sequencing, mRNA sequencing, RIP-RT-qPCR and bioinformatics analysis were mainly used to screen and validate the direct common targets of YTHDF2 and METTL3. In addition, TCGA database was also used to analyze the expression pattern of YTHDF2, METTL3 and the common target LHPP in PCa, and their correlation with clinical prognosis. Results The upregulated YTHDF2 and METTL3 in PCa predicted a worse overall survival rate. Knocking down YTHDF2 or METTL3 markedly inhibited the proliferation and migration of PCa in vivo and in vitro. LHPP and NKX3–1 were identified as the direct targets of both YTHDF2 and METTL3. YTHDF2 directly bound to the m6A modification sites of LHPP and NKX3–1 to mediate the mRNA degradation. Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and NKX3–1 at both mRNA and protein level with inhibited phosphorylated AKT. Overexpression of LHPP and NKX3–1 presented the consistent phenotypes and AKT phosphorylation inhibition with knock-down of YTHDF2 or METTL3. Phosphorylated AKT was consequently confirmed as the downstream of METTL3/YTHDF2/LHPP/NKX3–1 to induce tumor proliferation and migration. Conclusion We propose a novel regulatory mechanism in which YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3–1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer. We hope our findings may provide new concepts of PCa biology.

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