Deterministic model to evaluate the impact of lactational treatment of subclinical mastitis due to coagulase-negative staphylococci

Coagulase-negative staphylococci (CNS) are the most frequently isolated bacteria from milk samples in several studies worldwide. Despite their relative frequency, specific measures aiming at their control are not well established. One possible measure to include in a control programme is lactational antimicrobial treatment. The decision to perform such treatment, as well as other actions on farm, should be based on the likelihood of financial return. A deterministic model was used to evaluate whether performing an antimicrobial treatment during the lactation for quarters infected with CNS was financially justifiable. Input variables for the impact of CNS on udder health were based on a previous study by the same authors and on available literature on the subject. Prices included in the model were based on 2009/2010 conditions in Portugal. The average result per antimicrobial treated quarter was a net loss of (sic)38.74. Performing a sensitivity analysis to evaluate how systematic variation of the input variables of the model would lead to outcome changes showed that variation in input variables nearly always led to a negative outcome, with the greatest variation in losses observed for variation in the length of treatment and milk withdrawal period (-(sic)46.26 to -(sic)28.49). The situations in which a net benefit was to be expected included the bulk tank somatic cell count decreasing to a level corresponding to a premium payment or to penalties being avoided, and the prevention of transmission of CNS in the milking parlour when the possibility of transmission was at its highest level. For most situations, lactational treatment of CNS subclinical mastitis was not financially justifiable

Sickle cell disease

Female patient with past medical history of anaemia associated with multiple painful crises, characterized by severe skeletal pain and fever

Dynamics of bovine intramammary infections due to coagulase-negative staphylococci on four farms

The objectives of this study were to compare the impact of different coagulase-negative species (CNS) on udder health measured in terms of individual quarter milk somatic cell count (SCC) and duration of intramammary infection, and to get some insight into most likely routes of infection for different CNS species. This longitudinal observational study was performed on four farms that were sampled at 4-week intervals for a total of 12 visits each. Quarters infected with CNS were followed through time with milk samples being submitted for bacteriological culture and SCC determination. PCR amplification of the internal transcribed spacer region and sequencing of the sodA and rpoB genes were used for species allocation. Pulsed-field gel electrophoresis (PFGE) was performed to assess strain identity. The percentage of quarters affected per farm varied between 6 and 35%, with the most frequently isolated CNS species being Staphylococcus epidermidis, followed by Staph. simulans, Staph. chromogenes and Staph. haemolyticus. It was possible to follow 111 intramammary infections due to CNS through time. Duration of infection had a mean of 188 d and was not significantly different between CNS species. Geometric mean quarter SCC overall was 132 000 cells/ml and was also not significantly different between CNS species. Despite the possibility of a different epidemiology of infection, the impact in terms of udder health seems to be similar for different CNS species

Time resolved study of cell death mechanisms induced by amine-modified polystyrene nanoparticles

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Biosensors for On-Farm Diagnosis of Mastitis

Bovine mastitis is an inflammation of the mammary gland caused by a multitude of pathogens with devastating consequences for the dairy industry. Global annual losses are estimated to be around €30 bn and are caused by significant milk losses, poor milk quality, culling of chronically infected animals, and occasional deaths. Moreover, mastitis management routinely implies the administration of antibiotics to treat and prevent the disease which poses serious risks regarding the emergence of antibiotic resistance. Conventional diagnostic methods based on somatic cell counts (SCC) and plate-culture techniques are accurate in identifying the disease, the respective infectious agents and antibiotic resistant phenotypes. However, pressure exists to develop less lengthy approaches, capable of providing on-site information concerning the infection, and in this way, guide, and hasten the most adequate treatment. Biosensors are analytical tools that convert the presence of biological compounds into an electric signal. Benefitting from high signal-to-noise ratios and fast response times, when properly tuned, they can detect the presence of specific cells and cell markers with high sensitivity. In combination with microfluidics, they provide the means for development of automated and portable diagnostic devices. Still, while biosensors are growing at a fast pace in human diagnostics, applications for the veterinary market, and specifically, for the diagnosis of mastitis remain limited. This review highlights current approaches for mastitis diagnosis and describes the latest outcomes in biosensors and lab-on-chip devices with the potential to become real alternatives to standard practices. Focus is given to those technologies that, in a near future, will enable for an on-farm diagnosis of mastitisinfo:eu-repo/semantics/publishedVersio

Binding site plasticity in viral PPxY Late domain recognition by the third WW domain of human NEDD4

The recognition of PPxY viral Late domains by the third WW domain of the HECT-E3 ubiquitin ligase NEDD4 (hNEDD4-WW3) is essential for the completion of the budding process of numerous enveloped viruses, including Ebola, Marburg, HTLV1 or Rabies. hNEDD4-WW3 has been validated as a promising target for the development of novel host-oriented broad spectrum antivirals. Nonetheless, finding inhibitors with good properties as therapeutic agents remains a challenge since the key determinants of binding affinity and specificity are still poorly understood. We present here a detailed structural and thermodynamic study of the interactions of hNEDD4-WW3 with viral Late domains combining isothermal titration calorimetry, NMR structural determination and molecular dynamics simulations. Structural and energetic differences in Late domain recognition reveal a highly plastic hNEDD4-WW3 binding site that can accommodate PPxY-containing ligands with varying orientations. These orientations are mostly determined by specific conformations adopted by residues I859 and T866. Our results suggest a conformational selection mechanism, extensive to other WW domains, and highlight the functional relevance of hNEDD4-WW3 domain conformational flexibility at the binding interface, which emerges as a key element to consider in the search for potent and selective inhibitors of therapeutic interest.This research has been financed by grants BIO2009-13261-C02, BIO2012-39922-CO2 and BIO2016-78746-C2-1-R from the Spanish Ministry of Education and Science (I.L.) including AEI/FEDER EU funds, by CTQ2017-83810-R grant (F.J.B) and by BFU2014-53787-P, the IRB Barcelona and the BBVA Foundation (M.J.M)