A cohort study of the associations between udder conformation, milk somatic cell count, and lamb weight in suckler ewes

A cohort study of 67 suckler ewes from 1 farm was carried out from January to May 2010 to investigate associations between udder conformation, udder half milk somatic cell count (SCC), and lamb weight. Ewes and lambs were observed at lambing. Ewe health and teat condition and lamb health and weight were recorded on 4 to 5 further occasions at 14-d intervals. At each observation, a milk sample was collected from each udder half for somatic cell counting. Two weeks after lambing, ewe udder conformation and teat placement were scored. Low lamb weight was associated with ewe SCC >400,000 cells/mL (−0.73kg), a new teat lesion 14 d previously (−0.91kg), suboptimal teat position (−1.38kg), rearing in a multiple litter (−1.45kg), presence of diarrhea at the examination (−1.19kg), and rearing by a 9-yr-old ewe compared with a 6-yr-old ewe (−2.36kg). High lamb weight was associated with increasing lamb age (0.21kg/d), increasing birth weight (1.65kg/kg at birth), and increasing number of days the ewe was given supplementary feed before lambing (0.06kg/d). High udder half SCC was associated with pendulous udders (9.6% increase in SCC/cm of drop) and greater total cross-sectional area of the teats (7.2% increase of SCC/cm2). Low SCC were associated with a heavier mean litter weight (6.7% decrease in SCC/kg). Linear, quadratic, and cubic terms for days in lactation were also significant. We conclude that poor udder and teat conformation are associated with high levels of intramammary infection, as indicated by increased SCC and that both physical attributes of the udder and SCC are linked to lamb growth, suggesting that selection of suckler ewes with better udder and teat conformation would reduce intramammary infection and increase lamb growth rate

Improved Methods for Acrylic-Free Implants in Non-Human Primates for Neuroscience Research

Traditionally, head fixation devices and recording cylinders have been implanted in nonhuman primates (NHP) using dental acrylic despite several shortcomings associated with acrylic. The use of more biocompatible materials such as titanium and PEEK is becoming more prevalent in NHP research. We describe a cost effective set of procedures that maximizes the integration of headposts and recording cylinders with the animal’s tissues while reducing surgery time. Nine rhesus monkeys were implanted with titanium headposts, and one of these was also implanted with a recording chamber. In each case, a three-dimensional printed replica of the skull was created based on computerized tomography scans. The titanium feet of the headposts were shaped, and the skull thickness was measured preoperatively, reducing surgery time by up to 70%. The recording cylinder was manufactured to conform tightly to the skull, which was fastened to the skull with four screws and remained watertight for 8.5 mo. We quantified the amount of regression of the skin edge at the headpost. We found a large degree of variability in the timing and extent of skin regression that could not be explained by any single recorded factor. However, there was not a single case of bone exposure; although skin retracted from the titanium, skin also remained adhered to the skull adjacent to those regions. The headposts remained fully functional and free of complications for the experimental life of each animal, several of which are still participating in experiments more than 4 yr after implant

Engineered Single-Domain Antibodies with High Protease Resistance and Thermal Stability

The extreme pH and protease-rich environment of the upper gastrointestinal tract is a major obstacle facing orally-administered protein therapeutics, including antibodies. Through protein engineering, several Clostridium difficile toxin A-specific heavy chain antibody variable domains (VHHs) were expressed with an additional disulfide bond by introducing Ala/Gly54Cys and Ile78Cys mutations. Mutant antibodies were compared to their wild-type counterparts with respect to expression yield, non-aggregation status, affinity for toxin A, circular dichroism (CD) structural signatures, thermal stability, protease resistance, and toxin A-neutralizing capacity. The mutant VHHs were found to be well expressed, although with lower yields compared to wild-type counterparts, were non-aggregating monomers, retained low nM affinity for toxin A, albeit the majority showed somewhat reduced affinity compared to wild-type counterparts, and were capable of in vitro toxin A neutralization in cell-based assays. Far-UV and near-UV CD spectroscopy consistently showed shifts in peak intensity and selective peak minima for wild-type and mutant VHH pairs; however, the overall CD profile remained very similar. A significant increase in the thermal unfolding midpoint temperature was observed for all mutants at both neutral and acidic pH. Digestion of the VHHs with the major gastrointestinal proteases, at biologically relevant concentrations, revealed a significant increase in pepsin resistance for all mutants and an increase in chymotrypsin resistance for the majority of mutants. Mutant VHH trypsin resistance was similar to that of wild-type VHHs, although the trypsin resistance of one VHH mutant was significantly reduced. Therefore, the introduction of a second disulfide bond in the hydrophobic core not only increases VHH thermal stability at neutral pH, as previously shown, but also represents a generic strategy to increase VHH stability at low pH and impart protease resistance, with only minor perturbations in target binding affinities. These are all desirable characteristics for the design of protein-based oral therapeutics

Clinical Use and Therapeutic Potential of IVIG/SCIG, Plasma-Derived IgA or IgM, and Other Alternative Immunoglobulin Preparations

Intravenous and subcutaneous immunoglobulin preparations, consisting of IgG class antibodies, are increasingly used to treat a broad range of pathological conditions, including humoral immune deficiencies, as well as acute and chronic inflammatory or autoimmune disorders. A plethora of Fab- or Fc-mediated immune regulatory mechanisms has been described that might act separately or in concert, depending on pathogenesis or stage of clinical condition. Attempts have been undertaken to improve the efficacy of polyclonal IgG preparations, including the identification of relevant subfractions, mild chemical modification of molecules, or modification of carbohydrate side chains. Furthermore, plasma-derived IgA or IgM preparations may exhibit characteristics that might be exploited therapeutically. The need for improved treatment strategies without increase in plasma demand is a goal and might be achieved by more optimal use of plasma-derived proteins, including the IgA and the IgM fractions. This article provides an overview on the current knowledge and future strategies to improve the efficacy of regular IgG preparations and discusses the potential of human plasma-derived IgA, IgM, and preparations composed of mixtures of IgG, IgA, and IgM

Safety of Adding Oats to a Gluten-free Diet for Patients with Celiac Disease: Systematic Review and Meta-analysis of Clinical and Observational Studies

Background & Aims: Patients with celiac disease should maintain a gluten-free diet (GFD), excluding wheat, rye, and barley. Oats might increase the nutritional value of a GFD, but their inclusion is controversial. We performed a systematic review and meta-analysis to evaluate the safety of oats as part of a GFD in patients with celiac disease. Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases for clinical trials and observational studies of the effects of including oats in GFD of patients with celiac disease. The studies reported patients’ symptoms, results from serology tests, and findings from histologic analyses. We used the GRADE approach to assess the quality of evidence. Results: We identified 433 studies; 28 were eligible for analysis. Of these, 6 were randomized and 2 were not randomized controlled trials comprising a total of 661 patients—the remaining studies were observational. All randomized controlled trials used pure/uncontaminated oats. Oat consumption for 12 months did not affect symptoms (standardized mean difference: reduction in symptom scores in patients who did and did not consume oats, −0.22; 95% CI, −0.56 to 0.13; P = .22), histologic scores (relative risk for histologic findings in patients who consumed oats, 0.24; 95% CI, 0.01–4.8; P = .35), intraepithelial lymphocyte counts (standardized mean difference, 0.21; 95% CI, reduction of 1.44 to increase in 1.86), or results from serologic tests. Subgroup analyses of adults vs children did not reveal differences. The overall quality of evidence was low. Conclusions: In a systematic review and meta-analysis, we found no evidence that addition of oats to a GFD affects symptoms, histology, immunity, or serologic features of patients with celiac disease. However, there were few studies for many endpoints, as well as limited geographic distribution and low quality of evidence. Rigorous double-blind, placebo-controlled, randomized controlled trials, using commonly available oats sourced from different regions, are needed