Using a runway paradigm to assess the relative strength of rats' motivations for enrichment objects

Laboratory animals should be provided with enrichment objects in their cages; however, it is first necessary to test whether the proposed enrichment objects provide benefits that increase the animals’ welfare. The two main paradigms currently used to assess proposed enrichment objects are the choice test, which is limited to determining relative frequency of choice, and consumer demand studies, which can indicate the strength of a preference but are complex to design. Here, we propose a third methodology: a runway paradigm, which can be used to assess the strength of an animal’s motivation for enrichment objects, is simpler to use than consumer demand studies, and is faster to complete than typical choice tests. Time spent with objects in a standard choice test was used to rank several enrichment objects in order to compare with the ranking found in our runway paradigm. The rats ran significantly more times, ran faster, and interacted longer with objects with which they had previously spent the most time. It was concluded that this simple methodology is suitable for measuring rats’ motivation to reach enrichment objects. This can be used to assess the preference for different types of enrichment objects or to measure reward system processes

Polyubiquitin binding to ABIN1 is required to prevent autoimmunity

The protein ABIN1 possesses a polyubiquitin-binding domain homologous to that present in nuclear factor kappa B (NF-kappa B) essential modulator (NEMO), a component of the inhibitor of NF-kappa B (I kappa B) kinase (IKK) complex. To address the physiological significance of polyubiquitin binding, we generated knockin mice expressing the ABIN1[D485N] mutant instead of the wild-type (WT) protein. These mice developed all the hallmarks of autoimmunity, including spontaneous formation of germinal centers, isotype switching, and production of autoreactive antibodies. Autoimmunity was suppressed by crossing to MyD88(-/-) mice, demonstrating that toll-like receptor (TLR)-MyD88 signaling pathways are needed for the phenotype to develop. The B cells and myeloid cells of the ABIN1[D485N] mice showed enhanced activation of the protein kinases TAK, IKK-alpha/beta, c-Jun N-terminal kinases, and p38 alpha mitogen-activated protein kinase and produced more IL-6 and IL-12 than WT. The mutant B cells also proliferated more rapidly in response to TLR ligands. Our results indicate that the interaction of ABIN1 with polyubiquitin is required to limit the activation of TLR-MyD88 pathways and prevent autoimmunity

Hyperpolarized13c mri of tumor metabolism demonstrates early metabolic response to neoadjuvant chemotherapy in breast cancer

Purpose: To compare hyperpolarized carbon 13 (13C) MRI with dynamic contrast material–enhanced (DCE) MRI in the detection of early treatment response in breast cancer. Materials and Methods: In this institutional review board–approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent13C MRI after injection of hyperpolarized [1–carbon 13 {13C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The13C-labeled lactate-to-pyruvate ratio derived from hyperpolarized13C MRI and the pharmacokinetic parameters transfer constant (Ktrans) and washout parameter (kep ) derived from DCE MRI were compared before and after treatment. Results: Exchange of the13C label between injected hyperpolarized [1-13C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the13C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean Ktrans (132%) and mean kep (31%), which could be incorrectly interpreted as a poor response to treatment. Conclusion: Hyperpolarized13C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI

Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model

Abstract Background Mesenchymal stromal cells (MSC) have shown promising results in the treatment of tendinopathy in equine medicine, making this therapeutic approach seem favorable for translation to human medicine. Having demonstrated that MSC engraft within the tendon lesions after local injection in an equine model, we hypothesized that they would improve tendon healing superior to serum injection alone. Methods Quadrilateral tendon lesions were induced in six horses by mechanical tissue disruption combined with collagenase application 3 weeks before treatment. Adipose-derived MSC suspended in serum or serum alone were then injected intralesionally. Clinical examinations, ultrasound and magnetic resonance imaging were performed over 24 weeks. Tendon biopsies for histological assessment were taken from the hindlimbs 3 weeks after treatment. Horses were sacrificed after 24 weeks and forelimb tendons were subjected to macroscopic and histological examination as well as analysis of musculoskeletal marker expression. Results Tendons injected with MSC showed a transient increase in inflammation and lesion size, as indicated by clinical and imaging parameters between week 3 and 6 (p < 0.05). Thereafter, symptoms decreased in both groups and, except that in MSC-treated tendons, mean lesion signal intensity as seen in T2w magnetic resonance imaging and cellularity as seen in the histology (p < 0.05) were lower, no major differences could be found at week 24. Conclusions These data suggest that MSC have influenced the inflammatory reaction in a way not described in tendinopathy studies before. However, at the endpoint of the current study, 24 weeks after treatment, no distinct improvement was observed in MSC-treated tendons compared to the serum-injected controls. Future studies are necessary to elucidate whether and under which conditions MSC are beneficial for tendon healing before translation into human medicine

The need for a convergence of agricultural/laboratory and zoo-based approaches to animal welfare

Advances in animal welfare science have led to a high number of studies published for farm, laboratory and zoo animals, with a huge breadth of innovative topic areas and methodologies. This paper investigates the different approaches used to undertake welfare research in farm, laboratory and zoo animals due to the variety of constraints that each group brings. We also set recommendations to how groups can support each other in moving forwards to reduce animal suffering and promote a life worth living, a goal that all parties aim to achieve. We propose that researchers develop more collaborations across species, in particular to focus on the applied component of animal welfare and utilizing positive welfare indicators; facilitate knowledge transfer and share good practice worldwide; and accept small n based studies that can still be scientifically robust and provide individual-based steps into advances in our knowledge. Ultimately, we need to be progressing animal welfare science to a point beyond legislative needs, and ensure that ‘high animal welfare’ becomes an additional mission statement for all animal-based industries

Tracing Changes in Families Who Participated in the Home-Start Parenting Program: Parental Sense of Competence as Mechanism of Change

The present study aimed to (1) determine the long-term effectiveness of Home-Start, a preventive parenting program, and (2) test the hypothesis that changes in maternal sense of competence mediate the program’s effects. Participants were 124 mothers (n = 66 intervention, n = 58 comparison). Four assessments took place during a 1-year period. Latent growth modeling showed that Home-Start enhanced growth in maternal sense of competence and supportive parenting, and led to a decrease in the use of inept discipline. Results of mediational and cross-lagged analyses were consistent with the hypothesized model: Participation in Home-Start was related to the changes in maternal sense of competence, which in turn predicted changes in parenting. The results affirm the importance of directly targeting parental sense of competence in the context of prevention work with parents

Gene expression and matrix turnover in overused and damaged tendons

Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries