The effect of a traditional and a stick gang-line on the body position of working sled dogs

This study aimed to investigate the effect of two different gang-lines on the pulling angle of sled dogs. It was hypothesised that dogs would run with a straighter angle of pull (in relation to the main-line) in stick gang-lines (STICK) than they would do in traditional gang-lines (TRAD). Eight sled dogs, divided into two teams, ran a 3.1 km trail twice in both types of gang-lines, pulling a quadbike on dry ground. Each dog remained in its team in the same position (side of gang line, and forward or back in the line) for both runs, using both types of lines in randomised order between the runs. Markers were placed on the dogs and on the main lines, and the runs were recorded by a video camera. The dogs' angle of pull measured from the video recordings was compared between the two conditions. Thirteen positional measurements for each dog during each run were taken. The dogs were used to running in TRAD and were not acclimatised to STICK. Data was analysed using Wilcoxon and Spearmans rho tests. Data regarding individual dogs (n=13), teams (n=52), dogs' placements in teams (n=4), and gang-line related pulling angles (n=104) was analysed. Overall, the position of the dogs was straighter when pulling in STICK, than when pulling in TRAD, with a median of 19 degrees (inter quartile range (IQR) 24.75 degrees) and 32 degrees (IQR 25.75 degrees), respectively (PPeer reviewe

Part I of Finnish Agility Dog Survey: Training and Management of Competition-Level Agility Dogs

Simple Summary Information on training, competition, and management of agility dogs is sparse. To decrease this knowledge gap, Finnish owners and handlers of competition-level agility dogs completed an online questionnaire to describe the agility routines of their dog during one injury-free year. Additional information on competition routines was retrieved from the national competition results database. Typically, competition-level agility dogs trained agility once or twice a week and competed two runs a month. The median total weekly training time was 18 min. Usual speed over the competition course was 4.3 m/s. Artificial turf, with or without filling, and dirt surfaces are used most often. Dogs are warmed up before and cooled down after agility performance. Most dogs visit a massage therapist, physiotherapist, osteopath or other professionals of musculoskeletal care at least every three months. Many dogs undergo conditioning exercises, although often less often than every two weeks. Additionally, agility dogs are walked for a total of 1.5 h a day. Dogs competing at the highest levels competed more but trained less than dogs at lower levels. This is the first investigation of agility-related routines in competing agility dogs. Knowledge regarding training, competition, and management routines of agility dogs is lacking. Through a retrospective online questionnaire, Finnish owners and handlers of 745 competition-level agility dogs provided information on training routines and management of these dogs during one year free of agility-related injuries. Competition routines were collected from the national competition results database. Most dogs trained agility 1-2 times a week, with a median active training time of 18 min a week. Dogs competed in a median of 2.1 runs per month at a speed of 4.3 m/s. Common field surfaces were different types of artificial turfs and dirt surface. Warm-up and cool-down were established routines, and 62% of dogs received regular musculoskeletal care. Moreover, 77% of dogs underwent conditioning exercises, but their frequency was often low. Additionally, dogs were walked for a median of 1.5 h daily. Pearson's chi-squared and Kruskal-Wallis tests were used to evaluate the association between a dog's competition level and training and competition variables. A dog's competition level was associated with competition (p < 0.001) and training frequency (p < 0.001); dogs at higher levels compete more but train less than dogs at lower levels. This study provides information on training, competition, and management routines of competing agility dogs

Crawling-induced floor dust resuspension affects the microbiota of the infant breathing zone

Background: Floor dust is commonly used for microbial determinations in epidemiological studies to estimate early-life indoor microbial exposures. Resuspension of floor dust and its impact on infant microbial exposure is, however, little explored. The aim of our study was to investigate how floor dust resuspension induced by an infant's crawling motion and an adult walking affects infant inhalation exposure to microbes. Results: We conducted controlled chamber experiments with a simplified mechanical crawling infant robot and an adult volunteer walking over carpeted flooring. We applied bacterial 16S rRNA gene sequencing and quantitative PCR to monitor the infant breathing zone microbial content and compared that to the adult breathing zone and the carpet dust as the source. During crawling, fungal and bacterial levels were, on average, 8- to 21-fold higher in the infant breathing zone compared to measurements from the adult breathing zone. During walking experiments, the increase in microbial levels in the infant breathing zone was far less pronounced. The correlation in rank orders of microbial levels in the carpet dust and the corresponding infant breathing zone sample varied between different microbial groups but was mostly moderate. The relative abundance of bacterial taxa was characteristically distinct in carpet dust and infant and adult breathing zones during the infant crawling experiments. Bacterial diversity in carpet dust and the infant breathing zone did not correlate significantly. Conclusions: The microbiota in the infant breathing zone differ in absolute quantitative and compositional terms from that of the adult breathing zone and of floor dust. Crawling induces resuspension of floor dust from carpeted flooring, creating a concentrated and localized cloud of microbial content around the infant. Thus, the microbial exposure of infants following dust resuspension is difficult to predict based on common house dust or bulk air measurements. Improved approaches for the assessment of infant microbial exposure, such as sampling at the infant breathing zone level, are needed.Peer reviewe

Latent transforming growth factor binding protein 4 (LTBP4) is downregulated in mouse and human DCIS and mammary carcinomas

Transforming growth factor beta (TGF-) is able to inhibit the proliferation of epithelial cells and is involved in the carcinogenesis of mammary tumors. Three latent transforming growth factor- binding proteins (LTBPs) are known to modulate TGF- functions. The current study analyses the expression profiles of LTBP4, its isoforms LTBP1 and LTBP3, and TGF-1, TGF-2, TGF-3, and SMAD2, SMAD3 and SMAD4 in human and murine (WAP-TNP8) DCIS compared to invasive mammary tumors. Additionally mammary malignant (MCF7, Hs578T, MDA-MB361) and non malignant cell lines (Hs578BsT) were analysed. Microarray, q-PCR, immunoblot, immunohistochemistry and immunofluorescence were used. In comparison to non-malignant tissues (n = 5), LTBP4 was downregulated in all human and mouse DCIS (n = 9) and invasive mammary adenocarcinomas (n = 5) that were investigated. We also found decreased expression of bone morphogenic protein 4 (BMP4) and increased expression of its inhibitor gremlin (GREM1). Treatment of the mammary tumor cell line (Hs578T) with recombinant TGF-1 rescued BMP4 and GREM1 expression. We conclude that the lack of LTBP4-mediated targeting in malignant mammary tumor tissues may lead to a possible modification of TGF-1 and BMP bioavailability and function

Advanced glycation end products cause increased CCN family and extracellular matrix gene expression in the diabetic rodent retina

Aims/hypothesis Referred to as CCN, the family of growth factors consisting of cystein-rich protein 61 (CYR61, also known as CCN1), connective tissue growth factor (CTGF, also known as CCN2), nephroblastoma overexpressed gene (NOV, also known as CCN3) and WNT1-inducible signalling pathway proteins 1, 2 and 3 (WISP1, -2 and -3; also known as CCN4, -5 and -6) affects cellular growth, differentiation, adhesion and locomotion in wound repair, fibrotic disorders, inflammation and angiogenesis. AGEs formed in the diabetic milieu affect the same processes, leading to diabetic complications including diabetic retinopathy. We hypothesised that pathological effects of AGEs in the diabetic retina are a consequence of AGE-induced alterations in CCN family expression. Materials and methods CCN gene expression levels were studied at the mRNA and protein level in retinas of control and diabetic rats using real-time quantitative PCR, western blotting and immunohistochemistry at 6 and 12 weeks of streptozotocin-induced diabetes in the presence or absence of aminoguanidine, an AGE inhibitor. In addition, C57BL/6 mice were repeatedly injected with exogenously formed AGE to establish whether AGE modulate retinal CCN growth factors in vivo. Results After 6 weeks of diabetes, Cyr61 expression levels were increased more than threefold. At 12 weeks of diabetes, Ctgf expression levels were increased twofold. Treatment with aminoguanidine inhibited Cyr61 and Ctgf expression in diabetic rats, with reductions of 31 and 36%, respectively, compared with untreated animals. Western blotting showed a twofold increase in CTGF production, which was prevented by aminoguanidine treatment. In mice infused with exogenous AGE, Cyr61 expression increased fourfold and Ctgf expression increased twofold in the retina. Conclusion/interpretation CTGF and CYR61 are downstream effectors of AGE in the diabetic retina, implicating them as possible targets for future intervention strategies against the development of diabetic retinopath

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting