Pressure sensing mat as an objective and sensitive tool for the evaluation of lameness in rabbits

In orthopaedic research, the analysis of the gait pattern is an often-used evaluation method. It allows an assessment of changes in motion sequence and pain level during postoperative follow up periods. Visual assessments are highly subjective and dependent on the circumstances. Particular challenge in rabbits is their hopping gait pattern. The aim of the present study was to establish a more objective and sensitive lameness evaluation using a pressure sensing mat. Twelve NZW rabbits were implemented in the study. They got an artificial anterior cruciate ligament transection of the right knee in connection with an experimental study, which investigated PTOA treatment. Rabbits were examined by a visual lameness score. Additionally, load of the hindlimbs was measured by the use of a pressure sensing mat and a video was recorded. Peak pressure and time force integral, defined as cumulated integral of all sensors associated to a hind paw, were evaluated. Preoperative data were collected on three independent days. As postoperative measurement time points, week 1 and week 12 after surgery were chosen. The subjective visual scoring was compared to the objective data of the pressure sensing mat. Following the visual score, lameness in week one was mild to moderate. In week twelve, rabbits were evaluated as lame free bar one. Contrary, following the values of the sensor mat, lameness in week one appeared to be more pronounced and almost all rabbits still showed low-grade lameness in week twelve. Consequently, the pressure sensing mat is more sensitive than the visual score and captures the grade of lameness much more accurately. For specific orthopaedic issues, where subtle differences in lameness are important to detect, the used system is a good supplementary evaluation method

Treatment of osteoarthritis by implantation of Mg- and WE43-cylinders: a preclinical study on bone and cartilage changes and their influence on pain sensation in rabbits

With its main features of cartilage degeneration, subchondral bone sclerosis and osteophyte formation, osteoarthritis represents a multifactorial disease with no effective treatment options. As biomechanical shift in the trabecular network may be a driver for further cartilage degeneration, bone enhancement could possibly delay OA progression. Magnesium is known to be osteoconductive and already showed positive effects in OA models. We aimed to use magnesium cylinders to enhance subchondral bone quality, condition of cartilage and pain sensation compared to sole drilling in vivo. After eight weeks of implantation in rabbits, significant increase in subchondral bone volume and trabecular thickness with constant bone mineral density was found indicating favored biomechanics. As representative for pain, a higher number of CD271+ vessels were present in control samples without magnesium. However, this result could not be confirmed by sensitive, objective lameness evaluation using a pressure sensing mat and no positive effect could be shown on either cartilage degeneration evaluated by OARSI score nor the presence of regenerative cells in CD271-stained samples. The presented results show a relevant impact of implanted magnesium on key structures in OA pain with missing clinical relevance regarding pain. Further studies with shifted focus should examine additional structures as joint capsule or osteophytes

Preparation and PET/CT imaging of implant directed 68Ga-labeled magnetic nanoporous silica nanoparticles

Background: Implant infections caused by biofilm forming bacteria are a major threat in orthopedic surgery. Delivering antibiotics directly to an implant affected by a bacterial biofilm via superparamagnetic nanoporous silica nanoparticles could present a promising approach. Nevertheless, short blood circulation half-life because of rapid interactions of nanoparticles with the host’s immune system hinder them from being clinically used. The aim of this study was to determine the temporal in vivo resolution of magnetic nanoporous silica nanoparticle (MNPSNP) distribution and the effect of PEGylation and clodronate application using PET/CT imaging and gamma counting in an implant mouse model. Methods: PEGylated and non-PEGylated MNPSNPs were radiolabeled with gallium-68 (68Ga), implementing the chelator tris(hydroxypyridinone). 36 mice were included in the study, 24 mice received a magnetic implant subcutaneously on the left and a titanium implant on the right hind leg. MNPSNP pharmacokinetics and implant accumulation was analyzed in dependence on PEGylation and additional clodronate application. Subsequently gamma counting was performed for further final analysis. Results: The pharmacokinetics and biodistribution of all radiolabeled nanoparticles could clearly be visualized and followed by dynamic PET/CT imaging. Both variants of 68Ga-labeled MNPSNP accumulated mainly in liver and spleen. PEGylation of the nanoparticles already resulted in lower liver uptakes. Combination with macrophage depletion led to a highly significant effect whereas macrophage depletion alone could not reveal significant differences. Although MNPSNP accumulation around implants was low in comparison to the inner organs in PET/CT imaging, gamma counting displayed a significantly higher %I.D./g for the tissue surrounding the magnetic implants compared to the titanium control. Additional PEGylation and/or macrophage depletion revealed no significant differences regarding nanoparticle accumulation at the implantation site. Conclusion: Tracking of 68Ga-labeled nanoparticles in a mouse model in the first critical hours post-injection by PET/CT imaging provided a better understanding of MNPSNP distribution, elimination and accumulation. Although PEGylation increases circulation time, nanoparticle accumulation at the implantation site was still insufficient for infection treatment and additional efforts are needed to increase local accumulation

Different treatment strategies versus a common standard arm (CSA) in patients with newly diagnosed AML over the age of 60 years: a randomized German inter-group study

A randomized inter-group trial comparing more intensive treatment strategies to a common standard arm 3 + 7 (CSA) was conducted in patients with non-M3 AML. Untreated patients ≥ 60 years were allocated to the CSA ( n  = 132) or to the study group arms ( n  = 1154) of the AMLCG (TAD/HAM versus HAM/HAM ± G-CSF followed by TAD and maintenance) and the OSHO (intermediate-dose ara-C/mitoxantrone followed by ara-C/mitoxantrone). Median age of the 1147 eligible patients was 69 (range 60–87) years. CR/CRi status at 90 days was not significantly different between the CSA (54% (95%CI: 45–64)) and the study group arms (53% (95%CI: 47–60) and 59% (95%CI: 58–63)). The five-year event-free survival (EFS) probability (primary endpoint) was 6.2% (95%CI: 2.7–14.0) in the CSA, 7.6% (95%CI: 4.5–12.8) in study group A and 11.1% (95%CI: 9.0–13.7) in B. The 5-year OS was 17.2% (95%CI: 11.0–26.9), 17.0% (95%CI: 2.0–23.9), and 19.5% (95%CI: 16.7–22.8) in CSA, study group A and B, respectively. Neither study group differed significantly from the CSA regarding EFS, OS, or relapse-free survival. In multivariate analyses, allocation to the treatment strategy was not significantly associated with the time-to-event endpoints. The evaluation of more intensive treatment strategies did not show clinically relevant outcome differences when compared to CSA

Patterns and dynamics of neutral lipid fatty acids in ants – implications for ecological studies

Background: Trophic interactions are a fundamental aspect of ecosystem functioning, but often difficult to observe directly. Several indirect techniques, such as fatty acid analysis, were developed to assess these interactions. Fatty acid profiles may indicate dietary differences, while individual fatty acids can be used as biomarkers. Ants are among the most important terrestrial animal groups, but little is known about their lipid metabolism, and no study so far used fatty acids to study their trophic ecology. We set up a feeding experiment with high- and low-fat food to elucidate patterns and dynamics of neutral lipid fatty acids (NLFAs) assimilation in ants. We asked whether dietary fatty acids are assimilated through direct trophic transfer, how diet influences NLFA total amounts and patterns over time, and whether these assimilation processes are similar across species and life stages. Results: Ants fed with high-fat food quickly accumulated specific dietary fatty acids (C18:2n6, C18:3n3 and C18:3n6), compared to ants fed with low-fat food. Dietary fat content did not affect total body fat of workers or amounts of fatty acids extensively biosynthesized by animals (C16:0, C18:0, C18:1n9). Larval development had a strong effect on the composition and amounts of C16:0, C18:0 and C18:1n9. NLFA compositions reflected dietary differences, which became more pronounced over time. Assimilation of specific dietary NLFAs was similar regardless of species or life stage, but these factors affected dynamics of other NLFAs, composition and total fat. Conclusions: We showed that ants accumulated certain dietary fatty acids via direct trophic transfer. Fat content of the diet had no effect on lipids stored by ants, which were able to synthesize high amounts of NLFAs from a sugar-based diet. Nevertheless, dietary NLFAs had a strong effect on metabolic dynamics and profiles. Fatty acids are a useful tool to study trophic biology of ants, and could be applied in an ecological context, although factors that affect NLFA patterns should be taken into account. Further studies should address which NLFAs can be used as biomarkers in natural ant communities, and how factors other than diet affect fatty acid dynamics and composition of species with distinct life histories