In many animal experiments scientists and local authorities define a body-weight reduction of 20% or more as severe suffering and thereby as a potential parameter for humane endpoint decisions. In this study, we evaluated distinct animal experiments in multiple research facilities, and assessed whether 20% body-weight reduction is a valid humane endpoint criterion in rodents. In most experiments (restraint stress, distinct models for epilepsy, pancreatic resection, liver resection, caloric restrictive feeding and a mouse model for Dravet syndrome) the animals lost less than 20% of their original body weight. In a glioma model, a fast deterioration in body weight of less than 20% was observed as a reliable predictor for clinical deterioration. In contrast, after induction of chronic diabetes or acute colitis some animals lost more than 20% of their body weight without exhibiting major signs of distress. In these two animal models an exclusive application of the 20% weight loss criterion for euthanasia might therefore result in an unnecessary loss of animals. However, we also confirmed that this criterion can be a valid parameter for defining the humane endpoint in other animal models, especially when it is combined with additional criteria for evaluating distress. In conclusion, our findings strongly suggest that experiment and model specific considerations are necessary for the rational integration of the parameter ‘weight loss’ in severity assessment schemes and humane endpoint criteria. A flexible implementation tailored to the experiment or intervention by scientists and authorities is therefore highly recommended.

Caloric restriction (CR) decelerates the aging process, extends lifespan and exerts neuroprotective effects in diverse species by so far unknown mechanisms. Based on known neuroprotective effects of fibroblastic growth factor 21 (Fgf21) we speculate that CR upregulates Fgf21, which phosphorylates neuronal AMP-activated protein kinase (AMPK), leading to a decrease of mammalian target of rapamycin (mTOR) signaling activity and an inhibition of tau-hyperphosphorylation. This in turn reduces the formation of neurofibrillary tangles, a neuropathological hallmark of Alzheimer's disease. ApoE-deficient mice (ApoE−/−), serving as a model of neurodegeneration, showed upon CR vs. ad libitum feeding increased Fgf21 levels in both, plasma and brain as well as higher phosphorylation of fibroblastic growth factor receptor 1c (Fgfr1c), extracellular signal-regulated kinases 1/2 (ERK1/2) and AMPK in brain, lower activity of mTOR and decreased Tau-phosphorylation. Finally, CR in ApoE−/− mice caused neuroprotection as indicated by a higher synaptic plasticity shown by immunohistochemical analysis with increased numbers of PSD95-positive neurons and a better cognitive performance as analyzed with Morris water maze test. These data provide substantial evidence that neuroprotection upon CR seems to be Fgf21-dependent. Further experiments are necessary to evaluate Fgf21 as a therapeutic tool to treat tauopathy for improvement of cognitive performance.

Conservative or operative treatment for rotator cuff calcifying tendinitis was investigated in 100 patients in a matched-pair analysis. They were examined clinically and ultrasonographically 35-60 months after the initial visit. The mean Patte score was 91.8 for the patients who underwent surgical treatment and 81 for the ones who received conservative therapy (p < 0.004), while the age-related Constant-score was 103.4 and 95, respectively. Ultrasonography showed 28% calcifications in the surgical group, 18% newly formed and 10% that did not resolve after surgery. In the conservatively treated group, 33% calcifications were seen, of which 67% resolved. The number of rotator cuff ruptures was significantly higher in the conservative group. In the surgical group, 2% of partial tears and in the conservative group 5% of partial and 4% of complete cuff ruptures were found. Conservative treatment for calcifying tendinitis leads to less favourable pain results in the long term than surgical treatment. Surgery shortens the painful period and may reduce the number of future rotator cuff ruptures. Finally, the subjective functional outcome is significantly better after surgery.

In the treatment of calcifying tendinitis the conservative methods achieve good and excellent results in 70%. Patients should be treated with analgetics, subacromial injections, physiotherapy and ice therapy up to a period of twelve months, above all with small deposits and radiologic resorptive stadiums. The results of this study should be compared with any invasive regimen.