Behavioral Voluntary and Social Bioassays Enabling Identification of Complex and Sex-Dependent Pain-(-Related) Phenotypes in Rats with Bone Cancer

Simple Summary Bone metastases are one of the most common complications in patients with advanced cancer that result in pain, which is usually severe, thereby significantly reducing the patient's quality of life. Although preclinical pain research in rodents is improving, the pain phenotyping methods currently used have been criticized. This study aimed to identify in detail pain phenotypes of cancer-induced bone pain (CIBP) in both sexes of rats. CIBP in the splint bone on one side results in a distinct CIBP-related phenotype characterized by mechanical hypersensitivity, resting pain, and antalgic gait in both sexes. Progression of tumor growth leads to the establishment of the CIBP phenotype that appears earlier in male than in female rats and affects rat-specific social behaviors in both sexes. We demonstrate social transfer of pain in a bone cancer model in both sexes, resulting in mechanical and, in females, also heat hypervigilance in non-tumor bearing control rats. Cancer-induced bone pain (CIBP) is a common and devastating symptom with limited treatment options in patients, significantly affecting their quality of life. The use of rodent models is the most common approach to uncovering the mechanisms underlying CIBP; however, the translation of results to the clinic may be hindered because the assessment of pain-related behavior is often based exclusively on reflexive-based methods, which are only partially indicative of relevant pain in patients. To improve the accuracy and strength of the preclinical, experimental model of CIBP in rodents, we used a battery of multimodal behavioral tests that were also aimed at identifying rodent-specific behavioral components by using a home-cage monitoring assay (HCM). Rats of all sexes received an injection with either heat-deactivated (sham-group) or potent mammary gland carcinoma Walker 256 cells into the tibia. By integrating multimodal datasets, we assessed pain-related behavioral trajectories of the CIBP-phenotype, including evoked and non-evoked based assays and HCM. Using principal component analysis (PCA), we discovered sex-specific differences in establishing the CIBP-phenotype, which occurred earlier (and differently) in males. Additionally, HCM phenotyping revealed the occurrence of sensory-affective states manifested by mechanical hypersensitivity in sham when housed with a tumor-bearing cagemate (CIBP) of the same sex. This multimodal battery allows for an in-depth characterization of the CIBP-phenotype under social aspects in rats. The detailed, sex-specific, and rat-specific social phenotyping of CIBP enabled by PCA provides the basis for mechanism-driven studies to ensure robustness and generalizability of results and provide information for targeted drug development in the future

Effect of the displacement rate and inclination angle in steel fiber pullout tests

This paper summarizes the results obtained in an experimental campaign on the effect of the displacement pullout rate and the inclination angle of the steel fiber pullout tests. For that purpose, specimens were obtained from a self-compacting concrete with a compressive strength of 86 MPa. In the experimental program, hooked-end steel fibers of 0.75 mm diameter and 60 mm length were used. Tests were executed with both hooked-end fibers, and smooth fibers obtained from the former by cutting the hooked end. For both type of fibers, their embedment length into concrete was 20 mm, and the influence of fiber inclination angle toward the load direction was investigated by adopting values of 0∘, 30∘ and 60∘. The tests were performed at displacement rates of 0.01, 0.1 and 1 mm/s. The results have shown that the peak pullout load increased with the inclination angle, in particular for the smooth series. Furthermore, higher displacement rates led to a higher energy absorption capacity for the pullout of the smooth fibers, while the energy absorption remained almost stable for hooked-end fibers.project BIA2015-68678-C2-1-R. M. Tarifa appreciates the financial support from the Department of Applied Mechanics and Project Engineering, UCLM (2018), and from the Programa propio de I+D+i de la Universidad Politécnica de Madrid para realizar estancias de investigación internacional igual o superior a un mes (2019), to do two stays at the University of Minho, Guimarães, Portugal. E. Poveda acknowledges the funding from the International Campus of Excellence CYTEMA and the University of Castilla-La Mancha, throughout Ayudas para estancias en universidades y centros de investigación en el extranjero en 2019 en el ámbito del plan propio de investigación susceptibles de cofinanciación por el Fondo Europeo de Desarrollo Regional (FEDER), Programa 010100021 to fund her stays in the University of Minho during 2018 and 2019, respectively. The authors thank the support of the Department of Civil Engineering and the Laboratory of the Structural Division (LEST), University of Minh

Non-Linear Viscoelastic Behavior of Poly-Ether-Ether-Ketone (PEEK) and PEEK-Based Composites

It has been recognized for some time that, immediately upon cooling to temperatures below their glass transition, polymers are characterized by departure from the equilibrium chain conformation. The viscoelastic properties of the amorphous and semicrystalline PEEK and of a PEEK-based composite (APC2) have been analyzed as a function of the aging time and related free volume relaxation at temperatures close to the glass transition region. The effect of thermal treatments on the three systems is presented. The presence of a second phase, namely crystallite and fibers, determines a loss of the mobility of the polymeric amorphous chains and consequently a decrease of the rate of the free volume relaxation. Creep tests approaching ''zero stress'' were performed on samples subjected to different thermal histories