Teriparatide in fracture healing: Case series and review of literature

Teriparatide (TPTD) (recombinant Parathyroid Hormone 1-34) is one of the pioneer osteo-anabolic agents approved for management of osteoporosis. Being an anabolic agent, it increases bone mineral density by inducing formation of new bone by the action on osteoblasts. As new bone formation is an important aspect of fracture healing as well, Teriparatide has long been a product of interest with respect to its effect on the process of fracture healing. Though fracture healing is not an approved indication for Teriparatide, there is quite a substantial amount of published data related to its effectiveness in fracture healing. With an intent to better understand the role of teriparatide in fracture, we share few case reports of successful fracture healing after giving Teriparatide and also review the published evidences of union taking place in difficult delayed union and non-union cases secondary to mechanical instability, inadequate fixation support or other reasons. This article thus, intended to summarize the accumulating preclinical and clinical evidence for role of TPTD in accelerating fracture healing in various conditions like conservative management of fractures, vertebral fractures, non-unions, delayed unions and atypical femoral fractures.

Modeling and analysis of an electro-magneto-elastic rotating cylindrical tube actuator

This paper presents the static modeling and analysis of a novel cylindrical tube actuator subjected to a rotation about longitudinal axis with an internally applied air pressure under an electromagnetic field. The current tube actuator belongs to a smart actuator category and is made of an electro-magneto-active polymer filled with a particular volume fraction of suitable fillers. A continuum mechanics-based electro-magneto-mechanical model is developed to predict the response of the actuator for a combined pressure and electromagnetic field loading. To validate the same, the model is compared with the outputs of an existing spring roll actuator. Parametric studies are subsequently performed for varying input pressure, electric field, magnetic field, fillers content, and actuator’s rotational speed. The output sensitivity in terms of strain intensity at inner and outer surfaces of the actuator is also checked at different controlling inputs. In addition, various electro-magneto-mechanical instability curves are drawn to examine the critical inflation of the tube actuator. In general, the developed model provides initial steps toward the modern actuator designs for applications where a precise control with high load-carrying capability of the actuator plays a significant role.

Percutaneous Endoscopic Interbody Debridement and Fusion for Pyogenic Lumbar Spondylodiskitis: Surgical Technique and the Comparison With Percutaneous Endoscopic Drainage and Debridement

Objective: Surgical treatment of severe infectious spondylodiskitis remains challenging. Although minimally invasive percutaneous endoscopic drainage and debridement (PEDD) may yield good results in complicated cases, outcomes of patients with extensive structural damage and mechanical instability may be unsatisfactory. To address severe infectious spondylodiskitis, we have developed a surgical technique called percutaneous endoscopic interbody debridement and fusion (PEIDF), which comprises endoscopic debridement, bonegraft interbody fusion, and percutaneous posterior instrumentation.Methods: Outcomes of PEIDF in 12 patients and PEDD in 15 patients with infectious spondylodiskitis from April 2014 to July 2018 were reviewed retrospectively. Outcome were compared between 2 kinds of surgical procedures.Results: Patients in PEIDF group had significantly lower rate of revision surgery (8.3% vs. 58.3%), better kyphosis angle (-5.73° ± 8.74 vs. 1.07° ± 2.70 in postoperative; 7.09° ± 7.23 vs. 0.79° ± 4.08 in kyphosis correction at 1 year), and higher fusion rate (83.3% vs. 46.7%) than those who received PEDD.Conclusion: PEIDF is an effective approach for treating infectious spondylodiskitis, especially in patients with spinal instability and multiple medical comorbidities.

Phase-field investigation of lithium electrodeposition under different applied overpotentials and operating temperatures

Despite the high promise, the commercialization of Li-metal-based batteries has been hampered due to the formation of dendrites that lead to mechanical instability, energy loss and eventual internal short circuits. The mechanism of dendrite formation and the strategies to suppress their growth have been studied intensively. However, the effect of applied overpotential and operating temperature on dendrite growth remains to be fully understood. Here, we elucidate the correlation of overpotential and temperature with the surface modulation during electrodeposition using phase-field simulations. We identify an optimal operating temperature of half-cell consisting of a Li metal anode and 1M LiPF6 in EC:DMC(1:1), which increases gradually as the overpotential increases. The investigation reveals that the temperature dependence identified in the simulations and experiments often disagree because they are primarily conducted in galvanostatic and potentiostatic conditions, respectively. The temperature increase under potentiostatic conditions increases the induced current while it decreases the induced overpotential under galvanostatic conditions. Therefore, the analysis and comparison of temperature-dependent characteristics must be carried out with care.

Effect of Flow Induced Parameters on the Output of A High Repetition Rate Dye Laser

The factors influencing the optical path stability in a dye laser flow cell are studied numerically and experimentally. A specially designed curved metallic dye flow cell providing a gain medium of 25 mm x 0.5 mm x 0.2 mm along with a compact resonator mechanical assembly is used in the study. The same configuration with gain medium of 15 mm x 0.5 mm x 0.2 mm is successfully used for single mode dye laser. The effects of flow induced vibrations on dye flow cell are studied with and without mechanically coupling it with the resonator structure for flow speeds varying from 1.33 m/s to 6.67 m/s at laser pump position. The effect of the mechanical instability, velocity fluctuation and temperature fluctuations in flowing dye solution on dye laser performance are studied at different flow speeds. These results are compared with the dye laser output parameters and found to be in good agreement. This study is useful in designing a high stability narrowband dye laser.

CircStrn3 Targeting microRNA-9-5p Is Involved in the Regulation of Cartilage Degeneration and Subchondral Bone Remodeling in Osteoarthritis

Background: Osteoarthritis (OA) is the most frequent chronic degenerative joint disease, which is a “whole joint” disease including the pathological changes in the cartilage, subchondral bone and the synovium. Mechanical instability is the initiation of the development of OA. Methods: Minus RNA sequencing, fluorescence in situ hybridization and quantitative real-time PCR were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Stimulate chondrocytes to secrete exosomes miR-9-5p by stretching strain. Intra-articular injection of exosomes miR-9-5p into the OA model induced by the operation of instability of the medial meniscus in mice.Results: In the present study, minus RNA sequencing data showed that tensile strain could decrease the expression of circStrn3 in chondrocytes. The results of fluorescence in situ hybridization and quantitative Real-time PCR showed that circStrn3 expression was significantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively 'sponging' miRNA-9-5p targeting kruppel-like factor 5 (KLF5), indicating that the decreasing of circStrn3 might be a protective factor in mechanical instability-induced OA. Further studies showed that the tensile strain stimulated chondrocytes to secrete exosomes miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblasts differentiation by targeting KLF5. In addition, intra-articular injection of exosomal miR-9-5p obviously alleviated the progression of OA induced by destabilized medial meniscus surgery in mice. Conclusions: Taken together, these results demonstrated that the reduction of circStrn3 caused the increasing of miR-9-5p, which acted as a protective factor in mechanical instability-induced OA and provided a novel mechanism of communication among joint components and a potential application for the treatment of OA.

Efficacy of a semirigid ankle brace in reducing mechanical ankle instability evaluated by 3D stress-MRI

Background Novel imaging technologies like 3D stress-MRI of the ankle allow a quantification of the mechanical instability contributing to chronic ankle instability. In the present study, we have tested the efficacy of a semirigid ankle brace on joint congruency in a plantarflexion/supination position with and without load. Methods In this controlled observational study of n = 25 patients suffering from mechanical ankle instability, a custom-built ankle arthrometer implementing a novel 3D-stress MRI technique was used to evaluate the stabilizing effect of an ankle brace. Three parameters of joint congruency (i.e., 3D cartilage contact area fibulotalar, tibiotalar horizontal and tibiotalar vertical) were measured. The loss of cartilage contact area from neutral position to a position combined of 40° of plantarflexion and 30° of supination without and with axial load of 200 N was calculated. A semirigid ankle brace was applied in plantarflexion/supination to evaluate its effect on joint congruence. Furthermore, the perceived stability of the brace during a hopping task was analyzed using visual analogue scale (VAS). Results The application of a semirigid brace led to an increase in cartilage contact area (CCA) when the foot was placed in plantarflexion and supination. This effect was visible for all three compartments of the upper ankle joint (P < 0.001; η2 = 0.54). The effect of axial loading did not result in significant differences. The subjective stability provided by the brace (VAS 7.6/10) did not correlate to the magnitude of the improvement of the overall joint congruency. Conclusions The stabilizing effect of the semirigid ankle brace can be verified using 3D stress-MRI. Providing better joint congruency with an ankle brace may reduce peak loads at certain areas of the talus, which possibly cause osteochondral or degenerative lesions. However, the perceived stability provided by the brace does not seem to reflect into the mechanical effect of the brace. Trial registration The study protocol was prospectively registered at the German Clinical Trials Register (#DRKS00016356).

Understanding cytoskeletal avalanches using mechanical stability analysis

Eukaryotic cells are mechanically supported by a polymer network called the cytoskeleton, which consumes chemical energy to dynamically remodel its structure. Recent experiments in vivo have revealed that this remodeling occasionally happens through anomalously large displacements, reminiscent of earthquakes or avalanches. These cytoskeletal avalanches might indicate that the cytoskeleton’s structural response to a changing cellular environment is highly sensitive, and they are therefore of significant biological interest. However, the physics underlying “cytoquakes” is poorly understood. Here, we use agent-based simulations of cytoskeletal self-organization to study fluctuations in the network’s mechanical energy. We robustly observe non-Gaussian statistics and asymmetrically large rates of energy release compared to accumulation in a minimal cytoskeletal model. The large events of energy release are found to correlate with large, collective displacements of the cytoskeletal filaments. We also find that the changes in the localization of tension and the projections of the network motion onto the vibrational normal modes are asymmetrically distributed for energy release and accumulation. These results imply an avalanche-like process of slow energy storage punctuated by fast, large events of energy release involving a collective network rearrangement. We further show that mechanical instability precedes cytoquake occurrence through a machine-learning model that dynamically forecasts cytoquakes using the vibrational spectrum as input. Our results provide a connection between the cytoquake phenomenon and the network’s mechanical energy and can help guide future investigations of the cytoskeleton’s structural susceptibility.