Hypoxic-mediated oxidative stress condition and hydroxyapatite-inducing osteogenic differentiation of human mesenchymal stem cells: a mathematical modelling study

Avascular necrosis (AVN) of the bones remains a major clinical challenge. Fractures in the talus, the scaphoid, and the neck of the femur are especially challenging to heal due to the low blood vessel network and the lack of collateral blood supply. These fractures are associated with high rates of nonunion and increased infections that require repeated operations. Conventional treatments by autografting or allografting bone replacement and synthetic bone implants have limitations, including the invasiveness of operative procedures, tissue supply insufficiency, and the risk of host rejection. The advancement in tissue engineering has revealed the potential of stem cells as restorative agents for bone injuries. The administration of mesenchymal stem cells (MSCs) into the talus, the scaphoid, and the neck of the femur could produce enhanced osteogenesis via the manipulation of MSC culture conditions. In this study, we used hydroxyapatite as the nanomaterial, and hypoxic milieu to enhance MSC differentiation capacity into the osteogenic lineage, allowing for more rapid and efficient bone cell replacement treatment. Our results demonstrate 1% oxygen and 12.5 μg/mL of hydroxyapatite (HAP) as the optimal conditions to incorporate the osteogenic medium for the osteogenic induction of MSCs. We also established a proof of concept that the addition of HAP and hypoxic conditions could augment the osteoinductive capacity of MSCs. We also developed an accurate mathematical model to support future bone cell replacement therapy

Silicon Oxynitride: A Versatile Material for Integrated Optics Applications

Silicon oxynitride is a very attractive material for integrated optics application, because of its excellent optical properties (e.g., optical loss below 0.2 dB/cm), the large refractive index range (between 1.45 for silicon oxide and 2.0 for silicon nitride), and last but not least, the availability of reliable, low-cost fabrication technologies. Since good uniformity and reproducibility of the layers is extremely important for integrated optics applications, we have optimized the plasma-enhanced chemical vapor deposition and low-pressure chemical vapor deposition technologies of silicon oxynitride with respect to these requirements. Over a 50× 50 mm area on a 3 in. wafer, an inhomogeneity of the refractive index of Deltan<5×10–4 and a nonuniformity of the layer thickness of deltad<1% can be obtained. Furthermore, new challenges such as the conditioning of the reactor, in order to guarantee process reproducibility in the same order of magnitude, are discussed. The high optical loss of silicon oxynitride in the third telecommunication window (wavelength range lambda= 1530-1605 nm), which is caused by the overtones of the Si[Single Bond]H and N[Single Bond]H bonds, was decreased by thermal treatment. Silicon oxynitride waveguides having a refractive index of 1.48 and an optical loss below 0.2 dB/cm (at lambda>=1550 nm) were realized

Individual effects of stride length and frequency on shock attenuation during running

BACKGROUND: Published evaluations of skin disease signs and health-related quality of life (HRQoL) upon therapy withdrawal and retreatment in psoriatic patients are limited to results of drug withdrawal after short-term treatment. Analyses are lacking that evaluate patients' response to retreatment for patients treated successfully long-term. OBJECTIVE: To study the efficacy and safety of adalimumab in patients with long-term clinical responses to adalimumab who then discontinue therapy and are retreated with the same dosing regimen as the initial course. Skin disease signs and patients' HRQoL are evaluated. METHODS: This post hoc analysis of an open-label study (NCT00195676) included patients who had responded favourably to adalimumab during initial treatment (>/=75% improvement in Psoriasis Area and Severity Index [PASI 75 response]) and had maintained good clinical response for an extended period (up to 252 weeks); patients had Physician's Global Assessment (PGA) 0 or 1 before treatment interruption. Following drug withdrawal (up to 40 weeks), all patients were retreated with adalimumab 80 mg initial dose, followed by 40 mg every-other-week for 16 weeks. PASI response and HRQoL were evaluated. RESULTS: Of the 133 patients in this analysis, 24 (18%) relapsed during therapy withdrawal. After 16 weeks of retreatment, 75% who relapsed and 89.9% who did not relapse, had a PASI 75 response; 89.5% achieved European Consensus Programme treatment goals after 16 weeks of retreatment. During drug withdrawal, HRQoL disproportionally worsened compared to skin disease signs; HROoL also considerably worsened for patients who did not relapse. Patients regained HRQoL upon retreatment with adalimumab. No new safety signals were identified in this study. CONCLUSION: Retreatment with adalimumab was successful in improving psoriasis skin signs and HRQoL in this subgroup with initial and extended responses to therapy followed by relapse after treatment withdrawal. Patient's HRQoL should be considered, as it may substantially worsen during therapy interruption

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