Site-Directed Immobilization of an Engineered Bone Morphogenetic Protein 2 (BMP2) Variant to Collagen-Based Microspheres Induces Bone Formation In Vivo

For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2′s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs

Testing the potential of a virtual reality neurorehabilitation system during performance of observation, imagery and imitation of motor actions recorded by wireless functional near-infrared spectroscopy (fNIRS)

Background Several neurorehabilitation strategies have been introduced over the last decade based on the so-called simulation hypothesis. This hypothesis states that a neural network located in primary and secondary motor areas is activated not only during overt motor execution, but also during observation or imagery of the same motor action. Based on this hypothesis, we investigated the combination of a virtual reality (VR) based neurorehabilitation system together with a wireless functional near infrared spectroscopy (fNIRS) instrument. This combination is particularly appealing from a rehabilitation perspective as it may allow minimally constrained monitoring during neurorehabilitative training. Methods fNIRS was applied over F3 of healthy subjects during task performance in a virtual reality (VR) environment: 1) 'unilateral' group (N = 15), contralateral recording during observation, motor imagery, observation & motor imagery, and imitation of a grasping task performed by a virtual limb (first-person perspective view) using the right hand; 2) 'bilateral' group (N = 8), bilateral recording during observation and imitation of the same task using the right and left hand alternately. Results In the unilateral group, significant within-condition oxy-hemoglobin concentration Δ[O2Hb] changes (mean ± SD μmol/l) were found for motor imagery (0.0868 ± 0.5201 μmol/l) and imitation (0.1715 ± 0.4567 μmol/l). In addition, the bilateral group showed a significant within-condition Δ[O2Hb] change for observation (0.0924 ± 0.3369 μmol/l) as well as between-conditions with lower Δ[O2Hb] amplitudes during observation compared to imitation, especially in the ipsilateral hemisphere (p < 0.001). Further, in the bilateral group, imitation using the non-dominant (left) hand resulted in larger Δ[O2Hb] changes in both the ipsi- and contralateral hemispheres as compared to using the dominant (right) hand. Conclusions This study shows that our combined VR-fNIRS based neurorehabilitation system can activate the action-observation system as described by the simulation hypothesis during performance of observation, motor imagery and imitation of hand actions elicited by a VR environment. Further, in accordance with previous studies, the findings of this study revealed that both inter-subject variability and handedness need to be taken into account when recording in untrained subjects. These findings are of relevance for demonstrating the potential of the VR-fNIRS instrument in neurofeedback applications

The Empirics of Agglomeration Economies

We propose an integrated framework to discuss the empirical literature on the local determinants of agglomeration effects. We start by presenting the theoretical mechanisms that ground individual and aggregate empirical specifications. We gradually introduce static effects, dynamic effects, and workers' endogenous location choices. We emphasise the impact of local density on productivity but we also consider many other local determinants supported by theory. Empirical issues are then addressed. Most important concerns are about endogeneity at the local and individual levels, the choice of a productivity measure between wage and TFP, and the roles of spatial scale, firms' characteristics, and functional forms. Estimated impacts of local determinants of productivity, employment, and firms' locations choices are surveyed for both developed and developing economies. We finally provide a discussion of attempts to identify and quantify specific agglomeration mechanisms

Wireless miniaturized in-vivo near infrared imaging

Our group measures tissue oxygenation and the cortical hemodynamic response to sensory stimuli applying continuous wave near-infrared imaging (NIRI). To improve the method's quality and applicability and to explore new fields in clinical practice and research, we developed a miniaturized wireless NIRI system. It was validated by measuring muscle oxygenation in a blood-flow occlusion experiment and brain activity in adults

Precision of cerebral oxygenation and hemoglobin concentration measurements in neonates measured by near-infrared spectroscopy

The precision of NIRS measurements correlates with tissue homogeneity

The effect of sudden depressurization on pilots at cruising altitude

The standard flight level for commercial airliners is ∼12 km (40 kft; air pressure: ∼ 200 hPa), the maximum certification altitude of modern airliners may be as high as 43-45 kft. Loss of structural integrity of an airplane may result in sudden depressurization of the cabin potentially leading to hypoxia with loss of consciousness of the pilots. Specialized breathing masks supply the pilots with oxygen. The aim of this study was to experimentally simulate such sudden depressurization to maximum design altitude in a pressure chamber while measuring the arterial and brain oxygenation saturation (SaO(2) and StO(2)) of the pilots. Ten healthy subjects with a median age of 50 (range 29-70) years were placed in a pressure chamber, breathing air from a cockpit mask. Pressure was reduced from 753 to 148 hPa within 20 s, and the test mask was switched to pure O(2) within 2 s after initiation of depressurization. During the whole procedure SaO(2) and StO(2) were measured by pulse oximetry, respectively near-infrared spectroscopy (NIRS; in-house built prototype) of the left frontal cortex. During the depressurization the SaO(2) dropped from median 93% (range 91-98%) to 78% (62-92%) by 16% (6-30%), while StO(2) decreased from 62% (47-67%) to 57% (43-62%) by 5% (3-14%). Considerable drops in oxygenation were observed during sudden depressurization. The inter-subject variability was high, for SaO(2) depending on the subjects' ability to preoxygenate before the depressurization. The drop in StO(2) was lower than the one in SaO(2) maybe due to compensation in blood flow

Cerebral oxygenation in patients with OSA: Effects of hypoxia at altitude and impact of acetazolamide

BACKGROUND: Sleep-disordered breathing may impair cerebral oxygenation in patients with OSA syndrome, in particular during altitude travel. We studied cerebral tissue oxygenation (CTO) at low and moderate altitude in patients with OSA and evaluated whether acetazolamide improved CTO. METHODS: Eighteen patients with OSA living at < 600 m discontinued CPAP therapy during studies in Zurich (490 m) and during two sojourns of 3 days in the Swiss Alps (2 days at 1,860 m and 1 day at 2,590 m) separated by a 2-week washout period at < 600 m. Patients received acetazolamide (2 × 250 mg/d) or placebo at altitude in a randomized, double-blind, crossover design. Nocturnal polysomnography, including CTO monitoring by near-infrared spectroscopy (NIRS), was performed. RESULTS: At 490 m, medians of CTO, peripheral oxygen saturation as measured by pulse oximetry (Spo2), and apnea/hypopnea index were 65%, 93%, and 57.3/h, respectively. At 2,590 m, on placebo, the corresponding values were 59%, 86%, and 86.4/h, respectively (P < .05, all corresponding comparisons). Acetazolamide increased CTO and Spo2 at 2,590 m by mean values of 2% (95% CI, 0%-4%) and 2% (95% CI, 1%-3%), respectively, and reduced the apnea/hypopnea index by 23.4/h (95% CI, 14.0-32.8/h) (P < .05, all changes). Cerebral total hemoglobin concentration, a NIRS-derived surrogate reflecting regional cerebral blood volume, increased by a similar degree in response to apneas at 490 m and 2,590 m and during acetazolamide and placebo treatment. CONCLUSIONS: In patients with OSA staying at altitude, nocturnal cerebral and arterial oxygenation were reduced in association with exacerbated sleep apnea. Acetazolamide partially improved CTO, Spo2, and sleep apnea without impairing the cerebral blood flow response to apneas. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00714740; URL: www.clinicaltrials.gov

Site-Directed Immobilization of an Engineered Bone Morphogenetic Protein 2 (BMP2) Variant to Collagen-Based Microspheres Induces Bone Formation In Vivo

For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2&prime;s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs

Textile integrated sensors and actuators for near-infrared spectroscopy

Being the closest layer to our body, textiles provide an ideal platform for integrating sensors and actuators to monitor physiological signals. We used a woven textile to integrate photodiodes and light emitting diodes. LEDs and photodiodes enable near-infrared spectroscopy (NIRS) systems to monitor arterial oxygen saturation and oxygenated and deoxygenated hemoglobin in human tissue. Photodiodes and LEDs are mounted on flexible plastic strips with widths of 4 mm and 2 mm, respectively. The strips are woven during the textile fabrication process in weft direction and interconnected with copper wires with a diameter of 71 μm in warp direction. The sensor textile is applied to measure the pulse waves in the fingertip and the changes in oxygenated and deoxygenated hemoglobin during a venous occlusion at the calf. The system has a signal-to-noise ratio of more than 70 dB and a system drift of 0.37% ± 0.48%. The presented work demonstrates the feasibility of integrating photodiodes and LEDs into woven textiles, a step towards wearable health monitoring devices