State based model of long-term potentiation and synaptic tagging and capture

Recent data indicate that plasticity protocols have not only synapse-specific but also more widespread effects. In particular, in synaptic tagging and capture (STC), tagged synapses can capture plasticity-related proteins, synthesized in response to strong stimulation of other synapses. This leads to long-lasting modification of only weakly stimulated synapses. Here we present a biophysical model of synaptic plasticity in the hippocampus that incorporates several key results from experiments on STC. The model specifies a set of physical states in which a synapse can exist, together with transition rates that are affected by high- and low-frequency stimulation protocols. In contrast to most standard plasticity models, the model exhibits both early- and late-phase LTP/D, de-potentiation, and STC. As such, it provides a useful starting point for further theoretical work on the role of STC in learning and memory

Semi-quantitative CT assessment of fracture healing: How many and which CT reformats should be analyzed?

To assess how many and which CT reformats of long bone non-unions should be analyzed to best approximate the analysis of a larger number of CT reformats obtained in the three orthogonal planes. We used 29 CT examinations of tibial or femoral non-unions to obtain 87 stacks of 7 CT reformats each in the coronal (n = 29), sagittal (n = 29) or transverse (n = 29) planes. Two independent radiologists scored two fracture sites on each CT reformat by using a Tomographic Union Score (TUS) (1: no callus, 2: non-bridging callus; 3: bridging immature callus; 4: bridging remodeled callus). The reference standard was the mean of the three TUS calculated from the cortical scores obtained on all the sagittal, coronal and transverse CT reformats. We determined the agreement (intra-class correlation coefficient (ICC) between the reference standard and 33 models combining one to seven CT reformats from one to three planes. The three best models were compared following a resampling procedure by a Wilcoxon's signed rank test. Three models combining two (mid-coronal and mid-sagittal), three (mid-coronal, mid-sagittal and mid-transverse) or four (two paramedian coronal and sagittal) CT reformats had the highest ICC (ICC ≥ 0.89) for both observers. After resampling, the model combining the two paramedian sagittal and coronal CT reformats statistically outperformed the two other models. Semi-quantitative analysis of the two paramedian sagittal and coronal CT reformats is an acceptable alternative to the analysis of more numerous reformats

Effect of two bioabsorbable barrier membranes on bone regeneration of standardized defects in calvarial bone: a comparative histomorphometric study in pigs

BACKGROUND: The effect of two different bioabsorbable collagen membranes on bone regeneration was assessed in standardized, membrane-protected calvarial defects in pigs. METHODS: Two standardized defect types (6 x 6 x 6 mm and 9 x 9 x 9 mm) were produced in the calvaria of pigs: empty defects without a membrane (group 1; eight defects per size); defects filled with deproteinized bovine bone mineral (DBBM) without a membrane (group 2; eight defects per size); defects filled with DBBM and covered by a collagen membrane (group 3; eight defects per size); and defects filled with DBBM and covered by a cross-linked collagen membrane (CCM) (group 4; eight defects per size). Sacrifice took place 16 weeks after surgery, and the following parameters were analyzed: descriptive histology; semiquantitative histology (SQH), assessing bone regeneration in the whole defect area; and histomorphometric analysis of the percentage of bone and DBBM in the regenerated area at three different depth levels of the defect. RESULTS: Using SQH, both membrane types resulted in significantly better bone regeneration compared to groups 1 and 2, irrespective of the defect size (P <0.005), with no difference between the two membranes. In the histomorphometric analysis, the layer immediately below the surface exhibited a significantly higher percentage of bone in groups 3 (27%) and 4 (36%) versus the two other groups for the 9 x 9 x 9-mm defects. No such differences were apparent for the 6 x 6 x 6-mm defects or the other two depth levels (bottom and middle layer) for either defect size. CONCLUSIONS: The two collagen membranes tested significantly enhanced bone regeneration, especially in the superficial level of the calvarial bone defects. The prototype CCM did not provide any further advantage in the present animal model

Percutaneous administration of allogeneic bone-forming cells for the treatment of delayed unions of fractures: a pilot study

BACKGROUND: Overall, 5-10% of fractures result in delayed unions or non-unions, causing major disabilities and a huge socioeconomic burden. Since rescue surgery with autologous bone grafts can cause additional challenges, alternative treatment options have been developed to stimulate a deficient healing process. This study assessed the technical feasibility, safety and preliminary efficacy of local percutaneous implantation of allogeneic bone-forming cells in delayed unions of long bone fractures. METHODS: In this phase I/IIA open-label pilot trial, 22 adult patients with non-infected delayed unions of long bone fractures, which failed to consolidate after 3 to 7 months, received a percutaneous implantation of allogeneic bone-forming cells derived from bone marrow mesenchymal stem cells (ALLOB; Bone Therapeutics) into the fracture site (50 × 106 to 100 × 106 cells). Patients were monitored for adverse events and need for rescue surgery for 30 months. Fracture healing was monitored by Tomographic Union Score (TUS) and modified Radiographic Union Score. The health status was evaluated using the Global Disease Evaluation (GDE) score and pain at palpation using a visual analogue scale. The presence of reactive anti-human leukocyte antigen (HLA) antibodies was evaluated. RESULTS: During the 6-month follow-up, three serious treatment-emergent adverse events were reported in two patients, of which two were considered as possibly treatment-related. None of the 21 patients in the per-protocol efficacy population needed rescue surgery within 6 months, but 2/21 (9.5%) patients had rescue surgery within 30 months post-treatment. At 6 months post-treatment, an improvement of at least 2 points in TUS was reached in 76.2% of patients, the GDE score improved by a mean of 48%, and pain at palpation at the fracture site was reduced by an average of 61% compared to baseline. The proportion of blood samples containing donor-specific anti-HLA antibodies increased from 8/22 (36.4%) before treatment to 13/22 (59.1%) at 6 months post-treatment, but no treatment-mediated allogeneic immune reactions were observed. CONCLUSION: This pilot study showed that the percutaneous implantation of allogeneic bone-forming cells was technically feasible and well tolerated in patients with delayed unions of long bone fractures. Preliminary efficacy evidence is supporting the further development of this treatment. TRIAL REGISTRATION: NCT02020590 .Registered on 25 December 2013. ALLOB-DU1, A pilot Phase I/IIa, multicentre, open proof-of-concept study on the efficacy and safetyof allogeneic osteoblastic cells (ALLOB®) implantation in non-infected delayed-union fractures.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Thermal Eco-cities: Green Building and Urban Thermal Metabolism

Eco-city projects are becoming increasingly prevalent throughout the globe and are often marketed as ‘new’ urban environments focused on achieving sustainable urban living while promoting environmental–economic transitions towards a low-carbon technological and industrial base. The article argues for the need to consider the thermal aspects of urban metabolism, while at the same time focusing on the link between individual buildings and eco-city master plans and wider economic development strategies at a state level. In so doing, the article encourages critical analysis of eco-city design and planning, while keeping a focus on the role of specific building structures within eco-cities as examples of the intermeshing of what can be termed a ‘political ecology of scale’ which stretches from specific buildings' climatic characteristics, to the metabolic master plan for eco-cities, to provincial, regional and state-level plans for the integration of eco-cities within wider economic and political development trajectories. The article focuses on Masdar, in Abu Dhabi, an eco-city under construction at the time of writing. <br/