Scaffold-cell bone engineering in a validated preclinical animal model: precursors vs differentiated cell source.

The properties of osteoblasts (OBs) isolated from the axial skeleton (tOBs) differ from OBs of the orofacial skeleton (mOBs) due to the different embryological origins of the bones. The aim of the study was to assess and compare the regenerative potential of allogenic bone marrow-derived mesenchymal progenitor cells with allogenic tOBs and allogenic mOBs in combination with a mPCL-TCP scaffold in critical-sized segmental bone defects in sheep tibiae. After 6 months, the tibiae were explanted and underwent biomechanical testing, micro-computed tomography (microCT) and histological and immunohistochemical analyses. Allogenic MPCs demonstrated a trend towards a better outcome in biomechanical testing and the mean values of newly formed bone. Biomechanical, microCT and histological analysis showed no significant differences in the bone regeneration potential of tOBs and mOBs in our in vitro study, as well as in the bone regeneration potential of different cell types in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

Identifying environmental health priorities in underserved populations: a study of rural versus urban communities.

OBJECTIVES: Understanding and effectively addressing persistent health disparities in minority communities requires a clear picture of members' concerns and priorities. This study was intended to engage residents in urban and rural communities in order to identify environmental health priorities. Specific emphasis was placed on how the communities: defined the term environment; their perceptions of environmental exposures as affecting their health; specific priorities in their communities; and differences in urban versus rural populations. STUDY DESIGN: A community-engaged approach was used to develop and implement focus groups and compare environmental health priorities in urban versus rural communities. METHODS: A total of eight focus groups were conducted: four in rural and four in urban communities. Topics included: defining the term environment; how the environment may affect health; and environmental priorities within their communities, using both open discussion and a predefined list. Data were analysed both qualitatively and quantitatively to identify patterns and trends. RESULTS: There were important areas of overlap in priorities between urban and rural communities; both emphasized the importance of the social environment and shared a concern over air pollution from industrial sources. In contrast, for urban focus groups, abandoned houses and their social and physical sequelae were a high priority while concerns about adequate sewer and water services and road maintenance were high priorities in rural communities. CONCLUSIONS: This study was able to identify environmental health priorities in urban versus rural minority communities. In contrast to some previous risk perception research, the results of this study suggest prioritization of tangible, known risks in everyday life instead of rare, disaster-related events, even in communities that have recently experienced devastating damage from tornadoes. The findings can help inform future efforts to study, understand and effectively address environmental issues, and are particularly relevant to developing effective community-based strategies in vulnerable populations.

Mesodermal and neural crest derived ovine tibial and mandibular osteoblasts display distinct molecular differences.

Mandibular osteoblasts originate from the neural crest and deposit bone intramembranously, mesoderm derived tibial osteoblasts by endochondral mechanisms. Bone synthesized by both cell types is identical in structure, yet functional differences between the two cell types may exist. Thus, both matched juvenile and adult mandibular and tibial osteoblasts were studied regarding their proliferative capacity, their osteogenic potential and the expression of osteogenic and origin related marker genes. Juvenile tibial cells proliferated at the highest rate while juvenile mandibular cells exhibited higher ALP activity depositing more mineralized matrix. Expression of Hoxa4 in tibial cells verified their mesodermal origin, whereas very low levels in mandibular cells confirmed their ectodermal descent. Distinct differences in the expression pattern of bone development related genes (collagen type I, osteonectin, osteocalcin, Runx2, MSX1/2, TGF-ß1, BAMBI, TWIST1, ß-catenin) were found between the different cell types. The distinct dissimilarities in proliferation, alkaline phosphatase activity, the expression of characteristic genes, and mineralization may aid to explain the differences in bone healing time observed in mandibular bone when compared to long bones of the extremities.

A systems-based computational model for dose-response comparisons of two mode of action hypotheses for ethanol-induced neurodevelopmental toxicity.

Investigations into the potential mechanisms for ethanol-induced developmental toxicity have been ongoing for over 30 years since Fetal Alcohol Syndrome (FAS) was first described. Neurodevelopmental endpoints are particularly sensitive to in utero exposure to alcohol as suggested by the more prevalent alcohol-related neurodevelopmental disorder (ARND). The inhibition of proliferation during neurogenesis and the induction of apoptosis during the period of synaptogenesis have been identified as potentially important mechanisms for ARND. However, it is unclear how these two mechanisms quantitatively relate to the dose and timing of exposure. We have extended our model of neocortical neurogenesis to evaluate apoptosis during synaptogenesis. This model construct allows quantitative evaluation of the relative impacts on neuronal proliferation versus apoptosis during neocortical development. Ethanol-induced lengthening of the cell cycle of neural progenitor cells during rat neocortical neurogenesis (G13-G19) is used to compute the number of neurons lost after exposure during neurogenesis. Ethanol-induced dose-dependent increases in cell death rates are applied to our apoptosis model during rat synaptogenesis (P0-P14), when programmed cell death plays a major role in shaping the future neocortex. At a human blood ethanol concentration that occurs after 3-5 drinks ( approximately 150 mg/dl), our model predicts a 20-30% neuronal deficit due to inhibition of proliferation during neurogenesis, while a similar exposure during synaptogenesis suggests a 7-9% neuronal loss through induction of cell death. Experimental in vitro and in vivo dose-response research and stereological research on long-term neuronal loss after developmental exposure to ethanol is compared to our model predictions. Our computational model allows for quantitative, systems-level comparisons of mechanistic hypotheses for perturbations during specific neurodevelopmental periods.

A computational model for neocortical neuronogenesis predicts ethanol-induced neocortical neuron number deficits.

We have developed a computational model that allows for the evaluation of normal and perturbed neurodevelopmental processes. This mathematical construct is used to test the hypothesis that reduced neuronal production is the critical mechanism behind fetal alcohol syndrome. Model predictions of normal neurodevelopment match independent stereological measures but challenge estimates generated using a previously published model of normal neocortical neuronogenesis. Evaluation of data showing an increased cell cycle length after prenatal exposure to ethanol during neocortical neuronogenesis yields predictions of cellular deficits that can account for the permanent neocortical neuronal loss seen in rodents exposed to ethanol concentrations of public health relevance.

[Popliteal aneurysms--surgical management versus conservative procedure]. / Poplitea-Aneurysmen--operative Versorgung versus konservatives Vorgehen.

217 patients with 349 popliteal aneurysms (PA) were studied. 45% presented with symptomatic complications, mainly thrombosis (21% acute, 15% chronic) and embolisation (7%). The mean diameter was significantly larger in acutely thrombosed (2.69 cm) than in patent PA (2.15 cm). The amputation rate in patients requiring emergency treatment was 36.1% after 2 years. The difference to patients undergoing bypass surgery in an asymptomatic stage (4-year graft patency 89%, limb salvage 100%) is highly significant. Of 128 PA treated conservatively, 53% were free of complications after 5 years. We conclude that prophylactic surgery of PA is justified in cases at high risk of developing complications, but that characteristics of those cases are not yet well defined.

Rapid identification of Enterobacteriaceae with microbial enzyme activity profiles.

A total of 539 clinical isolates belonging to 10 species of the Enterobacteriaceae family were identified by enzyme activity profiles within 30 min of test inoculation. Each isolate was grown at 37 degrees C for 18 h on Mueller-Hinton agar and suspended to an optical density of 200 Klett units on 0.85% saline. Enzyme activity profiles were obtained by inoculating 18 fluorogenic substrates with the standardized bacterial suspension and monitoring initial rates of hydrolysis over the first 30 min of analysis. Individual enzyme activity profiles were entered into a coded data bank, and identifications were based on the Bayesian theory of probabilities. At a confidence level of 95%, five species were identified with a greater than 90% efficiency, three species were identified between 83 and 88% efficiency, and two species demonstrated a 72 and 75% efficiency of identification. The enzyme activity profile method of bacterial identification is rapid, easily automated, and reproducible.

Levels and rates of synthesis of ribosomal ribonucleic acid, transfer ribonucleic acid, and protein in Neurospora crassa in different steady states of growth.

The levels of ribosomes, tRNA molecules, and total protein per genome in Neurospora mycelia have been determined in eight different conditions of exponential growth. By increasing the rate of growth the number of ribosomes per genome increases dramatically while the level of total protein remains almost unchanged and the level of tRNA increases only slightly. The rates of synthesis of each of the macromolecules have been estimated. Increasing the rate of growth (mu) up to 0.5, the ratio between the rates of synthesis of tRNA and rRNA decreases reaching a constant value. The equations that best describe the dependence of the rate of synthesis of the macromolecules on the rate of growth (mu) have been determined. The rate of rRNA synthesis (rr), expressed as nucleotides polymerized, min- minus 1 per genome, is given by the equation: rr equals 6.51 times 10-7 mu-2-19. The rate of protein synthesis (rp), expressed as amino acids polymerized, min- minus 1 per genome is given by the following relationship: rp equals -1.43 times 10-7 + 3.43 times 10-8 mu. The equation describing the tRNA synthesis (rt) expressed as nucleotides, min- minus 1 per genome is rt equals 6.45 times 10-5 times exp 2.30 mu; however, more accurate determinations appear to be required for a firmer assignment of this latter equation. The significance of these equations for the studies on the regulation of rRNA and protein synthesis is discussed. For instance the rate of rRNA synthesis may set the limit for the maximal growth rate attainable by a cell, as the maximal rate of rRNA synthesis that may take place in a given cell is limited by the degree of redundancy of the rRNA genes.