Non-equivalence of antibiotic generic drugs and risk for intensive care patients

Background: The underlying axiom in applying generic drugs is the equivalence of their active ingredient with the (usually more expensive) innovator product, an all-embracing statement with the insidious result that physicians assume that the generic products have been subjected to the same rigorous testing regimens as the brand-name products. The present paper presents novel experimental data on an investigator-blinded comparison between the innovator imipenem antibiotic, and a number of its generics. Methods: Particulate matter contamination of each group was visualized by means of a membrane filter method. Functional studies in an animal model–the dorsal skinfold chamber technique in mice-designed to simulate the state of microcirculatory dysfunction in intensive care patients was performed, in order to assess the influence of the particulate matter of each group on the functional capillary density of the striated skin muscle, after their intravenous injection. Results: The results showed massive particulate contamination of the generics, in a size range relevant for impacting the microcirculation. The particulate contamination contributed in some generic groups to a significant shutdown of tissue perfusion. Conclusion: The presented data underscore the need to raise the regulatory barriers for the entry of generics to the market, well beyond the simplistic proof of “bioequivalence”, which in no measure deals with the essential questions of quality and patient safety. If generics are used, they should be tested by a filter technique and optical microscopy, to ensure the absence especially of small particulate contaminants and their purity

Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation

Background: Osteoinductive bone substitutes are defined by their ability to induce new bone formation even at heterotopic implantation sites. The present study was designed to analyze the potential osteoinductivity of two different bone substitute materials in caprine muscle tissue. Materials and methods: One gram each of either a porous beta-tricalcium phosphate (β-TCP) or an hydroxyapatite/silicon dioxide (HA/SiO2)-based nanocrystalline bone substitute material was implanted in several muscle pouches of goats. The biomaterials were explanted at 29, 91 and 181 days after implantation. Conventional histology and special histochemical stains were performed to detect osteoblast precursor cells as well as mineralized and unmineralized bone matrix. Results: Both materials underwent cellular degradation in which tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and TRAP-negative multinucleated giant cells were involved. The ß-TCP was completely resorbed within the observation period, whereas some granules of the HA-groups were still detectable after 180 days. Neither osteoblasts, osteoblast precursor cells nor extracellular bone matrix were found within the implantation bed of any of the analyzed biomaterials at any of the observed time points. Conclusions: This study showed that ß-TCP underwent a faster degradation than the HA-based material. The lack of osteoinductivity for both materials might be due to their granular shape, as osteoinductivity in goat muscle has been mainly attributed to cylindrical or disc-shaped bone substitute materials. This hypothesis however requires further investigation to systematically analyze various materials with comparable characteristics in the same experimental setting

Application of artificial neural network to classify fuel octane number using essential engine operating parameters

Real-time fuel octane number classification is essential to ensure that spark ignition engines operation are free of knock at best combustion efficiency. Combustion with knock is an abnormal phenomenon which constrains the engine performance, thermal efficiency and longevity. The advance timing of the ignition system requires it to be updated with respect to fuel octane number variation. The production series engines are calibrated by the manufacturer to run with a special fuel octane number. Presently, there is no research which takes into account the fuel tendency to knock in real-time engine operation. This research proposed the use of on-board detection of fuel octane number by implementing a simple methodology and use of a non-intrusive sensor. In the experiment, the engine was operated at different speeds, load, spark advance and consumed commercial gasoline with research octane numbers (RON) 95, 97 and 100. The RON classification procedure was investigated using regression analysis as a classic pattern recognition methodology and artificial neural network (ANN) by executing combustion properties derived from in-cylinder pressure signal and engine rotational speed signal. The in-cylinder pressure analysis illustrated the knock-free, light-knock and heavy-knock regions for all engine operating points. The results showed a special pattern for each fuel RON using peak in-cylinder pressure, maximum rate of pressure rise and maximum amplitude of pressure oscillations. Besides, there is a requirement for pre-defined threshold or formula to restrict the implementation of these parameters for on-board fuel identification. The ANN model efficiency with pressure signal as network input had the highest accuracy for all spark advance timing. However, the ANN model with rotational speed signal input only had the ability to identify the fuel octane number after a specific advance timing which was detected at the beginning of noisy combustion due to knock. The confusion matrix for the ANN with speed signal input had increased from 68.1% to 100% by advancing the ignition from -10° to -30° before top dead centre. The results established the ability of rotational speed signal for fuel octane classification using the relation between knock and RON. The implication is that all the production spark ignition engines are equipped with engine speed sensor, thus, this technique can be applied to all engines with any number of cylinders

Cloud-based Modelling and Optimization of the PHEV Controller Using Artificial Intelligence

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Rapid vascularization of starchâ poly(caprolactone) in vivo by outgrowth endothelial cells in co-culture with primary osteoblasts

The successful integration of in vitro-generated tissues is dependent on adequate vascularization in vivo. Human outgrowth endothelial cells (OECs) isolated from the mononuclear cell fraction of peripheral blood represent a potent population of circulating endothelial progenitors that could provide a cell source for rapid anastomosis and scaffold vascularization. Our previous work with these cells in co-culture with primary human osteoblasts has demonstrated their potential to form perfused vascular structures within a starch–poly(caprolactone) biomaterial in vivo. In the present study, we demonstrate the ability of OECs to form perfused vascular structures as early as 48 h following subcutaneous implantation of the biomaterial in vivo. The number of OECderived vessels increased throughout the study, an effect that was independent of the OEC donor. This finding of rapid and thorough OEC-mediated scaffold vascularization demonstrates the great potential for OEC-based strategies to promote vascularization in tissue engineering. OECs have the potential to contribute to host-derived scaffold vascularization, and formed vascular structures at a similar density as those arising from the host. Additionally, immunohistochemical evidence demonstrated the close interaction between OECs and the co-cultured osteoblasts. In addition to the known paracrine activity osteoblasts have in modulating angiogenesis of co-cultured OECs, we demonstrate the potential of osteoblasts to provide additional structural support for OEC-derived vessels, perhaps acting in a pericyte-like role.The authors would like to thank Mrs B Pavic and Mrs U. Hilbig for their excellent technical assistance. This work was financially supported by grants from the European Commission (EXPERTISSUES Contract No. 500283-2) and the German Federal Ministry of Education and Research, BMBF (German-Chinese Cooperation in Regenerative Medicine; Contract No. 0315033)

Grading of Glioma Tumors by Analysis of Minimum Apparent Diffusion Coefficient and Maximum Relative Cerebral Blood Volume

Gliomas are the most common primary neoplasms of the central nervous system. Relative cerebral blood volume (rCBV) could estimate high-grade Gliomas computed with dynamic susceptibility contrast MR imaging which it is artificially lowered by contrast extravasation through a disrupted blood-brain barrier. Objectives: Our intent was to clarify the usefulness of diffusion-weighted magnetic resonance imaging (DWI) and perfusion weighted magnetic resonance imaging (PWI) in the grading of Gliomas. Materials and Methods: Both PWI and DWI with a three-tesla scanner investigated nineteen consecutive patients with Gliomas. The means of rCBV and ADC values have been compared among the tumor groups with t-test and ROC curve analysis to determine threshold values of Gliomas grading. Results: Mean maximum rCBV were 2.71±1.41 for low grades (I & II), and 8.14±2.58 for high grades (III & IV) Gliomas (p=0.001). Mean minimum ADC were 1.47±.46 ×103 mm2 /s for low grades (I & II), and .47±.38×103 mm2 /s for high grades (III & IV) Gliomas (p=0.001). We can get 0.94×103 mm2 /s for minimum ADC and 3.85 for maximum rCBV as a difference cutoff point between low and high-grade Gliomas. Conclusion: Combination of both DWI and PWI techniques, with measurement of minimum ADC and maximum rCBV can be used to distinguish between high grade and low-grade Glioma tumors

PTCH-1 and MDM2 expression in ameloblastoma from a West African sub-population: Implication for chemotherapeutics

Introduction: Ameloblastoma is a slow growing, painless odontogenic swelling which can attain sizes that result in severe deformities of thecraniofacial complex. It is the most commonly encountered odontogenic tumor in Nigeria. Surgical intervention is currently the method of treatment; however identification of altered molecular pathways may inform  chemotherapeutic potential. The Protein Patched homolog 1 (PTCH-1)is overexpressed in ameloblastoma. Also, mutation in the MDM2 gene can reduce the tumor suppressor function of p53 and promote ameloblastoma growth. No study however has characterized the molecular profile of African cases of ameloblastoma with a view to developing chemotherapeutic alternatives. The objective was to characterize the PTCH-1 genetic profile of Ameloblastoma in Nigerian patients as a first step in investigating its potential for chemotherapeutic intervention.Methods: Twenty-eight FFPE blocks of ameloblastoma cases from Nigerian patients were prepared for antibody processing to PTCH-1 (Polyclonal  Anti-PTCH antibody ab39266) and MDM2 (Monoclonal Anti-MDM2 antibody (2A10) ab16895). Cytoplasmic brown staining was considered as positive for PTCH while nuclear staining was positive for MDM2.Results: Moderate and strong expressions for PTCH in ameloblast and stellate reticulum were 78.6% and 60.7% respectively. Only 3 (10.7%) cases expressed MDM2.Conclusion: The importance of our study is that it supports, in theory, anti-PTCH/SHH chemotherapeutics for Nigerian ameloblastoma cases andalso infers the possible additional use of anti-p53 agents

Osteocalcin, Azan and Toluidine blue staining in fibrous dysplasia and ossifying fibroma of the jaws

Background: Fibrous dysplasia (FD) and ossifying fibroma (OF) are fibro-osseous lesions (FOLs) having several overlaps that may make final diagnosis difficult by hematoxylin and eosin (H/E) alone.Aim: This study seeks to detect any association between Azan and Toluidine blue staining as compared with osteocalcin in FD and OF diagnosis.Methods: Forty formalin fixed paraffin embedded (FFPE) blocks of FD and OF were prepared for Azan, Toluidine blue and osteocalcin staining. Brown staining of calcified structures was considered as positive for osteocalcin. Scoring for Azan and Toluidine blue was evaluated based on intensity and localization. Level of agreement of original and revised diagnosis was determined.Results: Six (40%) of 15 FD were corroborated by osteocalcin. Eight cases initially diagnosed as OF were revised to FD. There were 25 OF according to H/E, and 17 (68%) were validated by osteocalcin. Measure of agreement between histology and immunohistochemistry was 0.081; p = .608. Eleven (42.3%) OF expressed strong toluidine blue staining of the intervening fibrous connective tissue stroma while only 2 (14.2%) FD showed similar staining, this difference was statistically significant [p = .001].Conclusions: Histomorphometric analysis with Toluidine blue may reduce diagnostic errors of OF and FD.Keywords: Osteocalcin, Azan, Toluidine blue, Fibrous dysplasia, Ossifying fibrom