Interaction of adult human neural crest-derived stem cells with a nanoporous titanium surface is sufficient to induce their osteogenic differentiation

Osteogenic differentiation of various adult stem cell populations such as neural crest-derived stem cells is of great interest in the context of bone regeneration. Ideally, exogenous differentiation should mimic an endogenous differentiation process, which is partly mediated by topological cues. To elucidate the osteoinductive potential of porous substrates with different pore diameters (30 nm, 100 nm), human neural crest-derived stem cells isolated from the inferior nasal turbinate were cultivated on the surface of nanoporous titanium covered membranes without additional chemical or biological osteoinductive cues. As controls, flat titanium without any topological features and osteogenic medium was used. Cultivation of human neural crest-derived stem cells on 30 nm pores resulted in osteogenic differentiation as demonstrated by alkaline phosphatase activity after seven days as well as by calcium deposition after 3 weeks of cultivation. In contrast, cultivation on flat titanium and on membranes equipped with 100 nm pores was not sufficient to induce osteogenic differentiation. Moreover, we demonstrate an increase of osteogenic transcripts including Osterix, Osteocalcin and up-regulation of Integrin β1 and α2 in the 30 nm pore approach only. Thus, transplantation of stem cells pre-cultivated on nanostructured implants might improve the clinical outcome by support of the graft adherence and acceleration of the regeneration process

Патентная система как метод налогового регулирования малого бизнеса

В современной рыночной экономике малый бизнес играет важную роль. Но существование малого бизнеса практически невозможно без активной поддержки со стороны государства, которая должна заключаться в разработке различных программ содействия малому бизнесу, в том числе формирование льготной налоговой политики, направленной на стимулирование его развития. В настоящей работе дана характеристика новой патентной системы налогообложения, введенной в действие с 2013 г., проанализированы ее основные отличия от действующих специальных налоговых режимов. Сделан вывод о том, что новая патентная система как метод налогового регулирования малого бизнеса требует существенной доработки

Ureaplasma-driven neonatal neuroinflammation: novel insights from an ovine model

Ureaplasma species (spp.) are considered commensals of the adult genitourinary tract, but have been associated with chorioamnionitis, preterm birth, and invasive infections in neonates, including meningitis. Data on mechanisms involved in Ureaplasma-driven neuroinflammation are scarce. The present study addressed brain inflammatory responses in preterm lambs exposed to Ureaplasma parvum (UP) in utero. 7 days after intra-amniotic injection of UP (n = 10) or saline (n = 11), lambs were surgically delivered at gestational day 128–129. Expression of inflammatory markers was assessed in different brain regions using qRT-PCR and in cerebrospinal fluid (CSF) by multiplex immunoassay. CSF was analyzed for UP presence using ureB-based real-time PCR, and MRI scans documented cerebral white matter area and cortical folding. Cerebral tissue levels of atypical chemokine receptor (ACKR) 3, caspases 1-like, 2, 7, and C–X–C chemokine receptor (CXCR) 4 mRNA, as well as CSF interleukin-8 protein concentrations were significantly increased in UP-exposed lambs. UP presence in CSF was confirmed in one animal. Cortical folding and white matter area did not differ among groups. The present study confirms a role of caspases and the transmembrane receptors ACKR3 and CXCR4 in Ureaplasma-driven neuroinflammation. Enhanced caspase 1-like, 2, and 7 expression may reflect cell death. Increased ACKR3 and CXCR4 expression has been associated with inflammatory central nervous system (CNS) diseases and impaired blood–brain barrier function. According to these data and previous in vitro findings from our group, we speculate that Ureaplasma-induced caspase and receptor responses affect CNS barrier properties and thus facilitate neuroinflammation

Quantitative Signal- und Artefaktuntersuchungen zur Kategorisierung von Gefäßendoprothesen in vitro : Möglichkeiten der kontrastverstärkten 3D-Magnetresonanz-Angiographie im Vergleich zur Computertomographie

For treatment of abdominal aortic aneurysms transfemoral, endovascular stented graft repair can satisfactorily be performed. Postinterventional, typical complications as endoleaks, thrombosis and structural failure are described, which make long-term follow-up imaging necessary. Computed tomography (CT) has been recommended as a primary imaging technique. However, metallic implants such as stents often cause severe artifacts (such as beam-hardening and partial volume artifacts), which can limit the assessment of both the lumen and the surrounding tissue. Additionally the required radiation dose should be considered. Three-dimensional contrast-enhanced magnetic resonance angiography (3D CE-MRA) has become competitive as a diagnostic modality. The MR compatibility of stents regarding security and visualization has already been confirmed both in vitro and in vivo. However, typical susceptibility and nonsusceptibility artifacts like eddy currents or radio-frequency shielding are known to drastically reduce MR image quality. The aim of this study is to evaluate the imaging appearance of routinely used bifurcated and tubular endoprostheses in contrast-enhanced 3D-MRA. Firstly, the influence of different sequence parameters on the representation is evaluated, in order to specify the optimal sequence for further investigations. Secondly, quantitative signal and artifact investigations allow the identification of stent characteristics in order to establish a ranking of visualization. Thirdly, these images are evaluated in comparison with the appearance of the endoprotheses in computed tomography. Finally, diagnostic recommendations are drafted for each endoprosthesis. The variation of sequence parameters shows that the echo time (TE) affects the visualization most strongly; a short echo time reduces susceptibility artifacts of gradient echo sequences. The flip angle (FA) affects the RF caging inside the stents. A flip angle of 40° provides good visualization, the application of higher flip angles may even improve in-stent visualization.A smaller field-of-view (FOV) leads to a better representation of the prosthesis lumen by reducing the signal-to-noise-ratio (SNR). A change of the water fat shift (WFS) does not affect the lumen visualization. Parameters of the optimized sequence are TR 8.1 ms, TE 1.3 ms, FA 40°, FOV 300 mm³, WFS 0.700. Both geometry of the stents and underlying material composition are associated with MR imaging artifacts. Due to the different susceptibility bifurcated protheses made from Nitinol show a better in-stent lumen visualization than stents from cobalt alloys; the stainless steel prosthesis is not MR compatible. A close meshed geometry relates to worse lumen visualization, probably because of radio frequency shielding. In CT, the influence of beamlike artifacts on the lumen visualization is evident. These mainly derive from platinum and gold markers. Finally, diagnostic recommendations are drafted for each endoprosthesis: MRA should be preferred for the bifurcated stentgrafts by Talent and Vanguard. The Gore prostheses and the Talent tubular prosthesis are suitable both for CT and MRA. CT is the prime imaging modality for AneuRx , Lifepath and Bard bifurcated stentgrafts and the only suitable imaging modality for the prostheses by Corvita and Zenith. For the Ancure prostheses the combination of both imaging modalities is recommended

Neonatal cholestasis, hyperferritinemia, hypoglycemia and deafness:a diagnostic challenge

Neonatal conjugated hyperbilirubinemia is a diagnostic challenge. A full term, small for gestational age boy presented with cholestasis, hypoglycemia, hyperferritinemia and severe bilateral deafness. Diagnostic work-up revealed two hereditary diseases: alpha-1-antitrypsin deficiency (PI*ZZ genotype) and autosomal recessive deafness type 3 (compound heterozygous MYO15A gene mutation). In addition, we found late hypoglycemia on full enteral feeding which complicated this case. Hyperferritinemia is an uncommon finding in newborn cholestasis without liver failure