Systematic Review: Adipose-Derived Mesenchymal Stem Cells,Platelet-Rich Plasma and Biomaterials as New Regenerative Strategies in Chronic Skin Wounds and Soft Tissue Defects

The number of clinical trials evaluating adipose-derived mesenchymal stem cells (AD-MSCs), platelet-rich plasma (PRP), and biomaterials efficacy in regenerative plastic surgery has exponentially increased during the last ten years. AD-MSCs are easily accessible from various fat depots and show intrinsic plasticity in giving rise to cell types involved in wound healing and angiogenesis. AD-MSCs have been used in the treatment of soft tissue defects and chronic wounds, employed in conjunction with a fat grafting technique or with dermal substitute scaffolds and platelet-rich plasma. In this systematic review, an overview of the current knowledge on this topic has been provided, based on existing studies and the authors’ experience. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, PRP, and biomaterials used in soft tissue defects and chronic wounds. Of the 2136 articles initially identified, 422 articles focusing on regenerative strategies in wound healing were selected and, consequently, only 278 articles apparently related to AD-MSC, PRP, and biomaterials were initially assessed for eligibility. Of these, 85 articles were excluded as pre-clinical, experimental, and in vitro studies. For the above-mentioned reasons, 193 articles were selected; of this amount, 121 letters, expert opinions, commentary, and editorials were removed. The remaining 72 articles, strictly regarding the use of AD-MSCs, PRP, and biomaterials in chronic skin wounds and soft tissue defects, were analyzed. The studies included had to match predetermined criteria according to the patients, intervention, comparator, outcomes, and study design (PICOS) approach. The information analyzed highlights the safety and efficacy of AD-MSCs, PRP, and biomaterials on soft tissue defects and chronic wounds, without major side effects.     

了解高级处理器特点提高编码效率

如今的数字信号处理器(DSP)在性能、外围设备集成、功耗和成本方面都具备很多优势,很多系统设计人员希望在原有系统设计中利用DSP获得比传统处理器更好的效益。但其中一个     

Blackfin处理器面向开源应用

在嵌入式应用中。随着“开源”C／C 代码越来越成为流行的用于替代基于版权算法的另一选择，挑战也随之而来。其中，最重要的问题是如何优化代码．使其在选定的处理器中更好地运行。本文将探讨开源算法在Blockfin处理器上的移植以及代码优化。     

Good teaching inputs do not correspond to desired responses in ecological neural networks

In this paper we analyze how supervised learning occurs in ecological neural networks, i.e. networks that interact with an autonomous external environment and, therefore, at least partially determine with their behavior their own input. Using an evolutionary method for selecting good teaching inputs we surprisingly find that to obtain a desired outputX it is better to use a teaching input different fromX. To explain this fact we claim that teaching inputs in ecological networks have two different effects: (a) to reduce the discrepancy between the actual output of the network and the teaching input, (b) to modify the network's behavior and, as a consequence, the network's learning experiences. Evolved teaching inputs appear to represent a compromise between these two needs. We finally show that evolved teaching inputs that are allowed to change during the learning process function differently at different stages of learning, first giving more weight to (b) and, later on, to (a).     

Synthesis and antitumor evaluation of 2,5-disubstituted-indazolo[4, 3-gh]isoquinolin-6(2H)-ones (9-aza-anthrapyrazoles)

The synthesis and antitumor evaluation of 2, 5-disubstituted-indazolo[4,3-gh]isoquinolin-6(2H)-ones (9-aza-APs) are described. The key intermediates in the synthesis are benz[g]isoquinoline-5,10-diones which are substituted at positions 6 and 9 with groups of different nucleofugacity for SNAr displacements. The initial displacement of fluoride by a substituted hydrazine leads to the pyrazole analogues. Substitution of the remaining leaving group by an amine or BOC-protected amines leads to the 9-aza-APs 12. These analogues were converted into their maleate or hydrochloride salts 13. In two cases, namely, 13x and 13z, sidearm buildup was also employed in the synthetic pathway. In vitro evaluation of 9-aza-APs against the human colon tumor cell line LoVo uncovered for most of the compounds a cytotoxic potency lower than that of DuP-941 or mitoxantrone and comparable to that of doxorubicin. Only analogues 13c, 13n, and 13ff were as cytotoxic as DuP-941. Interestingly, while DuP-941 was highly cross-resistant in the LoVo cell line resistant to doxorubicin (LoVo/Dx), the 9-aza-APs carrying a distal lipophilic tertiary amine moiety in both chains were capable of overcoming the MDR resistance induced in this cell line. The 9-aza-APs show outstanding in vivo antitumor activity against both systemic P388 murine leukemia and MX-1 human mammary carcinoma transplanted in nude mice. At their optimal dosages, congeners 13a-c, 13f, 13n, 13q, 13x, and 13dd were highly effective against P388 leukemia with T/C% of 200-381, while the T/C% value of DuP-941 was 147. In the MX-1 tumor model, 24 compounds elicited percentages of tumor weight inhibitions (TWI) ranging from 50% to 99%. Congeners 13d, 13k, 13l, 13x, 13z, and 13ee emerged as the most effective ones, with TWI% 96, simliar to that of DuP-941 (TWI% = 95). On the basis of their efficacy profile in additional experimental tumors and lack of cardiotoxicity in preclinical models, two congeners have surfaced as potential clinical candidates.     

The Tenet experience and the design of protocols for integrated-services internetworks

The research done by the Tenet Group in multimedia networking has reached a point where it may be useful to reflect on the significance of its results for the current debate on how integrated-services internetworks should be designed. Such reflections constitute the main subject of this paper. The principles of the work and the conclusions reached so far by the Tenet researchers are discussed in the light of the conflict between the two major technologies being proposed to build future information infrastructures: namely, the Internet and the ATM technologies. The Tenet approach suggests one feasible way for resolving the conflict to the advantage of all the users of those infrastructures. This paper discusses various fundamental aspects of integrated-services network design: the choice of the service model, the type of charging policy to be adopted, and the selection of a suitable architecture.     

Simultaneous detection of HPV and other sexually transmitted agents in chronic urethritis

Three tests are routinely done to assess blood status of selenium in cattle: serum selenium, whole blood selenium, and glutathione peroxidase. The objective of this study was to compare the various analytical methods for determining blood selenium status in groups of mature cows and beef calves. Twenty to 30 blood samples per herd were collected from 8 beef herds in central Alberta and 1 dairy in Alberta herd twice a year from the spring of 1992 through the fall of 1995, and once from 185 spring calves in 2 beef herds in Saskatchewan. Serum and whole blood samples were submitted to 1 laboratory and whole blood samples were submitted to a 2nd laboratory. Samples for glutathione peroxidase determinations were submitted to a 3rd laboratory. Pearson's correlation coefficients and Cohen's kappa were calculated for each possible comparison among the different measures. The best agreement was observed between serum and whole blood analysis within Laboratory A. The remaining comparisons reflected poor agreement. Comparison of herd-level assessment resulted in better agreement than comparison of individual sample results among laboratories and procedures for all combinations tested. Serum selenium analysis was the only laboratory procedure for which external reference material was utilized. Serum selenium, whole blood selenium, and glutathione peroxidase measure different compartments of the blood selenium pool. The time frame of interest, supplementation practices, and the stability of recent dietary intake determine the optimum assessment method for individual animals or herds. Determination of the serum status or of blood selenium is more consistently measured at the herd-level than for individual samples.     

High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer’s Disease Signatures

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.     

Confocal Blood Flow Videomicroscopy of Thrombus Formation over Human Arteries and Local Targeting of P2X7

Atherothrombosis exposes vascular components to blood. Currently, new antithrombotic therapies are emerging. Herein we investigated thrombogenesis of human arteries with/without atherosclerosis, and the interaction of coagulation and vascular components, we and explored the anti-thrombogenic efficacy of blockade of the P2X purinoceptor 7 (P2X7). A confocal blood flow videomicroscopy system was performed on cryosections of internal mammary artery (IMA) or carotid plaque (CPL) determining/localizing platelets and fibrin. Blood from healthy donors elicited thrombi over arterial layers. Confocal microscopy associated thrombus with tissue presence of collagen type I, laminin, fibrin(ogen) and tissue factor (TF). The addition of antibodies blocking TF (aTF) or factor XI (aFXI) to blood significantly reduced fibrin deposition, variable platelet aggregation and aTF + aFXI almost abolished thrombus formation, showing synergy between coagulation pathways. A scarce effect of aTF over sub-endothelial regions, more abundant in tissue TF and bundles of laminin and collagen type I than deep intima, may suggest tissue thrombogenicity as molecular structure-related. Consistently with TF-related vascular function and expression of P2X7, the sections from CPL but not IMA tissue cultures pre-treated with the P2X7 antagonist A740003 demonstrated poor thrombogenesis in flow experiments. These data hint to local targeting studies on P2X7 modulation for atherothrombosis prevention/therapy.